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Barbier F, Buetti N, Dupuis C, Schwebel C, Azoulay É, Argaud L, Cohen Y, Hong Tuan Ha V, Gainnier M, Siami S, Forel JM, Adrie C, de Montmollin É, Reignier J, Ruckly S, Zahar JR, Timsit JF. Prognostic Impact of Early Appropriate Antimicrobial Therapy in Critically Ill Patients With Nosocomial Pneumonia Due to Gram-Negative Pathogens: A Multicenter Cohort Study. Crit Care Med 2025:00003246-990000000-00481. [PMID: 40009040 DOI: 10.1097/ccm.0000000000006606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/27/2025]
Abstract
OBJECTIVES To evaluate whether early appropriate antimicrobial therapy (EAAT) is associated with improved outcomes in critically ill patients with hospital-acquired pneumonia (HAP), ventilated HAP (vHAP), or ventilator-associated pneumonia (VAP) involving Gram-negative bacteria (GNB). DESIGN Retrospective cohort study based on prospectively collected data. SETTING Thirty-two-French ICUs (OutcomeRéa network). PATIENTS All patients with a first HAP, vHAP, or VAP due to GNB during their ICU stay. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS The relationship between EAAT and day 28 all-cause mortality (primary endpoint) was explored through Cox proportional-hazard models, with subgroup analyses according to pneumonia types, causative GNB, features of EAAT, and the occurrence of septic shock at pneumonia diagnosis. The course of Sequential Organ Failure Assessment (SOFA) score values, the clinical cure rate at day 14, and the time to mechanical ventilation (MV) weaning and ICU discharge after pneumonia diagnosis were investigated as secondary endpoints. Among the 804 included patients, 495 (61.6%) received EAAT (single-drug, 25.4%; combination, 36.2%). Day 28 mortality was 32.6%. EAAT was not independently associated with this outcome (adjusted hazard ratio, 0.87; 95% CI, 0.67-1.12). This result was confirmed in subgroup analyses as in a second model considering all episodes of pneumonia occurring during the ICU stay. EAAT was not associated with a faster decrease in SOFA score values (p = 0.11), a higher day 14 clinical cure rate (overall, 43.7%), or a shorter MV duration (cause-specific hazard ratio [HR] for extubation, 0.84; 95% CI, 0.69-1.01) or ICU stay (cause-specific HR for discharge alive, 0.85; 95% CI, 0.72-1.00). CONCLUSIONS In this study, EAAT was not associated with a reduced day 28 mortality, a faster resolution of organ failure, a higher day 14 clinical cure rate, or a shorter time to MV weaning or ICU discharge in critically ill patients with HAP, vHAP, or VAP due to GNB. However, a prognostic benefit from EAAT cannot be ruled out due to lack of statistical power.
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Affiliation(s)
- François Barbier
- Médecine Intensive Réanimation, Centre Hospitalier Universitaire d'Orléans, Orléans, France
| | - Niccolò Buetti
- Infection Control Programme, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland
- IAME UMR 1137, INSERM, Université Paris-Cité, Paris, France
| | - Claire Dupuis
- Médecine Intensive Réanimation, Centre Hospitalier Universitaire Gabriel Montpied, Clermont-Ferrand, France
| | - Carole Schwebel
- Médecine Intensive Réanimation, Centre Hospitalier Universitaire Grenoble-Alpes, La Tronche, France
| | - Élie Azoulay
- Médecine Intensive Réanimation, Centre Hospitalier Universitaire Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Laurent Argaud
- Médecine Intensive Réanimation, Centre Hospitalier Universitaire Edouard Herriot, Hospices Civils de Lyon, Lyon, France
| | - Yves Cohen
- Médecine Intensive Réanimation, Centre Hospitalier Universitaire Avicenne, Assistance Publique-Hôpitaux de Paris, Bobigny, France
| | | | - Marc Gainnier
- Réanimation des Urgences, Centre Hospitalier Universitaire La Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France
| | - Shidasp Siami
- Réanimation Polyvalente, Centre Hospitalier Sud-Essonne, Étampes, France
| | - Jean-Marie Forel
- Médecine Intensive Réanimation, Centre Hospitalier Universitaire Nord, Assistance Publique-Hôpitaux de Marseille, Marseille, France
| | - Christophe Adrie
- Réanimation Polyvalente, Centre Hospitalier Delafontaine, Saint-Denis, France
| | - Étienne de Montmollin
- Service de Médecine Intensive et Réanimation Infectieuse, Centre Hospitalier Universitaire Bichat-Claude Bernard, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Jean Reignier
- Médecine Intensive Réanimation, Centre Hospitalier Universitaire de Nantes, Nantes, France
| | | | - Jean-Ralph Zahar
- IAME UMR 1137, INSERM, Université Paris-Cité, Paris, France
- Département de Microbiologie Clinique, Centre Hospitalier Universitaire Avicenne, Assistance Publique-Hôpitaux de Paris, Bobigny, France
| | - Jean-François Timsit
- IAME UMR 1137, INSERM, Université Paris-Cité, Paris, France
- Service de Médecine Intensive et Réanimation Infectieuse, Centre Hospitalier Universitaire Bichat-Claude Bernard, Assistance Publique-Hôpitaux de Paris, Paris, France
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Shanmugavel Geetha H, Teo YX, Ravichandran S, Lal A. Ventilator-Associated Pneumonia After Cardiac Arrest and Prevention Strategies: A Narrative Review. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:78. [PMID: 39859060 PMCID: PMC11767168 DOI: 10.3390/medicina61010078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Revised: 12/24/2024] [Accepted: 01/03/2025] [Indexed: 01/27/2025]
Abstract
Background and Objectives: Ventilator-associated pneumonia (VAP) poses a significant threat to the clinical outcomes and hospital stays of mechanically ventilated patients, particularly those recovering from cardiac arrest. Given the already elevated mortality rates in cardiac arrest cases, the addition of VAP further diminishes the chances of survival. Consequently, a paramount focus on VAP prevention becomes imperative. This review endeavors to comprehensively delve into the nuances of VAP, specifically in patients requiring mechanical ventilation in post-cardiac arrest care. The overarching objectives encompass (I) exploring the etiology, risk factors, and pathophysiology of VAP, (II) delving into available diagnostic modalities, and (III) providing insights into the management options and recent treatment guidelines. Methods: A literature search was conducted using PubMed, MEDLINE, and Google Scholar databases for articles about VAP and Cardiac arrest. We used the MeSH terms "VAP", "Cardiac arrest", "postcardiac arrest syndrome", and "postcardiac arrest syndrome". The clinical presentation, diagnostic, and management strategies of VAP were summarized, and all authors reviewed the selection and decided which studies to include. Key Content and Findings: The incidence and mortality rates of VAP exhibit significant variability, yet a recurring pattern emerges, marked by prolonged hospitalization and exacerbated clinical outcomes. This pattern is attributed to the elevated incidence of drug-resistant infections and the delayed initiation of antimicrobial treatment. This review focuses on VAP, aiming to offer valuable insights into the efficient identification and management of this fatal complication in post-cardiac arrest patients. Conclusion: The prognosis for survival after cardiac arrest is already challenging, and the outlook becomes even more daunting when complicated by VAP. The timely diagnosis of VAP and initiation of antibiotics pose considerable challenges, primarily due to the invasive nature of obtaining high-quality samples and the time required for speciation and identification of antimicrobial sensitivity. The controversy surrounding prophylactic antibiotics persists, but promising new strategies have been proposed; however, they are still awaiting well-designed clinical trials.
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Affiliation(s)
| | - Yi Xiang Teo
- Division of Pulmonary and Critical Care Medicine, UMass-Baystate Hospital, Springfield, MA 01107, USA;
| | - Sharmitha Ravichandran
- Department of Internal Medicine, Saint Vincent Hospital, Worcester, MA 01608, USA; (H.S.G.)
| | - Amos Lal
- Division of Pulmonary and Critical Care Medicine Mayo Clinic, Rochester, MN 55905, USA
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Oh Y, Kim K, Kim HJ, Hong SB, Lim CM, Koh Y, Ahn HS, Huh JW. Proteome signature for differential diagnosis of patients with bilateral lung infiltrates. ERJ Open Res 2025; 11:00762-2024. [PMID: 39963163 PMCID: PMC11831621 DOI: 10.1183/23120541.00762-2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Accepted: 08/05/2024] [Indexed: 02/20/2025] Open
Abstract
Background The differential diagnosis of bilateral lung infiltrates and prognosis prediction can be challenging for clinicians in the intensive care unit (ICU). We analysed the proteome from bronchoalveolar lavage fluid (BALF) and determined its usefulness for evaluating the infectious causes and mortality associated with bilateral lung infiltrates. Methods In the ICU cohort, 136 patients with bilateral infiltrate on chest radiographs were selected, and bronchoscopy with bronchoalveolar lavage (BAL) was performed. Proteomic profiling of the exosomes in the BALF (n=20) was conducted to identify candidate protein biomarkers potentially associated with infection or mortality. The BAL samples (n=116) were used to measure the candidate biomarker levels. Results The candidate biomarkers, CD20, CLIC4, SCFD1 and TAP1, were selected for the differential diagnosis of infection or mortality. The levels of CD20 were significantly elevated in patients with non-infectious causes, compared with those with infectious causes (248.6±154.5 versus 177.6±150.9 ng·mL-1, p=0.014). The levels of CLIC4, SCFD1 and TAP1 did not differ between the two groups. As per the receiver operating characteristic analysis, CD20 was a significant predictor of non-infectious causes (area under curve 0.668; 95% confidence interval 0.567-0.769; p=0.002; cut-off value 167.6 ng·mL-1; sensitivity 74.1%; specificity 63.2%). There were no significant differences in the concentrations of the biomarkers between survivors and non-survivors. Conclusions Our results suggest that CD20 levels in BALF might be a useful biomarker for differentiating non-infectious and infectious diseases in patients with bilateral lung infiltrates.
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Affiliation(s)
- Yumi Oh
- Department of Digital Medicine, BK21 project, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
- Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea
- These authors contributed equally
| | - Kyunggon Kim
- Department of Digital Medicine, BK21 project, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
- Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea
- These authors contributed equally
| | - Ho Jeong Kim
- Department of Pulmonary and Critical Care Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Sang-Bum Hong
- Department of Pulmonary and Critical Care Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Chae-Man Lim
- Department of Pulmonary and Critical Care Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Younsuck Koh
- Department of Pulmonary and Critical Care Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Hee-Sung Ahn
- AMC science, Asan Medical Center, Seoul, Republic of Korea
| | - Jin Won Huh
- Department of Digital Medicine, BK21 project, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
- Department of Pulmonary and Critical Care Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
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Xu T, Shen Q, He Y, Pan X, Huang H, Xu H. Value of bronchial amylase level for predicting ventilator associated pneumonia in intubated adults: a systematic review and meta-analysis. BMC Pulm Med 2024; 24:571. [PMID: 39550558 PMCID: PMC11569614 DOI: 10.1186/s12890-024-03393-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Accepted: 11/12/2024] [Indexed: 11/18/2024] Open
Abstract
BACKGROUND The ability of bronchial amylase level for predicting ventilator associated pneumonia (VAP) has been extensively studied with conflicting results. This meta-analysis aimed to explore the value of bronchial amylase for predicting VAP in intubated adults. METHODS PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched up to November 2023. The diagnostic odds ratio (DOR), sensitivity, and specificity were calculated. The summary receiver operating characteristic curve was estimated, and the area under the curve (AUROC) was calculated. RESULTS Overall, six studies including 769 patients were included in this review, of whom 273 (36%) were developed VAP. The cutoff values of bronchial amylase level were ranged from 8.1 U/L to 4681.5U/L. Heterogeneity between studies was assessed with an overall Q = 1.99, I2 = 0, and P = 0.185, The pooled sensitivity and specificity for the overall population were 0.78 [95% confidence interval (CI) 0.67-0.86] and 0.75(95% CI 0.56-0.88) respectively. The DOR was 11(95% CI 3.0-40.0). The pooled AUROC was 0.83 (95%CI 0.80-0.86). CONCLUSIONS The bronchial amylase is a helpful marker for predicting VAP in intubated adults. However, it cannot be recommended as the single definitive test for VAP, but rather it must be interpreted in context with information from careful medical history, physical examination, and when feasible, microbiological assessment.
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Affiliation(s)
- Tingzhen Xu
- Department of Emergency, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Zhejiang, 310018, Hangzhou, China
| | - Qinkang Shen
- Department of Emergency, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Zhejiang, 310018, Hangzhou, China
| | - Yuting He
- Department of Emergency, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Zhejiang, 310018, Hangzhou, China
| | - Xiaozhuang Pan
- Department of Emergency, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Zhejiang, 310018, Hangzhou, China
| | - Haijun Huang
- Department of Emergency, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Zhejiang, 310018, Hangzhou, China.
| | - Hua Xu
- Department of Emergency, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Zhejiang, 310018, Hangzhou, China.
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Röder M, Ng AYKC, Conway Morris A. Bronchoscopic Diagnosis of Severe Respiratory Infections. J Clin Med 2024; 13:6020. [PMID: 39408080 PMCID: PMC11477651 DOI: 10.3390/jcm13196020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 10/01/2024] [Accepted: 10/08/2024] [Indexed: 10/20/2024] Open
Abstract
The diagnosis of severe respiratory infections in intensive care remains an area of uncertainty and involves a complex balancing of risks and benefits. Due to the frequent colonisation of the lower respiratory tract in mechanically ventilated patients, there is an ever-present possibility of microbiological samples being contaminated by bystander organisms. This, coupled with the frequency of alveolar infiltrates arising from sterile insults, risks over-treatment and antimicrobial-associated harm. The use of bronchoscopic sampling to obtain protected lower respiratory samples has long been advocated to overcome this problem. The use of bronchoscopy further enables accurate cytological assessment of the alveolar space and direct inspection of the proximal airways for signs of fungal infection or alternative pathologies. With a growing range of molecular techniques, including those based on nucleic acid amplification and even alveolar visualisation and direct bacterial detection, the potential for bronchoscopy is increasing concomitantly. Despite this, there remain concerns regarding the safety of the technique and its benefits versus less invasive sampling techniques. These discussions are reflected in the lack of consensus among international guidelines on the topic. This review will consider the benefits and challenges of diagnostic bronchoscopy in the context of severe respiratory infection.
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Affiliation(s)
- Maire Röder
- School of Clinical Medicine, Addenbrooke’s Hospital, University of Cambridge, Hills Road, Cambridge CB2 0QQ, UK;
| | | | - Andrew Conway Morris
- Department of Medicine, Addenbrooke’s Hospital, University of Cambridge, Hills Road, Cambridge CB2 0QQ, UK;
- Division of Immunology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 0QQ, UK
- JVF Intensive Care Unit, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, UK
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Dong T, Wang Y, Qi C, Fan W, Xie J, Chen H, Zhou H, Han X. Sequencing Methods to Study the Microbiome with Antibiotic Resistance Genes in Patients with Pulmonary Infections. J Microbiol Biotechnol 2024; 34:1617-1626. [PMID: 39113195 PMCID: PMC11380506 DOI: 10.4014/jmb.2402.02004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Revised: 05/20/2024] [Accepted: 05/29/2024] [Indexed: 08/29/2024]
Abstract
Various antibiotic-resistant bacteria (ARB) are known to induce repeated pulmonary infections and increase morbidity and mortality. A thorough knowledge of antibiotic resistance is imperative for clinical practice to treat resistant pulmonary infections. In this study, we used a reads-based method and an assembly-based method according to the metagenomic next-generation sequencing (mNGS) data to reveal the spectra of ARB and corresponding antibiotic resistance genes (ARGs) in samples from patients with pulmonary infections. A total of 151 clinical samples from 144 patients with pulmonary infections were collected for retrospective analysis. The ARB and ARGs detection performance was compared by the reads-based method and assembly-based method with the culture method and antibiotic susceptibility testing (AST), respectively. In addition, ARGs and the attribution relationship of common ARB were analyzed by the two methods. The comparison results showed that the assembly-based method could assist in determining pathogens detected by the reads-based method as true ARB and improve the predictive capabilities (46% > 13%). ARG-ARB network analysis revealed that assembly-based method could promote determining clear ARG-bacteria attribution and 101 ARGs were detected both in two methods. 25 ARB were obtained by both methods, of which the most predominant ARB and its ARGs in the samples of pulmonary infections were Acinetobacter baumannii (ade), Pseudomonas aeruginosa (mex), Klebsiella pneumoniae (emr), and Stenotrophomonas maltophilia (sme). Collectively, our findings demonstrated that the assembly-based method could be a supplement to the reads-based method and uncovered pulmonary infection-associated ARB and ARGs as potential antibiotic treatment targets.
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Affiliation(s)
- Tingyan Dong
- Integrated Diagnostic Centre for Infectious Diseases, Guangzhou Huayin Medical Laboratory Center, Guangzhou, P.R. China
- Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Sciences, Medical School, Nanjing University, Nanjing, P.R. China
| | - Yongsi Wang
- Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Sciences, Medical School, Nanjing University, Nanjing, P.R. China
| | - Chunxia Qi
- Department of Hospital Infection Management, NanFang Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Wentao Fan
- Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Sciences, Medical School, Nanjing University, Nanjing, P.R. China
| | - Junting Xie
- Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Sciences, Medical School, Nanjing University, Nanjing, P.R. China
| | - Haitao Chen
- Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Sciences, Medical School, Nanjing University, Nanjing, P.R. China
| | - Hao Zhou
- Department of Hospital Infection Management, NanFang Hospital, Southern Medical University, Guangzhou, P.R. China
| | - Xiaodong Han
- Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Sciences, Medical School, Nanjing University, Nanjing, P.R. China
- Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, P.R. China
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Srivastava S, Sharad N, Kiro VV, Ningombam A, Shrivastava S, Farooque K, Mathur P. Utility of a multiplex pathogen detection system directly from respiratory specimens for treatment and diagnostic stewardship. Microbiol Spectr 2024; 12:e0375923. [PMID: 38712971 PMCID: PMC11237763 DOI: 10.1128/spectrum.03759-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Accepted: 03/29/2024] [Indexed: 05/08/2024] Open
Abstract
The availability of syndrome-based panels for various ailments has widened the scope of diagnostics in many clinical settings. These panels can detect a multitude of pathogens responsible for a particular condition, which can lead to a timely diagnosis and better treatment outcomes. In contrast to traditional identification methods based on pathogen growth on culture, syndrome-based panels offer a quicker diagnosis, which can be especially beneficial in situations requiring urgent care, such as intensive care units. One such panel is the Biofire Filmarray Pneumonia plus Panel (BFP), which we have compared against microbiological culture and identification. The lower respiratory samples from patients were tested with BFP, culture, and identification with culture considered the gold standard. The phenotypic antibiotic susceptibility results (Vitek 2) were compared with the antimicrobial resistance (AMR) genes detected in BFP. Statistical analysis was carried out using GraphPad 7.0 and MS Excel (Microsoft Inc.). The results showed a positive percent agreement of 100% and a negative percent agreement of 47.8% with an overall agreement of 76.72% compared to culture. BFP was better at identifying fastidious bacteria, and the agreement with culture was higher for high bacterial identification numbers (107 and 106). There was also a correlation between the number of pathogens detected and growth in culture. Carbapenemase genes were detected in around 80% of phenotypically resistant samples and correlated with in-house PCR 60% of the time. Hence, BFP results need to be interpreted with caution especially when multiple pathogens are detected. Similarly, the presence or absence of AMR genes should be used to guide the therapy while being watchful of unusual resistance or susceptibility. The cost constraints and low throughput call for patient selection criteria and prioritization in emergency or resource-limited conditions.IMPORTANCEApplication of syndrome-based panels in clinical microbiology is of huge support in infectious conditions requiring urgent interventions, such as pneumonia. Interpreting the results requires caution; hence, we have compared the results obtained from Biofire Filmarray Pneumonia plus Panel with standard microbiological methods.
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Affiliation(s)
| | - Neha Sharad
- Department of Microbiology, AIIMS, New Delhi, India
| | | | - Aparna Ningombam
- Department of Laboratory Medicine, JPNATC, AIIMS, New Delhi, India
| | | | | | - Purva Mathur
- Department of Laboratory Medicine, JPNATC, AIIMS, New Delhi, India
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Duputié G, Darrouzain F, Forme N, Cohen B, Rémérand F, Miguel Montanes R. Subtherapeutic beta-lactam plasma concentrations in critically ill burned patients in the era of continuous intravenous administration. Burns 2024; 50:1352-1354. [PMID: 38494396 DOI: 10.1016/j.burns.2024.03.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 03/05/2024] [Indexed: 03/19/2024]
Affiliation(s)
- Germain Duputié
- Anaesthesia and Critical Care Department, Tours University Hospital, Tours, France; Faculty of Medicine, Tours University, France
| | - François Darrouzain
- Department of Pharmacology and Toxicology, Tours University Hospital, Tours, France
| | - Nathalie Forme
- Maxillofacial and Plastic Surgery Department, Tours University Hospital, Tours, France
| | - Benjamin Cohen
- Anaesthesia and Critical Care Department, Tours University Hospital, Tours, France
| | - Francis Rémérand
- Anaesthesia and Critical Care Department, Tours University Hospital, Tours, France; UMR 1253, iBrain, Université de Tours, Inserm, Tours, France
| | - Romain Miguel Montanes
- Anaesthesia and Critical Care Department, Tours University Hospital, Tours, France; LIPHA, Gustave Eiffel University, Marne-la-Vallée, France.
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Hoblick S, Denagamage TN, Morton AJ, McCarrel TM. Antimicrobial prophylaxis is not indicated for horses undergoing general anaesthesia for elective orthopaedic MRI. Equine Vet J 2024; 56:475-483. [PMID: 37531950 DOI: 10.1111/evj.13978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Accepted: 07/18/2023] [Indexed: 08/04/2023]
Abstract
BACKGROUND Post-anaesthetic fever is a known complication of general anaesthesia, however, its incidence in horses undergoing elective magnetic resonance imaging (MRI) is unknown. OBJECTIVE To determine the incidence of post-anaesthetic fever in horses undergoing elective orthopaedic MRI and determine whether prophylactic antimicrobial therapy would be associated with a reduction in the incidence of post-anaesthetic fever. We hypothesised that prophylactic antimicrobials would be associated with a reduction in the incidence of post-anaesthetic fever. STUDY DESIGN Retrospective cross-sectional study. METHODS This retrospective study included 791 elective orthopaedic MRIs in systemically healthy horses between June 2006 and March 2020 that recovered from general anaesthesia and did not undergo surgery or intensive medical therapy soon after recovery. Potential factors associated with post-anaesthetic fever were evaluated using multivariable logistic regression. Case signalment, travel time, preanaesthetic haematology and fibrinogen abnormalities, use of prophylactic antimicrobials, peri-anaesthetic nonsteroidal anti-inflammatories, anaesthesia time and recovery time were all evaluated for association with post-anaesthetic fever. RESULTS Of 791 MRI cases, 44 (5.6%) developed a post-anaesthetic fever. Horses that received prophylactic antimicrobials were [odds ratio (OR) 3.8, 95% confidence interval (CI) 1.98-7.46; p ≤ 0.001] more likely to develop a post-anaesthetic fever than those that did not receive antimicrobials. Young horses (1-4 years of age) were (OR 2.8, 95% CI 1.26-6.17; p = 0.01) more likely to develop fever compared with adult horses (≥5 years of age). MAIN LIMITATIONS Limitations of this study pertain to retrospective analysis including nonrandomised case selection and incomplete data records. CONCLUSIONS While fever may indicate infection, the majority of early post-anaesthetic fevers resolved before discharge from the hospital with no identified cause. The use of prophylactic antimicrobials to reduce the risk of post-anaesthetic fever for elective MRI is not supported by this study.
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Affiliation(s)
- Sloane Hoblick
- Department of Large Animal Clinical Sciences, University of Florida College of Veterinary Medicine, Gainesville, Florida, USA
| | - Thomas N Denagamage
- Department of Large Animal Clinical Sciences, University of Florida College of Veterinary Medicine, Gainesville, Florida, USA
| | - Alison J Morton
- Department of Large Animal Clinical Sciences, University of Florida College of Veterinary Medicine, Gainesville, Florida, USA
| | - Taralyn M McCarrel
- Department of Large Animal Clinical Sciences, University of Florida College of Veterinary Medicine, Gainesville, Florida, USA
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Chen CL, Tseng HY, Chen WC, Liang SJ, Tu CY, Lin YC, Hsueh PR. Application of a multiplex molecular pneumonia panel and real-world impact on antimicrobial stewardship among patients with hospital-acquired and ventilator-associated pneumonia in intensive care units. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2024:S1684-1182(24)00037-9. [PMID: 38471985 DOI: 10.1016/j.jmii.2024.02.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Accepted: 02/08/2024] [Indexed: 03/14/2024]
Abstract
BACKGROUND The optimal timing for applying the BioFire FilmArray Pneumonia Panel (FAPP) in intensive care unit (ICU) patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) remains undefined, and there are limited data on its impact on antimicrobial stewardship. METHODS This retrospective study was conducted at a referral hospital in Taiwan from November 2019 to October 2022. Adult ICU patients with HAP/VAP who underwent FAPP testing were enrolled. Patient data, FAPP results, conventional microbiological testing results, and the real-world impact of FAPP results on antimicrobial therapy adjustments were assessed. Logistic regression was used to determine the predictive factors for bacterial detection by FAPP. RESULTS Among 592 respiratory specimens, including 564 (95.3%) endotracheal aspirate specimens, 19 (3.2%) expectorated sputum specimens and 9 (1.5%) bronchoalveolar lavage specimens, from 467 patients with HAP/VAP, FAPP testing yielded 368 (62.2%) positive results. Independent predictors for positive bacterial detection by FAPP included prolonged hospital stay (odds ratio [OR], 3.14), recent admissions (OR, 1.59), elevated C-reactive protein levels (OR, 1.85), Acute Physiology and Chronic Health Evaluation II scores (OR, 1.58), and septic shock (OR, 1.79). Approximately 50% of antimicrobial therapy for infections caused by Gram-negative bacteria and 58.4% for Gram-positive bacteria were adjusted or confirmed after obtaining FAPP results. CONCLUSIONS This study identified several factors predicting bacterial detection by FAPP in critically ill patients with HAP/VAP. More than 50% real-world clinical practices were adjusted or confirmed based on the FAPP results. Clinical algorithms for the use of FAPP and antimicrobial stewardship guidelines may further enhance its benefits.
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Affiliation(s)
- Chieh-Lung Chen
- Division of Pulmonary and Critical Care, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - How-Yang Tseng
- Division of Pulmonary and Critical Care, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - Wei-Cheng Chen
- Division of Pulmonary and Critical Care, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan; Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; Department of Education, China Medical University Hospital, Taichung, Taiwan
| | - Shinn-Jye Liang
- Division of Pulmonary and Critical Care, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - Chih-Yen Tu
- Division of Pulmonary and Critical Care, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan
| | - Yu-Chao Lin
- Division of Pulmonary and Critical Care, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan.
| | - Po-Ren Hsueh
- Departments of Laboratory Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan; Division of Infectious Diseases, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan; Department of Laboratory Medicine, School of Medicine, China Medical University, Taichung, Taiwan.
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11
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Guillamet CV, Kollef MH. Is Zero Ventilator-Associated Pneumonia Achievable? Updated Practical Approaches to Ventilator-Associated Pneumonia Prevention. Infect Dis Clin North Am 2024; 38:65-86. [PMID: 38040518 DOI: 10.1016/j.idc.2023.11.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2023]
Abstract
Ventilator-associated pneumonia (VAP) remains a significant clinical entity with reported incidence rates of 7% to 15%. Given the considerable adverse consequences associated with this infection, VAP prevention became a core measure required in most US hospitals. Many institutions took pride in implementing effective VAP prevention bundles that combined at least head of bed elevation, hand hygiene, chlorhexidine oral care, and subglottic drainage. Spontaneous breathing and awakening trials have also consistently been shown to shorten the duration of mechanical ventilation and secondarily reduce the occurrence of VAP.
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Affiliation(s)
| | - Marin H Kollef
- Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO, USA.
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12
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Martin M, Forveille S, Lascarrou JB, Seguin A, Canet E, Lemarié J, Agbakou M, Desmedt L, Blonz G, Zambon O, Corvec S, Le Thuaut A, Reignier J. Immediate vs. culture-initiated antibiotic therapy in suspected non-severe ventilator-associated pneumonia: a before-after study (DELAVAP). Ann Intensive Care 2024; 14:33. [PMID: 38411756 PMCID: PMC10897643 DOI: 10.1186/s13613-024-01243-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Accepted: 01/02/2024] [Indexed: 02/28/2024] Open
Abstract
BACKGROUND Ventilator-associated pneumonia (VAP) is the leading nosocomial infection in critical care and is associated with adverse outcomes. When VAP is suspected, starting antibiotic therapy (AT) immediately after pulmonary sampling may expose uninfected patients to unnecessary treatment, whereas waiting for bacteriological confirmation may delay AT in infected patients. As no robust data exist to choose between these strategies, the decision must balance the pre-test diagnostic probability, clinical severity, and risk of antimicrobial resistance. The objective of this study in patients with suspected non-severe VAP was to compare immediate AT started after sampling to conservative AT upon receipt of positive microbiological results. The outcomes were antibiotic sparing, AT suitability, and patient outcomes. METHODS This single-center, before-after study included consecutive patients who underwent distal respiratory sampling for a first suspected non-severe VAP episode (no shock requiring vasopressor therapy or severe acute respiratory distress syndrome). AT was started immediately after sampling in 2019 and upon culture positivity in 2022 (conservative strategy). The primary outcome was the number of days alive without AT by day 28. The secondary outcomes were mechanical ventilation duration, day-28 mortality, and AT suitability (active necessary AT or spared AT). RESULTS The immediate and conservative strategies were applied in 44 and 43 patients, respectively. Conservative and immediate AT were associated with similar days alive without AT (median [interquartile range], 18.0 [0-21.0] vs. 16.0 [0-20.0], p = 0.50) and without broad-spectrum AT (p = 0.53) by day 28. AT was more often suitable in the conservative group (88.4% vs. 63.6%, p = 0.01), in which 27.9% of patients received no AT at all. No significant differences were found for mechanical ventilation duration (median [95%CI], 9.0 [6-19] vs. 9.0 [6-24] days, p = 0.65) or day-28 mortality (hazard ratio [95%CI], 0.85 [0.4-2.0], p = 0.71). CONCLUSION In patients with suspected non-severe VAP, waiting for microbiological confirmation was not associated with antibiotic sparing, compared to immediate AT. This result may be ascribable to low statistical power. AT suitability was better with the conservative strategy. None of the safety outcomes differed between groups. These findings would seem to allow a large, randomized trial comparing immediate and conservative AT strategies.
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Affiliation(s)
- Maëlle Martin
- Nantes Université, CHU Nantes, Médecine Intensive Réanimation, Nantes, France.
| | - Solène Forveille
- Nantes Université, CHU Nantes, Médecine Intensive Réanimation, Nantes, France
| | | | - Amélie Seguin
- Nantes Université, CHU Nantes, Médecine Intensive Réanimation, Nantes, France
| | - Emmanuel Canet
- Nantes Université, CHU Nantes, Médecine Intensive Réanimation, Nantes, France
| | - Jérémie Lemarié
- Nantes Université, CHU Nantes, Médecine Intensive Réanimation, Nantes, France
| | - Maïté Agbakou
- Nantes Université, CHU Nantes, Médecine Intensive Réanimation, Nantes, France
| | - Luc Desmedt
- Nantes Université, CHU Nantes, Médecine Intensive Réanimation, Nantes, France
| | - Gauthier Blonz
- Nantes Université, CHU Nantes, Médecine Intensive Réanimation, Nantes, France
| | - Olivier Zambon
- Nantes Université, CHU Nantes, Médecine Intensive Réanimation, Nantes, France
| | - Stéphane Corvec
- Nantes Université, CHU Nantes, Institut de Biologie des Hôpitaux de Nantes, Service de Bactériologie Et Des Contrôles Microbiologiques, Nantes, France
| | - Aurélie Le Thuaut
- Nantes Université, CHU Nantes, Plateforme de méthodologie et biostatistique, Direction de la recherche et de l'innovation, Nantes, France
| | - Jean Reignier
- Nantes Université, CHU Nantes, Médecine Intensive Réanimation, Nantes, France
- Nantes Université, CHU Nantes, Médecine Intensive Réanimation, Movement - Interactions - Performance, MIP, UR 4334, Nantes, France
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13
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Dung TTN, Phat VV, Vinh C, Lan NPH, Phuong NLN, Ngan LTQ, Thwaites G, Thwaites L, Rabaa M, Nguyen ATK, Duy PT. Development and validation of multiplex real-time PCR for simultaneous detection of six bacterial pathogens causing lower respiratory tract infections and antimicrobial resistance genes. BMC Infect Dis 2024; 24:164. [PMID: 38326753 PMCID: PMC10848345 DOI: 10.1186/s12879-024-09028-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2023] [Accepted: 01/18/2024] [Indexed: 02/09/2024] Open
Abstract
BACKGROUND Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, Streptococcus pneumoniae and Staphylococcus aureus are major bacterial causes of lower respiratory tract infections (LRTIs) globally, leading to substantial morbidity and mortality. The rapid increase of antimicrobial resistance (AMR) in these pathogens poses significant challenges for their effective antibiotic therapy. In low-resourced settings, patients with LRTIs are prescribed antibiotics empirically while awaiting several days for culture results. Rapid pathogen and AMR gene detection could prompt optimal antibiotic use and improve outcomes. METHODS Here, we developed multiplex quantitative real-time PCR using EvaGreen dye and melting curve analysis to rapidly identify six major pathogens and fourteen AMR genes directly from respiratory samples. The reproducibility, linearity, limit of detection (LOD) of real-time PCR assays for pathogen detection were evaluated using DNA control mixes and spiked tracheal aspirate. The performance of RT-PCR assays was subsequently compared with the gold standard, conventional culture on 50 tracheal aspirate and sputum specimens of ICU patients. RESULTS The sensitivity of RT-PCR assays was 100% for K. pneumoniae, A. baumannii, P. aeruginosa, E. coli and 63.6% for S. aureus and the specificity ranged from 87.5% to 97.6%. The kappa correlation values of all pathogens between the two methods varied from 0.63 to 0.95. The limit of detection of target bacteria was 1600 CFU/ml. The quantitative results from the PCR assays demonstrated 100% concordance with quantitative culture of tracheal aspirates. Compared to culture, PCR assays exhibited higher sensitivity in detecting mixed infections and S. pneumoniae. There was a high level of concordance between the detection of AMR gene and AMR phenotype in single infections. CONCLUSIONS Our multiplex quantitative RT-PCR assays are fast and simple, but sensitive and specific in detecting six bacterial pathogens of LRTIs and their antimicrobial resistance genes and should be further evaluated for clinical utility.
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Affiliation(s)
- Tran Thi Ngoc Dung
- Molecular Epidemiology Group, Oxford University Clinical Research Unit, 764 Vo Van Kiet Street, Ward 1, District 5, Ho Chi Minh City, Vietnam
| | - Voong Vinh Phat
- Molecular Epidemiology Group, Oxford University Clinical Research Unit, 764 Vo Van Kiet Street, Ward 1, District 5, Ho Chi Minh City, Vietnam
| | - Chau Vinh
- Molecular Epidemiology Group, Oxford University Clinical Research Unit, 764 Vo Van Kiet Street, Ward 1, District 5, Ho Chi Minh City, Vietnam
| | | | | | | | - Guy Thwaites
- Molecular Epidemiology Group, Oxford University Clinical Research Unit, 764 Vo Van Kiet Street, Ward 1, District 5, Ho Chi Minh City, Vietnam
- Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK
| | - Louise Thwaites
- Molecular Epidemiology Group, Oxford University Clinical Research Unit, 764 Vo Van Kiet Street, Ward 1, District 5, Ho Chi Minh City, Vietnam
- Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK
| | - Maia Rabaa
- Molecular Epidemiology Group, Oxford University Clinical Research Unit, 764 Vo Van Kiet Street, Ward 1, District 5, Ho Chi Minh City, Vietnam
- Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK
| | - Anh T K Nguyen
- Molecular Epidemiology Group, Oxford University Clinical Research Unit, 764 Vo Van Kiet Street, Ward 1, District 5, Ho Chi Minh City, Vietnam
- Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
| | - Pham Thanh Duy
- Molecular Epidemiology Group, Oxford University Clinical Research Unit, 764 Vo Van Kiet Street, Ward 1, District 5, Ho Chi Minh City, Vietnam.
- Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK.
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14
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Wei S, Tang Q, Hu X, Ouyang W, Shao H, Li J, Yan H, Chen Y, Liu L. Rapid, Ultrasensitive, and Visual Detection of Pathogens Based on Cation Dye-Triggered Gold Nanoparticle Electrokinetic Agglutination Analysis. ACS Sens 2024; 9:325-336. [PMID: 38214583 DOI: 10.1021/acssensors.3c02014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2024]
Abstract
Rapid prescribing of the right antibiotic is the key to treat infectious diseases and decelerate the challenge of bacterial antibiotic resistance. Herein, by targeting the 16S rRNA of bacteria, we developed a cation dye-triggered electrokinetic gold nanoparticle (AuNP) agglutination (CD-TEAA) method, which is rapid, visual, ultrasensitive, culture-independent, and low in cost. The limit of detection (LOD) is as low as 1 CFU mL-1 Escherichia coli. The infection identifications of aseptic fluid samples (n = 11) and urine samples with a clinically suspected urinary tract infection (UTI, n = 78) were accomplished within 50 and 30 min for each sample, respectively. The antimicrobial susceptibility testing (AST) of UTI urine samples was achieved within 2.5 h. In ROC analysis of urine, the sensitivity and specificity were 100 and 96% for infection identification, and 100 and 98% for AST, respectively. Moreover, the overall cost of materials for each test is about US$0.69. Therefore, the CD-TEAA method is a superior approach to existing, time-consuming, and expensive methods, especially in less developed areas.
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Affiliation(s)
- Siqi Wei
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Qing Tang
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Xiumei Hu
- Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Wei Ouyang
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, Illinois 60208, United States
| | - Huaze Shao
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Jincheng Li
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Hong Yan
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Yue Chen
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Lihong Liu
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
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15
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Dessajan J, Timsit JF. Impact of Multiplex PCR in the Therapeutic Management of Severe Bacterial Pneumonia. Antibiotics (Basel) 2024; 13:95. [PMID: 38247654 PMCID: PMC10812737 DOI: 10.3390/antibiotics13010095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Revised: 01/15/2024] [Accepted: 01/16/2024] [Indexed: 01/23/2024] Open
Abstract
Pneumonia is a common and severe illness that requires prompt and effective management. Advanced, rapid, and accurate tools are needed to diagnose patients with severe bacterial pneumonia, and to rapidly select appropriate antimicrobial therapy, which must be initiated within the first few hours of care. Two multiplex molecular tests, Unyvero HPN and FilmArray Pneumonia+ Panel, have been developed using the multiplex polymerase chain reaction (mPCR) technique to rapidly identify pathogens and their main antibiotic resistance mechanisms from patient respiratory specimens. Performance evaluation of these tests showed strong correlations with reference techniques. However, good knowledge of their indications, targets, and limitations is essential. Collaboration with microbiologists is, therefore, crucial for their appropriate use. Under these conditions, and with standardized management, these rapid tests can improve the therapeutic management of severe pneumonia faster, more precisely, and with narrow-spectrum antibiotic therapy. Further randomized controlled trials are needed to address the many unanswered questions about multiplex rapid molecular testing during the diagnosis and the management of severe pneumonia. This narrative review will address the current knowledge, advantages, and disadvantages of these tests, and propose solutions for their routine use.
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Affiliation(s)
- Julien Dessajan
- Assistance Publique Hôpitaux de Paris (AP-HP), Medical and Infectious Diseases Intensive Care Unit, Bichat Claude-Bernard Hospital, Paris Cité University, 46 Rue Henri Huchard, 75018 Paris, France;
| | - Jean-François Timsit
- Assistance Publique Hôpitaux de Paris (AP-HP), Medical and Infectious Diseases Intensive Care Unit, Bichat Claude-Bernard Hospital, Paris Cité University, 46 Rue Henri Huchard, 75018 Paris, France;
- Mixt Research Unit (UMR) 1137, Infection, Antimicrobials, Modelization, Epidemiology (IAME), Institut National de la Recherche Médicale (INSERM), Paris Cité University, 75018 Paris, France
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16
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Rodríguez A, Gómez F, Sarvisé C, Gutiérrez C, Giralt MG, Guerrero-Torres MD, Pardo-Granell S, Picó-Plana E, Benavent-Bofill C, Trefler S, Berrueta J, Canadell L, Claverias L, Esteve Pitarch E, Olona M, García Pardo G, Teixidó X, Bordonado L, Sans MT, Bodí M. Clinical and Microbiological Impact of Implementing a Decision Support Algorithm through Microbiologic Rapid Diagnosis in Critically Ill Patients: An Epidemiological Retrospective Pre-/Post-Intervention Study. Biomedicines 2023; 11:3330. [PMID: 38137551 PMCID: PMC10741655 DOI: 10.3390/biomedicines11123330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 12/07/2023] [Accepted: 12/08/2023] [Indexed: 12/24/2023] Open
Abstract
BACKGROUND Data on the benefits of rapid microbiological testing on antimicrobial consumption (AC) and antimicrobial resistance patterns (ARPs) are scarce. We evaluated the impact of a protocol based on rapid techniques on AC and ARP in intensive care (ICU) patients. METHODS A retrospective pre- (2018) and post-intervention (2019-2021) study was conducted in ICU patients. A rapid diagnostic algorithm was applied starting in 2019 in patients with a lower respiratory tract infection. The incidence of nosocomial infections, ARPs, and AC as DDDs (defined daily doses) were monitored. RESULTS A total of 3635 patients were included: 987 in the pre-intervention group and 2648 in the post-intervention group. The median age was 60 years, the sample was 64% male, and the average APACHE II and SOFA scores were 19 points and 3 points. The overall ICU mortality was 17.2% without any differences between the groups. An increase in the number of infections was observed in the post-intervention group (44.5% vs. 17.9%, p < 0.01), especially due to an increase in the incidence of ventilator-associated pneumonia (44.6% vs. 25%, p < 0.001). AC decreased from 128.7 DDD in 2018 to 66.0 DDD in 2021 (rate ratio = 0.51). An increase in Pseudomonas aeruginosa susceptibility of 23% for Piperacillin/tazobactam and 31% for Meropenem was observed. CONCLUSION The implementation of an algorithm based on rapid microbiological diagnostic techniques allowed for a significant reduction in AC and ARPs without affecting the prognosis of critically ill patients.
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Affiliation(s)
- Alejandro Rodríguez
- Critical Care Department, Hospital Universitari de Tarragona Joan XXIII, Mallafre Guasch 4, 43005 Tarragona, Spain; (S.T.); (J.B.); (L.C.); (M.B.)
- Faculty of Medicine, Department of Basic Medical Sciences, Rovira & Virgili University, 43005 Tarragona, Spain;
- Pere Virgili Health Research Institute (IISPV), 43005 Tarragona, Spain; (F.G.); (C.S.); (C.G.); (M.G.G.); (M.D.G.-T.); (S.P.-G.); (E.P.-P.); (C.B.-B.); (E.E.P.); (M.O.); (G.G.P.); (M.T.S.)
- Centre for Biomedical Research in Respiratory Diseases Network (CIBERES), 43005 Tarragona, Spain
| | - Frederic Gómez
- Pere Virgili Health Research Institute (IISPV), 43005 Tarragona, Spain; (F.G.); (C.S.); (C.G.); (M.G.G.); (M.D.G.-T.); (S.P.-G.); (E.P.-P.); (C.B.-B.); (E.E.P.); (M.O.); (G.G.P.); (M.T.S.)
- Microbiology/Clinical Analysis Laboratory, Hospital Universitari de Tarragona Joan XXIII, 43005 Tarragona, Spain
- Faculty of Medicine, Department of Medicine and Surgery, Rovira & Virgili University, 43005 Tarragona, Spain
- Centre for Biomedical Research in Infectious Diseases Network (CIBERINFEC), 28220 Madrid, Spain
| | - Carolina Sarvisé
- Pere Virgili Health Research Institute (IISPV), 43005 Tarragona, Spain; (F.G.); (C.S.); (C.G.); (M.G.G.); (M.D.G.-T.); (S.P.-G.); (E.P.-P.); (C.B.-B.); (E.E.P.); (M.O.); (G.G.P.); (M.T.S.)
- Microbiology/Clinical Analysis Laboratory, Hospital Universitari de Tarragona Joan XXIII, 43005 Tarragona, Spain
| | - Cristina Gutiérrez
- Pere Virgili Health Research Institute (IISPV), 43005 Tarragona, Spain; (F.G.); (C.S.); (C.G.); (M.G.G.); (M.D.G.-T.); (S.P.-G.); (E.P.-P.); (C.B.-B.); (E.E.P.); (M.O.); (G.G.P.); (M.T.S.)
- Molecular Biology/Clinical Analysis Laboratory, Hospital Universitari de Tarragona Joan XXIII, 43005 Tarragona, Spain
| | - Montserrat Galofre Giralt
- Pere Virgili Health Research Institute (IISPV), 43005 Tarragona, Spain; (F.G.); (C.S.); (C.G.); (M.G.G.); (M.D.G.-T.); (S.P.-G.); (E.P.-P.); (C.B.-B.); (E.E.P.); (M.O.); (G.G.P.); (M.T.S.)
- Microbiology/Clinical Analysis Laboratory, Hospital Universitari de Tarragona Joan XXIII, 43005 Tarragona, Spain
| | - María Dolores Guerrero-Torres
- Pere Virgili Health Research Institute (IISPV), 43005 Tarragona, Spain; (F.G.); (C.S.); (C.G.); (M.G.G.); (M.D.G.-T.); (S.P.-G.); (E.P.-P.); (C.B.-B.); (E.E.P.); (M.O.); (G.G.P.); (M.T.S.)
- Microbiology/Clinical Analysis Laboratory, Hospital Universitari de Tarragona Joan XXIII, 43005 Tarragona, Spain
| | - Sergio Pardo-Granell
- Pere Virgili Health Research Institute (IISPV), 43005 Tarragona, Spain; (F.G.); (C.S.); (C.G.); (M.G.G.); (M.D.G.-T.); (S.P.-G.); (E.P.-P.); (C.B.-B.); (E.E.P.); (M.O.); (G.G.P.); (M.T.S.)
- Microbiology/Clinical Analysis Laboratory, Hospital Universitari de Tarragona Joan XXIII, 43005 Tarragona, Spain
| | - Ester Picó-Plana
- Pere Virgili Health Research Institute (IISPV), 43005 Tarragona, Spain; (F.G.); (C.S.); (C.G.); (M.G.G.); (M.D.G.-T.); (S.P.-G.); (E.P.-P.); (C.B.-B.); (E.E.P.); (M.O.); (G.G.P.); (M.T.S.)
- Microbiology/Clinical Analysis Laboratory, Hospital Universitari de Tarragona Joan XXIII, 43005 Tarragona, Spain
| | - Clara Benavent-Bofill
- Pere Virgili Health Research Institute (IISPV), 43005 Tarragona, Spain; (F.G.); (C.S.); (C.G.); (M.G.G.); (M.D.G.-T.); (S.P.-G.); (E.P.-P.); (C.B.-B.); (E.E.P.); (M.O.); (G.G.P.); (M.T.S.)
- Molecular Biology/Clinical Analysis Laboratory, Hospital Universitari de Tarragona Joan XXIII, 43005 Tarragona, Spain
| | - Sandra Trefler
- Critical Care Department, Hospital Universitari de Tarragona Joan XXIII, Mallafre Guasch 4, 43005 Tarragona, Spain; (S.T.); (J.B.); (L.C.); (M.B.)
- Pere Virgili Health Research Institute (IISPV), 43005 Tarragona, Spain; (F.G.); (C.S.); (C.G.); (M.G.G.); (M.D.G.-T.); (S.P.-G.); (E.P.-P.); (C.B.-B.); (E.E.P.); (M.O.); (G.G.P.); (M.T.S.)
| | - Julen Berrueta
- Critical Care Department, Hospital Universitari de Tarragona Joan XXIII, Mallafre Guasch 4, 43005 Tarragona, Spain; (S.T.); (J.B.); (L.C.); (M.B.)
- Tarragona Health Data Research Working Group (THeDaR), Critical Care Department, Hospital Universitari de Tarragona Joan XXIII, 43005 Tarragona, Spain
| | - Laura Canadell
- Faculty of Medicine, Department of Basic Medical Sciences, Rovira & Virgili University, 43005 Tarragona, Spain;
- Pere Virgili Health Research Institute (IISPV), 43005 Tarragona, Spain; (F.G.); (C.S.); (C.G.); (M.G.G.); (M.D.G.-T.); (S.P.-G.); (E.P.-P.); (C.B.-B.); (E.E.P.); (M.O.); (G.G.P.); (M.T.S.)
- Hospital Pharmacy, Hospital Universitari de Tarragona Joan XXIII, 43005 Tarragona, Spain
| | - Laura Claverias
- Critical Care Department, Hospital Universitari de Tarragona Joan XXIII, Mallafre Guasch 4, 43005 Tarragona, Spain; (S.T.); (J.B.); (L.C.); (M.B.)
- Pere Virgili Health Research Institute (IISPV), 43005 Tarragona, Spain; (F.G.); (C.S.); (C.G.); (M.G.G.); (M.D.G.-T.); (S.P.-G.); (E.P.-P.); (C.B.-B.); (E.E.P.); (M.O.); (G.G.P.); (M.T.S.)
| | - Erika Esteve Pitarch
- Pere Virgili Health Research Institute (IISPV), 43005 Tarragona, Spain; (F.G.); (C.S.); (C.G.); (M.G.G.); (M.D.G.-T.); (S.P.-G.); (E.P.-P.); (C.B.-B.); (E.E.P.); (M.O.); (G.G.P.); (M.T.S.)
- Hospital Pharmacy, Hospital Universitari de Tarragona Joan XXIII, 43005 Tarragona, Spain
| | - Montserrat Olona
- Pere Virgili Health Research Institute (IISPV), 43005 Tarragona, Spain; (F.G.); (C.S.); (C.G.); (M.G.G.); (M.D.G.-T.); (S.P.-G.); (E.P.-P.); (C.B.-B.); (E.E.P.); (M.O.); (G.G.P.); (M.T.S.)
- Faculty of Medicine, Department of Medicine and Surgery, Rovira & Virgili University, 43005 Tarragona, Spain
- Preventive Medicine, Infection Control Group, Hospital Universitari de Tarragona Joan XXIII, 43005 Tarragona, Spain
| | - Graciano García Pardo
- Pere Virgili Health Research Institute (IISPV), 43005 Tarragona, Spain; (F.G.); (C.S.); (C.G.); (M.G.G.); (M.D.G.-T.); (S.P.-G.); (E.P.-P.); (C.B.-B.); (E.E.P.); (M.O.); (G.G.P.); (M.T.S.)
- Preventive Medicine, Infection Control Group, Hospital Universitari de Tarragona Joan XXIII, 43005 Tarragona, Spain
| | - Xavier Teixidó
- ICU Nursing, Hospital Universitari de Tarragona Joan XXIII, 43005 Tarragona, Spain; (X.T.); (L.B.)
| | - Laura Bordonado
- ICU Nursing, Hospital Universitari de Tarragona Joan XXIII, 43005 Tarragona, Spain; (X.T.); (L.B.)
| | - María Teresa Sans
- Pere Virgili Health Research Institute (IISPV), 43005 Tarragona, Spain; (F.G.); (C.S.); (C.G.); (M.G.G.); (M.D.G.-T.); (S.P.-G.); (E.P.-P.); (C.B.-B.); (E.E.P.); (M.O.); (G.G.P.); (M.T.S.)
- Microbiology/Clinical Analysis Laboratory, Hospital Universitari de Tarragona Joan XXIII, 43005 Tarragona, Spain
- Molecular Biology/Clinical Analysis Laboratory, Hospital Universitari de Tarragona Joan XXIII, 43005 Tarragona, Spain
| | - María Bodí
- Critical Care Department, Hospital Universitari de Tarragona Joan XXIII, Mallafre Guasch 4, 43005 Tarragona, Spain; (S.T.); (J.B.); (L.C.); (M.B.)
- Pere Virgili Health Research Institute (IISPV), 43005 Tarragona, Spain; (F.G.); (C.S.); (C.G.); (M.G.G.); (M.D.G.-T.); (S.P.-G.); (E.P.-P.); (C.B.-B.); (E.E.P.); (M.O.); (G.G.P.); (M.T.S.)
- Centre for Biomedical Research in Respiratory Diseases Network (CIBERES), 43005 Tarragona, Spain
- Faculty of Medicine, Department of Medicine and Surgery, Rovira & Virgili University, 43005 Tarragona, Spain
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17
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Chogtu B, Mariya Elenjickal V, Shetty DU, Asbin M, Guddattu V, Magazine R. Change in Antimicrobial Therapy Based on Bronchoalveolar Lavage Data Improves Outcomes in ICU Patients with Suspected Pneumonia. Crit Care Res Pract 2023; 2023:6928319. [PMID: 37608868 PMCID: PMC10442184 DOI: 10.1155/2023/6928319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 07/20/2023] [Accepted: 08/03/2023] [Indexed: 08/24/2023] Open
Abstract
Flexible bronchoscopy (FB) is often performed in critically ill patients with suspected pneumonia. It is assumed that there will be an association with improved outcomes when bronchoalveolar lavage (BAL) data lead to a change in antimicrobial therapy. Methods. This study included a retrospective cohort of intensive care unit (ICU) patients who underwent FB for a diagnosis of suspected pneumonia. The study compared the outcome of patients in whom antimicrobial modification was carried out based on BAL reports versus those in whom it was not carried out. Cases where the procedure could not be completed or had incomplete records were excluded. The FB reports were accessed from the register maintained in the Department of Respiratory Medicine. The demographic details, clinical symptoms, laboratory investigations, and microbiological and radiology reports were recorded. Data on the antmicrobial therapy that the patients received during treatment and the outcome of the treatment were obtained from the case records and noted in the data collection form. Results. Data from a total of 150 patients admitted to the ICU, who underwent FB, were analyzed. The outcomes in the group where antimicrobial modification based on bronchoalveolar lavage (BAL) fluid reports was carried out versus the no-change group were as follows: expired 23, improved 82, unchanged 8 versus expired 12, improved 18, and unchanged 7 (p = 0.018); total duration of ICU stay 13.12 ± 10.61 versus 19.43 ± 13.4 days (p = 0.012); and duration from FB to discharge from ICU 6.33 ± 3.76 days versus 8.46 ± 5.99 (p = 0.047). The median total duration of ICU stay and clinical outcomes were significantly better in the nonintubated patients in whom BAL-directed antimicrobial modification was implemented. Distribution of microorganisms based on BAL reports was as follows: Acinetobacter baumanii 45 (30%), Klebsiella pneumoniae 37 (24.66%), Escherichia coli 9 (6%), and Pseudomonas aeruginosa 9 (6%). Conclusion. A change in antimicrobial therapy based on BAL data was associated with improved outcomes. The commonest bacterial isolate in the BAL fluid was Acinetobacter baumanii.
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Affiliation(s)
- Bharti Chogtu
- Department of Pharmacology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
| | - Vrinda Mariya Elenjickal
- Department of Respiratory Medicine, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Dharma U. Shetty
- Department of Respiratory Medicine, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Mahsheeba Asbin
- Department of Respiratory Medicine, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Vasudeva Guddattu
- Department of Data Science, Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
| | - Rahul Magazine
- Department of Respiratory Medicine, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India
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18
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Guilhaumou R, Chevrier C, Setti JL, Jouve E, Marsot A, Julian N, Blin O, Simeone P, Lagier D, Mokart D, Bruder N, Garnier M, Velly L. β-Lactam Pharmacokinetic/Pharmacodynamic Target Attainment in Intensive Care Unit Patients: A Prospective, Observational, Cohort Study. Antibiotics (Basel) 2023; 12:1289. [PMID: 37627709 PMCID: PMC10451857 DOI: 10.3390/antibiotics12081289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 07/31/2023] [Accepted: 08/02/2023] [Indexed: 08/27/2023] Open
Abstract
BACKGROUND The aims of this study were to describe pharmacokinetic/pharmacodynamic target attainment in intensive care unit (ICU) patients treated with continuously infused ß-lactam antibiotics, their associated covariates, and the impact of dosage adjustment. METHODS This prospective, observational, cohort study was performed in three ICUs. Four ß-lactams were continuously infused, and therapeutic drug monitoring (TDM) was performed at days 1, 4, and 7. The primary pharmacokinetic/pharmacodynamic target was an unbound ß-lactam plasma concentration four times above the bacteria's minimal inhibitory concentration during the whole dosing interval. The demographic and clinical covariates associated with target attainment were evaluated. RESULTS A total of 170 patients were included (426 blood samples). The percentages of empirical ß-lactam underdosing at D1 were 66% for cefepime, 43% for cefotaxime, 47% for ceftazidime, and 14% for meropenem. Indexed creatinine clearance was independently associated with treatment underdose if increased (adjusted odds ratio per unit, 1.01; 95% CI, 1.00 to 1.01; p = 0.014) or overdose if decreased (adjusted odds ratio per unit, 0.95; 95% CI, 0.94 to 0.97; p < 0.001). Pharmacokinetic/pharmacodynamic target attainment was significantly increased after ß-lactam dosage adjustment between day 1 and day 4 vs. no adjustment (53.1% vs. 26.2%; p = 0.018). CONCLUSIONS This study increases our knowledge on the optimization of ß-lactam therapy in ICU patients. A large inter- and intra-patient variability in plasmatic concentrations was observed, leading to inadequate exposure. A combined indexed creatinine clearance and TDM approach enables adequate dosing for better pharmacokinetic/pharmacodynamic target attainment.
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Affiliation(s)
- Romain Guilhaumou
- Department of Clinical Pharmacology and Pharmacosurveillance, La Timone University Hospital; 13005 Marseille, France
- Institut de Neurosciences des Systèmes, Aix Marseille University, INSERM UMR 1106, 13005 Marseille, France
| | - Constance Chevrier
- Department of Clinical Pharmacology and Pharmacosurveillance, La Timone University Hospital; 13005 Marseille, France
- Institut de Neurosciences des Systèmes, Aix Marseille University, INSERM UMR 1106, 13005 Marseille, France
| | - Jean Loup Setti
- University Hospital Timone, Department of Anaesthesiology and Critical Care Medicine, APHM, Aix Marseille University, 13005 Marseille, France; (J.L.S.); (P.S.); (D.L.)
| | - Elisabeth Jouve
- Department of Clinical Pharmacology and Pharmacosurveillance, La Timone University Hospital; 13005 Marseille, France
- Institut de Neurosciences des Systèmes, Aix Marseille University, INSERM UMR 1106, 13005 Marseille, France
| | - Amélie Marsot
- Faculté de Pharmacie, Université de Montréal, Montreal, QC H3T 1J4, Canada;
| | - Nathan Julian
- University Hospital Timone, Department of Anaesthesiology and Critical Care Medicine, APHM, Aix Marseille University, 13005 Marseille, France; (J.L.S.); (P.S.); (D.L.)
| | - Olivier Blin
- Department of Clinical Pharmacology and Pharmacosurveillance, La Timone University Hospital; 13005 Marseille, France
- Institut de Neurosciences des Systèmes, Aix Marseille University, INSERM UMR 1106, 13005 Marseille, France
| | - Pierre Simeone
- University Hospital Timone, Department of Anaesthesiology and Critical Care Medicine, APHM, Aix Marseille University, 13005 Marseille, France; (J.L.S.); (P.S.); (D.L.)
- Inst Neurosci Timone, INT, CNRS, Aix Marseille University, UMR7289, 13005 Marseille, France
| | - David Lagier
- University Hospital Timone, Department of Anaesthesiology and Critical Care Medicine, APHM, Aix Marseille University, 13005 Marseille, France; (J.L.S.); (P.S.); (D.L.)
- C2VN, Inserm 1263, Inra 1260, Aix Marseille Université, 13005 Marseille, France
| | - Djamel Mokart
- Department of Anaesthesiology and Critical Care Medicine, Institut Paoli-Calmette, 13009 Marseille, France
| | - Nicolas Bruder
- University Hospital Timone, Department of Anaesthesiology and Critical Care Medicine, APHM, Aix Marseille University, 13005 Marseille, France; (J.L.S.); (P.S.); (D.L.)
| | - Marc Garnier
- Sorbonne University, GRC29, APHP, DMU DREAM, Rive Droite, Site Tenon, 75020 Paris, France
- Département d’Anesthésie-Réanimation et Médecine Périopératoire, CHU de Clermont-Ferrand, University Clermont Auvergne, 63000 Clermont-Ferrand, France
| | - Lionel Velly
- University Hospital Timone, Department of Anaesthesiology and Critical Care Medicine, APHM, Aix Marseille University, 13005 Marseille, France; (J.L.S.); (P.S.); (D.L.)
- Inst Neurosci Timone, INT, CNRS, Aix Marseille University, UMR7289, 13005 Marseille, France
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19
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Rando E, Cutuli SL, Sangiorgi F, Tanzarella ES, Giovannenze F, De Angelis G, Murri R, Antonelli M, Fantoni M, De Pascale G. Cefiderocol-containing regimens for the treatment of carbapenem-resistant A. baumannii ventilator-associated pneumonia: a propensity-weighted cohort study. JAC Antimicrob Resist 2023; 5:dlad085. [PMID: 37484029 PMCID: PMC10359102 DOI: 10.1093/jacamr/dlad085] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 06/27/2023] [Indexed: 07/25/2023] Open
Abstract
Background Cefiderocol is a novel β-lactam with activity against carbapenem-resistant Acinetobacter baumannii (CRAB), but its role in CRAB pulmonary infections is controversial due to limited evidence. Objectives To assess the association between cefiderocol-containing regimens treatment and 28-day mortality in carbapenem-resistant A. baumannii ventilator-associated pneumonia (VAP). Methods An observational cohort study including critically ill COVID-19 patients with CRAB-VAP admitted to two ICUs of a large academic hospital in Rome between September 2020 and December 2022. The primary outcome was 28-day all-cause mortality. A propensity score was created to balance the cefiderocol- and non-cefiderocol-containing groups. A propensity-weighted multiple logistic regression model was calculated to evaluate risk factors for 28-day mortality. Survival curves were calculated using the Kaplan-Meier method. Results 121 patients were enrolled, 55 were treated with cefiderocol- and 66 with non-cefiderocol-containing regimens. The 28-day all-cause mortality was 56% (68/121). A statistically significant difference in 28-day mortality was found between cefiderocol- and non-cefiderocol- containing regimens groups (44% versus 67%, P = 0.011). In the propensity-adjusted multiple logistic regression, cefiderocol (OR 0.35 95% CI 0.14, 0.83) was a predictor of 28-day survival, Charlson comorbidity index (OR 1.36 95% CI 1.16, 1.78), SOFA score (OR 1.24 95% CI 1.09, 1.57) and septic shock (OR 3.71 95% CI 1.44, 12.73) were all associated with increased 28-day mortality. Conclusion Cefiderocol-containing regimens were associated with reduced 28-day mortality in CRAB-VAP. The sample size and the observational design limit the study's conclusions. Future RCTs are needed to establish cefiderocol's definite role in these infections.
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Affiliation(s)
| | - Salvatore Lucio Cutuli
- Dipartimento di Scienza dell'Emergenza, Anestesiologiche e della Rianimazione, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy
| | - Flavio Sangiorgi
- Dipartimento di Sicurezza e Bioetica—Sezione di Malattie Infettive, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Eloisa Sofia Tanzarella
- Dipartimento di Scienza dell'Emergenza, Anestesiologiche e della Rianimazione, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy
| | - Francesca Giovannenze
- Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy
| | - Giulia De Angelis
- Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy
- Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Rita Murri
- Dipartimento di Sicurezza e Bioetica—Sezione di Malattie Infettive, Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy
| | - Massimo Antonelli
- Dipartimento di Scienza dell'Emergenza, Anestesiologiche e della Rianimazione, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy
- Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Massimo Fantoni
- Dipartimento di Sicurezza e Bioetica—Sezione di Malattie Infettive, Università Cattolica del Sacro Cuore, Rome, Italy
- Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy
| | - Gennaro De Pascale
- Dipartimento di Scienza dell'Emergenza, Anestesiologiche e della Rianimazione, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy
- Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy
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20
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Damico V, Murano L, Margosio V, Teli M, Ripamonti C, Demoro G, D'Alessandro A, Russello G. Co-infections in critically ill adults with severe acute respiratory syndrome coronavirus 2 infection: an Italian multi-center prospective study. Minerva Med 2023; 114:444-453. [PMID: 35156788 DOI: 10.23736/s0026-4806.22.08026-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/27/2023]
Abstract
BACKGROUND To date, few studies have described Hospital-acquired infections (HAIs) during COVID-19 outbreak. To examine the incidence of HAIs in critically ill adult patients with SARS-CoV-2 infection and to observe risk factors, and the impact on outcome of HAI. METHODS A prospective multicenter study was conducted that included adult patients with SARS-CoV-2 infection admitted to 18 Italian Intensive Care Units from September 2020 to November 2021. RESULTS A total of 589 patients were included. A total of 233 patients were diagnosed with at least one HAI (39.6%). The co-infection/co-colonization rate >48 hours after admission was 31.0 per 1000 person-days (95% CI 18.8-34.8). Age, length of ICU stay >7 days, obesity, type 2 diabetes mellitus, cardiovascular disease, inserted central venous catheter, intubation, APACHE II score >25, mechanical ventilation (MV) >48 hours, obesity and inserted urinary catheter are associated outcomes for infection acquisition. The overall mortality rate of patients was found to be significantly higher in patients who had acquired a HAI (RR=4.37; 95% CI 3.30-5.78; P<0.001). CONCLUSIONS Associated factors for HAI acquisition and mortality in ICU patients were identified and cause for revision of existing infection control policies.
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Affiliation(s)
- Vincenzo Damico
- Department of Anesthesia and Critical Care, ASST Lecco, Lecco, Italy -
| | - Liana Murano
- Sanitary Assistance Residency, Madonna della Neve Nonprofit Organization, Premana, Lecco, Italy
| | - Viola Margosio
- Department of Anesthesia and Critical Care, ASST Lecco, Lecco, Italy
| | - Mauro Teli
- Department of Anesthesia and Critical Care, ASST Lecco, Lecco, Italy
| | - Clara Ripamonti
- Department of Anesthesia and Critical Care, ASST Lecco, Lecco, Italy
| | - Giuseppe Demoro
- Department of Anesthesia and Critical Care, Azienda Sanitaria Sette Laghi, Varese, Italy
| | - Antonella D'Alessandro
- Department of Anesthesia and Critical Care, Ospedale Santissima Annunziata, Taranto, Italy
| | - Giuseppe Russello
- Department of Anesthesia and Critical Care, Caltanissetta Hospital, Caltanissetta, Italy
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21
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Cortegiani A, Antonelli M, Falcone M, Giarratano A, Girardis M, Leone M, Pea F, Stefani S, Viaggi B, Viale P. Rationale and clinical application of antimicrobial stewardship principles in the intensive care unit: a multidisciplinary statement. JOURNAL OF ANESTHESIA, ANALGESIA AND CRITICAL CARE 2023; 3:11. [PMID: 37386615 PMCID: PMC10245548 DOI: 10.1186/s44158-023-00095-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 04/21/2023] [Indexed: 07/01/2023]
Abstract
BACKGROUND Antimicrobial resistance represents a major critical issue for the management of the critically ill patients hospitalized in the intensive care unit (ICU), since infections by multidrug-resistant bacteria are characterized by high morbidity and mortality, high rates of treatment failure, and increased healthcare costs worldwide. It is also well known that antimicrobial resistance can emerge as a result of inadequate antimicrobial therapy, in terms of drug selection and/or treatment duration. The application of antimicrobial stewardship principles in ICUs improves the quality of antimicrobial therapy management. However, it needs specific considerations related to the critical setting. METHODS The aim of this consensus document gathering a multidisciplinary panel of experts was to discuss principles of antimicrobial stewardship in ICU and to produce statements that facilitate their clinical application and optimize their effectiveness. The methodology used was a modified nominal group discussion. CONCLUSION The final set of statements underlined the importance of the specific interpretation of antimicrobial stewardship's principles in critically ill patient management, quasi-targeted therapy, the use of rapid diagnostic methods, the personalization of antimicrobial therapies' duration, obtaining microbiological surveillance data, the use of PK/PD targets, and the use of specific indicators in antimicrobial stewardship programs.
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Affiliation(s)
- Andrea Cortegiani
- Department of Surgical, Oncological and Oral Science, University of Palermo, Via Liborio Giuffrè 5, 90127, Palermo, Italy.
- Department of Anaesthesia, Intensive Care and Emergency, University Hospital Policlinico Paolo Giaccone, 90127, Palermo, Italy.
| | - Massimo Antonelli
- Department of Anesthesiology and Intensive Care Medicine, Università Cattolica del Sacro Cuore, Rome, Italy
- Anesthesia and Intensive Care, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Marco Falcone
- Infectious Diseases Unit, Department of Clinical and Experimental Medicine, Azienda Ospedaliera Universitaria Pisana, University of Pisa, Pisa, Italy
| | - Antonino Giarratano
- Department of Surgical, Oncological and Oral Science, University of Palermo, Via Liborio Giuffrè 5, 90127, Palermo, Italy
- Department of Anaesthesia, Intensive Care and Emergency, University Hospital Policlinico Paolo Giaccone, 90127, Palermo, Italy
| | - Massimo Girardis
- Intensive Care Unit, University Hospital of Modena, Modena, Italy
| | - Marc Leone
- Department of Anaesthesia and Intensive Care Unit, Aix-Marseille University, AP-HM, North Hospital, Marseille, France
| | - Federico Pea
- Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, 40138, Bologna, Italy
- Clinical Pharmacology Unit, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, 40138, Bologna, Italy
| | - Stefania Stefani
- Microbiology Section, Dept of Biomedical and Biotechnological Science, University of Catania, Catania, Italy
- Unità Operativa Complessa (UOC) Laboratory Analysis, University Hospital Policlinico-San Marco, Catania, Italy
| | - Bruno Viaggi
- Department of Anesthesiology, Neuro-Intensive Care Unit, Careggi University Hospital, 50139, Florence, Italy
| | - Pierluigi Viale
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Infectious Disease Unit, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
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22
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Conway Morris A, Hellyer TP. Sniffing out pneumonia in the ICU. Anaesthesia 2023; 78:684-687. [PMID: 36947845 DOI: 10.1111/anae.16005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/06/2023] [Indexed: 03/24/2023]
Affiliation(s)
- A Conway Morris
- Division of Anaesthesia, Department of Medicine, University of Cambridge, UK
- Division of Immunology, Department of Pathology, University of Cambridge, UK
- John V Farman Intensive Care Unit, Addenbrooke's Hospital, Cambridge, UK
| | - T P Hellyer
- Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK
- Critical Care Department, Royal Victoria Infirmary, Newcastle Upon Tyne, UK
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23
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Palayer M, Chaussenery-Lorentz O, Boubekeur L, Urbina T, Maury E, Maubert MA, Pilon A, Bourgogne E. Quantitation of 10 antibiotics in plasma: sulfosalicylic acid combined with 2D-LC-MS/MS is a robust assay for beta-lactam therapeutic drug monitoring. J Chromatogr B Analyt Technol Biomed Life Sci 2023; 1221:123685. [PMID: 37023569 DOI: 10.1016/j.jchromb.2023.123685] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Revised: 03/17/2023] [Accepted: 03/19/2023] [Indexed: 03/30/2023]
Abstract
Therapeutic drug monitoring (TDM) of antibiotics is particularly important in populations with high pharmacokinetic variabilities, such as critically ill patients, leading to unpredictable plasma concentrations and clinical outcomes. Here, we i) describe an original method for the simultaneous quantification of ten antibiotics (cefepime, ceftazidime, ampicillin, piperacillin/tazobactam, cefotaxime, amoxicillin, cloxacillin, oxacillin, linezolid) using 5-sulfosalicylic acid dihydrate (SSA) solution for protein precipitation together with 2D-LC-MS/MS, and ii) evaluate its impact in a one-year retrospective study. The method involved simple dilution with an aqueous mix of deuterated internal standards and plasma protein precipitation with SSA. Twenty microliters of the supernatant was injected into a C8 SPE online cartridge (30 × 2.1 mm) without any evaporation step and back-flushed onto a C18 UHPLC (100 × 2.1 mm) analytical column. Mass spectrometry detection (Xevo TQD) was performed in positive electrospray, in scheduled MRM mode. Overall analytical runtime was 7 min. Due to analytical constraints and the physicochemical properties of the antibiotics, protein precipitation using organic solvents could not be applied. As an alternative, SSA used with 2D-LC offered various advantages: i) lack of dilution resulting in better assay sensitivity, and ii) good chromatography of hydrophilic compounds. Ten microliters of 30% SSA in water eliminated>90% of plasma proteins, including the most abundant high molecular weight proteins at 55 and 72 kDa. The assay was successfully validated according to FDA and EMA guidelines for all the antibiotics, and the coefficients of variation of the quality control (QC) run during sample analysis over one year were below 10%, whatever the QC levels or the antibiotics. The use of 2D-LC combined with SSA precipitation allowed development of a robust, sensitive and rapid quantification assay. Feedback to clinicians was reduced to 24 h, thus allowing rapid dosage adjustment. During one year, 3,304 determinations were performed in our laboratory: 41% were not in the therapeutic range, 58% of which were sub-therapeutic, underlining the importance of early TDM of antibiotics to limit therapeutic failures and the emergence of bacterial resistance.
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Determinants of Mortality for Ventilated Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia. Crit Care Explor 2023; 5:e0867. [PMID: 36861046 PMCID: PMC9970264 DOI: 10.1097/cce.0000000000000867] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/26/2023] Open
Abstract
Hospital-acquired pneumonia (HAP) is the most common hospital-acquired infection, accounting for 22% of all nosocomial infections. The available studies to date have not attempted to assess whether confounding factors may account for the observed difference in mortality for the two forms of nosocomial pneumonia associated with mechanical ventilation, namely ventilated HAP (vHAP) and ventilator-associated pneumonia (VAP). OBJECTIVES To determine if vHAP is an independent predictor of mortality among patients with nosocomial pneumonia. DESIGN SETTING AND PARTICIPANTS Single-center retrospective cohort study conducted at Barnes-Jewish Hospital, St. Louis, MO, between 2016 and 2019. Adult patients with a pneumonia discharge diagnosis were screened and patients diagnosed with vHAP and VAP were included. All patient data was extracted from the electronic health record. MAIN OUTCOMES AND MEASURES The primary outcome was 30-day all-cause mortality (ACM). RESULTS One thousand one-hundred twenty unique patient admissions were included (410 vHAP, 710 VAP). Thirty-day ACM was greater for patients with vHAP compared with VAP (37.1% vs 28.5%; p = 0.003). Logistic regression analysis identified vHAP (adjusted odds ratio [AOR], 1.77; 95% CI, 1.51-2.07), vasopressor use (AOR, 2.34; 95% CI, 1.94-2.82), Charlson Comorbidity Index (1-point increments) (AOR, 1.21; 95% CI, 1.18-1.24), total antibiotic treatment days (1-d increments) (AOR, 1.13; 95% CI, 1.11-1.14), and Acute Physiology and Chronic Health Evaluation II score (1-point increments) (AOR, 1.04; 95% CI, 1.03-1.06) as independent predictors of 30-day ACM. The most common bacterial pathogens identified as causes of vHAP and VAP were Staphylococcus aureus, Enterobacterales species, and Pseudomonas aeruginosa. CONCLUSIONS AND RELEVANCE In this single-center cohort study with low rates of initial inappropriate antibiotic therapy, vHAP had greater 30-day ACM compared with VAP after adjusting for potential confounding variables including disease severity and comorbidities. This finding suggests that clinical trials enrolling patients with vHAP need to account for this outcome difference in their trial design and data interpretation.
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Karruli A, Catalini C, D’Amore C, Foglia F, Mari F, Harxhi A, Galdiero M, Durante-Mangoni E. Evidence-Based Treatment of Pseudomonas aeruginosa Infections: A Critical Reappraisal. Antibiotics (Basel) 2023; 12:antibiotics12020399. [PMID: 36830309 PMCID: PMC9952410 DOI: 10.3390/antibiotics12020399] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2023] [Revised: 02/11/2023] [Accepted: 02/14/2023] [Indexed: 02/18/2023] Open
Abstract
Multidrug-resistant (MDR)/extensively drug-resistant (XDR) Pseudomonas aeruginosa is emerging as a major threat related to adverse patient outcomes. The goal of this review is to describe evidence-based empiric and targeted treatment regimens that can be exploited when dealing with suspected or confirmed infections due to MDR/XDR P. aeruginosa. P. aeruginosa has inherent resistance to many drug classes, the capacity to form biofilms, and most importantly, the ability to quickly acquire resistance to ongoing treatments. Based on the presence of risk factors for MDR/XDR infections and local epidemiology, where large proportions of strains are resistant to classic beta-lactams, the recommended empirical treatment for suspected P. aeruginosa infections is based on ceftolozane-tazobactam or ceftazidime-avibactam. Where local epidemiology indicates low rates of MDR/XDR and there are no risk factors, a third or fourth generation cephalosporin can be used in the context of a "carbapenem-sparing" strategy. Whenever feasible, antibiotic de-escalation is recommended after antimicrobial susceptibility tests suggest that it is appropriate, and de-escalation is based on different resistance mechanisms. Cefiderocol and imipenem-cilastatin-relebactam withstand most resistance mechanisms and may remain active in cases with resistance to other new antibiotics. Confronting the growing threat of MDR/XDR P. aeruginosa, treatment choices should be wise, sparing newer antibiotics when dealing with a suspected/confirmed susceptible P. aeruginosa strain and choosing the right option for MDR/XDR P. aeruginosa based on specific types and resistance mechanisms.
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Affiliation(s)
- Arta Karruli
- Department of Precision Medicine, University of Campania ‘Luigi Vanvitelli’, 80138 Naples, Italy
- Department of Infectious Diseases, University Hospital “Mother Teresa”, 10001 Tirana, Albania
- Correspondence: ; Tel.: +39-324-6222295
| | - Christian Catalini
- Department of Advanced Medical and Surgical Sciences, University of Campania ‘Luigi Vanvitelli’, 80138 Naples, Italy
| | - Chiara D’Amore
- Infectious Diseases Unit, San Giovanni di Dio e Ruggi D’Aragona Hospital, 84131 Salerno, Italy
| | - Francesco Foglia
- Unit of Microbiology and Virology, Department of Experimental Medicine, University of Campania ‘Luigi Vanvitelli’, 80138 Naples, Italy
| | - Fabio Mari
- Department of Emergency Medicine, University “Federico II”, 80138 Naples, Italy
| | - Arjan Harxhi
- Department of Infectious Diseases, University Hospital “Mother Teresa”, 10001 Tirana, Albania
| | - Massimiliano Galdiero
- Unit of Microbiology and Virology, Department of Experimental Medicine, University of Campania ‘Luigi Vanvitelli’, 80138 Naples, Italy
| | - Emanuele Durante-Mangoni
- Department of Precision Medicine, University of Campania ‘Luigi Vanvitelli’, 80138 Naples, Italy
- Unit of Infectious and Transplant Medicine, AORN Ospedali dei Colli-Monaldi Hospital, 80131 Naples, Italy
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Reynolds D, Burnham JP, Vazquez Guillamet C, McCabe M, Yuenger V, Betthauser K, Micek ST, Kollef MH. The threat of multidrug-resistant/extensively drug-resistant Gram-negative respiratory infections: another pandemic. Eur Respir Rev 2022; 31:220068. [PMID: 36261159 PMCID: PMC9724833 DOI: 10.1183/16000617.0068-2022] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 06/09/2022] [Indexed: 12/22/2022] Open
Abstract
Antibiotic resistance is recognised as a global threat to human health by national healthcare agencies, governments and medical societies, as well as the World Health Organization. Increasing resistance to available antimicrobial agents is of concern for bacterial, fungal, viral and parasitic pathogens. One of the greatest concerns is the continuing escalation of antimicrobial resistance among Gram-negative bacteria resulting in the endemic presence of multidrug-resistant (MDR) and extremely drug-resistant (XDR) pathogens. This concern is heightened by the identification of such MDR/XDR Gram-negative bacteria in water and food sources, as colonisers of the intestine and other locations in both hospitalised patients and individuals in the community, and as agents of all types of infections. Pneumonia and other types of respiratory infections are among the most common infections caused by MDR/XDR Gram-negative bacteria and are associated with high rates of mortality. Future concerns are already heightened due to emergence of resistance to all existing antimicrobial agents developed in the past decade to treat MDR/XDR Gram-negative bacteria and a scarcity of novel agents in the developmental pipeline. This clinical scenario increases the likelihood of a future pandemic caused by MDR/XDR Gram-negative bacteria.
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Affiliation(s)
- Daniel Reynolds
- Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Jason P Burnham
- Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA
| | | | - Mikaela McCabe
- Dept of Pharmacy Practice, University of Health Sciences and Pharmacy, St. Louis, MO, USA
| | - Valerie Yuenger
- Dept of Pharmacy Practice, University of Health Sciences and Pharmacy, St. Louis, MO, USA
| | - Kevin Betthauser
- Dept of Pharmacy Practice, University of Health Sciences and Pharmacy, St. Louis, MO, USA
| | - Scott T Micek
- Dept of Pharmacy Practice, University of Health Sciences and Pharmacy, St. Louis, MO, USA
| | - Marin H Kollef
- Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO, USA
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Zilberberg MD, Nathanson BH, Puzniak LA, Zilberberg NWD, Shorr AF. Descriptive epidemiology of hospitalized patients with bacterial nosocomial pneumonia who experience 30-day readmission in the US, 2014-2019. PLoS One 2022; 17:e0276192. [PMID: 36490261 PMCID: PMC9733878 DOI: 10.1371/journal.pone.0276192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 09/30/2022] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION Nosocomial pneumonia (NP) remains associated with excess morbidity and mortality. The effect of NP on measures such as re-admission at 30 days remains unclear. Moreover, differing types of NP may have varying impacts on re-admissions. METHODS We conducted a multicenter retrospective cohort study within the Premier Research database, a source containing administrative, pharmacy, and microbiology data. We compared NP patients readmitted with pneumonia (RaP) as the principal diagnosis to those readmitted for other reasons (RaO) with respect to the type of NP (ventilator-associated bacterial pneumonia [VABP], ventilated hospital-acquired bacterial pneumonia [vHABP], and non-ventilated HABP [nvHABP]), and characteristics and outcomes of the index hospitalization. RESULTS Among 17,819 patients with NP, 14,123 (79.3%) survived to discharge, of whom 2,151 (15.2%) required an acute readmission within 30 days of index discharge. Of these, 106 (4.9%) were RaP, and the remainder were RaO. At index hospitalization, RaP patients were older (mean age [SD] 67.4 (13.9] vs. 63.0 [15.2] years), more likely medical (44.3% vs. 36.7%), and less chronically ill (median [IQR] Charlson scores (3 [2-5] vs. 4 [2-5]) than persons with RaO. Bacteremia (10.4% vs. 17.5%), need for vasopressors (15.1% vs. 20.0%), dialysis (9.4% vs. 16.5%), and/or sepsis (9.4% vs. 16.5%) or septic shock 14.2% vs. 17.1%) occurred less frequently in the RaP group. With respect to NP type, nvHABP was most common in RaP (47.2%) and VABP in RaO (38.1%). CONCLUSIONS One in seven survivors of a hospitalization complicated by NP requires an acute rehospitalization within 30 days. However, few of these readmissions had a principal diagnosis of pneumonia, irrespective of NP type. Of the 5% of NP subjects with RaP, the plurality initially suffered from nvHABP.
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Affiliation(s)
| | | | | | - Noah W. D. Zilberberg
- EviMed Research Group, LLC, Goshen, MA, United States of America
- Universty of Massachusetts, Amherst, MA, United States of America
| | - Andrew F. Shorr
- Washington Hospital Center, Washington, DC, United States of America
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28
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Fenn D, Abdel-Aziz MI, van Oort PMP, Brinkman P, Ahmed WM, Felton T, Artigas A, Póvoa P, Martin-Loeches I, Schultz MJ, Dark P, Fowler SJ, Bos LDJ, Ahmed WM, Raventos AA, Bannard-Smith J, Bos LDJ, Camprubi M, Coelho L, Dark P, Davie A, Diaz E, Goma G, Felton T, Fowler SJ, Goodacre R, Johnson C, Knobel H, Lawal O, Leopold JH, Martin-Loeches I, Nijsen TME, van Oort PMP, Povoa P, Rattray NJW, Rijnders G, Schultz MJ, Steenwelle R, Sterk PJ, Valles J, Verhoeckx F, Vink A, Weda H, White IR, Winters T, Zakharkina T. Composition and diversity analysis of the lung microbiome in patients with suspected ventilator-associated pneumonia. Crit Care 2022; 26:203. [PMID: 35794610 PMCID: PMC9261066 DOI: 10.1186/s13054-022-04068-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 06/22/2022] [Indexed: 11/23/2022] Open
Abstract
Background Ventilator-associated pneumonia (VAP) is associated with high morbidity and health care costs, yet diagnosis remains a challenge. Analysis of airway microbiota by amplicon sequencing provides a possible solution, as pneumonia is characterised by a disruption of the microbiome. However, studies evaluating the diagnostic capabilities of microbiome analysis are limited, with a lack of alignment on possible biomarkers. Using bronchoalveolar lavage fluid (BALF) from ventilated adult patients suspected of VAP, we aimed to explore how key characteristics of the microbiome differ between patients with positive and negative BALF cultures and whether any differences could have a clinically relevant role. Methods BALF from patients suspected of VAP was analysed using 16s rRNA sequencing in order to: (1) differentiate between patients with and without a positive culture; (2) determine if there was any association between microbiome diversity and local inflammatory response; and (3) correctly identify pathogens detected by conventional culture. Results Thirty-seven of 90 ICU patients with suspected VAP had positive cultures. Patients with a positive culture had significant microbiome dysbiosis with reduced alpha diversity. However, gross compositional variance was not strongly associated with culture positivity (AUROCC range 0.66–0.71). Patients with a positive culture had a significantly higher relative abundance of pathogenic bacteria compared to those without [0.45 (IQR 0.10–0.84), 0.02 (IQR 0.004–0.09), respectively], and an increased interleukin (IL)-1β was associated with reduced species evenness (rs = − 0.33, p < 0.01) and increased pathogenic bacteria presence (rs = 0.28, p = 0.013). Untargeted 16s rRNA pathogen detection was limited by false positives, while the use of pathogen-specific relative abundance thresholds showed better diagnostic accuracy (AUROCC range 0.89–0.998). Conclusion Patients with positive BALF culture had increased dysbiosis and genus dominance. An increased caspase-1-dependent IL-1b expression was associated with a reduced species evenness and increased pathogenic bacterial presence, providing a possible causal link between microbiome dysbiosis and lung injury development in VAP. However, measures of diversity were an unreliable predictor of culture positivity and 16s sequencing used agnostically could not usefully identify pathogens; this could be overcome if pathogen-specific relative abundance thresholds are used. Supplementary Information The online version contains supplementary material available at 10.1186/s13054-022-04068-z.
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Stafylaki D, Maraki S, Vaporidi K, Georgopoulos D, Kontoyiannis DP, Kofteridis DP, Chamilos G. Impact of Molecular Syndromic Diagnosis of Severe Pneumonia in the Management of Critically Ill Patients. Microbiol Spectr 2022; 10:e0161622. [PMID: 36154180 PMCID: PMC9603977 DOI: 10.1128/spectrum.01616-22] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 09/05/2022] [Indexed: 12/31/2022] Open
Abstract
The impact of syndromic molecular diagnosis in the management of nosocomial infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) pathogens has been incompletely characterized. We evaluated the performance of a molecular syndromic platform (BioFire FilmArray-Pneumonia plus Panel) in patients with pneumonia in the intensive care unit (ICU) of a University Hospital in Greece over a 2-year period. We evaluated 79 consecutive patients diagnosed with pneumonia in the ICU (2018-2020), including 55 patients with ventilator associated pneumonia (VAP). We included 40 control patients diagnosed with pneumonia in the ICU the year before the study (2017-2018). We identified 16 cases of VAP due to XDR bacterial pathogens. We found an excellent agreement (89.4% 76/85 reported results) between the results of syndromic platform and conventional cultures of tracheal aspirates. The molecular syndromic test significantly improved time to diagnosis versus conventional culture (3.5 h vs 72 h, P < 0.0001), and identified new pathogens not detected by cultures in 49% of the cases. However, three cases of pneumonia with targets not included in the molecular platform, were not detected. Implementation of the molecular syndromic facilitated treatment modification from broad to narrow spectrum antimicrobial therapy, resulting in significant reductions in antibiotic consumption in the study group compared to the control group, without a negative impact in patient outcome. The implementation of syndromic molecular diagnosis in critically ill patients with pneumonia is associated with timely and improved diagnosis and has significant impact on reduction of antibiotic consumption. IMPORTANCE The impact of syndromic molecular diagnosis in the management of nosocomial infections caused by MDR/XDR pathogens has been incompletely characterized. We evaluated the performance of a molecular syndromic platform (BioFire FilmArray -Pneumonia plus Panel) in 79 patients with pneumonia in the intensive care unit (ICU) of a University Hospital in Greece over a 2-year period (2018-2020) compared to 40 control patients diagnosed with pneumonia in the ICU the year before the study (2017-2018). Importantly, implementation of syndromic pneumonia panel improved time to diagnosis, identified new pathogens not detected by cultures in 49% of the cases and resulted in a significant reduction in antibiotic consumption compared to the year before initiation of the study without a negative impact in mortality of patients. Collectively, our study demonstrates the positive value of PCR syndromic testing in the management of pneumonia in ICUs high rates of MDR/XDR nosocomial pathogens.
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Affiliation(s)
- Dimitra Stafylaki
- Department of Clinical Microbiology and Microbial Pathogenesis, University Hospital of Heraklion, Heraklion, Crete, Greece
| | - Sofia Maraki
- Department of Clinical Microbiology and Microbial Pathogenesis, University Hospital of Heraklion, Heraklion, Crete, Greece
| | - Katerina Vaporidi
- ICU Department, University Hospital of Heraklion, Heraklion, Crete, Greece
| | | | - Dimitrios P. Kontoyiannis
- Department of Infectious Diseases, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA
| | | | - Georgios Chamilos
- Department of Clinical Microbiology and Microbial Pathogenesis, University Hospital of Heraklion, Heraklion, Crete, Greece
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Navapurkar V, Bartholdson Scott J, Maes M, Hellyer TP, Higginson E, Forrest S, Pereira-Dias J, Parmar S, Heasman-Hunt E, Polgarova P, Brown J, Titti L, Smith WPW, Scott J, Rostron A, Routledge M, Sapsford D, Török ME, McMullan R, Enoch DA, Wong V, Curran MD, Brown NM, Simpson AJ, Herre J, Dougan G, Conway Morris A. Development and implementation of a customised rapid syndromic diagnostic test for severe pneumonia. Wellcome Open Res 2022; 6:256. [PMID: 36337362 PMCID: PMC9617073 DOI: 10.12688/wellcomeopenres.17099.3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/10/2022] [Indexed: 02/02/2023] Open
Abstract
Background: The diagnosis of pneumonia has been hampered by a reliance on bacterial cultures which take several days to return a result, and are frequently negative. In critically ill patients this leads to the use of empiric, broad-spectrum antimicrobials and compromises good antimicrobial stewardship. The objective of this study was to establish the performance of a syndromic molecular diagnostic approach, using a custom TaqMan array card (TAC) covering 52 respiratory pathogens, and assess its impact on antimicrobial prescribing. Methods: The TAC was validated against a retrospective multi-centre cohort of broncho-alveolar lavage samples. The TAC was assessed prospectively in patients undergoing investigation for suspected pneumonia, with a comparator cohort formed of patients investigated when the TAC laboratory team were unavailable. Co-primary outcomes were sensitivity compared to conventional microbiology and, for the prospective study, time to result. Metagenomic sequencing was performed to validate findings in prospective samples. Antibiotic free days (AFD) were compared between the study cohort and comparator group. Results: 128 stored samples were tested, with sensitivity of 97% (95% confidence interval (CI) 88-100%). Prospectively, 95 patients were tested by TAC, with 71 forming the comparator group. TAC returned results 51 hours (interquartile range 41-69 hours) faster than culture and with sensitivity of 92% (95% CI 83-98%) compared to conventional microbiology. 94% of organisms identified by sequencing were detected by TAC. There was a significant difference in the distribution of AFDs with more AFDs in the TAC group (p=0.02). TAC group were more likely to experience antimicrobial de-escalation (odds ratio 2.9 (95%1.5-5.5)). Conclusions: Implementation of a syndromic molecular diagnostic approach to pneumonia led to faster results, with high sensitivity and impact on antibiotic prescribing.
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Affiliation(s)
- Vilas Navapurkar
- John V Farman Intensive Care Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Josefin Bartholdson Scott
- Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, CB2 0AW, UK
| | - Mailis Maes
- Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, CB2 0AW, UK
| | - Thomas P Hellyer
- Translational and Clinical Research Institute, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK
- Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE7 7DN, UK
| | - Ellen Higginson
- Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, CB2 0AW, UK
| | - Sally Forrest
- Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, CB2 0AW, UK
| | - Joana Pereira-Dias
- Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, CB2 0AW, UK
| | - Surendra Parmar
- Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Emma Heasman-Hunt
- Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Petra Polgarova
- John V Farman Intensive Care Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Joanne Brown
- John V Farman Intensive Care Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Lissamma Titti
- John V Farman Intensive Care Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - William PW Smith
- School of Clinical Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK
| | - Jonathan Scott
- Translational and Clinical Research Institute, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK
| | - Anthony Rostron
- Translational and Clinical Research Institute, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK
| | - Matthew Routledge
- Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- Infectious Diseases, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - David Sapsford
- Pharmacy Department, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - M. Estée Török
- Department of Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK
- Microbiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Ronan McMullan
- Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, BT9 7BL, UK
| | - David A Enoch
- Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Vanessa Wong
- Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- Infectious Diseases, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - VAP-Rapid investigators
- John V Farman Intensive Care Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, CB2 0AW, UK
- Translational and Clinical Research Institute, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK
- Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE7 7DN, UK
- Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- School of Clinical Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK
- Infectious Diseases, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- Pharmacy Department, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- Department of Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK
- Microbiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, BT9 7BL, UK
- Respiratory Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK
| | - Martin D Curran
- Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Nicholas M Brown
- Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - A John Simpson
- Translational and Clinical Research Institute, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK
- Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE7 7DN, UK
| | - Jurgen Herre
- Respiratory Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Gordon Dougan
- Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, CB2 0AW, UK
| | - Andrew Conway Morris
- John V Farman Intensive Care Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK
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Zilberberg MD, Nathanson BH, Puzniak LA, Dillon RJ, Shorr AF. The risk of inappropriate empiric treatment and its outcomes based on pathogens in non-ventilated (nvHABP), ventilated (vHABP) hospital-acquired and ventilator-associated (VABP) bacterial pneumonia in the US, 2012-2019. BMC Infect Dis 2022; 22:775. [PMID: 36199012 PMCID: PMC9533487 DOI: 10.1186/s12879-022-07755-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 09/21/2022] [Indexed: 11/10/2022] Open
Abstract
Background Inappropriate empiric antimicrobial treatment (IET) contributes to worsened outcomes. While IET’s differential impact across types of nosocomial pneumonia (NP: non-ventilated [nvHABP], ventilated [vHABP] hospital-acquired and ventilator-associated [VABP] bacterial pneumonia) is established, its potential interaction with the bacterial etiology is less clear.
Methods We conducted a multicenter retrospective cohort study in the Premier Healthcare Database using an administrative algorithm to identify NP. We paired respective pathogens with empiric treatments. Antimicrobial coverage was appropriate if a drug administered within 2 days of infection onset covered the recovered organism(s). All other treatment was IET. Results Among 17,819 patients with NP, 26.5% had nvHABP, 25.6% vHABP, and 47.9% VABP. Gram-negative (GN) organisms accounted for > 50% of all infections. GN pathogens were ~ 2 × as likely (7.4% vHABP to 10.7% nvHABP) to engender IET than Gram-positive (GP, 2.9% vHABP to 4.9% nvHABP) pathogens. Although rare (5.6% nvHABP to 8.3% VABP), GN + GP infections had the highest rates of IET (6.7% vHABP to 12.9% nvHABP). Carbapenem-resistant GNs were highly likely to receive IET (33.8% nvHABP to 40.2% VABP). Hospital mortality trended higher in the IET group, reaching statistical significance in GN + GP vHABP (47.8% IET vs. 29.3% non-IET, p = 0.016). 30-day readmission was more common with IET (16.0%) than non-IET (12.6%, p = 0.024) in GN VABP. Generally post-infection onset hospital length of stay and costs were higher with IET than non-IET. Conclusions IET is ~ 2 × more common in GN than GP infections. Although the magnitude of its impact varies by NP type, IET contributes to worsened clinical and economic outcomes.
Supplementary Information The online version contains supplementary material available at 10.1186/s12879-022-07755-y.
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Affiliation(s)
| | | | | | | | - Andrew F Shorr
- Washington Hospital Center, 110 Irving St. NW, Washington, DC, 20010, USA.
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Zagorovsky K, Fernández-Argüelles MT, Bona D, Elshawadfy AM, Syed AM, Kadhiresan P, Mazzulli T, Maxwell KL, Chan WCW. Gold Nanoparticle Smartphone Platform for Diagnosing Urinary Tract Infections. ACS NANOSCIENCE AU 2022; 2:324-332. [PMID: 35996437 PMCID: PMC9389610 DOI: 10.1021/acsnanoscienceau.2c00001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
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Current urinary tract
infection (UTI) diagnostic methods are slow
or provide limited information, resulting in prescribing antibiotic
therapy before bacterial pathogen identification. Here, we adapted
a gold nanoparticle colorimetric approach and developed a smartphone
platform for UTI detection. We show the parallel identification of
five major UTI pathogens at clinically relevant concentrations of
105 bacteria/mL using bacteria-specific and universal probes.
We validated the diagnostic technology using 115 positive and 19 negative
samples from patients with Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae infections. The assay successfully
identified the infecting pathogen (specificity: >98% and sensitivity:
51–73%) in 3 h. Our platform is faster than culturing and can
wirelessly store and transmit results at the cost of $0.38 per assay.
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Affiliation(s)
- Kyryl Zagorovsky
- Institute of Biomedical Engineering, University of Toronto, 164 College Street, Toronto, Ontario M5S 3G9, Canada.,Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada
| | - Maria Teresa Fernández-Argüelles
- Institute of Biomedical Engineering, University of Toronto, 164 College Street, Toronto, Ontario M5S 3G9, Canada.,Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.,Department of Physical and Analytical Chemistry, University of Oviedo, Julian Claveria 8, Oviedo, Asturias 33006, Spain
| | - Diane Bona
- Department of Biochemistry, University of Toronto, 661 University Avenue, Toronto, Ontario M5G 1M1, Canada
| | - Ashraf Mohamed Elshawadfy
- Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.,Department of Botany and Microbiology, Zagazig University, Zagazig 44519, Egypt
| | - Abdullah Muhammad Syed
- Institute of Biomedical Engineering, University of Toronto, 164 College Street, Toronto, Ontario M5S 3G9, Canada.,Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.,Gladstone Institute of Data Science and Biotechnology, 1650 Owens Street, San Francisco, California 94158, United States
| | - Pranav Kadhiresan
- Institute of Biomedical Engineering, University of Toronto, 164 College Street, Toronto, Ontario M5S 3G9, Canada.,Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada
| | - Tony Mazzulli
- Department of Microbiology, Mount Sinai Hospital/University Health Network, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada
| | - Karen L Maxwell
- Department of Biochemistry, University of Toronto, 661 University Avenue, Toronto, Ontario M5G 1M1, Canada
| | - Warren C W Chan
- Institute of Biomedical Engineering, University of Toronto, 164 College Street, Toronto, Ontario M5S 3G9, Canada.,Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada
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What’s new in antibiotic stewardship for pneumonia in ICU? Anaesth Crit Care Pain Med 2022; 41:101135. [DOI: 10.1016/j.accpm.2022.101135] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 05/19/2022] [Indexed: 11/23/2022]
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Fanning J, Panigada M, Li Bassi G. Nosocomial Pneumonia in the Mechanically Ventilated Patient. Semin Respir Crit Care Med 2022; 43:426-439. [PMID: 35714627 DOI: 10.1055/s-0042-1749448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Ventilator-associated pneumonia (VAP) is a common complication occurring in critically ill patients who are mechanically ventilated and is the leading cause of nosocomial infection-related death. Etiologic agents for VAP widely differ based on the population of intensive care unit patients, duration of hospital stay, and prior antimicrobial therapy. VAP due to multidrug-resistant pathogens is associated with the highest morbidity and mortality, likely due to delays in appropriate antimicrobial treatment. International guidelines are currently available to guide diagnostic and therapeutic strategies. VAP can be prevented through various pharmacological and non-pharmacological interventions, which are more effective when grouped as bundles. When VAP is clinically suspected, diagnostic strategies should include early collection of respiratory samples to guide antimicrobial therapy. Empirical treatment should be based on the most likely etiologic microorganisms and antibiotics likely to be active against these microorganisms. Response to therapy should be reassessed after 3 to 5 days and antimicrobials adjusted or de-escalated to reduce the burden of the disease. Finally, considering that drug resistance is increasing worldwide, several novel antibiotics are being tested to efficiently treat VAP in the coming decades.
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Affiliation(s)
- Jonathon Fanning
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Australia.,Intensive Care Unit, Royal Brisbane and Women's Hospital, Queensland, Australia.,Intensive Care Unit, St Andrew's War Memorial Hospital, Queensland, Australia.,Nuffield Department of Population Health, Oxford University, United Kingdom
| | - Mauro Panigada
- Department of Anaesthesiology, Intensive Care and EmergencyFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Gianluigi Li Bassi
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Australia.,Intensive Care Unit, St Andrew's War Memorial Hospital, Queensland, Australia.,Queensland University of Technology, Brisbane, Australia.,Intensive Care Unit, The Wesley Hospital, Auchenflower, Queensland, Australia.,Wesley Medical Research, The Wesley Hospital, Auchenflower, Australia
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35
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Martin B, DeWitt PE, Scott HF, Parker S, Bennett TD. Machine Learning Approach to Predicting Absence of Serious Bacterial Infection at PICU Admission. Hosp Pediatr 2022; 12:590-603. [PMID: 35634885 DOI: 10.1542/hpeds.2021-005998] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND OBJECTIVES Serious bacterial infection (SBI) is common in the PICU. Antibiotics can mitigate associated morbidity and mortality but have associated adverse effects. Our objective is to develop machine learning models able to identify SBI-negative children and reduce unnecessary antibiotics. METHODS We developed models to predict SBI-negative status at PICU admission using vital sign, laboratory, and demographic variables. Children 3-months to 18-years-old admitted to our PICU, between 2011 and 2020, were included if evaluated for infection within 24-hours, stratified by documented antibiotic exposure in the 48-hours prior. Area under the receiver operating characteristic curve (AUROC) was the primary model accuracy measure; secondarily, we calculated the number of SBI-negative children subsequently provided antibiotics in the PICU identified as low-risk by each model. RESULTS A total of 15 074 children met inclusion criteria; 4788 (32%) received antibiotics before PICU admission. Of these antibiotic-exposed patients, 2325 of 4788 (49%) had an SBI. Of the 10 286 antibiotic-unexposed patients, 2356 of 10 286 (23%) had an SBI. In antibiotic-exposed children, a radial support vector machine model had the highest AUROC (0.80) for evaluating SBI, identifying 48 of 442 (11%) SBI-negative children provided antibiotics in the PICU who could have been spared a median 3.7 (interquartile range 0.9-9.0) antibiotic-days per patient. In antibiotic-unexposed children, a random forest model performed best, but was less accurate overall (AUROC 0.76), identifying 33 of 469 (7%) SBI-negative children provided antibiotics in the PICU who could have been spared 1.1 (interquartile range 0.9-3.7) antibiotic-days per patient. CONCLUSIONS Among children who received antibiotics before PICU admission, machine learning models can identify children at low risk of SBI and potentially reduce antibiotic exposure.
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Affiliation(s)
- Blake Martin
- Department of Pediatrics, Sections of Critical Care
- Children's Hospital Colorado, Aurora, Colorado
| | | | - Halden F Scott
- Emergency Medicine
- Children's Hospital Colorado, Aurora, Colorado
| | - Sarah Parker
- Infectious Diseases, University of Colorado School of Medicine, Aurora, Colorado
- Children's Hospital Colorado, Aurora, Colorado
| | - Tellen D Bennett
- Department of Pediatrics, Sections of Critical Care
- Informatics and Data Science
- Children's Hospital Colorado, Aurora, Colorado
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36
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T. Nguyen K, T. Pham S, P.M. Vo T, X. Duong C, A. Perwitasari D, H.K. Truong N, T.H. Quach D, N.P. Nguyen T, T.T. Duong V, M. Nguyen P, H. Nguyen T, Taxis K, Nguyen T. Pneumonia: Drug-Related Problems and Hospital Readmissions. Infect Dis (Lond) 2022. [DOI: 10.5772/intechopen.100127] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Pneumonia is one of the most common infectious diseases and the fourth leading cause of death globally. According to US statistics in 2019, pneumonia is the most common cause of sepsis and septic shock. In the US, inpatient pneumonia hospitalizations account for the top 10 highest medical costs, totaling $9.5 billion for 960,000 hospital stays. The emergence of antibiotic resistance in the treatment of infectious diseases, including the treatment of pneumonia, is a globally alarming problem. Antibiotic resistance increases the risk of death and re-hospitalization, prolongs hospital stays, and increases treatment costs, and is one of the greatest threats in modern medicine. Drug-related problems (DRPs) in pneumonia - such as suboptimal antibiotic indications, prolonged treatment duration, and drug interactions - increase the rate of antibiotic resistance and adverse effects, thereby leading to an increased burden in treatment. In a context in which novel and effective antibiotics are scarce, mitigating DRPs in order to reduce antibiotic resistance is currently a prime concern. A variety of interventions proven useful in reducing DRPs are antibiotic stewardship programs, the use of biomarkers, computerized physician order entries and clinical decision support systems, and community-acquired pneumonia scores.
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37
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Navapurkar V, Bartholdson Scott J, Maes M, Hellyer TP, Higginson E, Forrest S, Pereira-Dias J, Parmar S, Heasman-Hunt E, Polgarova P, Brown J, Titti L, Smith WPW, Scott J, Rostron A, Routledge M, Sapsford D, Török ME, McMullan R, Enoch DA, Wong V, Curran MD, Brown NM, Simpson AJ, Herre J, Dougan G, Conway Morris A. Development and implementation of a customised rapid syndromic diagnostic test for severe pneumonia. Wellcome Open Res 2022; 6:256. [PMID: 36337362 PMCID: PMC9617073 DOI: 10.12688/wellcomeopenres.17099.2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/06/2022] [Indexed: 02/02/2023] Open
Abstract
Background: The diagnosis of pneumonia has been hampered by a reliance on bacterial cultures which take several days to return a result, and are frequently negative. In critically ill patients this leads to the use of empiric, broad-spectrum antimicrobials and compromises good antimicrobial stewardship. The objective of this study was to establish the performance of a syndromic molecular diagnostic approach, using a custom TaqMan array card (TAC) covering 52 respiratory pathogens, and assess its impact on antimicrobial prescribing. Methods: The TAC was validated against a retrospective multi-centre cohort of broncho-alveolar lavage samples. The TAC was assessed prospectively in patients undergoing investigation for suspected pneumonia, with a comparator cohort formed of patients investigated when the TAC laboratory team were unavailable. Co-primary outcomes were sensitivity compared to conventional microbiology and, for the prospective study, time to result. Metagenomic sequencing was performed to validate findings in prospective samples. Antibiotic free days (AFD) were compared between the study cohort and comparator group. Results: 128 stored samples were tested, with sensitivity of 97% (95% confidence interval (CI) 88-100%). Prospectively, 95 patients were tested by TAC, with 71 forming the comparator group. TAC returned results 51 hours (interquartile range 41-69 hours) faster than culture and with sensitivity of 92% (95% CI 83-98%) compared to conventional microbiology. 94% of organisms identified by sequencing were detected by TAC. There was a significant difference in the distribution of AFDs with more AFDs in the TAC group (p=0.02). TAC group were more likely to experience antimicrobial de-escalation (odds ratio 2.9 (95%1.5-5.5)). Conclusions: Implementation of a syndromic molecular diagnostic approach to pneumonia led to faster results, with high sensitivity and impact on antibiotic prescribing.
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Affiliation(s)
- Vilas Navapurkar
- John V Farman Intensive Care Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Josefin Bartholdson Scott
- Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, CB2 0AW, UK
| | - Mailis Maes
- Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, CB2 0AW, UK
| | - Thomas P Hellyer
- Translational and Clinical Research Institute, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK
- Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE7 7DN, UK
| | - Ellen Higginson
- Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, CB2 0AW, UK
| | - Sally Forrest
- Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, CB2 0AW, UK
| | - Joana Pereira-Dias
- Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, CB2 0AW, UK
| | - Surendra Parmar
- Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Emma Heasman-Hunt
- Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Petra Polgarova
- John V Farman Intensive Care Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Joanne Brown
- John V Farman Intensive Care Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Lissamma Titti
- John V Farman Intensive Care Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - William PW Smith
- School of Clinical Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK
| | - Jonathan Scott
- Translational and Clinical Research Institute, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK
| | - Anthony Rostron
- Translational and Clinical Research Institute, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK
| | - Matthew Routledge
- Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- Infectious Diseases, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - David Sapsford
- Pharmacy Department, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - M. Estée Török
- Department of Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK
- Microbiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Ronan McMullan
- Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, BT9 7BL, UK
| | - David A Enoch
- Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Vanessa Wong
- Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- Infectious Diseases, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - VAP-Rapid investigators
- John V Farman Intensive Care Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, CB2 0AW, UK
- Translational and Clinical Research Institute, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK
- Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE7 7DN, UK
- Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- School of Clinical Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK
- Infectious Diseases, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- Pharmacy Department, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- Department of Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK
- Microbiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, BT9 7BL, UK
- Respiratory Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK
| | - Martin D Curran
- Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Nicholas M Brown
- Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - A John Simpson
- Translational and Clinical Research Institute, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK
- Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE7 7DN, UK
| | - Jurgen Herre
- Respiratory Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Gordon Dougan
- Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, CB2 0AW, UK
| | - Andrew Conway Morris
- John V Farman Intensive Care Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK
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Abstract
PURPOSE OF REVIEW Ventilator-associated pneumonia (VAP) is a common nosocomial infection in critically ill patients requiring endotracheal intubation and mechanical ventilation. Recently, the emergence of multidrug-resistant Gram-negative bacteria, including carbapenem-resistant Enterobacterales, multidrug-resistant Pseudomonas aeruginosa and Acinetobacter species, has complicated the selection of appropriate antimicrobials and contributed to treatment failure. Although novel antimicrobials are crucial to treating VAP caused by these multidrug-resistant organisms, knowledge of how to optimize their efficacy while minimizing the development of resistance should be a requirement for their use. RECENT FINDINGS Several studies have assessed the efficacy of novel antimicrobials against multidrug-resistant organisms, but high-quality studies focusing on optimal dosing, infusion time and duration of therapy in patients with VAP are still lacking. Antimicrobial and diagnostic stewardship should be combined to optimize the use of these novel agents. SUMMARY Improvements in diagnostic tests, stewardship practices and a better understanding of dosing, infusion time, duration of treatment and the effects of combining various antimicrobials should help optimize the use of novel antimicrobials for VAP and maximize clinical outcomes while minimizing the development of resistance.
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Zilberberg MD, Nathanson BH, Puzniak LA, Zilberberg NWD, Shorr AF. Inappropriate Empiric Therapy Impacts Complications and Hospital Resource Utilization Differentially Among Different Types of Bacterial Nosocomial Pneumonia: A Cohort Study, United States, 2014-2019. Crit Care Explor 2022; 4:e0667. [PMID: 35415613 PMCID: PMC8994075 DOI: 10.1097/cce.0000000000000667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
Abstract
Nosocomial pneumonia (NP) remains a costly complication of hospitalization fraught with subsequent complications and augmented resource utilization. Consisting of ventilated hospital-acquired bacterial pneumonia (vHABP), nonventilated hospital-acquired bacterial pneumonia (nvHABP), and ventilator-associated bacterial pneumonia (VABP), each may respond differently to inappropriate empiric treatment (IET). We explored whether IET affects the three pneumonia types differently. DESIGN A multicenter, retrospective cohort study within the Premier Research database. SETTING Acute care hospitals in the United States. PATIENTS Patients with three types of NP were identified based on a previously published International Classification of Diseases, 9th Edition/International Classification of Diseases, 10th Edition Clinical Modification algorithm. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS We compared the impact of IET on hospital costs, length of stay (LOS), and development of Clostridium difficile infection (CDI), extubation failure (EF), and reintubation (RT). Marginal effects were derived from multivariable regression analyses. IET was present if no drug covering the organism recovered from the index culture was administered within 2 days of the culture date. Among 17,819 patients who met the enrollment criteria, 26.5% had nvHABP, 25.6% vHABP, and 47.9% VABP. Compared with non-IET, IET was associated with increased mean unadjusted hospital LOS across all NP types: nvHABP 12.5 versus 21.1, vHABP 16.7 versus 19.2, and VABP 18.6 versus 21.4 days. The adjusted marginal hospital LOS (4.9 d) and costs ($13,147) with IET were the highest in nvHABP. Incident CDI was rare and similar across NP types (2.4% nvHABP to 3.6% VABP). Both EF and RT were more common with IET in VABP (EF, 15.4% vs 19.2%; RT, 6.2% vs 10.4%), but not vHABP (EF, 15.1% vs 17.7%; RT, 8.1% vs 9.1%). CONCLUSIONS Although IET is relatively uncommon, it affects resource utilization and the risk of complications differently across NP types. The impact of IET is greatest on both LOS and costs in nvHABP and is greater on VABP than vHABP in terms of EF and RT.
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Affiliation(s)
| | | | - Laura A Puzniak
- Health Economics and Outcomes Research, Merck & Co., Inc., Kenilworth, NJ
| | - Noah W D Zilberberg
- Health Services Research, EviMed Research Group, LLC, Goshen, MA
- Engineering, Universty of Massachusetts, Amherst, MA
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40
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A Narrative Review on the Approach to Antimicrobial Use in Ventilated Patients with Multidrug Resistant Organisms in Respiratory Samples—To Treat or Not to Treat? That Is the Question. Antibiotics (Basel) 2022; 11:antibiotics11040452. [PMID: 35453203 PMCID: PMC9031060 DOI: 10.3390/antibiotics11040452] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 03/18/2022] [Accepted: 03/23/2022] [Indexed: 02/01/2023] Open
Abstract
Multidrug resistant organisms (MDRO) are commonly isolated in respiratory specimens taken from mechanically ventilated patients. The purpose of this narrative review is to discuss the approach to antimicrobial prescription in ventilated patients who have grown a new MDRO isolate in their respiratory specimen. A MEDLINE and PubMed literature search using keywords “multidrug resistant organisms”, “ventilator-associated pneumonia” and “decision making”, “treatment” or “strategy” was used to identify 329 references as background for this review. Lack of universally accepted diagnostic criteria for ventilator-associated pneumonia, or ventilator-associated tracheobronchitis complicates treatment decisions. Consideration of the clinical context including signs of respiratory infection or deterioration in respiratory or other organ function is essential. The higher the quality of respiratory specimens or the presence of bacteremia would suggest the MDRO is a true pathogen, rather than colonization, and warrants antimicrobial therapy. A patient with higher severity of illness has lower safety margins and may require initiation of antimicrobial therapy until an alternative diagnosis is established. A structured approach to the decision to treat with antimicrobial therapy is proposed.
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41
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Stahl K, Bode C, David S. Extrakorporale Behandlungsstrategien der Sepsis. TRANSFUSIONSMEDIZIN 2022. [DOI: 10.1055/a-1557-3201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Zusammenfassung
Hintergrund Die Mortalität der Sepsis bleibt auch im 21. Jahrhundert sehr hoch. Verschiedene adjuvante Strategien zur extrakorporalen Zytokinelimination wurden als zusätzliche
therapeutische Maßnahmen bei Sepsis und septischem Schock untersucht.
Ziele Zusammenfassung einer Auswahl extrakorporaler Blutreinigungstechniken und der aktuellen Erkenntnisse in der klinischen Anwendung mit besonderem Schwerpunkt auf dem
therapeutischen Plasmaaustausch.
Methoden Nicht systematische Literaturrecherche.
Ergebnisse Verschiedene extrakorporale Blutreinigungstechniken mit unterschiedlichen Evidenzniveaus hinsichtlich Zytokinelimination, Verbesserung der Hämodynamik und Verringerung der
Mortalität werden derzeit klinisch eingesetzt. Die am ausführlichsten untersuchten Modalitäten umfassen die hochvolumige Hämofiltration/Dialyse mit und ohne High-Cut-off-Filter sowie
Hämoadsorptionstechniken (einschließlich CytoSorb- und Polymyxin-B-Filter). Trotz teilweise ermutigender Beobachtungen bezüglich der Entfernung proinflammatorischer Zytokine und verbesserten
Hämodynamik zeigten randomisierte Outcome-Studien bislang keinen positiven Einfluss auf das Überleben. Aufgrund der Verwendung von Spenderplasma als Substitutionsflüssigkeit stellt der
therapeutische Plasmaaustausch das einzige Verfahren dar, das neben einer reinen Elimination zusätzlich verbrauchte protektive Faktoren ersetzen kann.
Schlussfolgerungen Die Anwendung extrakorporaler Blutreinigungsmethoden kann für Sepsispatienten außerhalb klinischer Studien bisher nicht empfohlen werden, da derzeit keine Beweise
für ihre Wirksamkeit vorliegen. Zukünftige Untersuchungen sollten darauf abzielen, das Patientenkollektiv hinsichtlich des klinischen Schweregrads, des Zeitpunkts der Intervention und
verschiedener inflammatorischer (Sub-)Phänotypen zu homogenisieren.
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Affiliation(s)
- Klaus Stahl
- Abteilung für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Deutschland
| | - Christian Bode
- Klinik für Anästhesie und operative Intensivmedizin, Universitätsklinikum Bonn, Deutschland
| | - Sascha David
- Abteilung für Nieren- und Hochdruckerkrankungen, Medizinische Hochschule Hannover & Institut für Intensivmedizin, Universitätsspital Zürich, Schweiz
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42
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Enne VI, Aydin A, Baldan R, Owen DR, Richardson H, Ricciardi F, Russell C, Nomamiukor-Ikeji BO, Swart AM, High J, Colles A, Barber J, Gant V, Livermore DM, O'Grady J. Multicentre evaluation of two multiplex PCR platforms for the rapid microbiological investigation of nosocomial pneumonia in UK ICUs: the INHALE WP1 study. Thorax 2022; 77:1220-1228. [PMID: 35027473 DOI: 10.1136/thoraxjnl-2021-216990] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 11/29/2021] [Indexed: 01/12/2023]
Abstract
BACKGROUND Culture-based microbiological investigation of hospital-acquired or ventilator-associated pneumonia (HAP or VAP) is insensitive, with aetiological agents often unidentified. This can lead to excess antimicrobial treatment of patients with susceptible pathogens, while those with resistant bacteria are treated inadequately for prolonged periods. Using PCR to seek pathogens and their resistance genes directly from clinical samples may improve therapy and stewardship. METHODS Surplus routine lower respiratory tract samples were collected from intensive care unit patients about to receive new or changed antibiotics for hospital-onset lower respiratory tract infections at 15 UK hospitals. Testing was performed using the BioFire FilmArray Pneumonia Panel (bioMérieux) and Unyvero Pneumonia Panel (Curetis). Concordance analysis compared machine and routine microbiology results, while Bayesian latent class (BLC) analysis estimated the sensitivity and specificity of each test, incorporating information from both PCR panels and routine microbiology. FINDINGS In 652 eligible samples; PCR identified pathogens in considerably more samples compared with routine microbiology: 60.4% and 74.2% for Unyvero and FilmArray respectively vs 44.2% by routine microbiology. PCR tests also detected more pathogens per sample than routine microbiology. For common HAP/VAP pathogens, FilmArray had sensitivity of 91.7%-100.0% and specificity of 87.5%-99.5%; Unyvero had sensitivity of 50.0%-100.0%%, and specificity of 89.4%-99.0%. BLC analysis indicated that, compared with PCR, routine microbiology had low sensitivity, ranging from 27.0% to 69.4%. INTERPRETATION Conventional and BLC analysis demonstrated that both platforms performed similarly and were considerably more sensitive than routine microbiology, detecting potential pathogens in patient samples reported as culture negative. The increased sensitivity of detection realised by PCR offers potential for improved antimicrobial prescribing.
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Affiliation(s)
- Virve I Enne
- Division of Infection and Immunity, University College London, London, UK
| | - Alp Aydin
- Division of Infection and Immunity, University College London, London, UK
| | - Rossella Baldan
- Centre for Clinical Infection and Diagnostic Research, King's College London, London, UK.,Norwich Medical School, University of East Anglia, Norwich, UK
| | - Dewi R Owen
- Division of Infection and Immunity, University College London, London, UK
| | | | - Federico Ricciardi
- Department of Statistical Science, University College London, London, UK
| | | | | | - Ann-Marie Swart
- Norwich Clinical Trials Unit, University of East Anglia, Norwich, UK
| | - Juliet High
- Norwich Clinical Trials Unit, University of East Anglia, Norwich, UK
| | - Antony Colles
- Norwich Clinical Trials Unit, University of East Anglia, Norwich, UK
| | - Julie Barber
- Department of Statistical Science, University College London, London, UK
| | - Vanya Gant
- Department of Clinical Microbiology, University College London Hospitals NHS Foundation Trust, London, UK.,NIHR Biomedical research Centre, University College London Hospitals, London, UK
| | | | - Justin O'Grady
- Norwich Medical School, University of East Anglia, Norwich, UK.,Quadram Institute Bioscience, Norwich, UK
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Gennequin M, Bachelet D, Eloy P, Moyer JD, Roquilly A, Gauss T, Weiss E, Foucrier A. Empiric antimicrobial therapy for early-onset pneumonia in severe trauma patients. Eur J Trauma Emerg Surg 2022; 48:2763-2771. [PMID: 35001179 DOI: 10.1007/s00068-021-01870-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 12/28/2021] [Indexed: 11/28/2022]
Abstract
PURPOSE The bacterial ecology involved in early pneumonia of severe trauma patients is mostly commensal and would allow wide use of narrow-spectrum antibiotics. We describe risk factors for treatment failure of severe trauma patients' pneumonia with the use of narrow-spectrum antimicrobial therapy in order to develop a score that could help clinicians to determine which patients might be treated with narrow-spectrum antibiotics. METHODS A retrospective, observational, monocentric cohort study was conducted of severe trauma patients requiring mechanical ventilation for > 48 h and developing a first episode of microbiologically confirmed pneumonia occurring within the first 10 days after admission. RESULTS Overall, 370 patients were included. The resistance rate against narrow-spectrum antibiotics (amoxicillin/clavulanic acid) was 22.7% (84 pneumonia). In a multivariate analysis, two independent risk factors were associated with this resistance: prior antimicrobial therapy ≥ 48 h (OR 4.00; 95 CI [2.39; 6.75]) and age ≥ 30y (OR 2.10; 95 CI [1.21; 3.78]). We created a prediction score that defined patient with one or two risk factors at high risk of resistance. This score presented a sensitivity of 0.92 [0.88; 0.94], a specificity of 0.33 [0.28; 0.38], a positive predictive value of 0.29 [0.24; 0.33] and a negative predictive value of 0.93 [0.90; 0.95]. CONCLUSION Simple risk factors may help clinicians to identify severe trauma patients at high risk of pneumonia treatment failure with the use of narrow-spectrum antimicrobial therapy and, thus, use better tailored empiric therapy and limit the use of unnecessary broad-spectrum antimicrobial therapy.
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Affiliation(s)
- Maël Gennequin
- Department of Anaesthesiology and Critical Care, Beaujon Hospital, DMU Parabol, AP-HP Nord, Université de Paris, 100 Boulevard du Général Leclerc, 92110, Clichy, France.
| | - Delphine Bachelet
- Département d'épidémiologie, Biostatistiques et Recherche Clinique, Hôpital Bichat, AP-HP Nord, Université de Paris, 75018, Paris, France
| | - Philippine Eloy
- Département d'épidémiologie, Biostatistiques et Recherche Clinique, Hôpital Bichat, AP-HP Nord, Université de Paris, 75018, Paris, France
| | - Jean-Denis Moyer
- Department of Anaesthesiology and Critical Care, Beaujon Hospital, DMU Parabol, AP-HP Nord, Université de Paris, 100 Boulevard du Général Leclerc, 92110, Clichy, France
| | - Antoine Roquilly
- Intensive Care Unit, Anaesthesia and Critical Care Dept, Hôtel Dieu-HME, University Hospital of Nantes, Nantes, France
| | - Tobias Gauss
- Department of Anaesthesiology and Critical Care, Beaujon Hospital, DMU Parabol, AP-HP Nord, Université de Paris, 100 Boulevard du Général Leclerc, 92110, Clichy, France
| | - Emmanuel Weiss
- Department of Anaesthesiology and Critical Care, Beaujon Hospital, DMU Parabol, AP-HP Nord, Université de Paris, 100 Boulevard du Général Leclerc, 92110, Clichy, France
| | - Arnaud Foucrier
- Department of Anaesthesiology and Critical Care, Beaujon Hospital, DMU Parabol, AP-HP Nord, Université de Paris, 100 Boulevard du Général Leclerc, 92110, Clichy, France
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Erich BJ, Kilic A, Palavecino E, Williamson J, Johnson J, Ohl C, Luther V, Beardsley J. Evaluation of the Potential Impact of a Multiplex Rapid Diagnostic Panel in Critically Ill Patients With Hospital-Acquired Pneumonia. Cureus 2022; 14:e21716. [PMID: 35251792 PMCID: PMC8887693 DOI: 10.7759/cureus.21716] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/29/2022] [Indexed: 12/30/2022] Open
Abstract
Background Rapid diagnostic tools have emerged as valuable assets assisting clinicians in decision-making regarding patient management in the hospital setting. Our study sought to identify the potential impact of the BioFire® FilmArray® Pneumonia Panel (FP Panel) (BioFire Diagnostics, Salt Lake City, UT, USA) in patients with hospital-acquired pneumonia (HAP). Methods Respiratory samples obtained by bronchoalveolar lavage (BAL) or tracheal aspiration (TA) from ICU patients with a diagnosis of HAP were tested by the FP panel in addition to routine bacterial cultures. In addition, the electronic health records of these patients were reviewed to determine what potential changes in antimicrobial therapy could have been implemented if the panel results were known to the treatment team in real-time. A cost analysis was also performed incorporating the cost of the pneumonia panel and the savings associated with the potential decrease of antibiotic use and avoidance of the rapid viral diagnostic panel. Results Fifty-six patients met the study criteria. The FP panel results could have prompted a change in therapy in 36 (64.3%) patients, with an anticipated mean reduction in time to optimized therapy of approximately 51 hours. In addition, the panel identified three cases where antimicrobials should have been altered because patients were not receiving empiric therapy with activity against the causative pathogen and 34 opportunities for antibiotic de-escalation. The cost analysis calculated an additional cost of $10 per patient associated with using the FP panel. Conclusions The FP panel could have prompted a change in therapy in about two-thirds of patients studied. Its potential benefits include a more rapid time to optimized therapy, reduced exposure to and cost of broad-spectrum antimicrobials, and reduced cost of other rapid diagnostic tests.
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Affiliation(s)
- Bradley J Erich
- Department of Inpatient Pharmacy, The University of Kansas Health System, Kansas City, USA
| | - Abdullah Kilic
- Department of Pathology, Atrium Health Wake Forest Baptist, Winston-Salem, USA
| | | | - John Williamson
- Department of Pharmacy, Atrium Health Wake Forest Baptist, Winston-Salem, USA.,Department of Internal Medicine, Section of Infectious Diseases, Wake Forest School of Medicine, Winston-Salem, USA
| | - James Johnson
- Department of Pharmacy, Atrium Health Wake Forest Baptist, Winston-Salem, USA.,Department of Internal Medicine, Section of Infectious Diseases, Wake Forest School of Medicine, Winston-Salem, USA
| | - Christopher Ohl
- Department of Internal Medicine, Section of Infectious Diseases, Wake Forest School of Medicine, Winston-Salem, USA
| | - Vera Luther
- Department of Internal Medicine, Section of Infectious Diseases, Wake Forest School of Medicine, Winston-Salem, USA
| | - James Beardsley
- Department of Pharmacy, Atrium Health Wake Forest Baptist, Winston-Salem, USA.,Department of Internal Medicine, Section of Infectious Diseases, Wake Forest School of Medicine, Winston-Salem, USA
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45
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Wu N, Ranjan P, Tao C, Liu C, Yang E, He B, Erb-Downward JR, Bo S, Zheng J, Guo C, Liu B, Sun L, Yan W, Wang M, Wang W, Wen J, Yang P, Yang L, Tian Q, Dickson RP, Shen N. Rapid identification of pathogens associated with ventilator-associated pneumonia by Nanopore sequencing. Respir Res 2021; 22:310. [PMID: 34893078 PMCID: PMC8665642 DOI: 10.1186/s12931-021-01909-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 11/26/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Aetiology detection is crucial in the diagnosis and treatment of ventilator-associated pneumonia (VAP). However, the detection method needs improvement. In this study, we used Nanopore sequencing to build a quick detection protocol and compared the efficiency of different methods for detecting 7 VAP pathogens. METHODS The endotracheal aspirate (ETA) of 83 patients with suspected VAP from Peking University Third Hospital (PUTH) was collected, saponins were used to deplete host genomes, and PCR- or non-PCR-amplified library construction methods were used and compared. Sequence was performed with MinION equipment and local data analysis methods were used for sequencing and data analysis. RESULTS Saponin depletion effectively removed 11 of 12 human genomes, while most pathogenic bacterial genome results showed no significant difference except for S. pneumoniae. Moreover, the average sequence time decreased from 19.6 h to 3.62 h. The non-PCR amplification method and PCR amplification method for library build has a similar average sensitivity (85.8% vs. 86.35%), but the non-PCR amplification method has a better average specificity (100% VS 91.15%), and required less time. The whole method takes 5-6 h from ETA extraction to pathogen classification. After analysing the 7 pathogens enrolled in our study, the average sensitivity of metagenomic sequencing was approximately 2.4 times higher than that of clinical culture (89.15% vs. 37.77%), and the average specificity was 98.8%. CONCLUSIONS Using saponins to remove the human genome and a non-PCR amplification method to build libraries can be used for the identification of pathogens in the ETA of VAP patients within 6 h by MinION, which provides a new approach for the rapid identification of pathogens in clinical departments.
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Affiliation(s)
- Nan Wu
- Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Piyush Ranjan
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA
| | - Changyu Tao
- Department of Human Anatomy and Histology and Embryology, Peking University, Beijing, 100191, People's Republic of China
| | - Chao Liu
- Department of Infectious Diseases, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Ence Yang
- Department of Medical Bioinformatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, People's Republic of China
| | - Bei He
- Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - John R Erb-Downward
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA
| | - Shining Bo
- Intensive Care Unit, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Jiajia Zheng
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Chenxia Guo
- Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Beibei Liu
- Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Lina Sun
- Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Wei Yan
- Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Meng Wang
- Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Wenting Wang
- Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Jianing Wen
- Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Ping Yang
- Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Lin Yang
- Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Qiaoshan Tian
- Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Robert P Dickson
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA
| | - Ning Shen
- Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing, 100191, People's Republic of China.
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Gant V, Hussain A, Bain M, Longshaw C, Henriksen AS. In vitro activity of cefiderocol and comparators against Gram-negative bacterial isolates from a series of surveillance studies in England: 2014-2018. J Glob Antimicrob Resist 2021; 27:1-11. [PMID: 34329792 DOI: 10.1016/j.jgar.2021.07.014] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 06/30/2021] [Accepted: 07/11/2021] [Indexed: 11/19/2022] Open
Abstract
OBJECTIVES The prevalence of Gram-negative bacteria (GNB) demonstrating extensive, multiple antimicrobial resistance is increasing in England, leaving few treatment choices. Cefiderocol is a novel siderophore cephalosporin approved in Europe for the treatment of aerobic GNB infections in adults with limited treatment options. We report pooled data for a clinical isolate set collected in England between 2014-2018. METHODS MICs were determined by broth microdilution according to International Organization for Standardization guidelines. Cefiderocol susceptibility was tested using iron-depleted cation-adjusted Muller-Hinton broth. Susceptibility rates were based on EUCAST breakpoints. In the absence of a species-specific breakpoint, pharmacokinetic/pharmacodynamic breakpoints were used. RESULTS Of 1886 isolates from England [74.1% Enterobacterales (18.7% Escherichia coli, 17.2% Klebsiella pneumoniae), 25.9% non-fermenters (18.4% Pseudomonas aeruginosa, 3.7% Acinetobacter baumannii)], 98.7% were cefiderocol-susceptible. Cefiderocol susceptibility in Enterobacterales (99.0%) was significantly (P < 0.01) greater than ceftolozane/tazobactam (94.3%), but similar to meropenem (99.3%) and ceftazidime/avibactam (99.4%). Overall, cefiderocol susceptibility (98.0%) in non-fermenters was significantly (P < 0.01) higher than comparators (range, 84.5-92.4%). Susceptibility to cefiderocol was 98.3-99.6% by infection source and was significantly (P < 0.01) greater than comparators for isolates from patients with nosocomial pneumonia (cefiderocol, 98.3%; comparators range, 79.8-93.8%). Excluding intrinsically meropenem-resistant Stenotrophomonas maltophilia, 47/1846 isolates (2.5%) were meropenem-resistant. A high proportion of meropenem-resistant P. aeruginosa were susceptible to cefiderocol (95.0%). All S. maltophilia isolates (40/40) were cefiderocol-susceptible. CONCLUSION A substantial proportion of clinical isolates from England, representing a wide range of pathogens across multiple infection sources, was cefiderocol-susceptible. Cefiderocol retained activity against meropenem-resistant strains.
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Affiliation(s)
- Vanya Gant
- University College London Hospitals NHS Foundation Trust, London, UK.
| | - Abid Hussain
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
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Dongol S, Kayastha G, Maharjan N, Pyatha S, K. C. R, Thwaites L, Basnyat B, Baker S, Karkey A. Epidemiology, etiology, and diagnosis of health care acquired pneumonia including ventilator-associated pneumonia in Nepal. PLoS One 2021; 16:e0259634. [PMID: 34788314 PMCID: PMC8598067 DOI: 10.1371/journal.pone.0259634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 10/22/2021] [Indexed: 11/19/2022] Open
Abstract
Epidemiologic data regarding health care acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) from Nepal are negligible. We conducted a prospective observational cohort study in the intensive care unit (ICU) of a major tertiary hospital in Nepal between April 2016 and March 2018, to calculate the incidence of VAP, and to describe clinical variables, microbiological etiology, and outcomes. Four hundred and thirty-eight patients were enrolled in the study. Demographic data, medical history, antimicrobial administration record, chest X-ray, biochemical, microbiological and haematological results, acute physiology and chronic health evaluation II score and the sequential organ failure assessment scores were recorded. Categorical variables were expressed as count and percentage and analyzed using the Fisher's exact test. Continuous variables were expressed as median and interquartile range and analyzed using Kruskal-Wallis rank sum test and the pairwise Wilcoxon rank-sum test. 46.8% (205/438) of the patients required intubation. Pneumonia was common in both intubated (94.14%; 193/205) and non-intubated (52.36%; 122/233) patients. Pneumonia developed among intubated patients in the ICU had longer days of stay in the ICU (median of 10, IQR 5-15, P< 0.001) when compared to non-intubated patients with pneumonia (median of 4, IQR 3-6, P< 0.001). The incidence rate of VAP was 20% (41/205) and incidence density was 16.45 cases per 1,000ventilator days. Mortality was significantly higher in patients with pneumonia requiring intubation (44.6%, 86/193) than patients with pneumonia not requiring intubation (10.7%, 13/122, p<0.001, Fisher's exact test). Gram negative bacteria such as Klebsiella and Acinetobacter species were the dominant organisms from both VAP and non-VAP categories. Multi-drug resistance was highly prevalent in bacterial isolates associated with VAP (90%; 99/110) and non-VAP categories (81.5%; 106/130). HAP including VAP remains to be the most prevalent hospital-acquired infections (HAIs) at Patan hospital. A local study of etiological agents and outcomes of HAP and VAP are required for setting more appropriate guidelines for management of such diseases.
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Affiliation(s)
- Sabina Dongol
- Patan Academy of Health Sciences, Patan Hospital, Oxford University Clinical Research Unit, Kathmandu, Nepal
| | - Gyan Kayastha
- Patan Academy of Health Sciences, Patan Hospital, Kathmandu, Nepal
| | - Nhukesh Maharjan
- Patan Academy of Health Sciences, Patan Hospital, Oxford University Clinical Research Unit, Kathmandu, Nepal
| | - Sarita Pyatha
- Patan Academy of Health Sciences, Patan Hospital, Oxford University Clinical Research Unit, Kathmandu, Nepal
| | - Rajkumar K. C.
- Patan Academy of Health Sciences, Patan Hospital, Oxford University Clinical Research Unit, Kathmandu, Nepal
| | - Louise Thwaites
- The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam
| | - Buddha Basnyat
- Patan Academy of Health Sciences, Patan Hospital, Oxford University Clinical Research Unit, Kathmandu, Nepal
| | - Stephen Baker
- Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, United Kingdom
| | - Abhilasha Karkey
- Patan Academy of Health Sciences, Patan Hospital, Oxford University Clinical Research Unit, Kathmandu, Nepal
- * E-mail:
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Wakabayashi T, Iwata H. Outcome, diagnosis, and microbiological profile comparison of community- and hospital-acquired bacteremia: A retrospective cohort study. J Gen Fam Med 2021; 22:327-333. [PMID: 34754710 PMCID: PMC8561096 DOI: 10.1002/jgf2.453] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 02/04/2021] [Accepted: 04/26/2021] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Although bacteremia is one of the most pressing situation in the field of hospital medicine, little is known about the differences between community- and hospital-acquired bacteremia (CAB and HAB, respectively). METHODS Objective is to know the epidemiologic characteristics of CAB and HAB. Study design is a single-center retrospective cohort study. Participants were all patients over the age of 16 years who were blood cultures positive at single acute care hospital from April 2013 to March 2018. HAB was defined as positive culture acquired at least 48 h after admission or blood culture-positive patients transferred from other hospital. The primary outcome was 30 day mortality, and the secondary outcome was 1 year mortality. We compared the primary and secondary outcomes between HAB and CAB using logistic regression analyses. RESULTS There were 325 participants in this study. The number of patients with CAB was 189 (58.1%). HAB was associated with a higher 30 day mortality rate than CAB (n = 31, 22.8% vs. n = 9, 4.8%, adjusted odds ratio (AOR) 2.60; 95% confidence interval (CI) 1.04-6.53, p < 0.05). In the secondary outcome, HAB was also associated with a higher 1 year mortality rate (n = 61/110, 55.5% vs. n = 32/143, 22.4%, AOR 2.27; 95% CI: 1.12-4.58). CONCLUSIONS Our study showed that HAB was associated with higher mortality than CAB in 30 day mortality and in 1 yr mortality. Thus, we confirmed that HAB is distinct from CAB concerning the differences of outcomes.
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Affiliation(s)
- Takao Wakabayashi
- Department of General and Emergency MedicineJapan Community Health‐care Organization Sapporo Hokushin HospitalSapporoJapan
| | - Hiroyoshi Iwata
- Department of Pharmacology and TherapeuticsUniversity of the RyukyusOkinawaJapan
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Navapurkar V, Bartholdson Scott J, Maes M, Hellyer TP, Higginson E, Forrest S, Pereira-Dias J, Parmar S, Heasman-Hunt E, Polgarova P, Brown J, Titti L, Smith WPW, Scott J, Rostron A, Routledge M, Sapsford D, Török ME, McMullan R, Enoch DA, Wong V, Curran MD, Brown NM, Simpson AJ, Herre J, Dougan G, Conway Morris A. Development and implementation of a customised rapid syndromic diagnostic test for severe pneumonia. Wellcome Open Res 2021; 6:256. [PMID: 36337362 PMCID: PMC9617073 DOI: 10.12688/wellcomeopenres.17099.1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/22/2021] [Indexed: 02/02/2023] Open
Abstract
Background: The diagnosis of pneumonia has been hampered by a reliance on bacterial cultures which take several days to return a result, and are frequently negative. In critically ill patients this leads to the use of empiric, broad-spectrum antimicrobials and compromises good antimicrobial stewardship. The objective of this study was to establish the performance of a syndromic molecular diagnostic approach, using a custom TaqMan array card (TAC) covering 52 respiratory pathogens, and assess its impact on antimicrobial prescribing. Methods: The TAC was validated against a retrospective multi-centre cohort of broncho-alveolar lavage samples. The TAC was assessed prospectively in patients undergoing investigation for suspected pneumonia, with a comparator cohort formed of patients investigated when the TAC laboratory team were unavailable. Co-primary outcomes were sensitivity compared to conventional microbiology and, for the prospective study, time to result. Metagenomic sequencing was performed to validate findings in prospective samples. Antibiotic free days (AFD) were compared between the study cohort and comparator group. Results: 128 stored samples were tested, with sensitivity of 97% (95% confidence interval (CI) 88-100%). Prospectively, 95 patients were tested by TAC, with 71 forming the comparator group. TAC returned results 51 hours (interquartile range 41-69 hours) faster than culture and with sensitivity of 92% (95% CI 83-98%) compared to conventional microbiology. 94% of organisms identified by sequencing were detected by TAC. There was a significant difference in the distribution of AFDs with more AFDs in the TAC group (p=0.02). TAC group were more likely to experience antimicrobial de-escalation (odds ratio 2.9 (95%1.5-5.5)). Conclusions: Implementation of a syndromic molecular diagnostic approach to pneumonia led to faster results, with high sensitivity and impact on antibiotic prescribing.
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Affiliation(s)
- Vilas Navapurkar
- John V Farman Intensive Care Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Josefin Bartholdson Scott
- Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, CB2 0AW, UK
| | - Mailis Maes
- Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, CB2 0AW, UK
| | - Thomas P Hellyer
- Translational and Clinical Research Institute, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK
- Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE7 7DN, UK
| | - Ellen Higginson
- Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, CB2 0AW, UK
| | - Sally Forrest
- Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, CB2 0AW, UK
| | - Joana Pereira-Dias
- Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, CB2 0AW, UK
| | - Surendra Parmar
- Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Emma Heasman-Hunt
- Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Petra Polgarova
- John V Farman Intensive Care Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Joanne Brown
- John V Farman Intensive Care Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Lissamma Titti
- John V Farman Intensive Care Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - William PW Smith
- School of Clinical Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK
| | - Jonathan Scott
- Translational and Clinical Research Institute, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK
| | - Anthony Rostron
- Translational and Clinical Research Institute, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK
| | - Matthew Routledge
- Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- Infectious Diseases, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - David Sapsford
- Pharmacy Department, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - M. Estée Török
- Department of Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK
- Microbiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Ronan McMullan
- Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, BT9 7BL, UK
| | - David A Enoch
- Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Vanessa Wong
- Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- Infectious Diseases, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - VAP-Rapid investigators
- John V Farman Intensive Care Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, CB2 0AW, UK
- Translational and Clinical Research Institute, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK
- Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE7 7DN, UK
- Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- School of Clinical Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK
- Infectious Diseases, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- Pharmacy Department, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- Department of Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK
- Microbiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, BT9 7BL, UK
- Respiratory Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK
| | - Martin D Curran
- Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Nicholas M Brown
- Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - A John Simpson
- Translational and Clinical Research Institute, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK
- Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE7 7DN, UK
| | - Jurgen Herre
- Respiratory Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Gordon Dougan
- Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, CB2 0AW, UK
| | - Andrew Conway Morris
- John V Farman Intensive Care Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
- Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK
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High J, Enne VI, Barber JA, Brealey D, Turner DA, Horne R, Peters M, Dhesi Z, Wagner AP, Pandolfo AM, Stirling S, Russell C, O'Grady J, Swart AM, Gant V, Livermore DM. INHALE: the impact of using FilmArray Pneumonia Panel molecular diagnostics for hospital-acquired and ventilator-associated pneumonia on antimicrobial stewardship and patient outcomes in UK Critical Care-study protocol for a multicentre randomised controlled trial. Trials 2021; 22:680. [PMID: 34620213 PMCID: PMC8496625 DOI: 10.1186/s13063-021-05618-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Accepted: 09/13/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Hospital-acquired and ventilator-associated pneumonias (HAP and VAP) are common in critical care and can be life-threatening. Rapid microbiological diagnostics, linked to an algorithm to translate their results into antibiotic choices, could simultaneously improve patient outcomes and antimicrobial stewardship. METHODS The INHALE Randomised Controlled Trial is a multi-centre, parallel study exploring the potential of the BioFire FilmArray molecular diagnostic to guide antibiotic treatment of HAP/VAP in intensive care units (ICU); it identifies pathogens and key antibiotic resistance in around 90 min. The comparator is standard care whereby the patient receives empirical antibiotics until microbiological culture results become available, typically after 48-72 h. Adult and paediatric ICU patients are eligible if they are about to receive antibiotics for a suspected lower respiratory infection (including HAP/VAP) for the first time or a change in antibiotic because of a deteriorating clinical condition. Breathing spontaneously or intubated, they must have been hospitalised for 48 h or more. Patients are randomised 1:1 to receive either antibiotics guided by the FilmArray molecular diagnostic and its trial-based prescribing algorithm or standard care, meaning empirical antibiotics based on local policy, adapted subsequently based upon local microbiology culture results. Co-primary outcomes are (i) non-inferiority in clinical cure of pneumonia at 14 days post-randomisation and (ii) superiority in antimicrobial stewardship at 24 h post-randomisation (defined as % of patients on active and proportionate antibiotics). Secondary outcomes include further stewardship reviews; length of ICU stay; co-morbidity indicators, including septic shock, change in sequential organ failure assessment scores, and secondary pneumonias; ventilator-free days; adverse events over 21 days; all-cause mortality; and total antibiotic usage. Both cost-effectiveness of the molecular diagnostic-guided therapy and behavioural aspects determining antibiotic prescribing are being explored. A sample size of 552 will be required to detect clinically significant results with 90% power and 5% significance for the co-primary outcomes. DISCUSSION This trial will test whether the potential merits of rapid molecular diagnostics for pathogen and resistance detection in HAP/VAP are realised in patient outcomes and/or improved antibiotic stewardship. TRIAL REGISTRATION ISRCTN Registry ISRCTN16483855 . Retrospectively registered on 15 July 2019.
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Affiliation(s)
- Juliet High
- Norwich Clinical Trials Unit, University of East Anglia, Norwich, NR4 7TJ, UK.
| | - Virve I Enne
- University College London, Gower Street, London, WC1E 6BT, UK
| | - Julie A Barber
- University College London, Gower Street, London, WC1E 6BT, UK
| | - David Brealey
- NIHR University College London Hospitals Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, NW1 2PG, UK
| | - David A Turner
- Norwich Clinical Trials Unit, University of East Anglia, Norwich, NR4 7TJ, UK
| | - Robert Horne
- University College London, Gower Street, London, WC1E 6BT, UK
| | - Mark Peters
- University College London Great Ormond Street Institute of Child Health and Great Ormond Street Hospital NIHR Biomedical Research Centre, WC1N 3JH, London, WC1N 3JH, UK
| | - Zaneeta Dhesi
- University College London, Gower Street, London, WC1E 6BT, UK
| | - Adam P Wagner
- Norwich Clinical Trials Unit, University of East Anglia, Norwich, NR4 7TJ, UK
| | | | - Sue Stirling
- Norwich Clinical Trials Unit, University of East Anglia, Norwich, NR4 7TJ, UK
| | - Charlotte Russell
- Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ, UK
| | - Justin O'Grady
- Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ, UK
- Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UA, UK
| | - Ann Marie Swart
- Norwich Clinical Trials Unit, University of East Anglia, Norwich, NR4 7TJ, UK
| | - Vanya Gant
- University College London Hospitals NHS Foundation Trust, London, NW1 2PG, UK
| | - David M Livermore
- Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ, UK
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