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Tamma PD, Harris PNA, Mathers AJ, Wenzler E, Humphries RM. Breaking Down the Breakpoints: Rationale for the 2022 Clinical and Laboratory Standards Institute Revised Piperacillin-Tazobactam Breakpoints Against Enterobacterales. Clin Infect Dis 2023; 77:1585-1590. [PMID: 36001445 DOI: 10.1093/cid/ciac688] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 08/11/2022] [Accepted: 08/22/2022] [Indexed: 11/14/2022] Open
Abstract
Piperacillin-tazobactam (PTZ) is one of the most common antibiotics administered to hospitalized patients. Its broad activity against gram-negative, gram-positive, and anaerobic pathogens; efficacy in clinical trials across diverse infection types and patient populations; and generally favorable toxicity profile make it a particularly appealing antibiotic agent. PTZ susceptibility interpretive criteria (ie, breakpoints) for the Enterobacterales were initially established in 1992, as the drug was undergoing approval by the US Food and Drug Administration. In the ensuing 30 years, changes in the molecular epidemiology of the Enterobacterales and its impact on PTZ susceptibility testing, mounting pharmacokinetic/pharmacodynamic data generated from sophisticated techniques such as population pharmacokinetic modeling and Monte Carlo simulation, and disturbing safety signals in a large clinical trial prompted the Clinical Laboratory and Standards Institute (CLSI) to review available evidence to determine the need for revision of the PTZ breakpoints for Enterobacterales. After an extensive literature review and formal voting process, the susceptibility criteria were revised in the 2022 CLSI M100 document to the following: ≤8/4 µg/mL (susceptible), 16/4 µg/mL (susceptible dose-dependent), and ≥32/4 µg/mL (resistant). Herein, we provide a brief overview of the CLSI process of antibiotic breakpoint revisions and elaborate on the available data that ultimately led to the decision to revise the PTZ breakpoints.
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Affiliation(s)
- Pranita D Tamma
- Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Patrick N A Harris
- Faculty of Medicine, UQ Center for Clinical Research, Royal Brisbane and Women's Hospital Campus, University of Queensland, Brisbane, Australia
| | - Amy J Mathers
- Department of Medicine and Pathology, University of Virginia, Charlottesville, Virginia, USA
| | - Eric Wenzler
- Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, Illinois, USA
| | - Romney M Humphries
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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Mokrani D, Chommeloux J, Pineton de Chambrun M, Hékimian G, Luyt CE. Antibiotic stewardship in the ICU: time to shift into overdrive. Ann Intensive Care 2023; 13:39. [PMID: 37148398 PMCID: PMC10163585 DOI: 10.1186/s13613-023-01134-9] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 04/20/2023] [Indexed: 05/08/2023] Open
Abstract
Antibiotic resistance is a major health problem and will be probably one of the leading causes of deaths in the coming years. One of the most effective ways to fight against resistance is to decrease antibiotic consumption. Intensive care units (ICUs) are places where antibiotics are widely prescribed, and where multidrug-resistant pathogens are frequently encountered. However, ICU physicians may have opportunities to decrease antibiotics consumption and to apply antimicrobial stewardship programs. The main measures that may be implemented include refraining from immediate prescription of antibiotics when infection is suspected (except in patients with shock, where immediate administration of antibiotics is essential); limiting empiric broad-spectrum antibiotics (including anti-MRSA antibiotics) in patients without risk factors for multidrug-resistant pathogens; switching to monotherapy instead of combination therapy and narrowing spectrum when culture and susceptibility tests results are available; limiting the use of carbapenems to extended-spectrum beta-lactamase-producing Enterobacteriaceae, and new beta-lactams to difficult-to-treat pathogen (when these news beta-lactams are the only available option); and shortening the duration of antimicrobial treatment, the use of procalcitonin being one tool to attain this goal. Antimicrobial stewardship programs should combine these measures rather than applying a single one. ICUs and ICU physicians should be at the frontline for developing antimicrobial stewardship programs.
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Affiliation(s)
- David Mokrani
- Service de Médecine Intensive Réanimation, Institut de Cardiologie, ICAN, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Sorbonne-Université, Hôpital Pitié-Salpêtrière, 47-83, Boulevard de l'Hôpital, 75651, Paris Cedex 13, France
| | - Juliette Chommeloux
- Service de Médecine Intensive Réanimation, Institut de Cardiologie, ICAN, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Sorbonne-Université, Hôpital Pitié-Salpêtrière, 47-83, Boulevard de l'Hôpital, 75651, Paris Cedex 13, France
| | - Marc Pineton de Chambrun
- Service de Médecine Intensive Réanimation, Institut de Cardiologie, ICAN, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Sorbonne-Université, Hôpital Pitié-Salpêtrière, 47-83, Boulevard de l'Hôpital, 75651, Paris Cedex 13, France
| | - Guillaume Hékimian
- Service de Médecine Intensive Réanimation, Institut de Cardiologie, ICAN, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Sorbonne-Université, Hôpital Pitié-Salpêtrière, 47-83, Boulevard de l'Hôpital, 75651, Paris Cedex 13, France
| | - Charles-Edouard Luyt
- Service de Médecine Intensive Réanimation, Institut de Cardiologie, ICAN, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Sorbonne-Université, Hôpital Pitié-Salpêtrière, 47-83, Boulevard de l'Hôpital, 75651, Paris Cedex 13, France.
- Sorbonne Université, INSERM, UMRS_1166-ICAN Institute of Cardiometabolism and Nutrition, Paris, France.
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Chen L, Hua J, Hong SJ, Yuan CY, Jing RC, Luo XY, Xue HW, Yue Y, He XP. Comparison of the relative efficacy of β-lactam/β-lactamase inhibitors and carbapenems in the treatment of complicated urinary tract infections caused by ceftriaxone-non-susceptible Enterobacterales: a multicentre retrospective observational cohort study. J Antimicrob Chemother 2023; 78:710-718. [PMID: 36691860 DOI: 10.1093/jac/dkac448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Accepted: 12/20/2022] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND Treating complicated urinary tract infections (cUTIs) caused by ESBL-producing Enterobacterales represents a significant clinical challenge. The present study was thus developed to explore the relative efficacy of β-lactam/β-lactamase inhibitors (BLBLIs) and carbapenems for the treatment of hospitalized patients suffering from cUTIs caused by BLBLI-susceptible ceftriaxone-non-susceptible Enterobacterales. METHODS Data from 557 patients from four Chinese teaching hospitals diagnosed with cUTIs caused by ceftriaxone-non-susceptible Enterobacterales from January 2017 to May 2022 were retrospectively assessed. RESULT The 30 day rate of treatment failure, defined by unresolved symptoms or mortality, was 10.4% (58/557). Independent predictors of 30 day treatment failure included immunocompromised status, bacteraemia, septic shock, lack of infection source control and appropriate empirical treatment. When data were controlled for potential confounding variables, BLBLI treatment exhibited a comparable risk of 14 day (OR 1.61, 95% CI 0.86-3.00, P = 0.133) and 30 day treatment failure (OR 1.45, 95% CI 0.66-3.15, P = 0.354) relative to carbapenem treatment for the overall cohort of patients. In contrast, BLBLI treatment in immunocompromised patients was associated with an elevated risk of both 14 day (OR 3.18, 95% CI 1.43-7.10, P = 0.005) and 30 day treatment failure (OR 3.06, 95% CI 1.07-8.80, P = 0.038) relative to carbapenem treatment. CONCLUSIONS These results suggested that carbapenem treatment may be superior to BLBLI treatment for immunocompromised patients suffering from cUTIs caused by ceftriaxone-non-susceptible Enterobacterales species. However, these results will need to be validated in appropriately constructed randomized controlled trials to ensure appropriate patient treatment.
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Affiliation(s)
- Liang Chen
- Department of Infectious Diseases, Nanjing Lishui People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, China
| | - Jie Hua
- Department of Gastroenterology, Liyang People's Hospital, Liyang Branch Hospital of Jiangsu Province Hospital, Nanjing, China
| | - Shu-Jie Hong
- Department of Clinical Medicine, Nanjing Medical University, Nanjing, China
| | - Chen-Yang Yuan
- Department of Clinical Medicine, Nanjing Medical University, Nanjing, China
| | - Ruo-Chen Jing
- Department of Clinical Medicine, Nanjing Medical University, Nanjing, China
| | - Xuan-Yu Luo
- Department of Clinical Medicine, Nanjing Medical University, Nanjing, China
| | - Hao-Wen Xue
- Department of Clinical Medicine, Nanjing Medical University, Nanjing, China
| | - Yue Yue
- Department of Clinical Medicine, Nanjing Medical University, Nanjing, China
| | - Xiao-Pu He
- Department of Geriatric Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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When and How to Use MIC in Clinical Practice? Antibiotics (Basel) 2022; 11:antibiotics11121748. [PMID: 36551405 PMCID: PMC9774413 DOI: 10.3390/antibiotics11121748] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/22/2022] [Accepted: 11/30/2022] [Indexed: 12/12/2022] Open
Abstract
Bacterial resistance to antibiotics continues to be a global public health problem. The choice of the most effective antibiotic and the use of an adapted dose in the initial phase of the infection are essential to limit the emergence of resistance. This will depend on (i) the isolated bacteria and its resistance profile, (ii) the pharmacodynamic (PD) profile of the antibiotic used and its level of toxicity, (iii) the site of infection, and (iv) the pharmacokinetic (PK) profile of the patient. In order to take account of both parameters to optimize the administered treatment, a minimal inhibitory concentration (MIC) determination associated with therapeutic drug monitoring (TDM) and their combined interpretation are required. The objective of this narrative review is thus to suggest microbiological, pharmacological, and/or clinical situations for which this approach could be useful. Regarding the microbiological aspect, such as the detection of antibiotic resistance and its level, the preservation of broad-spectrum β-lactams is particularly discussed. PK-PD profiles are relevant for difficult-to-reach infections and specific populations such as intensive care patients, cystic fibrosis patients, obese, or elderly patients. Finally, MIC and TDM are tools available to clinicians, who should not hesitate to use them to manage their patients.
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Is Piperacillin-Tazobactam an Appropriate Empirical Agent for Hospital-Acquired Sepsis and Community-Acquired Septic Shock of Unknown Origin in Australia? Healthcare (Basel) 2022; 10:healthcare10050851. [PMID: 35627988 PMCID: PMC9142067 DOI: 10.3390/healthcare10050851] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 04/30/2022] [Accepted: 05/01/2022] [Indexed: 11/17/2022] Open
Abstract
Early appropriate empirical antibiotics are critical for reducing mortality in sepsis. For hospital-acquired sepsis of unknown origin in Australia, piperacillin-tazobactam (TZP) is recommended as an empirical therapy. Anecdotally, some institutions also use TZP for community-acquired septic shock. This narrative review aimed to scrutinise the appropriateness of TZP as an empirical agent for undifferentiated hospital-acquired sepsis and community-acquired septic shock. An online database (Medline) was searched for relevant studies in adults published in the last 10 years. Studies were included if they addressed separately reported clinical outcomes related to a relevant aspect of TZP therapy in sepsis. Of 290 search results, no studies directly addressed the study aim. This review therefore explores several themes that emerged from the contemporary literature, all of which must be considered to fully interrogate the appropriateness of TZP use in this context. This review reveals the paucity and low quality of evidence available for TZP use in sepsis of unclear origin, while demonstrating the urgent need and equipoise for an Australian audit of TZP use in patients with sepsis of unknown origin.
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Pierce VM, Mathers AJ. Setting Antimicrobial Susceptibility Testing Breakpoints: A Primer for Pediatric Infectious Diseases Specialists on the Clinical and Laboratory Standards Institute Approach. J Pediatric Infect Dis Soc 2022; 11:73-80. [PMID: 34888640 DOI: 10.1093/jpids/piab106] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 10/22/2021] [Indexed: 01/22/2023]
Abstract
Breakpoints are the values used by clinical microbiology laboratories to interpret the results of antimicrobial susceptibility testing (AST) and classify isolates as susceptible or resistant. Whether the breakpoints applied by laboratories accurately predict the likelihood of successful treatment with a particular antimicrobial is an issue of critical importance to quality clinical care. In the United States, the Food and Drug Administration (FDA) sets breakpoints, and globally, breakpoints are also set by 2 standards development organizations, the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST); individual laboratories may choose which breakpoints to implement. Many CLSI breakpoints are recognized by FDA, facilitating their incorporation into widely used commercial AST devices. The CLSI Subcommittee on AST's consensus approach to establishing (and as needed, revising) breakpoints involves integration of currently available microbiological, pharmacokinetic-pharmacodynamic, and clinical data. Here, an overview of the CLSI process for establishing breakpoints is provided.
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Affiliation(s)
- Virginia M Pierce
- Clinical Microbiology Laboratory, Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.,Pediatric Infectious Disease Unit, MassGeneral Hospital for Children, Boston, Massachusetts, USA
| | - Amy J Mathers
- Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA.,Clinical Microbiology Laboratory, Department of Pathology, University of Virginia Health System, Charlottesville, Virginia, USA
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Zoratti C, Moretti R, Rebuzzi L, Albergati IV, Di Somma A, Decorti G, Di Bella S, Crocè LS, Giuffrè M. Antibiotics and Liver Cirrhosis: What the Physicians Need to Know. Antibiotics (Basel) 2021; 11:31. [PMID: 35052907 PMCID: PMC8772826 DOI: 10.3390/antibiotics11010031] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 12/23/2021] [Accepted: 12/24/2021] [Indexed: 12/13/2022] Open
Abstract
The liver is the primary site of drug metabolism, which can be altered by a variety of diseases affecting the liver parenchyma, especially in patients with liver cirrhosis. The use of antibiotics in patients with cirrhosis is usually a matter of concern for physicians, given the lack of practical knowledge for drug choice and eventual dose adjustments in several clinical scenarios. The aim of the current narrative review is to report, as broadly as possible, basic, and practical knowledge that any physician should have when approaching a patient with liver cirrhosis and an ongoing infection to efficiently choose the best antibiotic therapy.
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Affiliation(s)
- Caterina Zoratti
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (C.Z.); (R.M.); (L.R.); (I.V.A.); (A.D.S.); (S.D.B.); (L.S.C.)
| | - Rita Moretti
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (C.Z.); (R.M.); (L.R.); (I.V.A.); (A.D.S.); (S.D.B.); (L.S.C.)
| | - Lisa Rebuzzi
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (C.Z.); (R.M.); (L.R.); (I.V.A.); (A.D.S.); (S.D.B.); (L.S.C.)
| | - Irma Valeria Albergati
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (C.Z.); (R.M.); (L.R.); (I.V.A.); (A.D.S.); (S.D.B.); (L.S.C.)
| | - Antonietta Di Somma
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (C.Z.); (R.M.); (L.R.); (I.V.A.); (A.D.S.); (S.D.B.); (L.S.C.)
| | - Giuliana Decorti
- Institute for Maternal and Child Health-IRCCS Burlo Garofolo, 34137 Trieste, Italy;
| | - Stefano Di Bella
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (C.Z.); (R.M.); (L.R.); (I.V.A.); (A.D.S.); (S.D.B.); (L.S.C.)
| | - Lory Saveria Crocè
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (C.Z.); (R.M.); (L.R.); (I.V.A.); (A.D.S.); (S.D.B.); (L.S.C.)
- Italian Liver Foundation, 34149 Trieste, Italy
| | - Mauro Giuffrè
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (C.Z.); (R.M.); (L.R.); (I.V.A.); (A.D.S.); (S.D.B.); (L.S.C.)
- Italian Liver Foundation, 34149 Trieste, Italy
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Monogue ML, Heil EL, Aitken SL, Pogue JM. The role of tazobactam-based combinations for the management of infections due to extended-spectrum β-lactamase-producing Enterobacterales: Insights from the Society of Infectious Diseases Pharmacists. Pharmacotherapy 2021; 41:864-880. [PMID: 34689349 DOI: 10.1002/phar.2623] [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: 07/12/2021] [Revised: 08/17/2021] [Accepted: 08/22/2021] [Indexed: 11/07/2022]
Abstract
Extended-spectrum β-lactamase (ESBL)-producing Enterobacterales are a global threat to public health due to their antimicrobial resistance profile and, consequently, their limited available treatment options. Tazobactam is a sulfone β-lactamase inhibitor with in vitro inhibitory activity against common ESBLs in Enterobacterales, including CTX-M. However, the role of tazobactam-based combinations in treating infections caused by ESBL-producing Enterobacterales remains unclear. In the United States, two tazobactam-based combinations are available, piperacillin-tazobactam and ceftolozane-tazobactam. We evaluated and compared the roles of tazobactam-based combinations against ESBL-producing organisms with emphasis on pharmacokinetic/pharmacodynamic exposures in relation to MIC distributions and established breakpoints, clinical outcomes data specific to infection site, and considerations for downstream effects with these agents regarding antimicrobial resistance development. While limited data with ceftolozane-tazobactam are encouraging for its potential role in infections due to ESBL-producing Enterobacterales, further evidence is needed to determine its place in therapy. Conversely, currently available microbiologic, pharmacokinetic, pharmacodynamic, and clinical data do not suggest a role for piperacillin-tazobactam, and we caution clinicians against its usage for these infections.
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Affiliation(s)
- Marguerite L Monogue
- Department of Pharmacy, University of Texas Southwestern Medical Center, Dallas, Texas, USA
- Division of Infectious Diseases and Geographic Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Emily L Heil
- Department of Pharmacy Services, University of Maryland Medical Center, Baltimore, Maryland, USA
- Department of Pharmacy Practice and Science, University of Maryland School of Pharmacy, Baltimore, Maryland, USA
| | - Samuel L Aitken
- Department of Pharmacy, Michigan Medicine, Ann Arbor, Michigan, USA
- Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, Michigan, USA
| | - Jason M Pogue
- Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, Michigan, USA
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Luo H, Xiao Y, Hang Y, Chen Y, Zhu H, Fang X, Cao X, Zou S, Hu X, Xiong J, Zhong Q, Hu L. Comparison of therapy with β-lactam/β-lactamase inhibitor combinations or carbapenems for bacteraemia of nonurinary source caused by ESBL-producing Escherichia coli or Klebsiella pneumoniae. Ann Clin Microbiol Antimicrob 2021; 20:63. [PMID: 34488786 PMCID: PMC8422674 DOI: 10.1186/s12941-021-00471-6] [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: 04/12/2021] [Accepted: 08/31/2021] [Indexed: 11/23/2022] Open
Abstract
Background Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae has become a public health concern. This study aimed to compare the clinical outcomes of patients with nonurinary source bacteraemia caused by ESBL-producing Escherichia coli (E. coli) or Klebsiella pneumoniae (ESBL-producing EK) receiving β-lactam/β-lactamase inhibitor combinations (BLICs) versus carbapenem treatment and assess the risk factors of mortality with these two drugs. Methods We conducted a retrospective single-centre study of adult hospitalised patients with ESBL-producing EK bloodstream infection (BSI) from nonurinary source at our centre over a 4-year period. One hundred and eighty patients who received BLICs or carbapenems were included in the analysis. The outcome variables were 14-day treatment failure and 30-day mortality. For more reliable results, propensity score analysis was performed to compare the efficacy of the two drugs and analyse their risk factors for 30-day mortality. Results Out of 180 patients, 114 received BLICs, and 66 received carbapenem therapy. Compared to carbapenem-treated patients, those treated with BLICs were older and had higher age-adjusted Charlson comorbidity index, but they had shorter stay in the hospital. Additionally, their Pitt bacteraemia score, SOFA score, rate of leukaemia, and immune compromise were lower. After propensity score matching (PSM), the baseline characteristics of patients in the two treatment groups were balanced. BLICs were associated with a higher 14-day treatment failure rate (20.6%, 13/63) than carbapenems (16.3%, 7/43), although the difference was not significant in either univariate analysis (P = 0.429) or multivariate analysis (P = 0.122). And the 30-day mortality rate in BTG (11.1%, 7/63) and CTG (11.6%, 5/43) did not significantly differ (univariate analysis, P = 0.926; multivariate analysis, P = 0.420). In the multivariate analysis, after PSM, leukaemia was the only independent predictor of mortality in both BTG and CTG. Conclusions Our study showed that BLICs had higher 14-day treatment failure rate compared with carbapenems, although there were no statistically significant differences because of the small number of patients, therefore, further evaluation of the efficacy of BLICs is needed.
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Affiliation(s)
- Hong Luo
- Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Mingde Road No. 1, Nanchang, 330006, Jiangxi, People's Republic of China
| | - Yanping Xiao
- Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Mingde Road No. 1, Nanchang, 330006, Jiangxi, People's Republic of China
| | - Yaping Hang
- Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Mingde Road No. 1, Nanchang, 330006, Jiangxi, People's Republic of China
| | - Yanhui Chen
- Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Mingde Road No. 1, Nanchang, 330006, Jiangxi, People's Republic of China
| | - Hongying Zhu
- Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Mingde Road No. 1, Nanchang, 330006, Jiangxi, People's Republic of China
| | - Xueyao Fang
- Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Mingde Road No. 1, Nanchang, 330006, Jiangxi, People's Republic of China
| | - Xingwei Cao
- Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Mingde Road No. 1, Nanchang, 330006, Jiangxi, People's Republic of China
| | - Shan Zou
- Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Mingde Road No. 1, Nanchang, 330006, Jiangxi, People's Republic of China
| | - Xiaoyan Hu
- Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Mingde Road No. 1, Nanchang, 330006, Jiangxi, People's Republic of China
| | - Jianqiu Xiong
- Department of Nursing, The Second Affiliated Hospital of Nanchang University, Mingde Road No. 1, Nanchang, 330006, Jiangxi, People's Republic of China
| | - Qiaoshi Zhong
- Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Mingde Road No. 1, Nanchang, 330006, Jiangxi, People's Republic of China.
| | - Longhua Hu
- Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Mingde Road No. 1, Nanchang, 330006, Jiangxi, People's Republic of China.
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Rodríguez-Villodres Á, Gil-Marqués ML, Álvarez-Marín R, Bonnin RA, Pachón-Ibáñez ME, Aguilar-Guisado M, Naas T, Aznar J, Pachón J, Lepe JA, Smani Y. Extended-spectrum resistance to β-lactams/β-lactamase inhibitors (ESRI) evolved from low-level resistant Escherichia coli. J Antimicrob Chemother 2021; 75:77-85. [PMID: 31613964 DOI: 10.1093/jac/dkz393] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2019] [Revised: 07/29/2019] [Accepted: 08/12/2019] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES Escherichia coli is characterized by three resistance patterns to β-lactams/β-lactamase inhibitors (BLs/BLIs): (i) resistance to ampicillin/sulbactam and susceptibility to amoxicillin/clavulanic acid and piperacillin/tazobactam (RSS); (ii) resistance to ampicillin/sulbactam and amoxicillin/clavulanic acid, and susceptibility to piperacillin/tazobactam (RRS); and (iii) resistance to ampicillin/sulbactam, amoxicillin/clavulanic acid and piperacillin/tazobactam (RRR). These resistance patterns are acquired consecutively, indicating a potential risk of developing resistance to piperacillin/tazobactam, but the precise mechanism of this process is not completely understood. METHODS Clinical isolates incrementally pressured by piperacillin/tazobactam selection in vitro and in vivo were used. We determined the MIC of piperacillin/tazobactam in the presence and absence of piperacillin/tazobactam pressure. We deciphered the role of the blaTEM genes in the new concept of extended-spectrum resistance to BLs/BLIs (ESRI) using genomic analysis. The activity of β-lactamase was quantified in these isolates. RESULTS We show that piperacillin/tazobactam resistance is induced in E. coli carrying blaTEM genes. This resistance is due to the increase in copy numbers and transcription levels of the blaTEM gene, thus increasing β-lactamase activity and consequently increasing piperacillin/tazobactam MICs. Genome sequencing of two blaTEM-carrying representative isolates showed that piperacillin/tazobactam treatment produced two types of duplications of blaTEM (8 and 60 copies, respectively). In the clinical setting, piperacillin/tazobactam treatment of patients infected by E. coli carrying blaTEM is associated with a risk of therapeutic failure. CONCLUSIONS This study describes for the first time the ESRI in E. coli. This new concept is very important in the understanding of the mechanism involved in the acquisition of resistance to BLs/BLIs.
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Affiliation(s)
- Ángel Rodríguez-Villodres
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen del Rocío, Seville, Spain.,Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain
| | - María Luisa Gil-Marqués
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen del Rocío, Seville, Spain.,Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain
| | - Rocío Álvarez-Marín
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen del Rocío, Seville, Spain.,Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain
| | - Rémy A Bonnin
- EA7361, Université Paris-Saclay, LabEx Lermit, Bacteriology-Hygiene unit, APHP, Hôpital Bicêtre, EERA 'Evolution and Ecology of Resistance to Antibiotics' Unit, Institut Pasteur-APHP-Université Paris-Sud, Le Kremlin-Bicêtre, France
| | - María Eugenia Pachón-Ibáñez
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen del Rocío, Seville, Spain.,Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain
| | - Manuela Aguilar-Guisado
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen del Rocío, Seville, Spain.,Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain
| | - Thierry Naas
- EA7361, Université Paris-Saclay, LabEx Lermit, Bacteriology-Hygiene unit, APHP, Hôpital Bicêtre, EERA 'Evolution and Ecology of Resistance to Antibiotics' Unit, Institut Pasteur-APHP-Université Paris-Sud, Le Kremlin-Bicêtre, France
| | - Javier Aznar
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen del Rocío, Seville, Spain.,Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain.,Department of Microbiology, University of Seville, Seville, Spain
| | - Jerónimo Pachón
- Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain.,Department of Medicine, University of Seville, Seville, Spain
| | - José Antonio Lepe
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen del Rocío, Seville, Spain.,Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain
| | - Younes Smani
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen del Rocío, Seville, Spain.,Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain
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11
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Russo A, Berruti M, Giacobbe DR, Vena A, Bassetti M. Recent molecules in the treatment of severe infections caused by ESBL-producing bacteria. Expert Rev Anti Infect Ther 2021; 19:983-991. [PMID: 33596162 DOI: 10.1080/14787210.2021.1874918] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Introduction: The widespread increase in resistance to β-lactam antibiotics in Enterobacterales currently represents one of the main threats to human health worldwide. The primary mechanisms of resistance are the production of β-lactamase enzymes that are able to hydrolyze β-lactams.Areas covered: we summarize the most recent advances regarding the main characteristics and spectrum of activity of new available antibiotics and strategies for the treatment of ESBL-producing Enterobacterales infections.Expert opinion: ESBL-producing strains are recognized as a worldwide challenge in the treatment of both hospital- and community-acquired infections. Data from the literature point out the high mortality associated with severe infections due to ESBL strains, especially in patients who developed severe sepsis or septic shock, together with the importance of the source of infection and indicators of severity, as determinants of the patient's outcome. Carbapenems are currently considered the first-line therapy, although the diffusion of resistant strains is an evolving problem and is mandatory the introduction in clinical practice of new drug regimens and treatment strategies, based on clinical data, local epidemiology, and microbiology. As a possible carbapenem-sparing strategy, ceftolozane-tazobactam and ceftazidime-avibactam appear the best-available carbapenem-sparing therapies. The definitive role of new drugs should be definitively assessed.
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Affiliation(s)
- Alessandro Russo
- Policlinico Umberto I," Sapienza"University of Rome, Rome, Italy
| | - Marco Berruti
- Department of Health Sciences, University of Genoa, Genoa, Italy
| | | | - Antonio Vena
- Department of Health Sciences, University of Genoa, Genoa, Italy
| | - Matteo Bassetti
- Department of Health Sciences, University of Genoa, Genoa, Italy
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12
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Pierrotti LC, Pérez-Nadales E, Fernández-Ruiz M, Gutiérrez-Gutiérrez B, Tan BH, Carratalà J, Oriol I, Paul M, Cohen-Sinai N, López-Medrano F, San-Juan R, Montejo M, Freire MP, Cordero E, David MD, Merino E, Mehta Steinke S, Grossi PA, Cano Á, Seminari EM, Valerio M, Gunseren F, Rana M, Mularoni A, Martín-Dávila P, van Delden C, Hamiyet Demirkaya M, Koçak Tufan Z, Loeches B, Iyer RN, Soldani F, Eriksson BM, Pilmis B, Rizzi M, Coussement J, Clemente WT, Roilides E, Pascual Á, Martínez-Martínez L, Rodríguez-Baño J, Torre-Cisneros J, Aguado JM. Efficacy of β-lactam/β-lactamase inhibitors to treat extended-spectrum beta-lactamase-producing Enterobacterales bacteremia secondary to urinary tract infection in kidney transplant recipients (INCREMENT-SOT Project). Transpl Infect Dis 2021; 23:e13520. [PMID: 33222379 DOI: 10.1111/tid.13520] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 10/23/2020] [Accepted: 11/07/2020] [Indexed: 11/28/2022]
Abstract
BACKGROUND Whether active therapy with β-lactam/β-lactamase inhibitors (BLBLI) is as affective as carbapenems for extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear. METHODS We retrospectively evaluated 306 KTR admitted to 30 centers from January 2014 to October 2016. Therapeutic failure (lack of cure or clinical improvement and/or death from any cause) at days 7 and 30 from ESBL-E BSI onset was the primary and secondary study outcomes, respectively. RESULTS Therapeutic failure at days 7 and 30 occurred in 8.2% (25/306) and 13.4% (41/306) of patients. Hospital-acquired BSI (adjusted OR [aOR]: 4.10; 95% confidence interval [CI]: 1.50-11.20) and Pitt score (aOR: 1.47; 95% CI: 1.21-1.77) were independently associated with therapeutic failure at day 7. Age-adjusted Charlson Index (aOR: 1.25; 95% CI: 1.05-1.48), Pitt score (aOR: 1.72; 95% CI: 1.35-2.17), and lymphocyte count ≤500 cells/μL at presentation (aOR: 3.16; 95% CI: 1.42-7.06) predicted therapeutic failure at day 30. Carbapenem monotherapy (68.6%, primarily meropenem) was the most frequent active therapy, followed by BLBLI monotherapy (10.8%, mostly piperacillin-tazobactam). Propensity score (PS)-adjusted models revealed no significant impact of the choice of active therapy (carbapenem-containing vs any other regimen, BLBLI- vs carbapenem-based monotherapy) within the first 72 hours on any of the study outcomes. CONCLUSIONS Our data suggest that active therapy based on BLBLI may be as effective as carbapenem-containing regimens for ESBL-E BSI secondary to UTI in the specific population of KTR. Potential residual confounding and unpowered sample size cannot be excluded (ClinicalTrials.gov identifier: NCT02852902).
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Affiliation(s)
- Ligia C Pierrotti
- Infectious Diseases Division, Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil
| | - Elena Pérez-Nadales
- Spanish Network for Research in Infectious Diseases (REIPI), ISCIII, Madrid, Spain.,Infectious Diseases Group, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofía University Hospital, University of Cordoba, Cordoba, Spain
| | - Mario Fernández-Ruiz
- Spanish Network for Research in Infectious Diseases (REIPI), ISCIII, Madrid, Spain.,Unit of Infectious Diseases, "12 de Octubre" University Hospital, Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Universidad Complutense, Madrid, Spain
| | - Belén Gutiérrez-Gutiérrez
- Spanish Network for Research in Infectious Diseases (REIPI), ISCIII, Madrid, Spain.,Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Virgen Macarena University Hospital, Institute of Biomedicine of Seville, University of Seville, Seville, Spain
| | - Ban Hock Tan
- Department of Infectious Diseases, Singapore General Hospital, Singapore
| | - Jordi Carratalà
- Spanish Network for Research in Infectious Diseases (REIPI), ISCIII, Madrid, Spain.,Department of Infectious Diseases, Bellvitge University Hospital-IDIBELL, University of Barcelona, L´Hospitalet de Llobregat, Barcelona, Spain
| | - Isabel Oriol
- Spanish Network for Research in Infectious Diseases (REIPI), ISCIII, Madrid, Spain.,Department of Infectious Diseases, Bellvitge University Hospital-IDIBELL, University of Barcelona, L´Hospitalet de Llobregat, Barcelona, Spain
| | - Mical Paul
- Infectious Diseases Institute, Rambam Health Care Campus, Haifa, Israel
| | | | - Francisco López-Medrano
- Spanish Network for Research in Infectious Diseases (REIPI), ISCIII, Madrid, Spain.,Unit of Infectious Diseases, "12 de Octubre" University Hospital, Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Universidad Complutense, Madrid, Spain
| | - Rafael San-Juan
- Spanish Network for Research in Infectious Diseases (REIPI), ISCIII, Madrid, Spain.,Unit of Infectious Diseases, "12 de Octubre" University Hospital, Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Universidad Complutense, Madrid, Spain
| | - Miguel Montejo
- Infectious Diseases Unit, Cruces University Hospital, Bilbao, Spain
| | - Maristela P Freire
- Working Committee for Hospital Epidemiology and Infection Control, Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil
| | - Elisa Cordero
- Spanish Network for Research in Infectious Diseases (REIPI), ISCIII, Madrid, Spain.,Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, University Hospitals Virgen del Rocío/CSIC/University of Seville, Seville, Spain
| | - Miruna D David
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
| | - Esperanza Merino
- Unit of Infectious Diseases, General University Hospital of Alicante, ISABIAL, Alicante, Spain
| | | | - Paolo A Grossi
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Ángela Cano
- Spanish Network for Research in Infectious Diseases (REIPI), ISCIII, Madrid, Spain.,Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Virgen Macarena University Hospital, Institute of Biomedicine of Seville, University of Seville, Seville, Spain
| | - Elena M Seminari
- Infectious Diseases Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Maricela Valerio
- Clinical Microbiology and Infectious Disease Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Filiz Gunseren
- Department of Infectious Diseases and Clinical Microbiology, Akdeniz University Faculty of Medicine, Antalya, Turkey
| | | | - Alessandra Mularoni
- IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Palermo, Italy
| | - Pilar Martín-Dávila
- Spanish Network for Research in Infectious Diseases (REIPI), ISCIII, Madrid, Spain.,Infectious Diseases Department, Ramón y Cajal University Hospital, Madrid, Spain
| | - Christian van Delden
- Unit for Transplant Infectious Diseases, University Hospitals of Geneva, Geneva, Switzerland
| | | | - Zeliha Koçak Tufan
- Infectious Diseases and Clinical Microbiology Department, Medical School of Ankara Yildirim Beyazit University, Ankara, Turkey
| | - Belén Loeches
- Infectious Diseases Unit, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain
| | - Ranganathan N Iyer
- Clinical Microbiology ID & Infection control, Global Hospitals, Hyderabad, India
| | - Fabio Soldani
- Division of Infectious Diseases, Department of Medicine, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy
| | - Britt-Marie Eriksson
- Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, Uppsala, Sweden
| | - Benoît Pilmis
- Department of Infectious Diseases and Tropical Medicine, Paris Descartes University, Necker-Enfants Malades University Hospital, Centre d'Infectiologie Necker-Pasteur, Institut Imagine, AP-HP, Paris, France
| | - Marco Rizzi
- Infectious Diseases Unit, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Julien Coussement
- Division of Infectious Diseases, CUB-Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
| | - Wanessa T Clemente
- Faculdade de Medicina da Universidade Federal de Minas Gerais (UFMG), Transplant Infectious Disease, Liver Transplant Program, Hospital das Clínicas da UFMG, Belo Horizonte, Brazil
| | - Emmanuel Roilides
- Infectious Diseases Unit and 3rd Department of Pediatrics, Aristotle University School of Health Sciences, Hippokration Hospital, Thessaloniki, Greece
| | - Álvaro Pascual
- Spanish Network for Research in Infectious Diseases (REIPI), ISCIII, Madrid, Spain.,Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Virgen Macarena University Hospital, Institute of Biomedicine of Seville, University of Seville, Seville, Spain
| | - Luis Martínez-Martínez
- Spanish Network for Research in Infectious Diseases (REIPI), ISCIII, Madrid, Spain.,Clinical Unit of Microbiology, Department of Microbiology, Reina Sofía University Hospital, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Córdoba, Spain
| | - Jesús Rodríguez-Baño
- Spanish Network for Research in Infectious Diseases (REIPI), ISCIII, Madrid, Spain.,Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Virgen Macarena University Hospital, Institute of Biomedicine of Seville, University of Seville, Seville, Spain
| | - Julian Torre-Cisneros
- Spanish Network for Research in Infectious Diseases (REIPI), ISCIII, Madrid, Spain.,Clinical Unit of Infectious Diseases, Reina Sofía University Hospital, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Córdoba, Spain
| | - José María Aguado
- Spanish Network for Research in Infectious Diseases (REIPI), ISCIII, Madrid, Spain.,Unit of Infectious Diseases, "12 de Octubre" University Hospital, Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Universidad Complutense, Madrid, Spain
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13
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Perez-Lopez A, Sundararaju S, Al-Mana H, Tsui KM, Hasan MR, Suleiman M, Janahi M, Al Maslamani E, Tang P. Molecular Characterization of Extended-Spectrum β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Among the Pediatric Population in Qatar. Front Microbiol 2020; 11:581711. [PMID: 33262745 PMCID: PMC7686840 DOI: 10.3389/fmicb.2020.581711] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Accepted: 10/12/2020] [Indexed: 11/13/2022] Open
Abstract
INTRODUCTION Although extended-spectrum β-lactamase (ESBL)-producing Enterobacterales are a public health problem in the Arabian Peninsula, data on the molecular characteristic of their antimicrobial resistance determinants in children is limited. AIM To determine the molecular characteristics of ESBL-producing Escherichia coli and Klebsiella pneumoniae in the pediatric population of Qatar. METHODS Whole-genome sequencing was performed on ESBL-producing E. coli and K. pneumoniae isolates recovered from screening and clinical specimens from pediatric patients at Sidra Medicine in Doha from January to December 2018. RESULTS A total of 327 ESBL producers were sequenced: 254 E. coli and 73 K. pneumoniae. Non-susceptibility rates to non-β-lactam antibiotics for both species were 18.1 and 30.1% for gentamicin, 0.8 and 4.1% for amikacin, 41.3 and 41.1% for ciprofloxacin, and 65.8 and 76.1% for cotrimoxazole. The most common sequence types (STs) were ST131 (16.9%), ST38 and ST10 (8.2% each) in E. coli and ST307 (9.7%), and ST45 and ST268 (6.9% each) in K. pneumoniae. CTX-M type ESBLs were found in all but one isolate, with CTX-M-15 accounting for 87.8%. Among other β-lactamases, TEM-1B and OXA-1 were coproduced in 41 and 19.6% of isolates. The most common plasmid-mediated quinolone resistance genes cocarried were qnr A/B/E/S (45.3%). Ninety percent of gentamicin non-susceptible isolates harbored genes encoding AAC(3) enzymes, mainly aac(3)-IIa. Only two of 57 isolates harboring aac(6')-Ib-cr were non-susceptible to amikacin. Chromosomal mutations in genes encoding DNA gyrase and topoisomerase IV enzymes were detected in 96.2% fluoroquinolone-non-susceptible E. coli and 26.7% fluoroquinolone-non-susceptible K. pneumoniae. CONCLUSION Our data show that CTX-M enzymes are largely the most prevalent ESBLs in children in Qatar with a predominance of CTX-M-15. Carbapenem-sparing options to treat ESBL infections are limited, given the frequent coproduction of OXA-1 and TEM-1B enzymes and coresistance to antibiotic classes other than β-lactams.
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Affiliation(s)
- Andres Perez-Lopez
- Division of Microbiology, Department of Pathology, Sidra Medicine, Doha, Qatar
- Weill Cornell Medical College in Qatar, Doha, Qatar
| | | | - Hassan Al-Mana
- Division of Microbiology, Department of Pathology, Sidra Medicine, Doha, Qatar
- Biomedical Research Centre, Qatar University, Doha, Qatar
| | - Kin Ming Tsui
- Division of Microbiology, Department of Pathology, Sidra Medicine, Doha, Qatar
- Weill Cornell Medical College in Qatar, Doha, Qatar
- Division of Infectious Diseases, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Mohammad Rubayet Hasan
- Division of Microbiology, Department of Pathology, Sidra Medicine, Doha, Qatar
- Weill Cornell Medical College in Qatar, Doha, Qatar
| | - Mohammed Suleiman
- Division of Microbiology, Department of Pathology, Sidra Medicine, Doha, Qatar
| | - Mohammed Janahi
- Weill Cornell Medical College in Qatar, Doha, Qatar
- Division of Pediatric Infectious Diseases, Sidra Medicine, Doha, Qatar
| | - Eman Al Maslamani
- Weill Cornell Medical College in Qatar, Doha, Qatar
- Division of Pediatric Infectious Diseases, Sidra Medicine, Doha, Qatar
| | - Patrick Tang
- Division of Microbiology, Department of Pathology, Sidra Medicine, Doha, Qatar
- Weill Cornell Medical College in Qatar, Doha, Qatar
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14
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Henderson A, Paterson DL, Chatfield MD, Tambyah PA, Lye DC, De PP, Lin RTP, Chew KL, Yin M, Lee TH, Yilmaz M, Cakmak R, Alenazi TH, Arabi YM, Falcone M, Bassetti M, Righi E, Ba R, Kanj SS, Bhally H, Iredell J, Mendelson M, Boyles TH, Looke DFM, Runnegar NJ, Miyakis S, Walls G, Ai Khamis M, Zikri A, Crowe A, Ingram PR, Daneman NN, Griffin P, Athan E, Roberts L, Beatson SA, Peleg AY, Cottrell KK, Bauer MJ, Tan E, Chaw K, Nimmo GR, Harris-Brown T, Harris PNA. Association between minimum inhibitory concentration, beta-lactamase genes and mortality for patients treated with piperacillin/tazobactam or meropenem from the MERINO study. Clin Infect Dis 2020; 73:e3842-e3850. [PMID: 33106863 DOI: 10.1093/cid/ciaa1479] [Citation(s) in RCA: 100] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2019] [Indexed: 11/12/2022] Open
Abstract
INTRODUCTION This study aims to assess the association of piperacillin/tazobactam and meropenem minimum inhibitory concentration (MIC) and beta-lactam resistance genes with mortality in the MERINO trial. METHODS Blood culture isolates from enrolled patients were tested by broth microdilution and whole genome sequencing at a central laboratory. Multivariate logistic regression was performed to account for confounders. Absolute risk increase for 30-day mortality between treatment groups was calculated for the primary analysis (PA) and the microbiologic assessable (MA) populations. RESULTS 320 isolates from 379 enrolled patients were available with susceptibility to piperacillin/tazobactam 94% and meropenem 100%. The piperacillin/tazobactam non-susceptible breakpoint (MIC > 16 mg/L) best predicted 30-day mortality after accounting for confounders (odds ratio 14.9, 95% CI 2.8 - 87.2). The absolute risk increase for 30-day mortality for patients treated with piperacillin/tazobactam compared with meropenem was 9% (95% CI 3% - 15%) and 8% (95% CI 2% - 15%) for the original PA population and the post-hoc MA populations, which reduced to 5% (95% CI -1% - 10%) after excluding strains with piperacillin/tazobactam MIC values > 16 mg/L. Isolates co-harboring ESBL and OXA-1 genes were associated with elevated piperacillin/tazobactam MICs and the highest risk increase in 30-mortality of 14% (95% CI 2% - 28%). CONCLUSION After excluding non-susceptible strains, the 30-day mortality difference was from the MERINO trial was less pronounced for piperacillin/tazobactam. Poor reliability in susceptibility testing performance for piperacillin/tazobactam and the high prevalence of OXA co-harboring ESBLs suggests meropenem remains the preferred choice for definitive treatment of ceftriaxone non-susceptible E. coli and Klebsiella.
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Affiliation(s)
- A Henderson
- University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia.,Infection Management Services, Princess Alexandra Hospital, Brisbane, QLD
| | - D L Paterson
- University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia
| | - M D Chatfield
- University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia
| | - P A Tambyah
- Department of Infectious Diseases, National University Hospital, Singapore
| | - D C Lye
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore.,Department of Infectious Diseases, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng.,Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore,Hospital, Singapore
| | - P P De
- Department of Laboratory Medicine, Tan Tock Seng Hospital, Singapore
| | - R T P Lin
- Department of Laboratory Medicine, National University Hospital, Singapore
| | - K L Chew
- Division of Microbiology, National University Hospital, Singapore
| | - M Yin
- Department of Infectious Diseases, National University Hospital, Singapore
| | - T H Lee
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore.,Department of Infectious Diseases, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore.,Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - M Yilmaz
- Department of Infectious Diseases and Clinical Microbiology, School of Medicine, Istanbul Medipol University, Istanbul, Turkey
| | - R Cakmak
- Department of Infectious Diseases and Clinical Microbiology, School of Medicine, Istanbul Medipol University, Istanbul, Turkey
| | - T H Alenazi
- King Saud Bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
| | - Y M Arabi
- King Saud Bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
| | - M Falcone
- Division of Infectious Diseases, Department of Clinical and Experimental Medicine, University of Pisa, Italy
| | - M Bassetti
- Infectious Diseases Clinic, Department of Health Sciences, University of Genoa and Ospedale Policlinico San Martino Genoa, Italy
| | - E Righi
- Infectious Diseases Clinic, Department of Medicine University of Udine and Santa Maria Misericordia Hospital, Udine, Italy.,Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
| | - Rogers Ba
- Monash University, Centre for Inflammatory Diseases, Victoria, Australia.,Monash Infectious Diseases, Monash Health, Victoria, Australia
| | - S S Kanj
- Department of Internal Medicine, Division of Infectious Diseases, American University of Beirut Medical Center, Beirut, Lebanon
| | - H Bhally
- Department of Medicine and Infectious Diseases, North Shore Hospital, Auckland
| | - J Iredell
- Marie Bashir Institute for Infectious Disease and Biosecurity, University of Sydney, Sydney, Australia.,Centre for Infectious Diseases and Microbiology, Westmead Hospital, Westmead, Australia
| | - M Mendelson
- Division of Infectious Diseases & HIV Medicine, Department of Medicine, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa
| | - T H Boyles
- Division of Infectious Diseases & HIV Medicine, Department of Medicine, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa
| | - D F M Looke
- Infection Management Services, Princess Alexandra Hospital, Brisbane, QLD.,University of Queensland, Brisbane, Australia
| | - N J Runnegar
- Infection Management Services, Princess Alexandra Hospital, Brisbane, QLD.,University of Queensland, Brisbane, Australia
| | - S Miyakis
- School of Medicine, University of Wollongong, Wollongong, New South Wales, Australia.,Illawarra Health and Medical Research Institute, Wollongong, New South Wales, Australia.,Department of Infectious Diseases, Wollongong Hospital, Wollongong, New South Wales, Australia
| | - G Walls
- Department of Infectious Diseases, Middlemore Hospital, Auckland, New Zealand
| | - M Ai Khamis
- King Fahad Specialist Hospital, Dammam, Saudi Arabia
| | - A Zikri
- King Fahad Specialist Hospital, Dammam, Saudi Arabia
| | - A Crowe
- Department of Infectious Diseases, St Vincent's Hospital, Melbourne, Australia.,Department of Microbiology, St Vincent's Hospital, Melbourne, Australia
| | - P R Ingram
- School of Pathology and Laboratory Medicine, The University of Western Australia, Crawley, Australia.,Department of Infectious Diseases, Fiona Stanley Hospital, Murdoch , Australia.,Department of Microbiology, PathWest Laboratory Medicine, Perth, Western Australia
| | - N N Daneman
- Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada
| | - P Griffin
- University of Queensland, Brisbane, Australia.,Department of Medicine and Infectious Diseases, Mater Hospital and Mater Medical Research Institute, Brisbane, Australia.,QIMR Berghofer, Brisbane, Queensland, Australia
| | - E Athan
- Department of Infectious Diseases, Barwon Health and Deakin University, Geelong, Victoria, Australia
| | - L Roberts
- Australian Centre for Ecogenomics, School of Chemistry and Molecular Biosciences, The University of Queensland, Queensland, Australia
| | - S A Beatson
- Australian Centre for Ecogenomics, School of Chemistry and Molecular Biosciences, The University of Queensland, Queensland, Australia
| | - A Y Peleg
- Infection & Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Australia.,Department of Microbiology, Monash University, Clayton, Australia
| | - K K Cottrell
- University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia
| | - M J Bauer
- University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia
| | - E Tan
- University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia
| | - K Chaw
- Department of Microbiology, Pathology Queensland, Toowoomba Laboratory, Australia.,Department of Microbiology, Mater Pathology, Australia.,Infectious Diseases Department, Redcliffe Hospital, Australia
| | - G R Nimmo
- Department of Microbiology, Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane, Australia
| | - T Harris-Brown
- University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia
| | - P N A Harris
- University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia.,Department of Microbiology, Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane, Australia
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15
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Peiffer-Smadja N, Bouadma L, Mathy V, Allouche K, Patrier J, Reboul M, Montravers P, Timsit JF, Armand-Lefevre L. Performance and impact of a multiplex PCR in ICU patients with ventilator-associated pneumonia or ventilated hospital-acquired pneumonia. Crit Care 2020; 24:366. [PMID: 32560662 PMCID: PMC7303941 DOI: 10.1186/s13054-020-03067-2] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Accepted: 06/04/2020] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Early appropriate antibiotic therapy reduces morbidity and mortality of severe pneumonia. However, the emergence of bacterial resistance requires the earliest use of antibiotics with the narrowest possible spectrum. The Unyvero Hospitalized Pneumonia (HPN, Curetis) test is a multiplex PCR (M-PCR) system detecting 21 bacteria and 19 resistance genes on respiratory samples within 5 h. We assessed the performance and the potential impact of the M-PCR on the antibiotic therapy of ICU patients. METHODS In this prospective study, we performed a M-PCR on bronchoalveolar lavage (BAL) or plugged telescoping catheter (PTC) samples of patients with ventilated HAP or VAP with Gram-negative bacilli or clustered Gram-positive cocci. This study was conducted in 3 ICUs in a French academic hospital: the medical and infectious diseases ICU, the surgical ICU, and the cardio-surgical ICU. A multidisciplinary expert panel simulated the antibiotic changes they would have made if the M-PCR results had been available. RESULTS We analyzed 95 clinical samples of ventilated HAP or VAP (72 BAL and 23 PTC) from 85 patients (62 males, median age 64 years). The median turnaround time of the M-PCR was 4.6 h (IQR 4.4-5). A total of 90/112 bacteria were detected by the M-PCR system with a global sensitivity of 80% (95% CI, 73-88%) and specificity of 99% (95% CI 99-100). The sensitivity was better for Gram-negative bacteria (90%) than for Gram-positive cocci (62%) (p = 0.005). Moreover, 5/8 extended-spectrum beta-lactamases (CTX-M gene) and 4/4 carbapenemases genes (3 NDM, one oxa-48) were detected. The M-PCR could have led to the earlier initiation of an effective antibiotic in 20/95 patients (21%) and to early de-escalation in 37 patients (39%) but could also have led to one (1%) inadequate antimicrobial therapy. Among 17 empiric antibiotic treatments with carbapenems, 10 could have been de-escalated in the following hours according to the M-PCR results. The M-PCR also led to 2 unexpected diagnosis of severe legionellosis confirmed by culture methods. CONCLUSIONS Our results suggest that the use of a M-PCR system for respiratory samples of patients with VAP and ventilated HAP could improve empirical antimicrobial therapy and reduce the use of broad-spectrum antibiotics.
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Affiliation(s)
- Nathan Peiffer-Smadja
- Université de Paris, IAME, INSERM, Paris, F-75018, France.
- Infectious and Tropical Diseases Department, Bichat-Claude Bernard Hospital, AP-HP, Paris, 75018, France.
| | - Lila Bouadma
- Université de Paris, IAME, INSERM, Paris, F-75018, France
- Medical and Infectious Diseases ICU (MI2), Bichat-Claude Bernard Hospital, AP-HP, 75018, Paris, France
| | - Vincent Mathy
- Bacteriology Laboratory, Bichat-Claude Bernard Hospital, AP-HP, Paris, France
| | - Kahina Allouche
- Bacteriology Laboratory, Bichat-Claude Bernard Hospital, AP-HP, Paris, France
| | - Juliette Patrier
- Medical and Infectious Diseases ICU (MI2), Bichat-Claude Bernard Hospital, AP-HP, 75018, Paris, France
| | - Martin Reboul
- Bacteriology Laboratory, Bichat-Claude Bernard Hospital, AP-HP, Paris, France
| | - Philippe Montravers
- Département d'Anesthésie Réanimation, Bichat-Claude Bernard Hospital, AP-HP, Paris, France
- INSERM UMR 1152, Physiopathologie et Epidémiologie des Maladies respiratoires, Paris, France
| | - Jean-François Timsit
- Université de Paris, IAME, INSERM, Paris, F-75018, France
- Medical and Infectious Diseases ICU (MI2), Bichat-Claude Bernard Hospital, AP-HP, 75018, Paris, France
| | - Laurence Armand-Lefevre
- Université de Paris, IAME, INSERM, Paris, F-75018, France
- Bacteriology Laboratory, Bichat-Claude Bernard Hospital, AP-HP, Paris, France
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16
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Livermore DM, Day M, Cleary P, Hopkins KL, Toleman MA, Wareham DW, Wiuff C, Doumith M, Woodford N. OXA-1 β-lactamase and non-susceptibility to penicillin/β-lactamase inhibitor combinations among ESBL-producing Escherichia coli. J Antimicrob Chemother 2020; 74:326-333. [PMID: 30388219 DOI: 10.1093/jac/dky453] [Citation(s) in RCA: 76] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Accepted: 10/08/2018] [Indexed: 02/06/2023] Open
Abstract
Background ESBL-producing Escherichia coli have expanded globally since the turn of the century and present a major public health issue. Their in vitro susceptibility to penicillin/inhibitor combinations is variable, and clinical use of these combinations against ESBL producers remains controversial. We hypothesized that this variability related to co-production of OXA-1 penicillinase. Methods During a national study we collected 293 ESBL-producing E. coli from bacteraemias, determined MICs by BSAC agar dilution, and undertook genomic sequencing with Illumina methodology. Results The collection was dominated by ST131 (n = 188 isolates, 64.2%) and blaCTX-M-15 (present in 229 isolates, 78.2%); over half the isolates (159/293, 54.3%) were ST131 with blaCTX-M-15. blaOXA-1 was found in 149 ESBL producers (50.9%) and blaTEM-1/191 in 137 (46.8%). Irrespective of whether all isolates were considered, or ST131 alone, there were strong associations (P < 0.001) between co-carriage of blaOXA-1 and reduced susceptibility to penicillin/inhibitor combinations, whereas there was no significant association with co-carriage of blaTEM-1/191. For piperacillin/tazobactam the modal MIC rose from 2 mg/L in the absence of blaOXA-1 to 8 or 16 mg/L in its presence; for co-amoxiclav the shift was smaller, from 4 or 8 to 16 mg/L, but crossed the breakpoint. blaOXA-1 was strongly associated with co-carriage also of aac(6')-Ib-cr, which compromises amikacin and tobramycin. Conclusions Co-carriage of OXA-1, a penicillinase with weak affinity for inhibitors, is a major correlate of resistance to piperacillin/tazobactam and co-amoxiclav in E. coli and is commonly associated with co-carriage of aac(6')-Ib-cr, which narrows aminoglycoside options.
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Affiliation(s)
- David M Livermore
- Antimicrobial Resistance and Healthcare-Associated Infections Reference Unit, PHE National Infection Service, London, UK.,Norwich Medical School, University of East Anglia, Norwich, UK
| | - Michaela Day
- Antimicrobial Resistance and Healthcare-Associated Infections Reference Unit, PHE National Infection Service, London, UK
| | | | - Katie L Hopkins
- Antimicrobial Resistance and Healthcare-Associated Infections Reference Unit, PHE National Infection Service, London, UK
| | | | - David W Wareham
- Blizard Institute, Queen Mary University of London, London, UK
| | | | - Michel Doumith
- Antimicrobial Resistance and Healthcare-Associated Infections Reference Unit, PHE National Infection Service, London, UK
| | - Neil Woodford
- Antimicrobial Resistance and Healthcare-Associated Infections Reference Unit, PHE National Infection Service, London, UK
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17
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Abstract
The mortality of patients with sepsis and septic shock is still unacceptably high. An effective calculated antibiotic treatment within 1 h of recognition of sepsis is an important target of sepsis treatment. Delays lead to an increase in mortality; therefore, structured treatment concepts form a rational foundation, taking relevant diagnostic and treatment steps into consideration. In addition to the assumed infection and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account during the selection of anti-infective treatment. Many pathophysiologic alterations influence the pharmacokinetics (PK) of antibiotics during sepsis. The principle of standard dosing should be abandoned and replaced by an individual treatment approach with stronger weighting of the pharmacokinetics/pharmacodynamics (PK/PD) index of the substance groups. Although this is not yet the clinical standard, prolonged (or continuous) infusion of β‑lactam antibiotics and therapeutic drug monitoring (TDM) can help to achieve defined PK targets. Prolonged infusion is sufficient without TDM, but for continuous infusion, TDM is generally necessary. A further argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug-resistant (MDR) pathogens in the intensive care unit. For effective treatment, antibiotic stewardship teams (ABS teams) are becoming more established. Interdisciplinary cooperation of the ABS team with infectious disease (ID) specialists, microbiologists, and clinical pharmacists leads not only to rational administration of antibiotics, but also has a positive influence on treatment outcome. The gold standards for pathogen identification are still culture-based detection and microbiologic resistance testing for the various antibiotic groups. Despite the rapid investigation time, novel polymerase chain reaction(PCR)-based procedures for pathogen identification and resistance determination are currently only an adjunct to routine sepsis diagnostics, due to the limited number of studies, high costs, and limited availability. In complicated septic courses with multiple anti-infective therapies or recurrent sepsis, PCR-based procedures can be used in addition to treatment monitoring and diagnostics. Novel antibiotics represent potent alternatives in the treatment of MDR infections. Due to the often defined spectrum of pathogens and the practically (still) absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation). (Contribution available free of charge by "Free Access" [ https://link.springer.com/article/10.1007/s00101-017-0396-z ].).
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18
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Ibañez-Dosman JP, Salazar-Ospina JD, Loaiza-Betancurt S, Hernández-Botero JS. Panorama de resistencia antimicrobiana de los aislamientos urinarios de pacientes adultos en los servicios de urgencias de Manizales, Caldas, durante el 2018. INFECTIO 2020. [DOI: 10.22354/in.v24i3.859] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Introducción: los servicios de urgencias requieren de la toma de medidas eficaces y oportunas en el manejo de los pacientes, esto incluye el uso adecuado de antibióticos. La resistencia antimicrobiana dificulta la instauración de terapias empíricas adecuadas, por lo que su vigilancia toma un papel fundamental en los programas de optimización de uso de antimicrobianos. Objetivo: describir el perfil microbiológico y la resistencia antibiótica de los aislamientos urinarios obtenidos de pacientes adultos de los servicios de urgencias de 7 instituciones de tercer nivel de la ciudad de Manizales, durante el año 2018. Resultados: se recolectaron 1991 aislamientos urinarios, el microorganismo más frecuentemente aislado fue Escherichia coli con un 62%. Se encontraron altas tasas de resistencia a cefazolina, trimetoprim/sulfametoxazol, ciprofloxacina y ampicilina/sulbactam. La resistencia a nitrofurantoína y fosfomicina al igual que a carbapenémicos es baja para Escherichia coli. Los aislamientos urinarios de Pseudomonas aeruginosa muestran niveles de resistencia superiores al promedio nacional. Conclusiones: es importante individualizar el manejo antibiótico empírico, teniendo en cuenta la estratificación por severidad, la presencia de factores de riesgo para bacterias multidrogorresistentes, y la epidemiología local; los análisis de cada institución y los resultados de este trabajo, pueden ser utilizados para establecer conductas terapéuticas más precisas en los casos de infecciones del tracto urinario, mejorando los desenlaces de estos pacientes y los costos derivados de la atención en salud.
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19
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Aslan AT, Akova M. Extended spectrum β-lactamase producing enterobacteriaceae: carbapenem sparing options. Expert Rev Anti Infect Ther 2019; 17:969-981. [PMID: 31722185 DOI: 10.1080/14787210.2019.1693258] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Introduction: Carbapenems have an important place in our antibiotic armamentarium and have been trusted to effectively treat infections caused by ESBL-producing Enterobacteriaceae for many years. However, the utility of carbapenems has been compromised by the emergence of resistance especially in Enterobacteriaceae. Therefore, carbapenem-sparing alternative antibiotics are of extreme importance in clinical practice.Areas covered: We reviewed studies addressing currently available antibiotic options used as both empiric and definitive therapy for the treatment of infections due to ESBL-producing Enterobacteriaceae published in the PubMed/MEDLINE, Web of Science and Scopus databases without any date restriction. Current treatment alternatives included beta-lactam/beta-lactamase inhibitor combinations, cefepime, cephamycins, fluoroquinolones, aminoglycosides, fosfomycin, pivmecillinam, temocillin and, various oral alternative agents. We also summarized the clinical and molecular epidemiology, early prediction methods and impact of initial empirical therapy and de-escalation approach for ESBL-producing Enterobacteriaceae infections.Expert opinion: The current literature would endorse the carbapenem utilization for patients with severe and high inoculum-high risk infections. However, for milder infections particularly for urinary tract infections, various carbapenem-sparing antibiotics can be considered in selected cases. For infections including easily drainable intra-abdominal infections and catheter-related infections in which catheter removal is readily available more reliable data are needed to recommend non-carbapenem antibiotics confidently.
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Affiliation(s)
| | - Murat Akova
- Hacettepe University Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology, Hacettepe University Sıhhıye Campus, Sihhiye, Ankara, Turkey
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20
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Pogue JM, Heil EL. Laces out Dan! The role of tazobactam based combinations for invasive ESBL infections in a post-MERINO world. Expert Opin Pharmacother 2019; 20:2053-2057. [PMID: 31496320 DOI: 10.1080/14656566.2019.1663827] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Affiliation(s)
- Jason M Pogue
- Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI, USA
| | - Emily L Heil
- Department of Pharmacy Practice and Science, University of Maryland School of Pharmacy, Baltimore, MD, USA
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21
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Nguyen CP, Dan Do TN, Bruggemann R, Ten Oever J, Kolwijck E, Adang EMM, Wertheim HFL. Clinical cure rate and cost-effectiveness of carbapenem-sparing beta-lactams vs. meropenem for Gram-negative infections: A systematic review, meta-analysis, and cost-effectiveness analysis. Int J Antimicrob Agents 2019; 54:790-797. [PMID: 31284041 DOI: 10.1016/j.ijantimicag.2019.07.003] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Accepted: 07/03/2019] [Indexed: 01/05/2023]
Abstract
The increasing incidence of infections caused by extended-spectrum beta-lactamase (ESBL)/AmpC-producing bacteria leads to increasing use of carbapenems and risk of carbapenem resistance. Treatment success of carbapenem-sparing beta-lactams (CSBs) for ESBL infections is unclear. The aim of this study was to appraise the clinical cure rate and estimate the cost-effectiveness of meropenem vs. CSBs (piperacillin-tazobactam, temocillin, ceftazidime-avibactam, and ceftolozane-tazobactam) for urinary tract infections (UTIs) or intra-abdominal infections (IAIs) due to ESBL/AmpC-producing bacteria. A systematic literature search of the Cochrane library, EMBASE, PubMed, and Web of Science was conducted to identify studies assessing the clinical cure rate of the antibiotics. To assess the cost-effectiveness of CSBs vs. meropenem, a combined decision analytic and Markov model was probabilistically analysed over a 5-year period. The main outcome was presented as the incremental cost-effectiveness ratio and evaluated with a threshold of €20 000 per life year gained (LYG). From 656 identified articles, 17 and 14 studies were included in the qualitative synthesis and quantitative synthesis, respectively. A clinical cure of ceftazidime-avibactam and ceftolozane-tazobactam was comparable to meropenem in patients with complicated IAIs (cIAIs) due to ESBL (Risk ratio [RR]=1·04, 95% confidence interval [CI]=0·95-1·13). Both temocillin and ceftolozane-tazobactam were deemed cost-effective compared to meropenem with €157·58 and €13 398·34 per LYG, respectively, in patients with UTIs due to ESBL. However, only ceftazidime-avibactam (plus metronidazole) was cost-effective for the treatment of IAIs, with €16 916·77 per LYG. These results show that several CSBs can be considered as viable candidates for the treatment of UTIs and IAIs caused by ESBL.
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Affiliation(s)
- Chi Phuong Nguyen
- Department of Medical Microbiology, Radboud University Medical Centre, 6525 GA Nijmegen, the Netherlands; Department of Pharmaceutical Administration and Economics, Hanoi University of Pharmacy, 13 Le Thanh Tong, Hanoi, Vietnam.
| | - Thuc Nguyen Dan Do
- Department of Medical Microbiology, Radboud University Medical Centre, 6525 GA Nijmegen, the Netherlands
| | - Roger Bruggemann
- Department of Pharmacy, Radboud University Medical Centre, 6525 GA Nijmegen, the Netherlands
| | - Jaap Ten Oever
- Department of Internal Medicine, Radboud University Medical Centre, 6525 GA Nijmegen, the Netherlands
| | - Eva Kolwijck
- Department of Medical Microbiology, Radboud University Medical Centre, 6525 GA Nijmegen, the Netherlands
| | - Eddy M M Adang
- Department of Health Evidence, Radboud University Medical Centre, 6525 GA Nijmegen, the Netherlands
| | - Heiman F L Wertheim
- Department of Medical Microbiology, Radboud University Medical Centre, 6525 GA Nijmegen, the Netherlands.
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22
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Namikawa H, Yamada K, Yamairi K, Shibata W, Fujimoto H, Takizawa E, Niki M, Nakaie K, Oinuma KI, Niki M, Takemoto Y, Kaneko Y, Shuto T, Kakeya H. Mortality caused by extended-spectrum beta-lactamase–producing Enterobacteriaceae bacteremia; a case control study: alert to Enterobacteriaceae strains with high minimum inhibitory concentrations of piperacillin/tazobactam. Diagn Microbiol Infect Dis 2019; 94:287-292. [DOI: 10.1016/j.diagmicrobio.2019.01.018] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Revised: 01/23/2019] [Accepted: 01/24/2019] [Indexed: 11/27/2022]
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23
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Tascini C. Antibiotic stewardship: ripartiamo dalla pratica clinica. Urologia 2019; 85:S20-S23. [PMID: 30081776 DOI: 10.1177/0391560318770093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Antibiotic stewardship: a milestone in everyday clinical practice Infectious diseases caused by multi-resistant pathogens are increasing worldwide and are challenging for clinicians, also in urological setting. The alarming situation is worsened by the limited perspective of new antibiotic developments. Several authors demonstrated that in Italy we have alarming data about resistance rates: in Campania about 58% of Escherichia coli are resistant to fluroquinolones, as 46% to sulfamethoxazole-trimethoprim. On the other hand, the resistance rate against fosfomycin is still low less than 5%. More alarming data are reported about Klebsiella pneumoniae: resistance rate to flurquinolones 65% and 58% to sulfamethoxazole-trimethoprim. A continuing uncritical, non-guideline-conform and overuse of antibiotics leads to selection of multidrug-resistant pathogens, which can colonize patients and make the treatment a real challenge. A revision of our approach to urinary tract infections at the light of antibiotic stewardiship principles are urgently required, in particular starting from the everyday clinical practice.
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Affiliation(s)
- Carlo Tascini
- Direttore U.O.C, Malattie Infettive a indirizzo neurologico, Azienda Ospedaliera dei Colli, Ospedale Cotugno, Napoli, Italy
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24
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Hawkey PM, Warren RE, Livermore DM, McNulty CAM, Enoch DA, Otter JA, Wilson APR. Treatment of infections caused by multidrug-resistant Gram-negative bacteria: report of the British Society for Antimicrobial Chemotherapy/Healthcare Infection Society/British Infection Association Joint Working Party. J Antimicrob Chemother 2019. [PMID: 29514274 DOI: 10.1093/jac/dky027] [Citation(s) in RCA: 208] [Impact Index Per Article: 34.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
The Working Party makes more than 100 tabulated recommendations in antimicrobial prescribing for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB) and suggest further research, and algorithms for hospital and community antimicrobial usage in urinary infection. The international definition of MDR is complex, unsatisfactory and hinders the setting and monitoring of improvement programmes. We give a new definition of multiresistance. The background information on the mechanisms, global spread and UK prevalence of antibiotic prescribing and resistance has been systematically reviewed. The treatment options available in hospitals using intravenous antibiotics and in primary care using oral agents have been reviewed, ending with a consideration of antibiotic stewardship and recommendations. The guidance has been derived from current peer-reviewed publications and expert opinion with open consultation. Methods for systematic review were NICE compliant and in accordance with the SIGN 50 Handbook; critical appraisal was applied using AGREE II. Published guidelines were used as part of the evidence base and to support expert consensus. The guidance includes recommendations for stakeholders (including prescribers) and antibiotic-specific recommendations. The clinical efficacy of different agents is critically reviewed. We found there are very few good-quality comparative randomized clinical trials to support treatment regimens, particularly for licensed older agents. Susceptibility testing of MDR GNB causing infection to guide treatment needs critical enhancements. Meropenem- or imipenem-resistant Enterobacteriaceae should have their carbapenem MICs tested urgently, and any carbapenemase class should be identified: mandatory reporting of these isolates from all anatomical sites and specimens would improve risk assessments. Broth microdilution methods should be adopted for colistin susceptibility testing. Antimicrobial stewardship programmes should be instituted in all care settings, based on resistance rates and audit of compliance with guidelines, but should be augmented by improved surveillance of outcome in Gram-negative bacteraemia, and feedback to prescribers. Local and national surveillance of antibiotic use, resistance and outcomes should be supported and antibiotic prescribing guidelines should be informed by these data. The diagnosis and treatment of both presumptive and confirmed cases of infection by GNB should be improved. This guidance, with infection control to arrest increases in MDR, should be used to improve the outcome of infections with such strains. Anticipated users include medical, scientific, nursing, antimicrobial pharmacy and paramedical staff where they can be adapted for local use.
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Affiliation(s)
- Peter M Hawkey
- Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK
| | | | | | - Cliodna A M McNulty
- Microbiology Department, Gloucestershire Royal Hospital, Great Western Road, Gloucester GL1 3NN, UK
| | - David A Enoch
- Public Health England, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | | | - A Peter R Wilson
- Department of Microbiology and Virology, University College London Hospitals, London, UK
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25
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Giannella M, Pascale R, Ferraro G, Toschi A, Pancaldi L, Furii F, Bartoletti M, Tedeschi S, Ambretti S, Lewis RE, Viale P. Risk factors for treatment failure in patients receiving β-lactam/β-lactamase inhibitor combinations for Enterobacteriaceae bloodstream infection: A retrospective, single-centre, cohort study. Int J Antimicrob Agents 2019; 53:574-581. [PMID: 30639527 DOI: 10.1016/j.ijantimicag.2019.01.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Revised: 12/29/2018] [Accepted: 01/06/2019] [Indexed: 11/18/2022]
Abstract
The aim of this study was to investigate risk factors for treatment failure in patients receiving in vitro-active therapy with β-lactam/β-lactamase inhibitor (BL/BLI) for Enterobacteriaceae bloodstream infection (E-BSI). This was a retrospective, single-centre study of patients diagnosed with E-BSI at an Italian centre over a 4-year period. Exclusion criteria were age <18 years, clinical data unavailable, polymicrobial BSI, failure to receive in vitro-active therapy and death within 72 h from drawing the index blood culture. Patients who received BL/BLI as appropriate empirical and/or definitive therapy for ≥50% of the total treatment duration were selected. The primary endpoint was all-cause 30-day mortality. The secondary endpoint was 90-day relapse. Of 1319 eligible patients, 835 were selected. A total of 714 received BL/BLI as appropriate empirical therapy, of whom 522 remained on BL/BLI as definitive therapy and 192 shifted to another antibiotic for <50% of the treatment duration; 121 received BL/BLI as definitive therapy only. Non-susceptibility to extended-spectrum cephalosporins (NS-ESCs) was detected in 207 episodes (24.8%). All-cause 30-day mortality was 6.8%. In multivariate analysis adjusted for NS-ESC, independent predictors of mortality were Charlson comorbidity index, septic shock, Proteus spp. and CVC-related BSI, whilst urinary source was a protective factor. The 90-day relapse rate was 4.2%. Immunosuppression was the main independent predictor for relapse. BL/BLI was the most common antibiotic administered to patients with E-BSI in this cohort. Among patients appropriately treated with BL/BLI, failure rates were low and were primarily associated with underlying diseases, clinical severity at BSI onset and infection source.
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Affiliation(s)
- Maddalena Giannella
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, Policlinico Sant'Orsola Malpighi, University of Bologna, Via Massarenti 11, 40137 Bologna, Italy.
| | - Renato Pascale
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, Policlinico Sant'Orsola Malpighi, University of Bologna, Via Massarenti 11, 40137 Bologna, Italy
| | - Giuseppe Ferraro
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, Policlinico Sant'Orsola Malpighi, University of Bologna, Via Massarenti 11, 40137 Bologna, Italy
| | - Alice Toschi
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, Policlinico Sant'Orsola Malpighi, University of Bologna, Via Massarenti 11, 40137 Bologna, Italy
| | - Livia Pancaldi
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, Policlinico Sant'Orsola Malpighi, University of Bologna, Via Massarenti 11, 40137 Bologna, Italy
| | - Francesca Furii
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, Policlinico Sant'Orsola Malpighi, University of Bologna, Via Massarenti 11, 40137 Bologna, Italy
| | - Michele Bartoletti
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, Policlinico Sant'Orsola Malpighi, University of Bologna, Via Massarenti 11, 40137 Bologna, Italy
| | - Sara Tedeschi
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, Policlinico Sant'Orsola Malpighi, University of Bologna, Via Massarenti 11, 40137 Bologna, Italy
| | - Simone Ambretti
- Operative Unit of Clinical Microbiology, Policlinico Sant'Orsola Malpighi, University of Bologna, Bologna, Italy
| | - Russell Edward Lewis
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, Policlinico Sant'Orsola Malpighi, University of Bologna, Via Massarenti 11, 40137 Bologna, Italy
| | - Pierluigi Viale
- Infectious Diseases Unit, Department of Medical and Surgical Sciences, Policlinico Sant'Orsola Malpighi, University of Bologna, Via Massarenti 11, 40137 Bologna, Italy
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26
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Hayden MK, Won SY. Carbapenem-Sparing Therapy for Extended-Spectrum β-Lactamase-Producing E coli and Klebsiella pneumoniae Bloodstream Infection: The Search Continues. JAMA 2018; 320:979-981. [PMID: 30208439 DOI: 10.1001/jama.2018.12565] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Affiliation(s)
| | - Sarah Y Won
- Rush University Medical Center, Chicago, Illinois
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Pana ZD, Zaoutis T. Treatment of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBLs) infections: what have we learned until now? F1000Res 2018; 7. [PMID: 30228863 PMCID: PMC6117850 DOI: 10.12688/f1000research.14822.1] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/23/2018] [Indexed: 12/11/2022] Open
Abstract
The spread of extended-spectrum β-lactamase (ESBL)-producing
Enterobacteriaceae (ESBL-PE) has dramatically increased worldwide, and this “evolving crisis” is currently regarded as one of the most important public health threats. The growing problem of ESBL-PE antimicrobial resistance seems to have a dual face between “Scylla and Charybdis”: on one hand the potential for rapid spread and dissemination of resistance mechanisms and on the other hand the injudicious overuse of antimicrobial agents and the inadequate infection control measures, especially in the health-care setting. Given the World Health Organization’s warning against a “post antibiotic era”, health-care providers are at a critical standpoint to find a “balance” between safe and effective ESBL-PE treatment and avoidance of inducing further resistance mechanisms. The aim of the review is to summarize the updated published knowledge in an attempt to answer basic everyday clinical questions on how to proceed to effective and the best ESBL-PE treatment options based on the existing published data.
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Affiliation(s)
- Zoi Dorothea Pana
- Infectious Diseases Department, 3rd Department of Pediatrics, Hippokration General Hospital Aristotle University, Thessaloniki, Greece
| | - Theoklis Zaoutis
- Infectious Diseases Department, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
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Su J, Guo Q, Li Y, Wu S, Hu F, Xu S, Wang M. Comparison of empirical therapy with cefoperazone/sulbactam or a carbapenem for bloodstream infections due to ESBL-producing Enterobacteriaceae. J Antimicrob Chemother 2018; 73:3176-3180. [PMID: 30099554 DOI: 10.1093/jac/dky323] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Accepted: 07/13/2018] [Indexed: 01/10/2023] Open
Affiliation(s)
- Jiachun Su
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China
| | - Qinglan Guo
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China
| | - Ying Li
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China
| | - Shi Wu
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China
| | - Fupin Hu
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China
| | - Su Xu
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China
| | - Minggui Wang
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China
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Richter DC, Heininger A, Brenner T, Hochreiter M, Bernhard M, Briegel J, Dubler S, Grabein B, Hecker A, Krüger WA, Mayer K, Pletz MW, Störzinger D, Pinder N, Hoppe-Tichy T, Weiterer S, Zimmermann S, Brinkmann A, Weigand MA, Lichtenstern C. [Bacterial sepsis : Diagnostics and calculated antibiotic therapy]. Anaesthesist 2018; 66:737-761. [PMID: 28980026 DOI: 10.1007/s00101-017-0363-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The mortality of patients with sepsis and septic shock is still unacceptably high. An effective antibiotic treatment within 1 h of recognition of sepsis is an important target of sepsis treatment. Delays lead to an increase in mortality; therefore, structured treatment concepts form a rational foundation, taking relevant diagnostic and treatment steps into consideration. In addition to the assumed focus and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account for selection of anti-infection treatment. Many pathophysiological alterations influence the pharmacokinetics of antibiotics during sepsis. The principle of standard dosing should be abandoned and replaced by an individual treatment approach with stronger weighting of the pharmacokinetics/pharmacodynamics (PK/PD) index of the substance groups. Although this is not yet the clinical standard, prolonged (or continuous) infusion of beta-lactam antibiotics and therapeutic drug monitoring (TDM) can help to achieve defined PK targets. Prolonged infusion is sufficient without TDM but for continuous infusion TDM is basically necessary. A further argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug resistant pathogens (MDR) in the intensive care unit. For effective treatment antibiotic stewardship teams (ABS team) are becoming more established. Interdisciplinary cooperation of the ABS team with infectiologists, microbiologists and clinical pharmacists leads not only to a rational administration of antibiotics but also has a positive influence on the outcome. The gold standards for pathogen detection are still culture-based detection and microbiological resistance testing for the various antibiotic groups. Despite the rapid investigation time, novel polymerase chain reaction (PCR)-based procedures for pathogen identification and resistance determination, are currently only an adjunct to routine sepsis diagnostics due to the limited number of studies, high costs and limited availability. In complicated septic courses with multiple anti-infective treatment or recurrent sepsis, PCR-based procedures can be used in addition to therapy monitoring and diagnostics. Novel antibiotics represent potent alternatives in the treatment of MDR infections. Due to the often defined spectrum of pathogens and the practically absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation).
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Affiliation(s)
- D C Richter
- Klinik für Anästhesiologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Deutschland.
| | - A Heininger
- Zentrum für Infektiologie, Sektion für Krankenhaus- und Umwelthygiene, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
| | - T Brenner
- Klinik für Anästhesiologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Deutschland
| | - M Hochreiter
- Klinik für Anästhesiologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Deutschland
| | - M Bernhard
- Zentrale Notaufnahme, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - J Briegel
- Klinik für Anästhesiologie, Klinikum der Universität München, München, Deutschland
| | - S Dubler
- Klinik für Anästhesiologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Deutschland
| | - B Grabein
- Stabsstelle "Klinische Mikrobiologie und Krankenhaushygiene", Klinikum der Universität München, München, Deutschland
| | - A Hecker
- Klinik für Allgemein‑, Viszeral‑, Thorax‑, Transplantations- und Kinderchirurgie, Universitätsklinikum Gießen und Marburg, Standort Gießen, Gießen, Deutschland
| | - W A Krüger
- Klinik für Anästhesiologie und operative Intensivmedizin, Gesundheitsverbund Landkreis Konstanz, Klinikum Konstanz, Konstanz, Deutschland
| | - K Mayer
- Apotheke des Universitätsklinikums Heidelberg, Heidelberg, Deutschland
| | - M W Pletz
- Zentrum für Infektionsmedizin und Krankenhaushygiene, Universitätsklinikum Jena, Jena, Deutschland
| | - D Störzinger
- Apotheke des Universitätsklinikums Heidelberg, Heidelberg, Deutschland
| | - N Pinder
- Apotheke des Universitätsklinikums Heidelberg, Heidelberg, Deutschland
| | - T Hoppe-Tichy
- Zentrum für Infektiologie, Sektion für Krankenhaus- und Umwelthygiene, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
| | - S Weiterer
- Klinik für Anästhesiologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Deutschland
| | - S Zimmermann
- Zentrum für Infektiologie, Sektion für Krankenhaus- und Umwelthygiene, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
| | - A Brinkmann
- Klinik für Anästhesie, operative Intensivmedizin und spezielle Schmerztherapie, Klinikum Heidenheim, Heidenheim, Deutschland
| | - M A Weigand
- Klinik für Anästhesiologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Deutschland
| | - Christoph Lichtenstern
- Klinik für Anästhesiologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Deutschland
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Mizrahi A, Amzalag J, Couzigou C, Péan De Ponfilly G, Pilmis B, Le Monnier A. Clinical impact of rapid bacterial identification by MALDI-TOF MS combined with the bêta-LACTA™ test on early antibiotic adaptation by an antimicrobial stewardship team in bloodstream infections. Infect Dis (Lond) 2018; 50:668-677. [DOI: 10.1080/23744235.2018.1458147] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/17/2022] Open
Affiliation(s)
- A. Mizrahi
- Laboratoire de Microbiologie clinique, Groupe Hospitalier Paris Saint-Joseph, Paris, France
| | - J. Amzalag
- Laboratoire de Microbiologie clinique, Groupe Hospitalier Paris Saint-Joseph, Paris, France
| | - C. Couzigou
- Equipe mobile de Microbiologie clinique, Groupe Hospitalier Paris Saint-Joseph, Paris, France
| | - G. Péan De Ponfilly
- Laboratoire de Microbiologie clinique, Groupe Hospitalier Paris Saint-Joseph, Paris, France
| | - B. Pilmis
- Equipe mobile de Microbiologie clinique, Groupe Hospitalier Paris Saint-Joseph, Paris, France
| | - A. Le Monnier
- Laboratoire de Microbiologie clinique, Groupe Hospitalier Paris Saint-Joseph, Paris, France
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Point-Counterpoint: Piperacillin-Tazobactam Should Be Used To Treat Infections with Extended-Spectrum-Beta-Lactamase-Positive Organisms. J Clin Microbiol 2018; 56:JCM.01917-17. [PMID: 29237787 DOI: 10.1128/jcm.01917-17] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTIONBeta-lactam/beta-lactamase inhibitor combination antimicrobials (BLBLIs) are among the most controversial classes of antibiotic agents available for the treatment of infections caused by extended-spectrum-beta-lactamase (ESBL)-producing Gram-negative bacteria (ESBL-GNR). Piperacillin-tazobactam (PTZ) is one of the most frequently utilized antibiotic agents for empirical Gram-negative bacterial coverage and remains active against a large proportion of ESBL-GNR strains. Furthermore, good antimicrobial stewardship practices encourage the use of carbapenem-sparing treatment regimens for infections due to ESBL-GNR. As rapid diagnostics are increasingly used in the clinical microbiology laboratory and have the capability of detecting CTX-M type or other ESBL resistance mechanisms, this issue continues to be pertinent. Some data imply reduced efficacy of PTZ against ESBLs. Several factors may affect a clinician's choice to use BLBLIs, including the isolate's MIC, the site and severity of infection, and the type of resistance mechanism. These factors are explored in this review of the pros and cons of BLBLI treatment of invasive infections due to ESBL-producing bacteria, as well as how laboratories should report results for BLBLIs for these organisms as they relate to antimicrobial stewardship. In this Point-Counterpoint, Audrey Schuetz provides the pro point of view and Sergio Reyes and Pranita Tamma provide the con, counterpoint view.
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Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-Producing Enterobacteriaceae. Clin Microbiol Rev 2018; 31:31/2/e00079-17. [PMID: 29444952 DOI: 10.1128/cmr.00079-17] [Citation(s) in RCA: 441] [Impact Index Per Article: 63.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Therapy of invasive infections due to multidrug-resistant Enterobacteriaceae (MDR-E) is challenging, and some of the few active drugs are not available in many countries. For extended-spectrum β-lactamase and AmpC producers, carbapenems are the drugs of choice, but alternatives are needed because the rate of carbapenem resistance is rising. Potential active drugs include classic and newer β-lactam-β-lactamase inhibitor combinations, cephamycins, temocillin, aminoglycosides, tigecycline, fosfomycin, and, rarely, fluoroquinolones or trimethoprim-sulfamethoxazole. These drugs might be considered in some specific situations. AmpC producers are resistant to cephamycins, but cefepime is an option. In the case of carbapenemase-producing Enterobacteriaceae (CPE), only some "second-line" drugs, such as polymyxins, tigecycline, aminoglycosides, and fosfomycin, may be active; double carbapenems can also be considered in specific situations. Combination therapy is associated with better outcomes for high-risk patients, such as those in septic shock or with pneumonia. Ceftazidime-avibactam was recently approved and is active against KPC and OXA-48 producers; the available experience is scarce but promising, although development of resistance is a concern. New drugs active against some CPE isolates are in different stages of development, including meropenem-vaborbactam, imipenem-relebactam, plazomicin, cefiderocol, eravacycline, and aztreonam-avibactam. Overall, therapy of MDR-E infection must be individualized according to the susceptibility profile, type, and severity of infection and the features of the patient.
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Sheu CC, Lin SY, Chang YT, Lee CY, Chen YH, Hsueh PR. Management of infections caused by extended-spectrum β-lactamase-producing Enterobacteriaceae: current evidence and future prospects. Expert Rev Anti Infect Ther 2018; 16:205-218. [PMID: 29402125 DOI: 10.1080/14787210.2018.1436966] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION The spread of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae has become a major public health threat worldwide. Area covered: A thorough systematic literature review describing the current evidence and future prospects of therapeutic options for infections caused by ESBL-producing Enterobacteriaceae. Expert commentary: The methods of detecting ESBLs have been evolving. The Clinical and Laboratory Standards Institute and the European Committee on Antimicrobial Susceptibility Testing lowered the MIC breakpoints of cephalosporins against ESBL-producing Enterobacteriaceae in 2010. Phenotypic testing for ESBLs is no longer recommended. Instead, the selection of appropriate antimicrobial agents largely depends on the report of minimum inhibitory concentrations (MICs). To date, therapeutic options for these multidrug-resistant organisms remain limited. The clinical efficacy of piperacillin/tazobactam and cefepime on in vitro-susceptible ESBL-producing Enterobacteriaceae remains a concern. Many studies found an in vitro-in vivo discordance based on current breakpoints. Carbapenems are the most reliable antibiotics for severe infections caused by ESBL-producing Enterobacteriaceae. However, their overuse has led to a serious problem of increasing drug resistance. Recently, ceftolozane/tazobactam and ceftazidime/avibactam have been approved for the treatment of complicated urinary tract infections and complicated intra-abdominal infections. The introduction of these new β-lactam/β-lactamase inhibitor combinations offers new carbapenem-sparing options for the treatment of ESBL infections.
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Affiliation(s)
- Chau-Chyun Sheu
- a Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine , Kaohsiung Medical University Hospital , Kaohsiung , Taiwan.,b School of Medicine, Sepsis Research Institute, Graduate Institute of Medicine, College of Medicine , Kaohsiung Medical University , Kaohsiung , Taiwan
| | - Shang-Yi Lin
- b School of Medicine, Sepsis Research Institute, Graduate Institute of Medicine, College of Medicine , Kaohsiung Medical University , Kaohsiung , Taiwan.,c Division of Infectious Disease, Department of Internal Medicine , Kaohsiung Medical University Hospital , Kaohsiung , Taiwan
| | - Ya-Ting Chang
- b School of Medicine, Sepsis Research Institute, Graduate Institute of Medicine, College of Medicine , Kaohsiung Medical University , Kaohsiung , Taiwan.,c Division of Infectious Disease, Department of Internal Medicine , Kaohsiung Medical University Hospital , Kaohsiung , Taiwan
| | - Chun-Yuan Lee
- b School of Medicine, Sepsis Research Institute, Graduate Institute of Medicine, College of Medicine , Kaohsiung Medical University , Kaohsiung , Taiwan.,c Division of Infectious Disease, Department of Internal Medicine , Kaohsiung Medical University Hospital , Kaohsiung , Taiwan
| | - Yen-Hsu Chen
- b School of Medicine, Sepsis Research Institute, Graduate Institute of Medicine, College of Medicine , Kaohsiung Medical University , Kaohsiung , Taiwan.,c Division of Infectious Disease, Department of Internal Medicine , Kaohsiung Medical University Hospital , Kaohsiung , Taiwan.,d Department of Biological Science and Technology , College of Biological Science and Technology, National Chiao Tung University , Hsin Chu , Taiwan
| | - Po-Ren Hsueh
- e Department of Laboratory Medicine , National Taiwan University Hospital, College of Medicine, National Taiwan University , Taipei , Taiwan.,f Department of Internal Medicine , National Taiwan University Hospital, College of Medicine, National Taiwan University , Taipei , Taiwan
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Meini S, Laureano R, Tascini C, Arena F, Fani L, Frullini A, Passaleva MT, Roberts AT, Mannini D, Sbrana F, Ripoli A, Rossolini GM. Clinical outcomes of elderly patients with bloodstream infections due to extended-spectrum β-lactamase-producing Enterobacteriaceae in an Italian Internal Medicine ward. Eur J Intern Med 2018; 48:50-56. [PMID: 29089174 DOI: 10.1016/j.ejim.2017.10.014] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Revised: 08/31/2017] [Accepted: 10/21/2017] [Indexed: 10/18/2022]
Abstract
PURPOSE Infections caused by ESBL-producing Enterobacteriaceae (ESBL-EB) are a major health problem, but data regarding elderly patients is lacking. METHODS We performed a retrospective observational study quantifying the effects of antimicrobial treatment and primary infection site on clinical outcomes in an historical case series of 42 patients aged 80.7±10years admitted to an Internal Medicine ward in Italy for ESBL-EB bloodstream infections (BSI). RESULTS At multivariate risk analysis, we found that urinary tract as primary infection site (RR=0.181 [0.037-0.886], p=0.035) and definitive antibiotic therapy (RR=0.517 [0.147-0.799], p=0.038) decreased the relative risk of a negative clinical response, while the respiratory tract origin increased the relative risk (RR=2.788 [1.407-9.228], p=0.025). Also regarding 30days mortality, multivariate risk analysis identified that urinary tract as primary infection site (RR=0.098 [0.011-0.743], p=0.025) and definitive antibiotic therapy (RR=0.236 [0.058-0.961], p=0.044) decreased the relative risk, while the respiratory origin increased the relative risk (RR=4.241 [1.040-17.295], p=0.014). We observed similar outcomes in patients definitively treated with carbapenems or with carbapenem-free treatments. Additionally, an initially inappropriate therapy did not correlate with worse outcomes if a switch to an effective definitive treatment was performed promptly. CONCLUSIONS Carbapenem-sparing regimens (e.g. piperacillin-tazobactam alone or with an aminoglycoside) could be empirically safely used in elderly patients at high risk of ESBL-EB BSI and for definitive treatment of ascertained cases if the primary site is the urinary tract, leaving early carbapenem use for cases at higher risk of death, such as those with pneumonia.
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Affiliation(s)
- Simone Meini
- Internal Medicine Unit, Santa Maria Annunziata Hospital, Florence, Italy.
| | - Raffaele Laureano
- Internal Medicine Unit, Santa Maria Annunziata Hospital, Florence, Italy
| | - Carlo Tascini
- First Division of Infectious Diseases, Cotugno Hospital, Naples, Italy
| | - Fabio Arena
- Department of Medical Biotechnologies, University of Siena, Siena, Italy; Don Carlo Gnocchi Foundation, Florence, Italy
| | - Lucia Fani
- Internal Medicine Unit, Santa Maria Annunziata Hospital, Florence, Italy
| | - Anna Frullini
- Internal Medicine Unit, Santa Maria Annunziata Hospital, Florence, Italy
| | | | | | - Dario Mannini
- Internal Medicine Unit, Santa Maria Annunziata Hospital, Florence, Italy
| | | | | | - Gian Maria Rossolini
- Don Carlo Gnocchi Foundation, Florence, Italy.; Clinical Microbiology and Virology Unit, Florence Careggi University Hospital, Florence, Italy; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
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Vila J, Sáez-López E, Johnson JR, Römling U, Dobrindt U, Cantón R, Giske CG, Naas T, Carattoli A, Martínez-Medina M, Bosch J, Retamar P, Rodríguez-Baño J, Baquero F, Soto SM. Escherichia coli: an old friend with new tidings. FEMS Microbiol Rev 2018; 40:437-463. [PMID: 28201713 DOI: 10.1093/femsre/fuw005] [Citation(s) in RCA: 197] [Impact Index Per Article: 28.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Revised: 09/23/2015] [Accepted: 02/04/2016] [Indexed: 12/16/2022] Open
Abstract
Escherichia coli is one of the most-studied microorganisms worldwide but its characteristics are continually changing. Extraintestinal E. coli infections, such as urinary tract infections and neonatal sepsis, represent a huge public health problem. They are caused mainly by specialized extraintestinal pathogenic E. coli (ExPEC) strains that can innocuously colonize human hosts but can also cause disease upon entering a normally sterile body site. The virulence capability of such strains is determined by a combination of distinctive accessory traits, called virulence factors, in conjunction with their distinctive phylogenetic background. It is conceivable that by developing interventions against the most successful ExPEC lineages or their key virulence/colonization factors the associated burden of disease and health care costs could foreseeably be reduced in the future. On the other hand, one important problem worldwide is the increase of antimicrobial resistance shown by bacteria. As underscored in the last WHO global report, within a wide range of infectious agents including E. coli, antimicrobial resistance has reached an extremely worrisome situation that ‘threatens the achievements of modern medicine’. In the present review, an update of the knowledge about the pathogenicity, antimicrobial resistance and clinical aspects of this ‘old friend’ was presented.
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Affiliation(s)
- J Vila
- ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain
- Department of Clinical Microbiology, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain
- Spanish Network for Research in Infectious Diseases (REIPI), Instituto de Salud Carlos III, Madrid, Spain
| | - E Sáez-López
- ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain
| | - J R Johnson
- VA Medical Center, Minneapolis, MN, USA, and University of Minnesota, Minneapolis, MN, USA
| | - U Römling
- Karolinska Institute, Stockholm, Sweden
| | - U Dobrindt
- Institute of Hygiene, University of Münster, Münster, Germany
| | - R Cantón
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto de Investigación Sanitaria (IRYCIS), Madrid, Spain
- Spanish Network for Research in Infectious Diseases (REIPI), Instituto de Salud Carlos III, Madrid, Spain
| | - C G Giske
- Karolinska Institute, Stockholm, Sweden
| | - T Naas
- Hôpital de Bicêtre, Université Paris Sud, Le Kremlin-Bicêtre, France
| | - A Carattoli
- Department of infectious, parasitic and immune-mediated diseases, Istituto Superiore di Sanità, Rome, Italy
| | - M Martínez-Medina
- Laboratory of Molecular Microbiology, Department of Biology, University of Girona, Girona, Spain
| | - J Bosch
- ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain
- Department of Clinical Microbiology, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain
| | - P Retamar
- Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospitales Universitarios Virgen Macarena y Virgen del Rocío, Departamento de Medicina, Universidad de Sevilla, Seville, Spain
| | - J Rodríguez-Baño
- Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospitales Universitarios Virgen Macarena y Virgen del Rocío, Departamento de Medicina, Universidad de Sevilla, Seville, Spain
- Spanish Network for Research in Infectious Diseases (REIPI), Instituto de Salud Carlos III, Madrid, Spain
| | - F Baquero
- Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto de Investigación Sanitaria (IRYCIS), Madrid, Spain
| | - S M Soto
- ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain
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Chastain DB, White BP, Cretella DA, Bland CM. Is It Time to Rethink the Notion of Carbapenem-Sparing Therapy Against Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae Bloodstream Infections? A Critical Review. Ann Pharmacother 2017; 52:484-492. [PMID: 29239220 DOI: 10.1177/1060028017748943] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVE To present systematic recommendations for carbapenem-sparing therapy against extended-spectrum β-lactamases (ESBLs) Enterobacteriaceae bloodstream infections (BSIs) derived from a critical review of clinical data. DATA SOURCES A systematic literature search using PubMed and MEDLINE databases (January 1, 2012, to June 30, 2017) was performed using key MESH terms: ESBL or extended-spectrum β-lactamases and bacteremia or bloodstream infection with piperacillin/tazobactam, ciprofloxacin, levofloxacin, cefepime, cephamycins, carbapenem, doripenem, meropenem, and ertapenem. References within articles of interest were also evaluated. STUDY SELECTION AND DATA EXTRACTION All English language trials were considered, and results were limited to clinical efficacy trials. Articles were screened by title and abstract for inclusion. DATA SYNTHESIS Studies comparing noncarbapenem versus carbapenem therapy for ESBL BSIs were critically analyzed to identify heterogeneity among studies. Data abstracted included empirical or definitive therapy, patient population, dosing, source of infection and severity, infectious etiology, and outcome. CONCLUSIONS Completely sparing carbapenem therapy cannot be justified among patients with ESBL BSIs. Determining the source of infection is critical to identify patients for whom carbapenem-sparing therapy is appropriate.
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Affiliation(s)
| | - Bryan P White
- 2 Oklahoma University Medical Center, Oklahoma City, OK, USA
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Pilmis B, Jullien V, Tabah A, Zahar JR, Brun-Buisson C. Piperacillin-tazobactam as alternative to carbapenems for ICU patients. Ann Intensive Care 2017; 7:113. [PMID: 29127502 PMCID: PMC5681454 DOI: 10.1186/s13613-017-0334-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Accepted: 10/26/2017] [Indexed: 12/19/2022] Open
Abstract
Several studies suggest that alternatives to carbapenems, and particulary beta-lactam/beta-lactamase inhibitor combinations, can be used for therapy of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE)-related infections in non-ICU patients. Little is known concerning ICU patients in whom achieving the desired plasmatic pharmacokinetic/pharmacodynamic (PK/PD) target may be difficult. Also, in vitro susceptibility to beta-lactamase inhibitors might not translate into clinical efficacy. We reviewed the recent clinical studies examining the use of BL/BLI as alternatives to carbapenems for therapy of bloodstream infection, PK/PD data and discuss potential ecological benefit from avoiding the use of carbapenems. With the lack of prospective randomized studies, treating ICU patients with ESBL-PE-related infections using piperacillin-tazobactam should be done with caution. Current data suggest that BL/BLI empirical use should be avoided for therapy of ESBL-PE-related infection. Also, definitive therapy should be reserved to patients in clinical stable condition, after microbial documentation and results of susceptibility tests. Optimization of administration and higher dosage should be used in order to reach pharmacological targets.
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Affiliation(s)
- Benoit Pilmis
- Service de maladies infectieuses et tropicales, Hôpital Necker Enfants malades, Service de maladies infectieuses et tropicales, Université Paris Descartes, Paris, France.,Equipe mobile de microbiologie clinique, Groupe Hospitalier Paris Saint-Joseph, Paris, France
| | - Vincent Jullien
- Service de Pharmacologie, Hôpital Européen Georges Pompidou, Université Paris Descartes, Paris, France.,INSERM U1129, Paris, France
| | - Alexis Tabah
- Intensive Care Unit, The Redcliffe Hospital, Brisbane, Australia.,Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia
| | - Jean-Ralph Zahar
- Département de Microbiologie Clinique, Unité de Contrôle et de Prévention du risque Infectieux, Groupe Hospitalier Paris Seine Saint-Denis, AP-HP, CHU Avicenne, 125 rue de Stalingrad, 9300, Bobigny, France. .,Infection Control Unit, IAME, UMR 1137, Université Paris 13, Sorbonne Paris Cité, Paris, France.
| | - Christian Brun-Buisson
- Réanimation médicale, Hôpital Henri Mondor, Université Paris Est Créteil (UPEC), Créteil, France
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Fiore M, Maraolo AE, Gentile I, Borgia G, Leone S, Sansone P, Passavanti MB, Aurilio C, Pace MC. Current concepts and future strategies in the antimicrobial therapy of emerging Gram-positive spontaneous bacterial peritonitis. World J Hepatol 2017; 9:1166-1175. [PMID: 29109849 PMCID: PMC5666303 DOI: 10.4254/wjh.v9.i30.1166] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Revised: 08/03/2017] [Accepted: 09/16/2017] [Indexed: 02/06/2023] Open
Abstract
Spontaneous bacterial peritonitis (SBP) is the most common infection in end-stage liver disease patients. SBP is defined as an ascitic fluid infection with a polymorphonuclear leucocyte count ≥ 250/mm3 without an evident intra-abdominal surgically treatable source. Several mechanisms contribute to SBP occurrence, including translocation of gut bacteria and their products, reduced intestinal motility provoking bacterial overgrowth, alteration of the gut's barrier function and local immune responses. Historically, Gram-negative enteric bacteria have been the main causative agents of SBP, thereby guiding the empirical therapeutic choice. However, over the last decade, a worryingly increasing prevalence of Gram-positive and multi-drug resistant (MDR) SBP has been seen. Recently, the microbiological spectrum of SBP seems to have changed in Europe due to a high prevalence of Gram-positive bacteria (48%-62%). The overall proportion of MDR bacteria is up to 22%-73% of cases. Consequently, empirical therapy based on third-generation cephalosporins or amoxicillin/clavulanic acid, can no longer be considered the standard of care, as these drugs are associated with poor outcomes. The aim of this review is to describe, with an epidemiological focus, the evidence behind this rise in Gram-positive and MDR SBP from 2000 to present, and illustrate potential targeted therapeutic strategies. An appropriate treatment protocol should include daptomycin plus ceftaroline and meropenem, with prompt stepdown to a narrower spectrum when cultures and sensitivity data are available in order to reduce both cost and potential antibiotic resistance development.
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Affiliation(s)
- Marco Fiore
- Department of Anesthesiological, Surgical and Emergency Sciences, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.
| | - Alberto Enrico Maraolo
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131 Naples, Italy
| | - Ivan Gentile
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131 Naples, Italy
| | - Guglielmo Borgia
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, 80131 Naples, Italy
| | - Sebastiano Leone
- Division of Infectious Diseases, "San Giuseppe Moscati" Hospital, 83100 Avellino, Italy
| | - Pasquale Sansone
- Department of Anesthesiological, Surgical and Emergency Sciences, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy
| | - Maria Beatrice Passavanti
- Department of Anesthesiological, Surgical and Emergency Sciences, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy
| | - Caterina Aurilio
- Department of Anesthesiological, Surgical and Emergency Sciences, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy
| | - Maria Caterina Pace
- Department of Anesthesiological, Surgical and Emergency Sciences, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy
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Watkins RR, Deresinski S. Using β-lactam/β-lactamase inhibitors for infections due to extended-spectrum β-lactamase-producing Enterobacteriaceae to slow the emergence of carbapenem-resistant Enterobacteriaceae. Expert Rev Anti Infect Ther 2017; 15:893-895. [DOI: 10.1080/14787210.2017.1380519] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Richard R. Watkins
- Department of Internal Medicine, Northeast Ohio Medical University, Rootstown, OH, USA
- Division of Infectious Diseases, Cleveland Clinic Akron General, Akron, OH, USA
| | - Stan Deresinski
- Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA, USA
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40
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Fiore M, Maraolo AE, Gentile I, Borgia G, Leone S, Sansone P, Passavanti MB, Aurilio C, Pace MC. Nosocomial spontaneous bacterial peritonitis antibiotic treatment in the era of multi-drug resistance pathogens: A systematic review. World J Gastroenterol 2017; 23:4654-4660. [PMID: 28740354 PMCID: PMC5504381 DOI: 10.3748/wjg.v23.i25.4654] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2016] [Revised: 03/31/2017] [Accepted: 06/19/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To systematically review literature upon aetiology of nosocomial spontaneous bacterial peritonitis (N-SBP) given the rising importance of multidrug-resistant (MDR) bacteria. METHODS A literature search was performed on MEDLINE and Google Scholar databases from 2000 to 15th of November 2016, using the following search strategy: "spontaneous" AND "peritonitis". RESULTS The initial search through electronic databases retrieved 2556 records. After removing duplicates, 1958 records remained. One thousand seven hundred and thirty-five of them were excluded on the basis of the screening of titles and abstract, and the ensuing number of remaining articles was 223. Of these records, after careful evaluation, only 9 were included in the qualitative analysis. The overall proportion of MDR bacteria turned out to be from 22% to 73% of cases across the studies. CONCLUSION N-SBP is caused, in a remarkable proportion, by MDR pathogens. This should prompt a careful re-assessment of guidelines addressing the treatment of this clinical entity.
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Seo YB, Lee J, Kim YK, Lee SS, Lee JA, Kim HY, Uh Y, Kim HS, Song W. Randomized controlled trial of piperacillin-tazobactam, cefepime and ertapenem for the treatment of urinary tract infection caused by extended-spectrum beta-lactamase-producing Escherichia coli. BMC Infect Dis 2017; 17:404. [PMID: 28592240 PMCID: PMC5463388 DOI: 10.1186/s12879-017-2502-x] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2016] [Accepted: 05/30/2017] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Due to limited therapeutic options, the spread of extended-spectrum beta-lactamases (ESBLs) have become a major public health concern. We conducted a prospective, randomized, open-label comparison of the therapeutic efficacy of piperacillin-tazobactam (PTZ), cefepime, and ertapenem in febrile nosocomial urinary tract infection with ESBL-producing Escherichia coli (ESBL-EC). METHODS This study was conducted at three university hospitals between January 2013 and August 2015. Hospitalized adult patients presenting with fever were screened for healthcare-associated urinary tract infection (HA-UTI). When ESBL-EC was solely detected and susceptible to a randomized antibiotic in vitro, the case was included in the final analysis. Participants were treated for 10-14 days with PTZ, cefepime, or ertapenem. RESULTS A total of 66 participants were evenly assigned to the PTZ and ertapenem treatment groups. After the recruitment of six participants, assignment to the cefepime treatment group was stopped because of an unexpectedly high treatment failure rate. The baseline characteristics of these participants did not differ from participants in other treatment groups. The clinical and microbiological response to PTZ treatment was estimated to be 94% and was similar to the response to ertapenem treatment. The efficacy of cefepime was 33.3%. In the cefepime group, age, Charlson comorbidity index, genotype, and minimal inhibitory concentration (MIC) did not significantly affect the success of treatment. Similarly, genotype seemed to be irrelevant with respect to clinical outcome in the PTZ group. Expired cases tended to involve septic shock with a high Charlson comorbidity index and high MIC. CONCLUSION Results from this study suggest that PTZ is effective in the treatment of urinary tract infection caused by ESBL-EC when the in vitro test indicates susceptibility. In addition, cefepime should not be used as an alternative treatment for urinary tract infection caused by ESBL-EC. TRIAL REGISTRATION The trial was registered with the Clinical Research Information Service of Korea Centers for Disease Control and Prevention. (KCT0001895).
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Affiliation(s)
- Yu Bin Seo
- Division of Infectious Diseases, Department of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea
| | - Jacob Lee
- Division of Infectious Diseases, Department of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea
| | - Young Keun Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - Seung Soon Lee
- Division of Infectious Diseases, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea
| | - Jeong-A Lee
- Division of Infectious Diseases, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea
| | - Hyo Youl Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - Young Uh
- Department of Laboratory Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - Han-Sung Kim
- Department of Laboratory Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea
| | - Wonkeun Song
- Department of Laboratory Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, 1 Shingil-ro, Youngdeungpo-gu, Seoul, 150-950, Korea.
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Maitre T, Petitjean G, Chauffour A, Bernard C, El Helali N, Jarlier V, Reibel F, Chavanet P, Aubry A, Veziris N. Are moxifloxacin and levofloxacin equally effective to treat XDR tuberculosis? J Antimicrob Chemother 2017; 72:2326-2333. [DOI: 10.1093/jac/dkx150] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2016] [Accepted: 04/24/2017] [Indexed: 11/15/2022] Open
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Mutations in blaKPC-3 That Confer Ceftazidime-Avibactam Resistance Encode Novel KPC-3 Variants That Function as Extended-Spectrum β-Lactamases. Antimicrob Agents Chemother 2017; 61:AAC.02534-16. [PMID: 28223379 DOI: 10.1128/aac.02534-16] [Citation(s) in RCA: 158] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Accepted: 02/07/2017] [Indexed: 02/04/2023] Open
Abstract
We identified four blaKPC-3 mutations in ceftazidime-avibactam-resistant clinical Klebsiella pneumoniae isolates, corresponding to D179Y, T243M, D179Y/T243M, and EL165-166 KPC-3 variants. Using site-directed mutagenesis and transforming vectors into Escherichia coli, we conclusively demonstrated that mutant blaKPC-3 encoded enzymes that functioned as extended-spectrum β-lactamases; mutations directly conferred higher MICs of ceftazidime-avibactam and decreased the MICs of carbapenems and other β-lactams. Impact was strongest for the D179Y mutant, highlighting the importance of the KPC Ω-loop.
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Takesue Y, Kusachi S, Mikamo H, Sato J, Watanabe A, Kiyota H, Iwata S, Kaku M, Hanaki H, Sumiyama Y, Kitagawa Y, Mizuguchi T, Ambo Y, Konosu M, Ishibashi K, Matsuda A, Hase K, Harihara Y, Okabayashi K, Seki S, Hara T, Matsui K, Matsuo Y, Kobayashi M, Kubo S, Uchiyama K, Shimizu J, Kawabata R, Ohge H, Akagi S, Oka M, Wakatsuki T, Suzuki K, Okamoto K, Yanagihara K. Antimicrobial susceptibility of pathogens isolated from surgical site infections in Japan: Comparison of data from nationwide surveillance studies conducted in 2010 and 2014-2015. J Infect Chemother 2017; 23:339-348. [PMID: 28391954 DOI: 10.1016/j.jiac.2017.03.010] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2017] [Revised: 03/09/2017] [Accepted: 03/14/2017] [Indexed: 11/18/2022]
Abstract
A nationwide survey was conducted in Japan from 2014 to 2015 to investigate the antimicrobial susceptibility of pathogens isolated from surgical site infections (SSI). The resulting data were compared with that obtained in an earlier survey, conducted in 2010. Seven main organisms were collected, and 883 isolates were studied. A significant reduction in methicillin resistance was observed among Staphylococcus aureus isolates, dropping from 72.5% in 2010 to 53.8% in 2014-2015 (p < 0.001). MRSA isolates with a vancomycin minimum inhibitory concentration (MIC) of 2 μg/mL accounted for 1.2% of all MRSA isolates, which was significantly lower than in 2010 (9.7%, p = 0.029). Of the Escherichia coli isolates, 23.0% produced an extended spectrum β-lactamase (ESBL) in the 2014-2015 survey, which was a significant increase from 9.5% in 2010 (p = 0.011). The geometric mean MICs for ESBL-producing isolates were 0.07 μg/mL for meropenem, 9.51 μg/mL for tazobactam/piperacillin, 0.15 μg/mL for flomoxef, and 1.56 μg/mL for gentamycin. There was a significant increase in the isolation rate of non-fragilis Bacteroides among Bacteroides fragilis group species between the two study periods (35.2% vs. 53.1%, p = 0.007). More than 90% of isolates belonging to the B. fragilis group remained susceptible to tazobactam/piperacillin, meropenem, and metronidazole. In contrast, lower levels of susceptibility were observed for cefmetazole (49.6%), moxifloxacin (61.9%), and clindamycin (46.9%). Non-fragilis Bacteroides isolates had lower rates of antibiotic susceptibility compared with B. fragilis. Overall, the surveillance data clarified trends in antimicrobial susceptibility for organisms commonly associated with SSI.
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Affiliation(s)
- Yoshio Takesue
- The Surveillance Committee of Japanese Society of Chemotherapy (JSC), The Japanese Association for Infectious Disease (JAID) and the Japanese Society for Clinical Microbiology (JSCM), Tokyo, Japan; Hyogo College of Medicine, Hyogo, Japan.
| | - Shinya Kusachi
- The Surveillance Committee of Japanese Society of Chemotherapy (JSC), The Japanese Association for Infectious Disease (JAID) and the Japanese Society for Clinical Microbiology (JSCM), Tokyo, Japan; Department of Surgery, Toho University Medical Center Ohashi, Tokyo, Japan
| | - Hiroshige Mikamo
- The Surveillance Committee of Japanese Society of Chemotherapy (JSC), The Japanese Association for Infectious Disease (JAID) and the Japanese Society for Clinical Microbiology (JSCM), Tokyo, Japan; Aichi Medical University Hospital, Aichi, Japan
| | - Junko Sato
- The Surveillance Committee of Japanese Society of Chemotherapy (JSC), The Japanese Association for Infectious Disease (JAID) and the Japanese Society for Clinical Microbiology (JSCM), Tokyo, Japan
| | - Akira Watanabe
- The Surveillance Committee of Japanese Society of Chemotherapy (JSC), The Japanese Association for Infectious Disease (JAID) and the Japanese Society for Clinical Microbiology (JSCM), Tokyo, Japan
| | - Hiroshi Kiyota
- The Surveillance Committee of Japanese Society of Chemotherapy (JSC), The Japanese Association for Infectious Disease (JAID) and the Japanese Society for Clinical Microbiology (JSCM), Tokyo, Japan
| | - Satoshi Iwata
- The Surveillance Committee of Japanese Society of Chemotherapy (JSC), The Japanese Association for Infectious Disease (JAID) and the Japanese Society for Clinical Microbiology (JSCM), Tokyo, Japan
| | - Mitsuo Kaku
- The Surveillance Committee of Japanese Society of Chemotherapy (JSC), The Japanese Association for Infectious Disease (JAID) and the Japanese Society for Clinical Microbiology (JSCM), Tokyo, Japan
| | | | - Yoshinobu Sumiyama
- Japan Society for Surgical Infection, Tokyo, Japan; Department of Surgery, Toho University Medical Center Ohashi, Tokyo, Japan
| | - Yuko Kitagawa
- Japan Society for Surgical Infection, Tokyo, Japan; Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Toru Mizuguchi
- Department of Surgery, Surgical Oncology & Science Sapporo Medical University, Hokkaido, Japan
| | - Yoshiyasu Ambo
- Department of Surgery, Teine Keijinkai Hospital, Hokkaido, Japan
| | | | - Keiichiro Ishibashi
- Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan
| | - Akihisa Matsuda
- Department of Surgery, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan
| | - Kazuo Hase
- National Defense Medical College, Saitama, Japan
| | | | - Koji Okabayashi
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Shiko Seki
- Department of Surgery, National Hospital Organization Tokyo Medical Center, Tokyo, Japan
| | - Takuo Hara
- Department of Surgery, Kouseiren Takaoka Hospital, Toyama, Japan
| | - Koshi Matsui
- Department of Surgery and Science, University of Toyama, Toyama, Japan
| | - Yoichi Matsuo
- Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan
| | - Minako Kobayashi
- Department of Innovative Surgery, Mie University Graduate School of Medicine, Mie, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Kazuhisa Uchiyama
- Osaka Medical College, Department of General and Gastroenterological Surgery, Osaka, Japan
| | - Junzo Shimizu
- Department of Surgery, Osaka Rosai Hospital, Osaka, Japan
| | | | - Hiroki Ohge
- Department of Infectious Diseases, Hiroshima University Hospital, Hiroshima, Japan
| | - Shinji Akagi
- Department of Surgery, Mazda Hospital, Mazda Motor Corporation, Hiroshima, Japan
| | | | | | - Katsunori Suzuki
- University of Occupational and Environmental Health, Fukuoka, Japan
| | - Kohji Okamoto
- Department of Surgery, Gastroenterology and Hepatology Center, Kitakyushu City Yahata Hospital, Fukuoka, Japan
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Gudiol C, Royo-Cebrecos C, Tebe C, Abdala E, Akova M, Álvarez R, Maestro-de la Calle G, Cano A, Cervera C, Clemente WT, Martín-Dávila P, Freifeld A, Gómez L, Gottlieb T, Gurguí M, Herrera F, Manzur A, Maschmeyer G, Meije Y, Montejo M, Peghin M, Rodríguez-Baño J, Ruiz-Camps I, Sukiennik TC, Carratalà J. Clinical efficacy of β-lactam/β-lactamase inhibitor combinations for the treatment of bloodstream infection due to extended-spectrum β-lactamase-producing Enterobacteriaceae in haematological patients with neutropaenia: a study protocol for a retrospective observational study (BICAR). BMJ Open 2017; 7:e013268. [PMID: 28115333 PMCID: PMC5278288 DOI: 10.1136/bmjopen-2016-013268] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION Bloodstream infection (BSI) due to extended-spectrum β-lactamase-producing Gram-negative bacilli (ESBL-GNB) is increasing at an alarming pace worldwide. Although β-lactam/β-lactamase inhibitor (BLBLI) combinations have been suggested as an alternative to carbapenems for the treatment of BSI due to these resistant organisms in the general population, their usefulness for the treatment of BSI due to ESBL-GNB in haematological patients with neutropaenia is yet to be elucidated. The aim of the BICAR study is to compare the efficacy of BLBLI combinations with that of carbapenems for the treatment of BSI due to an ESBL-GNB in this population. METHODS AND ANALYSIS A multinational, multicentre, observational retrospective study. Episodes of BSI due to ESBL-GNB occurring in haematological patients and haematopoietic stem cell transplant recipients with neutropaenia from 1 January 2006 to 31 March 2015 will be analysed. The primary end point will be case-fatality rate within 30 days of onset of BSI. The secondary end points will be 7-day and 14-day case-fatality rates, microbiological failure, colonisation/infection by resistant bacteria, superinfection, intensive care unit admission and development of adverse events. SAMPLE SIZE The number of expected episodes of BSI due to ESBL-GNB in the participant centres will be 260 with a ratio of control to experimental participants of 2. ETHICS AND DISSEMINATION The protocol of the study was approved at the first site by the Research Ethics Committee (REC) of Hospital Universitari de Bellvitge. Approval will be also sought from all relevant RECs. Any formal presentation or publication of data from this study will be considered as a joint publication by the participating investigators and will follow the recommendations of the International Committee of Medical Journal Editors (ICMJE). The study has been endorsed by the European Study Group for Bloodstream Infection and Sepsis (ESGBIS) and the European Study Group for Infections in Compromised Hosts (ESGICH).
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Affiliation(s)
- C Gudiol
- Infectious Diseases Department, Bellvitge University Hospital, IDIBELL, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain
- Duran i Reynals Hospital, ICO, L'Hospitalet de Llobregat, Barcelona, Spain
- REIPI (Spanish Network for Research in Infectious Disease), Instituto de Salud Carlos III, Madrid, Spain
| | - C Royo-Cebrecos
- Infectious Diseases Department, Bellvitge University Hospital, IDIBELL, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain
- REIPI (Spanish Network for Research in Infectious Disease), Instituto de Salud Carlos III, Madrid, Spain
| | - C Tebe
- Statistics Advisory Service, Institute of Biomedical Research of Bellvitge, Rovira i Virgili University, L'Hospitalet de Llobregat, Barcelona, Spain
| | - E Abdala
- Faculty of Medicine, Instituto do Câncer do Estado de São Paulo, University of São Paulo, Sao Paulo, Brazil
| | - M Akova
- Hacettepe University School of Medicine, Ankara, Turkey
| | - R Álvarez
- Infectious Diseases Research Group, Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University of Seville/CSIC/University Hospitals Virgen del Rocio and Virgen Macarena, Seville, Spain
| | - G Maestro-de la Calle
- Infectious Diseases Unit, Instituto de Investigación Hospital “12 de Octubre” (i+12), “12 de Octubre” University Hospital; School of Medicine, Universidad Complutense, Madrid, Spain
| | - A Cano
- REIPI (Spanish Network for Research in Infectious Disease), Instituto de Salud Carlos III, Madrid, Spain
- Reina Sofía University Hospital-IMIBIC-UCO, Córdoba, Spain
| | - C Cervera
- University Hospital of Alberta, Edmonton, Alberta, Canada
| | - W T Clemente
- Infectious Disease Consultant, Digestive Transplant Service, Hospital das Clínicas, Universidade FederalMinas Gerais, Brazil
| | - P Martín-Dávila
- Infectious Diseases Department, Ramon y Cajal Hospital, Madrid, Spain
| | - A Freifeld
- Infectious Diseases Section, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - L Gómez
- Department of Internal Medicine, University Hospital Mútua de Terrassa, Barcelona, Spain
| | - T Gottlieb
- Department of Microbiology & Infectious Diseases, Concord Hospital, Concord, New South Wales, Australia
| | - M Gurguí
- Infectious Diseases Unit, Hospital de la Santa Creu i Sant Pau and Instituto de Investigación Biomédica Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - F Herrera
- Infectious Diseases Section, Department of Medicine, Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina
| | - A Manzur
- Infectious Diseases, Hospital Rawson, San Juan, Argentina
| | - G Maschmeyer
- Department of Hematology, Oncology and Palliative Care, Klinikum Ernst von Bergmann, Academic Teaching Hospital of Charité University Medical School, Berlin, Germany
| | - Y Meije
- REIPI (Spanish Network for Research in Infectious Disease), Instituto de Salud Carlos III, Madrid, Spain
- Infectious Disease Unit, Internal Medicine Department, Barcelona Hospital, SCIAS,Barcelona, Spain
| | - M Montejo
- REIPI (Spanish Network for Research in Infectious Disease), Instituto de Salud Carlos III, Madrid, Spain
- Infectious Diseases Unit, Cruces University Hospital, Bilbao, Spain
| | - M Peghin
- Infectious Diseases Division, Santa Maria Misericordia University Hospital, Udine, Italy
| | - J Rodríguez-Baño
- REIPI (Spanish Network for Research in Infectious Disease), Instituto de Salud Carlos III, Madrid, Spain
- Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospitals Virgen Macarena and Virgen del Rocío—IBiS; Department of Medicine, University of Seville, Seville, Spain
| | - I Ruiz-Camps
- REIPI (Spanish Network for Research in Infectious Disease), Instituto de Salud Carlos III, Madrid, Spain
- Infectious Diseases Department, Vall d'Hebrón University Hospital, Barcelona, Spain
| | - T C Sukiennik
- Hospital Santa Casa de Misericórdia de Porto Alegre, Brazil
| | - J Carratalà
- Infectious Diseases Department, Bellvitge University Hospital, IDIBELL, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain
- REIPI (Spanish Network for Research in Infectious Disease), Instituto de Salud Carlos III, Madrid, Spain
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Guet-Revillet H, Tomini E, Emirian A, Join-Lambert O, Lécuyer H, Zahar JR, Jullien V. Piperacillin/tazobactam as an alternative antibiotic therapy to carbapenems in the treatment of urinary tract infections due to extended-spectrum β-lactamase-producing Enterobacteriaceae: an in silico pharmacokinetic study. Int J Antimicrob Agents 2017; 49:62-66. [DOI: 10.1016/j.ijantimicag.2016.09.027] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2016] [Revised: 09/09/2016] [Accepted: 09/19/2016] [Indexed: 11/29/2022]
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Arizpe A, Reveles KR, Patel SD, Aitken SL. Updates in the Management of Cephalosporin-Resistant Gram-Negative Bacteria. Curr Infect Dis Rep 2016; 18:39. [PMID: 27743202 PMCID: PMC11801173 DOI: 10.1007/s11908-016-0552-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Resistance to cephalosporins is now common among Gram-negative bacterial infections, including those caused by the Enterobacteriaceae and Pseudomonas aeruginosa, posing a major threat to public health. As resistance to the traditional drugs of choice for these infections, carbapenems, has also become increasingly common, interest in cefepime and piperacillin-tazobactam as carbapenem-sparing alternatives has increased. Additionally, the availability of the novel β-lactam-β-lactamase inhibitor combinations ceftolozane-tazobactam and ceftazidime-avibactam has added to the antimicrobial armamentarium available to treat these multidrug-resistant infections. Here, we review the recent literature on the use of carbapenem-sparing alternatives and highlight the potential utility of novel antimicrobials.
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Affiliation(s)
- Andre Arizpe
- College of Pharmacy, The University of Texas at Austin, Austin, TX, USA
| | - Kelly R Reveles
- College of Pharmacy, The University of Texas at Austin, Austin, TX, USA
- Pharmacotherapy Education and Research Center, The University of Texas, Health Science Center at San Antonio, San Antonio, TX, USA
| | - Shrina D Patel
- Division of Pharmacy, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0090, Houston, TX, 77030, USA
| | - Samuel L Aitken
- Division of Pharmacy, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0090, Houston, TX, 77030, USA.
- Center for Antimicrobial Resistance and Microbial Genomics, UTHealth McGovern School of Medicine, Houston, TX, USA.
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48
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Fiore M. Nosocomial spontaneous bacterial peritonitis: discussing a specific infection treatment algorithm. Liver Int 2016; 36:1074-5. [PMID: 26787136 DOI: 10.1111/liv.13072] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- Marco Fiore
- Department of Anesthesiological, Surgical and Emergency Sciences, Second University of Naples, Naples, Italy.
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A Multinational, Preregistered Cohort Study of β-Lactam/β-Lactamase Inhibitor Combinations for Treatment of Bloodstream Infections Due to Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae. Antimicrob Agents Chemother 2016; 60:4159-69. [PMID: 27139473 DOI: 10.1128/aac.00365-16] [Citation(s) in RCA: 121] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Accepted: 04/24/2016] [Indexed: 12/13/2022] Open
Abstract
The spread of extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is leading to increased carbapenem consumption. Alternatives to carbapenems need to be investigated. We investigated whether β-lactam/β-lactamase inhibitor (BLBLI) combinations are as effective as carbapenems in the treatment of bloodstream infections (BSI) due to ESBL-E. A multinational, retrospective cohort study was performed. Patients with monomicrobial BSI due to ESBL-E were studied; specific criteria were applied for inclusion of patients in the empirical-therapy (ET) cohort (ETC; 365 patients), targeted-therapy (TT) cohort (TTC; 601 patients), and global cohort (GC; 627 patients). The main outcome variables were cure/improvement rate at day 14 and all-cause 30-day mortality. Multivariate analysis, propensity scores (PS), and sensitivity analyses were used to control for confounding. The cure/improvement rates with BLBLIs and carbapenems were 80.0% and 78.9% in the ETC and 90.2% and 85.5% in the TTC, respectively. The 30-day mortality rates were 17.6% and 20% in the ETC and 9.8% and 13.9% in the TTC, respectively. The adjusted odds ratio (OR) (95% confidence interval [CI]) values for cure/improvement rate with ET with BLBLIs were 1.37 (0.69 to 2.76); for TT, they were 1.61 (0.58 to 4.86). Regarding 30-day mortality, the adjusted OR (95% CI) values were 0.55 (0.25 to 1.18) for ET and 0.59 (0.19 to 1.71) for TT. The results were consistent in all subgroups studied, in a stratified analysis according to quartiles of PS, in PS-matched cases, and in the GC. BLBLIs, if active in vitro, appear to be as effective as carbapenems for ET and TT of BSI due to ESLB-E regardless of the source and specific species. These data may help to avoid the overuse of carbapenems. (This study has been registered at ClinicalTrials.gov under registration no. NCT01764490.).
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50
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D'Angelo RG, Johnson JK, Bork JT, Heil EL. Treatment options for extended-spectrum beta-lactamase (ESBL) and AmpC-producing bacteria. Expert Opin Pharmacother 2016; 17:953-67. [PMID: 26891857 DOI: 10.1517/14656566.2016.1154538] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
INTRODUCTION Extended spectrum β-lactamases (ESBL) and AmpC β-lactamases are increasing causes of resistance in many Gram-negative pathogens of common infections. This has led to a growing utilization of broad spectrum antibiotics, most predominately the carbapenem agents. As the prevalence of ESBL and AmpC-producing isolates and carbapenem resistance has increased, interest in effective alternatives for the management of these infections has also developed. AREAS COVERED This article summarizes clinical literature evaluating the utility of carbapenem-sparing regimens for the treatment of ESBL and AmpC-producing Enterobacteriaceae, mainly β-lactam-β-lactamase inhibitor combinations and cefepime (FEP). EXPERT OPINION Based on available data, the use of piperacillin-tazobactam (PTZ) and FEP in the treatment of ESBL-producing Enterobacteriaceae cannot be widely recommended. However, certain infections and patient characteristics may support for effective use of these alternative agents. In the treatment of infections caused by AmpC-producing Enterobacteriaceae, FEP has been shown to be a clinically useful carbapenem-sparing alternative. Carbapenems and FEP share many structurally similar characteristics in regards to susceptibility to AmpC β-lactamases, which further create confidence in the use FEP in these situations. Patient and infection specific characteristics should be used to employ FEP optimally.
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Affiliation(s)
- Ryan G D'Angelo
- a PGY-2 Pharmacotherapy Resident , University of Maryland School of Pharmacy , Baltimore , MD , USA
| | - Jennifer K Johnson
- b Departments of Pathology and Epidemiology and Public Health , University of Maryland School of Medicine and Microbiology and Virology Laboratories, University of Maryland Medical Center , Baltimore , MD , USA
| | - Jacqueline T Bork
- c Department of Medicine and Infectious Diseases , The Johns Hopkins Hospital , Baltimore , MD , USA
| | - Emily L Heil
- d Department of Pharmacy , University of Maryland Medical Center , Baltimore , MD , USA
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