1
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Saito T, Sato Y, Yamamoto S. Antimicrobial Combinations as Novel Indicators for Clostridioides difficile infection development: Population-Based, Nested Case-Controlled Study in Japan-The Shizuoka Kokuho Database Study. J Infect Chemother 2025; 31:102552. [PMID: 39510444 DOI: 10.1016/j.jiac.2024.11.002] [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: 07/07/2024] [Revised: 10/17/2024] [Accepted: 11/02/2024] [Indexed: 11/15/2024]
Abstract
BACKGROUND Clostridioides difficile is a major cause of antimicrobial-associated colitis. While antimicrobial stewardship has reduced the incidence of C. difficile infection (CDI), managing CDI is challenging because knowledge about preventing it is limited among healthcare professionals. To address this, we examined associations between antimicrobial use and CDI development. METHODS This observational, nested case-controlled study was conducted using the Shizuoka Kokuho Database (SKDB). Individuals with no record of CDI or antimicrobial-associated enterocolitis within 1 year after SKDB enrolment, but who subsequently developed CDI, were included as the Case group. The Control group comprised individuals selected via 1:4 matching sampling without replacement for sex, age, and month of CDI onset. Conditional logistic regression analysis was performed to assess associations between antimicrobial use (number and combination) and CDI development, controlling for matched variables, background factors, and underlying conditions. RESULTS Of the 2,398,393 individuals, 4917 were assigned to the Case group and 19,668 to the Control group. The adjusted odds ratios (ORs) for CDI were 3.65 for one antimicrobial and 8.58, 17.3, and 38.9 for combinations of two, three, or four or more agents (all p < 0.001). Penicillins, fourth-generation cephems, and carbapenems exhibited high ORs. Similar results were observed in certain demographic and comorbidity-free subgroups. Several combinations (penicillins + carbapenems, penicillins + cephems + carbapenems, cephems + fluoroquinolones, and penicillins + cephems + carbapenems) were notably associated with CDI development. CONCLUSION CDI prevalence increased with the number of antimicrobial classes used in combination. Certain types or combinations of antimicrobials may increase the OR for CDI.
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Affiliation(s)
- Takashi Saito
- Graduate School of Public Health, Shizuoka Graduate University of Public Health, Kita Ando 4-27-2, Aoi Ward, Shizuoka city, Shizuoka, 420-0881, Japan; Department of General Internal Medicine, Seirei Hamamatsu General Hospital, Sumiyoshi 2-12-12, Chuo Ward, Hamamatsu City, Shizuoka, 430-8558, Japan.
| | - Yoko Sato
- Graduate School of Public Health, Shizuoka Graduate University of Public Health, Kita Ando 4-27-2, Aoi Ward, Shizuoka city, Shizuoka, 420-0881, Japan
| | - Seiichiro Yamamoto
- Graduate School of Public Health, Shizuoka Graduate University of Public Health, Kita Ando 4-27-2, Aoi Ward, Shizuoka city, Shizuoka, 420-0881, Japan
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2
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Wang S, Heuler J, Bullock J, Qin J, Chakraborty S, Nathaniel AL, Wang S, Sun X. Cell Wall Protein 2 as a Vaccine Candidate Protects Mice Against Clostridioides difficile Infection. Vaccines (Basel) 2024; 13:21. [PMID: 39852800 PMCID: PMC11768939 DOI: 10.3390/vaccines13010021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 12/22/2024] [Accepted: 12/23/2024] [Indexed: 01/26/2025] Open
Abstract
BACKGROUND/OBJECTIVES Clostridioides difficile is a Gram-positive, spore-forming enteric pathogen that causes intestinal disorders, including inflammation and diarrhea, primarily through toxin production. Standard treatment options for C. difficile infection (CDI) involve a limited selection of antibiotics that are not fully effective, leading to high recurrence rates. Vaccination presents a promising strategy for preventing both CDI and its recurrence. Cell wall protein 2 (Cwp2), a highly immunogenic and abundant surface-exposed C. difficile cell wall protein, plays an important role in the bacterium's adherence in vitro. In this study, we aimed to analyze the homology and immunogenicity of Cwp2 and its protection efficacy as a vaccine candidate against CDI in mice. METHODS we conducted in silico analyses to assess the homology and immunogenicity of Cwp2, and we evaluated its potential as a vaccine candidate against CDI using a mouse model of immunization and infection. RESULTS Our in silico analyses predicted the immunogenic region (functional domain) of Cwp2 and revealed its high homology among various toxinotypes and ribotypes (R.T.s) or sequence types (S.T.s). Immunizations of mice with the Cwp2 functional domain (Cwp2_A) induced potent IgG/A antibody responses against Cwp2_A, protected mice from CDI, and reduced C. difficile spore and toxin levels in feces post-infection. Additionally, anti-Cwp2_A sera inhibited the binding of C. difficile vegetative cells to HCT8 cells. CONCLUSIONS Our report demonstrates for the first time the potential of Cwp2_A as an effective vaccine candidate against CDI in mice.
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Affiliation(s)
- Shaohui Wang
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33620, USA
| | - Joshua Heuler
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33620, USA
| | - Jessica Bullock
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33620, USA
| | - Junling Qin
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33620, USA
| | - Soumyadeep Chakraborty
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33620, USA
| | - Agbendeh Lubem Nathaniel
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33620, USA
- Department of Chemistry, University of South Florida, Tampa, FL 33620, USA
| | - Shifeng Wang
- Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 33620, USA
| | - Xingmin Sun
- Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33620, USA
- Department of Chemistry, University of South Florida, Tampa, FL 33620, USA
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3
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Lee A, Yoo JS, Yoon EJ. Gut Microbiota and New Microbiome-Targeted Drugs for Clostridioides difficile Infections. Antibiotics (Basel) 2024; 13:995. [PMID: 39452261 PMCID: PMC11505460 DOI: 10.3390/antibiotics13100995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 10/16/2024] [Accepted: 10/18/2024] [Indexed: 10/26/2024] Open
Abstract
Clostridioides difficile is a major causative pathogen for antibiotic-associated diarrhea and C. difficile infections (CDIs) may lead to life-threatening diseases in clinical settings. Most of the risk factors for the incidence of CDIs, i.e., antibiotic use, treatment by proton pump inhibitors, old age, and hospitalization, are associated with dysbiosis of gut microbiota and associated metabolites and, consequently, treatment options for CDIs include normalizing the composition of the intestinal microbiome. In this review, with an introduction to the CDI and its global epidemiology, CDI-associated traits of the gut microbiome and its metabolites were reviewed, and microbiome-targeting treatment options were introduced, which was approved recently as a new drug by the United States Food and Drug Administration (U.S. FDA), rather than a medical practice.
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Affiliation(s)
| | | | - Eun-Jeong Yoon
- Division of Antimicrobial Resistance Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju-si 28159, Republic of Korea
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4
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Okpala OE, Rondevaldova J, Osei-Owusu H, Kudera T, Kokoskova T, Kokoska L. Susceptibility of Staphylococcus aureus to Anti-Inflammatory Drugs with a Focus on the Combinatory Effect of Celecoxib with Oxacillin In Vitro. Molecules 2024; 29:3665. [PMID: 39125072 PMCID: PMC11314137 DOI: 10.3390/molecules29153665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 07/26/2024] [Accepted: 07/30/2024] [Indexed: 08/12/2024] Open
Abstract
Musculoskeletal infections (MIs) are among the most difficult-to-treat staphylococcal diseases due to antibiotic resistance. This has encouraged the development of innovative strategies, such as combination therapy, to combat MI. The aim of this study was to investigate the in vitro antistaphylococcal activity of anti-inflammatory drugs and the combined antimicrobial effect of celecoxib and oxacillin. The minimum inhibitory concentrations (MICs) of 17 anti-inflammatory drugs against standard strains and clinical isolates of S. aureus, including methicillin-resistant strains (MRSAs), were determined using the broth microdilution method. The fractional inhibitory concentration indices (FICIs) were evaluated using checkerboard assays. Celecoxib produced the most potent antistaphylococcal effect against all tested strains (MICs ranging from 32 to 64 mg/L), followed by that of diacerein against MRSA3 and MRSA ATCC 33592 (MIC 64 mg/L). Several synergistic effects were observed against the tested S. aureus strains, including MRSA (FICI ranging from 0.087 to 0.471). The strongest synergistic interaction (FICI 0.087) was against MRSA ATCC 33592 at a celecoxib concentration of 2 mg/L, with a 19-fold oxacillin MIC reduction (from 512 to 26.888 mg/L). This is the first report on the combined antistaphylococcal effect of celecoxib and oxacillin. These findings suggest celecoxib and its combination with oxacillin as perspective agents for research focused on the development of novel therapies for MI caused by S. aureus. This study further indicates that celecoxib could resensitize certain MRSA strains, in some cases, to be susceptible to β-lactams (e.g., oxacillin) that were not previously tested. It is essential to mention that the in vitro concentrations of anti-inflammatory drugs are higher than those typically obtained in patients. Therefore, an alternative option for its administration could be the use of a drug delivery system for the controlled slow release from an implant at the infection site.
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Affiliation(s)
- Onyedika Emmanuel Okpala
- Department of Crop Sciences and Agroforestry, Faculty of Tropical AgriSciences, Czech University of Life Sciences Prague, Kamycka 129, Suchdol, 165 00 Prague, Czech Republic; (O.E.O.); (J.R.); (H.O.-O.)
| | - Johana Rondevaldova
- Department of Crop Sciences and Agroforestry, Faculty of Tropical AgriSciences, Czech University of Life Sciences Prague, Kamycka 129, Suchdol, 165 00 Prague, Czech Republic; (O.E.O.); (J.R.); (H.O.-O.)
| | - Hayford Osei-Owusu
- Department of Crop Sciences and Agroforestry, Faculty of Tropical AgriSciences, Czech University of Life Sciences Prague, Kamycka 129, Suchdol, 165 00 Prague, Czech Republic; (O.E.O.); (J.R.); (H.O.-O.)
| | - Tomas Kudera
- Drift-Food Research Centre, Faculty of Agrobiology, Food and Natural Resources, Czech University of Life Sciences Prague, Kamycka 129, Suchdol, 165 00 Prague, Czech Republic;
| | - Tersia Kokoskova
- Department of Animal Science and Food Processing, Faculty of Tropical AgriSciences, Czech University of Life Sciences Prague, Kamycka 129, Suchdol, 165 00 Prague, Czech Republic;
| | - Ladislav Kokoska
- Department of Crop Sciences and Agroforestry, Faculty of Tropical AgriSciences, Czech University of Life Sciences Prague, Kamycka 129, Suchdol, 165 00 Prague, Czech Republic; (O.E.O.); (J.R.); (H.O.-O.)
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5
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Zaidi SMH, Haider R, Kazmi SAB, Husnain A, Khan S, Merchant S, Tayyab H, Wazeen FR, Chaudhary AJ. Beyond Antibiotics: Novel Approaches in the Treatment of Recurrent Clostridioides difficile Infection. ACG Case Rep J 2024; 11:e01333. [PMID: 39081300 PMCID: PMC11286250 DOI: 10.14309/crj.0000000000001333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Accepted: 03/06/2024] [Indexed: 08/02/2024] Open
Affiliation(s)
| | - Ramsha Haider
- Karachi Medical and Dental College, Karachi, Pakistan
| | | | - Ali Husnain
- Department of Medicine, King Edward Medical University, Lahore, Pakistan
| | - Saniah Khan
- Department of Medicine, King Edward Medical University, Lahore, Pakistan
| | | | - Hamnah Tayyab
- Department of Medicine, King Edward Medical University, Lahore, Pakistan
| | - Fazl Rahim Wazeen
- Department of Medicine, Greater Baltimore Medical Center, Towson, MD
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Kwon JH, Nickel KB, Reske KA, Stwalley D, Lyons PG, Michelson A, McMullen K, Sahrmann JM, Gandra S, Olsen MA, Dubberke ER, Burnham JP. Risk factors for hospital-onset Clostridioides difficile infections before and during the severe acute respiratory syndrome coronavirus 2 pandemic. Am J Infect Control 2023; 51:1285-1287. [PMID: 37263419 PMCID: PMC10228158 DOI: 10.1016/j.ajic.2023.05.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 05/23/2023] [Accepted: 05/25/2023] [Indexed: 06/03/2023]
Abstract
In this retrospective cohort from 3 Missouri hospitals from January 2017 to August 2020, hospital-onset Clostridioides difficile infections were more common during the severe acute respiratory syndrome coronavirus 2 pandemic at the tertiary care hospital. Risk factors associated with hospital-onset C difficile infection included the year of hospitalization, age, high-risk antibiotic use, acid-reducing medications, chronic comorbidities, and severe acute respiratory syndrome coronavirus 2 infection.
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Affiliation(s)
- Jennie H Kwon
- Division of Infectious Diseases, Washington University in St. Louis School of Medicine, St. Louis, MO
| | - Katelin B Nickel
- Division of Infectious Diseases, Washington University in St. Louis School of Medicine, St. Louis, MO
| | - Kimberly A Reske
- Division of Infectious Diseases, Washington University in St. Louis School of Medicine, St. Louis, MO
| | - Dustin Stwalley
- Division of Infectious Diseases, Washington University in St. Louis School of Medicine, St. Louis, MO
| | - Patrick G Lyons
- Division of Pulmonary and Critical Care Medicine, Washington University in St. Louis School of Medicine, St. Louis, MO
| | - Andrew Michelson
- Division of Pulmonary and Critical Care Medicine, Washington University in St. Louis School of Medicine, St. Louis, MO
| | | | - John M Sahrmann
- Division of Infectious Diseases, Washington University in St. Louis School of Medicine, St. Louis, MO
| | - Sumanth Gandra
- Division of Infectious Diseases, Washington University in St. Louis School of Medicine, St. Louis, MO
| | - Margaret A Olsen
- Division of Infectious Diseases, Washington University in St. Louis School of Medicine, St. Louis, MO
| | - Erik R Dubberke
- Division of Infectious Diseases, Washington University in St. Louis School of Medicine, St. Louis, MO
| | - Jason P Burnham
- Division of Infectious Diseases, Washington University in St. Louis School of Medicine, St. Louis, MO.
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7
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Shah PJ, Halawi H, Kay J, Akogun A, Wise S, Aly S, Daoura N, Putney D. A Single-Center, Retrospective Cohort Study Evaluating the Use of Probiotics for the Prevention of Hospital-Onset Clostridioides difficile Infection in Hospitalized Patients Receiving Intravenous Antibiotics. Hosp Pharm 2023; 58:57-61. [PMID: 36644740 PMCID: PMC9837316 DOI: 10.1177/00185787221120153] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Background Exposure to antimicrobials is a known risk factor for Clostridioides difficile infection (CDI). Antimicrobials cause collateral damage by disrupting the natural intestinal microbiota allowing for C. difficile to thrive and production of C. difficile toxins. Probiotics could modulate the onset and course of CDI. However, the data on probiotics for the prevention of CDI is conflicting. Objective To evaluate the rates of hospital-onset Clostridioides difficile infection (HO-CDI) among patients who received intravenous (IV) antibiotics plus probiotics versus IV antibiotics alone. Design Retrospective, single-center cohort study. Methods We included adult patients that received at least 1 dose of IV antibiotics and had a hospital length of stay of at least 3 days between August 2017 and July 2020. Patients were separated into 2 cohorts, either receipt of probiotics or non-receipt of probiotics. Patients with positive C. difficile toxin test prior to antibiotic therapy, or receipt of only C. difficile active treatment were excluded. The primary outcome was incidence of HO-CDI in patients who received IV antibiotics plus probiotics compared to those that received IV antibiotics alone. Logistic regression was performed to account for confounding variables. Results We identified 17 598 patients that received IV antibiotics alone and 2659 patients received IV antibiotics plus probiotics. HO-CDI occurred in 46 (0.26%) of those that received antibiotics alone compared to 5 (0.19%) of those that received probiotics with IV antibiotics (OR 0.72, 95% CI 0.28-1.81). ICU admission (OR 1.81, 95% CI 1.02-3.19) and history of CDI (OR 3.37, 95% CI 1.07-10.97) in the past 12 months were associated with a higher incidence of HO-CDI. Conclusion The addition of probiotics did not reduce the incidence of HO-CDI among inpatients receiving IV antibiotics.
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Affiliation(s)
| | - Hala Halawi
- Houston Methodist Hospital, Houston, TX, USA
| | - Jessica Kay
- Houston Methodist Sugar Land Hospital, Sugar Land, TX, USA
| | - Adanma Akogun
- Houston Methodist Sugar Land Hospital, Sugar Land, TX, USA
| | - Silvia Wise
- Houston Methodist Sugar Land Hospital, Sugar Land, TX, USA
| | - Sarfraz Aly
- Houston Methodist Sugar Land Hospital, Sugar Land, TX, USA
| | - Nicolas Daoura
- Houston Methodist Sugar Land Hospital, Sugar Land, TX, USA
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8
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Stavroulaki EM, Suchodolski JS, Xenoulis PG. Effects of antimicrobials on the gastrointestinal microbiota of dogs and cats. Vet J 2023; 291:105929. [PMID: 36427604 DOI: 10.1016/j.tvjl.2022.105929] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 11/12/2022] [Accepted: 11/21/2022] [Indexed: 11/25/2022]
Abstract
Among several environmental factors, exposure to antimicrobials has been in the spotlight as a cause of profound and long-term disturbance of the intestinal microbiota. Antimicrobial-induced dysbiosis is a general term and includes decreases in microbial richness and diversity, loss of beneficial bacterial groups, blooms of intestinal pathogens and alterations in the metabolic functions and end-products of the microbiota. Mounting evidence from human and experimental animal studies suggest an association between antimicrobial-induced dysbiosis and susceptibility to gastrointestinal, metabolic, endocrine, immune and neuropsychiatric diseases. These associations are commonly stronger after early life exposure to antimicrobials, a period during which maturation of the microbiota and immune system take place in parallel. In addition, these associations commonly become stronger as the number of antimicrobial courses increases. The repeatability of these findings among different studies as well as the presence of a dose-dependent relationship between antimicrobial exposure and disease development collectively require careful consideration of the need for antimicrobial use. There are limited studies are available in dogs and cats regarding the long-term effects of antimicrobials on the microbiota and subsequent susceptibility to diseases. This review discusses the effects of antimicrobials on the gastrointestinal microbiota and the most important associations between antimicrobial-induced dysbiosis and diseases in humans, dogs, and cats.
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Affiliation(s)
- Evangelia M Stavroulaki
- Clinic of Medicine, Faculty of Veterinary Science, University of Thessaly, Karditsa 43131, Greece.
| | - Jan S Suchodolski
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station 77845, TX, USA
| | - Panagiotis G Xenoulis
- Clinic of Medicine, Faculty of Veterinary Science, University of Thessaly, Karditsa 43131, Greece; Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station 77845, TX, USA
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9
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Tashiro S, Mihara T, Sasaki M, Shimamura C, Shimamura R, Suzuki S, Yoshikawa M, Hasegawa T, Enoki Y, Taguchi K, Matsumoto K, Ohge H, Suzuki H, Nakamura A, Mori N, Morinaga Y, Yamagishi Y, Yoshizawa S, Yanagihara K, Mikamo H, Kunishima H. Oral fidaxomicin versus vancomycin for the treatment of Clostridioides difficile infection: A systematic review and meta-analysis of randomized controlled trials. J Infect Chemother 2022; 28:1536-1545. [PMID: 35964806 DOI: 10.1016/j.jiac.2022.08.008] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 07/27/2022] [Accepted: 08/04/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Fidaxomicin (FDX) has received considerable attention as a novel therapeutic alternative agent to vancomycin (VCM) for Clostridioides difficile infection (CDI). However, the superiority and efficacy profile of FDX are not sufficiently determined by high-quality evidence. This study aimed to clarify the superiority of FDX for CDI treatment through a systematic review and meta-analysis. METHODS We conducted a meta-analysis of randomized controlled trials (RCTs) which evaluated the efficacy and safety of FDX and VCM in patients with CDI. Electronic databases (PubMed, Cochrane Library, Web of Science, and Clinicaltrials.gov) were searched for studies published until October 15, 2021. The primary endpoint was global cure. The secondary endpoints were clinical cure, recurrence, and adverse event. Risk ratios (RRs), risk differences (RDs), and 95% confidence intervals were calculated using Mantel-Haenszel random-effects model. The risk of bias was assessed using Cochrane Handbook for Systematic Reviews of Interventions and Assessment Criteria. RESULTS Six RCTs were included in this meta-analysis. Compared to VCM, FDX was associated with significantly higher global cure rates (RR = 1.18, P < 0.00001; RD = 0.11, 95% CI = 0.07-0.16). In addition, clinical cure rates were comparable between FDX and VCM (P = 0.31). FDX was associated with significantly lower recurrence rates compared to VCM (RR = 0.59, P < 0.0001). In addition, adverse event rates were not significantly different between the drugs (P = 0.41). CONCLUSION FDX achieves significantly higher global cure rates and lower recurrence rates and is comparable to VCM in clinical cure rates and adverse event rates in patients with CDI. Collectively, FDX is superior to VCM as a therapeutic agent for CDI.
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Affiliation(s)
- Sho Tashiro
- Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, Japan
| | - Takayuki Mihara
- Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, Japan
| | - Moe Sasaki
- Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, Japan
| | - Chiaki Shimamura
- Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, Japan
| | - Rina Shimamura
- Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, Japan
| | - Shiho Suzuki
- Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, Japan
| | - Maiko Yoshikawa
- Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, Japan
| | - Tatsuki Hasegawa
- Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, Japan
| | - Yuki Enoki
- Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, Japan.
| | - Kazuaki Taguchi
- Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, Japan
| | - Kazuaki Matsumoto
- Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, Japan
| | - Hiroki Ohge
- Department of Infectious Diseases, Hiroshima University Hospital, Hiroshima, Japan
| | - Hiromichi Suzuki
- Department of Infectious Diseases, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Atsushi Nakamura
- Department of Infection Prevention and Control, Graduate School of Medical Sciences, Nagoya City University, Aichi, Japan
| | - Nobuaki Mori
- Department of General Internal Medicine and Infectious Diseases, National Hospital Organization Tokyo Medical Center, Tokyo, Japan
| | - Yoshitomo Morinaga
- Department of Microbiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan
| | - Yuka Yamagishi
- Department of Clinical Infectious Diseases, Kochi Medical School, Kochi, Japan
| | - Sadako Yoshizawa
- Department of Clinical Laboratory / Department of Microbiology and Infectious Diseases, Toho University Faculty of Medicine, Tokyo, Japan
| | - Katsunori Yanagihara
- Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Hiroshige Mikamo
- Department of Clinical Infectious Diseases, Aichi Medical University Hospital, Aichi, Japan
| | - Hiroyuki Kunishima
- Department of Infectious Diseases, St. Marianna University School of Medicine, Kanagawa, Japan
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10
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Kunishima H, Ohge H, Suzuki H, Nakamura A, Matsumoto K, Mikamo H, Mori N, Morinaga Y, Yanagihara K, Yamagishi Y, Yoshizawa S. Japanese Clinical Practice Guidelines for Management of Clostridioides (Clostridium) difficile infection. J Infect Chemother 2022; 28:1045-1083. [PMID: 35618618 DOI: 10.1016/j.jiac.2021.12.011] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 11/16/2021] [Accepted: 12/13/2021] [Indexed: 12/19/2022]
Affiliation(s)
- Hiroyuki Kunishima
- Department of Infectious Diseases, St. Marianna University School of Medicine, Japan.
| | - Hiroki Ohge
- Department of Infectious Diseases, Hiroshima University Hospital, Japan
| | - Hiromichi Suzuki
- Division of Infectious Diseases, Department of Medicine, Tsukuba Medical Center Hospital, Japan
| | - Atsushi Nakamura
- Division of Infection Control and Prevention, Nagoya City University Hospital, Japan
| | - Kazuaki Matsumoto
- Division of Pharmacodynamics, Faculty of Pharmacy, Keio University, Japan
| | - Hiroshige Mikamo
- Clinical Infectious Diseases, Graduate School of Medicine, Aichi Medical University, Japan
| | - Nobuaki Mori
- Division of General Internal Medicine and Infectious Diseases, National Hospital Organization Tokyo Medical Center, Japan
| | - Yoshitomo Morinaga
- Department of Microbiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan
| | - Katsunori Yanagihara
- Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Japan
| | - Yuka Yamagishi
- Clinical Infectious Diseases, Graduate School of Medicine, Aichi Medical University, Japan
| | - Sadako Yoshizawa
- Department of Clinical Laboratory/Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Japan
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11
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Karbalaei M, Keikha M. Antimicrobial stewardship for surgeons; the urgent need for new directions - Correspondence. Int J Surg 2022; 104:106758. [PMID: 35809848 DOI: 10.1016/j.ijsu.2022.106758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Accepted: 07/02/2022] [Indexed: 11/28/2022]
Affiliation(s)
- Mohsen Karbalaei
- Department of Microbiology and Virology, Faculty of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran
| | - Masoud Keikha
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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12
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O'Donnell MM, Hegarty JW, Healy B, Schulz S, Walsh CJ, Hill C, Ross RP, Rea MC, Farquhar R, Chesnel L. Identification of ADS024, a newly characterized strain of Bacillus velezensis with direct Clostridiodes difficile killing and toxin degradation bio-activities. Sci Rep 2022; 12:9283. [PMID: 35662257 PMCID: PMC9166764 DOI: 10.1038/s41598-022-13248-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 05/23/2022] [Indexed: 12/30/2022] Open
Abstract
Clostridioides difficile infection (CDI) remains a significant health threat worldwide. C. difficile is an opportunistic, toxigenic pathogen that takes advantage of a disrupted gut microbiome to grow and produce signs and symptoms ranging from diarrhea to pseudomembranous colitis. Antibiotics used to treat C. difficile infection are usually broad spectrum and can further disrupt the commensal gut microbiota, leaving patients susceptible to recurrent C. difficile infection. There is a growing need for therapeutic options that can continue to inhibit the outgrowth of C. difficile after antibiotic treatment is completed. Treatments that degrade C. difficile toxins while having minimal collateral impact on gut bacteria are also needed to prevent recurrence. Therapeutic bacteria capable of producing a range of antimicrobial compounds, proteases, and other bioactive metabolites represent a potentially powerful tool for preventing CDI recurrence following resolution of symptoms. Here, we describe the identification and initial characterization of ADS024 (formerly ART24), a novel therapeutic bacterium that can kill C. difficile in vitro with limited impact on other commensal bacteria. In addition to directly killing C. difficile, ADS024 also produces proteases capable of degrading C. difficile toxins, the drivers of symptoms associated with most cases of CDI. ADS024 is in clinical development for the prevention of CDI recurrence as a single-strain live biotherapeutic product, and this initial data set supports further studies aimed at evaluating ADS024 in future human clinical trials.
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Affiliation(s)
| | - James W Hegarty
- Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland
| | - Brian Healy
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Sarah Schulz
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Calum J Walsh
- APC Microbiome Ireland, University College Cork, Cork, Ireland.,Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland
| | - Colin Hill
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - R Paul Ross
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Mary C Rea
- Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland
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Metzendorf NG, Lange LM, Lainer N, Schlüter R, Dittmann S, Paul LS, Troitzsch D, Sievers S. Destination and Specific Impact of Different Bile Acids in the Intestinal Pathogen Clostridioides difficile. Front Microbiol 2022; 13:814692. [PMID: 35401433 PMCID: PMC8989276 DOI: 10.3389/fmicb.2022.814692] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Accepted: 02/09/2022] [Indexed: 01/05/2023] Open
Abstract
The anaerobic bacterium Clostridioides difficile represents one of the most problematic pathogens, especially in hospitals. Dysbiosis has been proven to largely reduce colonization resistance against this intestinal pathogen. The beneficial effect of the microbiota is closely associated with the metabolic activity of intestinal microbes such as the ability to transform primary bile acids into secondary ones. However, the basis and the molecular action of bile acids (BAs) on the pathogen are not well understood. We stressed the pathogen with the four most abundant human bile acids: cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA) and lithocholic acid (LCA). Thin layer chromatography (TLC), confocal laser scanning microscopy (CLSM), and electron microscopy (EM) were employed to track the enrichment and destination of bile acids in the bacterial cell. TLC not only revealed a strong accumulation of LCA in C. difficile, but also indicated changes in the composition of membrane lipids in BA-treated cells. Furthermore, morphological changes induced by BAs were determined, most pronounced in the virtually complete loss of flagella in LCA-stressed cells and a flagella reduction after DCA and CDCA challenge. Quantification of both, protein and RNA of the main flagella component FliC proved the decrease in flagella to originate from a change in gene expression on transcriptional level. Notably, the loss of flagella provoked by LCA did not reduce adhesion ability of C. difficile to Caco-2 cells. Most remarkably, extracellular toxin A levels in the presence of BAs showed a similar pattern as flagella expression. That is, CA did not affect toxin expression, whereas lower secretion of toxin A was determined in cells stressed with LCA, DCA or CDCA. In summary, the various BAs were shown to differentially modify virulence determinants, such as flagella expression, host cell adhesion and toxin synthesis. Our results indicate differences of BAs in cellular localization and impact on membrane composition, which could be a reason of their diverse effects. This study is a starting point in the elucidation of the molecular mechanisms underlying the differences in BA action, which in turn can be vital regarding the outcome of a C. difficile infection.
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Affiliation(s)
| | - Lena Melanie Lange
- Department of Microbial Physiology and Molecular Biology, Institute of Microbiology, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
| | - Nina Lainer
- Department of Microbial Physiology and Molecular Biology, Institute of Microbiology, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
| | - Rabea Schlüter
- Imaging Center of the Department of Biology, University of Greifswald, Greifswald, Germany
| | - Silvia Dittmann
- Department of Microbial Physiology and Molecular Biology, Institute of Microbiology, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
| | - Lena-Sophie Paul
- Department of Microbial Physiology and Molecular Biology, Institute of Microbiology, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
| | - Daniel Troitzsch
- Department of Microbial Physiology and Molecular Biology, Institute of Microbiology, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
| | - Susanne Sievers
- Department of Microbial Physiology and Molecular Biology, Institute of Microbiology, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
- *Correspondence: Susanne Sievers,
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14
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Xiao X, Sarma S, Menegatti S, Crook N, Magness ST, Hall CK. In Silico Identification and Experimental Validation of Peptide-Based Inhibitors Targeting Clostridium difficile Toxin A. ACS Chem Biol 2022; 17:118-128. [PMID: 34965093 DOI: 10.1021/acschembio.1c00743] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Clostridium difficile infection is mediated by two major exotoxins: toxins A (TcdA) and B (TcdB). Inhibiting the biocatalytic activities of these toxins with targeted peptide-based drugs can reduce the risk of C. difficile infection. In this work, we used a computational strategy that integrates a peptide binding design (PepBD) algorithm and explicit-solvent atomistic molecular dynamics simulation to determine promising toxin A-targeting peptides that can recognize and bind to the catalytic site of the TcdA glucosyltransferase domain (GTD). Our simulation results revealed that two out of three in silico discovered peptides, viz. the neutralizing peptides A (NPA) and B (NPB), exhibit lower binding free energies when bound to the TcdA GTD than the phage-display discovered peptide, viz. the reference peptide (RP). These peptides may serve as potential inhibitors against C. difficile infection. The efficacy of the peptides RP, NPA, and NPB to neutralize the cytopathic effects of TcdA was tested in vitro in human jejunum cells. Both phage-display peptide RP and in silico peptide NPA were found to exhibit strong toxin-neutralizing properties, thereby preventing the TcdA toxicity. However, the in silico peptide NPB demonstrates a relatively low efficacy against TcdA.
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Affiliation(s)
- Xingqing Xiao
- Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina 27695, United States
| | - Sudeep Sarma
- Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina 27695, United States
| | - Stefano Menegatti
- Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina 27695, United States
- Biomanufacturing Training and Education Center (BTEC), North Carolina State University, Raleigh, North Carolina 27695, United States
| | - Nathan Crook
- Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina 27695, United States
| | - Scott T Magness
- Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514, United States
| | - Carol K Hall
- Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina 27695, United States
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15
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Jenior ML, Leslie JL, Powers DA, Garrett EM, Walker KA, Dickenson ME, Petri WA, Tamayo R, Papin JA. Novel Drivers of Virulence in Clostridioides difficile Identified via Context-Specific Metabolic Network Analysis. mSystems 2021; 6:e0091921. [PMID: 34609164 PMCID: PMC8547418 DOI: 10.1128/msystems.00919-21] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 09/17/2021] [Indexed: 12/20/2022] Open
Abstract
The pathogen Clostridioides difficile causes toxin-mediated diarrhea and is the leading cause of hospital-acquired infection in the United States. Due to growing antibiotic resistance and recurrent infection, targeting C. difficile metabolism presents a new approach to combat this infection. Genome-scale metabolic network reconstructions (GENREs) have been used to identify therapeutic targets and uncover properties that determine cellular behaviors. Thus, we constructed C. difficile GENREs for a hypervirulent isolate (strain [str.] R20291) and a historic strain (str. 630), validating both with in vitro and in vivo data sets. Growth simulations revealed significant correlations with measured carbon source usage (positive predictive value [PPV] ≥ 92.7%), and single-gene deletion analysis showed >89.0% accuracy. Next, we utilized each GENRE to identify metabolic drivers of both sporulation and biofilm formation. Through contextualization of each model using transcriptomes generated from in vitro and infection conditions, we discovered reliance on the pentose phosphate pathway as well as increased usage of cytidine and N-acetylneuraminate when virulence expression is reduced, which was subsequently supported experimentally. Our results highlight the ability of GENREs to identify novel metabolite signals in higher-order phenotypes like bacterial pathogenesis. IMPORTANCE Clostridioides difficile has become the leading single cause of hospital-acquired infections. Numerous studies have demonstrated the importance of specific metabolic pathways in aspects of C. difficile pathophysiology, from initial colonization to regulation of virulence factors. In the past, genome-scale metabolic network reconstruction (GENRE) analysis of bacteria has enabled systematic investigation of the genetic and metabolic properties that contribute to downstream virulence phenotypes. With this in mind, we generated and extensively curated C. difficile GENREs for both a well-studied laboratory strain (str. 630) and a more recently characterized hypervirulent isolate (str. R20291). In silico validation of both GENREs revealed high degrees of agreement with experimental gene essentiality and carbon source utilization data sets. Subsequent exploration of context-specific metabolism during both in vitro growth and infection revealed consistent patterns of metabolism which corresponded with experimentally measured increases in virulence factor expression. Our results support that differential C. difficile virulence is associated with distinct metabolic programs related to use of carbon sources and provide a platform for identification of novel therapeutic targets.
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Affiliation(s)
- Matthew L. Jenior
- Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA
| | - Jhansi L. Leslie
- Department of Medicine, Division of Infectious Diseases & International Health, University of Virginia, Charlottesville, Virginia, USA
| | - Deborah A. Powers
- Department of Biochemistry & Molecular Genetics, University of Virginia, Charlottesville, Virginia, USA
| | - Elizabeth M. Garrett
- Department of Microbiology & Immunology, University of North Carolina Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA
| | - Kimberly A. Walker
- Department of Microbiology & Immunology, University of North Carolina Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA
| | - Mary E. Dickenson
- Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA
| | - William A. Petri
- Department of Medicine, Division of Infectious Diseases & International Health, University of Virginia, Charlottesville, Virginia, USA
- Department of Microbiology, Immunology and Cancer Biology, University of Virginia Health System, Charlottesville, Virginia, USA
- Department of Pathology, University of Virginia Health System, Charlottesville, Virginia, USA
| | - Rita Tamayo
- Department of Microbiology & Immunology, University of North Carolina Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA
| | - Jason A. Papin
- Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA
- Department of Medicine, Division of Infectious Diseases & International Health, University of Virginia, Charlottesville, Virginia, USA
- Department of Biochemistry & Molecular Genetics, University of Virginia, Charlottesville, Virginia, USA
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16
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Pivazyan G, Mualem W, D'Antuono MR, Dowlati E, Nair N, Mueller KB. The Utility of Prolonged Prophylactic Systemic Antibiotics (PPSA) for Subfascial Drains After Degenerative Spine Surgery. Spine (Phila Pa 1976) 2021; 46:E1077-E1082. [PMID: 33710111 DOI: 10.1097/brs.0000000000004031] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
STUDY DESIGN Retrospective cohort study. OBJECTIVE The aim of the current investigation was to evaluate the impact of prolonged prophylactic systemic antibiotics (PPSA) on the development of surgical site infection rate (SSIR) in degenerative spine surgery. SUMMARY OF BACKGROUND DATA Surgical drains are utilized postoperatively in posterior spine surgery to help minimize the risk of seroma formation. Prophylactic antibiotics while drains are in place are frequently used to reduce SSIR, though the practice remains controversial. METHODS We performed a single center, retrospective review of all patients that underwent posterior spinal surgery for cervical and lumbar degenerative pathology over a 3.5 year period (January 2016-July 2019). Patients underwent a traditional open posterior midline procedure with postoperative placement of a subfascial surgical drain. Antibiotics were administered for the duration of the drain (PPSA group) or for 24 hours postoperatively (non-PPSA group). The number of surgical site infections, organism, and Clostridium difficile infections was recorded. RESULTS Three hundred thirty six patients were identified, 168 patients in the PPSA group and 168 in the non-PPSA groups. The overall SSIR was 5.36% (18/336). The SSIR for the non-PPSA and PPSA groups were 7.14% (12/168) and 3.57% (6/168), respectively (P = 0.146). While difference of SSIR between the groups was two-fold, it was not statistically significant. For the non-PPSA and PPSA groups, the SSIR for cervical (5.95% [5/84] vs. 2.38% [2/84], P = 0.443) and lumbar (8.33% [7/84], vs. 4.76% [4/84], P = 0.535) regions were not significantly different. C. difficile cases in the PPSA and non-PPSA groups were 1/168 and 0/168 respectively (P = 1.00). CONCLUSION Our series demonstrate a two-fold reduction of SSI with implementation of PPSA regimen. This benefit was demonstrated separately for both cervical and lumbar regions. Randomized trials and increase in sample size are warranted to elucidate the significance of PPSA in posterior spinal surgery.Level of Evidence: 3.
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Affiliation(s)
- Gnel Pivazyan
- Department of Neurosurgery, Medstar Georgetown University Hospital, Washington, DC
| | - William Mualem
- Georgetown University School of Medicine, Washington, DC
| | | | - Ehsan Dowlati
- Department of Neurosurgery, Medstar Georgetown University Hospital, Washington, DC
| | - Nathan Nair
- Department of Neurosurgery, Medstar Georgetown University Hospital, Washington, DC
| | - Kyle B Mueller
- Department of Neurosurgery, Medstar Georgetown University Hospital, Washington, DC
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17
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Nakarai H, Yamada K, Tonosu J, Abe H, Watanabe K, Yoshida Y, Ohya J, Sato Y, Hara N, Okazaki R, Azuma S, Nakamoto H, Kato S, Oshima Y, Tanaka S, Higashikawa A. The Impact of Cefazolin Shortage on Surgical Site Infection Following Spine Surgery in Japan. Spine (Phila Pa 1976) 2021; 46:923-930. [PMID: 34160370 DOI: 10.1097/brs.0000000000003946] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
STUDY DESIGN Retrospective study using prospectively collected data. OBJECTIVE This study aimed to investigate the effect of alternative antimicrobial prophylaxis agents on surgical site infections (SSIs) after spine surgery. SUMMARY OF BACKGROUND DATA Although the use of alternative antimicrobial prophylaxis agents might have a negative effect on SSI prevention, their association with SSI risk in spine surgery remains unclear. METHODS We used the registry data of consecutive patients undergoing spine surgery from April 2017 to January 2020 in four institutions participating in the University of Tokyo Spine Group. Before March 2019, all institutions used cefazolin for antimicrobial prophylaxis. After March 2019, the institutions used broad-spectrum beta-lactam agents as an alternative due to a cefazolin shortage in Japan. RESULTS Among the 3841 enrolled patients (2289 males), 2024 received cefazolin and 1117 received alternative agents. The risk of reoperation for deep SSI within 30 days of spine surgery was significantly higher in the alternative antimicrobial prophylaxis agent group (adjusted odds ratio [aOR] 1.96; 95% confidence interval [CI], 1.15-3.35; P = 0.014). In subgroup analyses, the SSI risk was significantly higher in the thoracolumbar surgery group (aOR 1.98; 95% CI, 1.06-3.73; P = 0.03). A nonsignificant consistent trend was found in all other subgroups: posterior decompression (aOR 1.91; 95% CI, 0.86-4.21; P = 0.11); posterior fixation (aOR 2.05; 95% CI, 0.99-4.24; P = 0.05); and cervical spine surgery (aOR 2.30; 95% CI, 0.82-6.46; P = 0.11). CONCLUSION Alternative antimicrobial prophylaxis agents increased the risk of reoperation for SSI after spine surgery compared with cefazolin. Our study supports the current practice of using first-generation cephalosporins as first-line antimicrobial prophylaxis agents in spine surgery as recommended in multiple guidelines.Level of Evidence: 3.
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Affiliation(s)
- Hiroyuki Nakarai
- Department of Orthopaedic Surgery, Japan Organization of Occupational Health and Safety, Kanto Rosai Hospital, Kanagawa, Japan
| | - Koji Yamada
- Department of Orthopaedic Surgery, Japan Organization of Occupational Health and Safety, Kanto Rosai Hospital, Kanagawa, Japan
| | - Juichi Tonosu
- Department of Orthopaedic Surgery, Japan Organization of Occupational Health and Safety, Kanto Rosai Hospital, Kanagawa, Japan
| | - Hiroaki Abe
- Department of Orthopaedic Surgery, Japan Organization of Occupational Health and Safety, Kanto Rosai Hospital, Kanagawa, Japan
| | - Kenichi Watanabe
- Department of Orthopaedic Surgery, Japan Organization of Occupational Health and Safety, Kanto Rosai Hospital, Kanagawa, Japan
| | - Yuichi Yoshida
- Department of Orthopaedic Surgery, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Junichi Ohya
- Department of Orthopaedic Surgery, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Yusuke Sato
- Department of Orthopaedic Surgery, Musashino Red Cross Hospital, Tokyo, Japan
| | - Nobuhiro Hara
- Department of Orthopaedic Surgery, Musashino Red Cross Hospital, Tokyo, Japan
| | - Rentaro Okazaki
- Department of Orthopaedic Surgery, Saitama Red Cross Hospital, Saitama, Japan
| | - Seiichi Azuma
- Department of Orthopaedic Surgery, Saitama Red Cross Hospital, Saitama, Japan
| | - Hideki Nakamoto
- Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo Hospital, Tokyo, Japan
| | - So Kato
- Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo Hospital, Tokyo, Japan
| | - Yasushi Oshima
- Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo Hospital, Tokyo, Japan
| | - Sakae Tanaka
- Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo Hospital, Tokyo, Japan
| | - Akiro Higashikawa
- Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo Hospital, Tokyo, Japan
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18
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Sattar AK, Zahid N, Shahzad H, Soomro R, Saleem O, Mahmood SF. Impact of duration of antibiotic prophylaxis on rates of surgical site infection (SSI) in patients undergoing mastectomy without immediate reconstruction, comparing a single prophylactic dose versus continued antibiotic prophylaxis postoperatively: a multicentre, double-blinded randomised control trial protocol. BMJ Open 2021; 11:e049572. [PMID: 34244280 PMCID: PMC8273486 DOI: 10.1136/bmjopen-2021-049572] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 06/11/2021] [Indexed: 12/26/2022] Open
Abstract
INTRODUCTION In breast surgeries, prophylactic antibiotics given before the surgical incision as per Joint Commission Surgical Care Improvement Project guidelines have been shown to decrease the rate of postoperative infections. There is, however, no clear consensus on postoperative antibiotic prophylaxis in patients undergoing mastectomy with indwelling drains. This trial protocol proposes to study the difference in rates of surgical site infection (SSI) with or without continuation of postoperative antibiotics in patients undergoing mastectomy without immediate reconstruction and with indwelling drains. METHODS AND ANALYSIS In this multicentre, double-blinded clinical trial, all patients undergoing mastectomy (without immediate reconstruction) will receive a single prophylactic dose of preoperative antibiotics at induction of anaesthesia and will then get randomised to either continue antibiotic prophylaxis or a placebo postoperatively, for the duration of indwelling drains. The primary and secondary outcomes will be development of an SSI and antibiotic-associated adverse effects, respectively. Data will be collected through a standard questionnaire by wound assessors. Intention-to-treat analysis will be carried out using STATA V.12. For categorical variables, frequencies and percentages will be assessed by χ2 test/Fisher's exact test as appropriate. The quantitative variables will be computed by their mean±SD or median (IQR) and will be assessed by independent t-test/Mann-Whitney test as appropriate. Unadjusted and adjusted relative risk with their 95% CI will be reported using Cox proportional regression. A p value of <0.05 will be considered statistically significant. ETHICS AND DISSEMINATION Ethical approval has been obtained from each site's Ethical Review Board. The study background and procedure will be explained to the study participants and informed consent will be obtained. Participation in the study is voluntary. All data will be deidentified and kept confidential. The study findings will be published in scientific media and authorship guidelines of International Committee of Medical Journal Editors will be followed. TRIAL REGISTRATION NUMBER NCT04577846. (patient recruitment).
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Affiliation(s)
| | - Nida Zahid
- Surgery, Aga Khan University, Karachi, Pakistan
| | | | - Rufina Soomro
- Liaquat National Hospital and Medical College, Karachi, Pakistan
| | - Omema Saleem
- Dow University of Health Sciences, Karachi, Pakistan
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19
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Slimings C, Riley TV. Antibiotics and healthcare facility-associated Clostridioides difficile infection: systematic review and meta-analysis 2020 update. J Antimicrob Chemother 2021; 76:1676-1688. [PMID: 33787887 DOI: 10.1093/jac/dkab091] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 03/01/2021] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Antibiotic use is the most important modifiable risk factor for healthcare facility-associated Clostridioides difficile infection (HCFA-CDI). Previous systematic reviews cover studies published until 31 December 2012. OBJECTIVES To update the evidence for associations between antibiotic classes and HCFA-CDI to 31 December 2020. METHODS PubMed, Scopus, Web of Science Core Collection, WorldCat and Proquest Dissertations & Theses were searched for studies published since 1 January 2013. Eligible studies were those conducted among adult hospital inpatients, measured exposure to individual antibiotics or antibiotic classes, included a comparison group and measured the occurrence of HCFA-CDI as an outcome. The Newcastle-Ottawa Scale was used to appraise study quality. To assess the association between each antibiotic class and HCFA-CDI, a pooled random-effects meta-analysis was undertaken. Meta-regression and subgroup analysis was used to investigate study characteristics identified a priori as potential sources of heterogeneity. RESULTS Carbapenems and third- and fourth-generation cephalosporin antibiotics remain the most strongly associated with HCFA-CDI, with cases more than twice as likely to have recent exposure to these antibiotics prior to developing HCFA-CDI. Modest associations were observed for fluoroquinolones, clindamycin and β-lactamase inhibitor combination penicillin antibiotics. Individual study effect sizes were variable and heterogeneity was observed for most antibiotic classes. CONCLUSIONS This review provides the most up-to-date synthesis of evidence in relation to the risk of HCFA-CDI associated with exposure to specific antibiotic classes. Studies were predominantly conducted in North America or Europe and more studies outside of these settings are needed.
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Affiliation(s)
- Claudia Slimings
- Medical School, College of Health and Medicine, Australian National University, Canberra, Australian Capital Territory, Western Australia
| | - Thomas V Riley
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia.,Department of Microbiology, PathWest Laboratory Medicine, Nedlands, Western Australia
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20
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Mullish BH, Allegretti JR. The contribution of bile acid metabolism to the pathogenesis of Clostridioides difficile infection. Therap Adv Gastroenterol 2021; 14:17562848211017725. [PMID: 34104212 PMCID: PMC8165815 DOI: 10.1177/17562848211017725] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Accepted: 04/26/2021] [Indexed: 02/04/2023] Open
Abstract
Clostridioides difficile infection (CDI) remains a major global cause of gastrointestinal infection, with significant associated morbidity, mortality and impact upon healthcare system resources. Recent antibiotic use is a key risk factor for the condition, with the marked antibiotic-mediated perturbations in gut microbiome diversity and composition that underpin the pathogenesis of CDI being well-recognised. However, only relatively recently has further insight been gained into the specific mechanistic links between these gut microbiome changes and CDI, with alteration of gut microbial metabolites - in particular, bile acid metabolism - being a particular area of focus. A variety of in vitro, ex vivo, animal model and human studies have now demonstrated that loss of gut microbiome members with bile-metabolising capacity (including bile salt hydrolases, and 7-α-dehydroxylase) - with a resulting alteration of the gut bile acid milieu - contributes significantly to the disease process in CDI. More specifically, this microbiome disruption results in the enrichment of primary conjugated bile acids (including taurocholic acid, which promotes the germination of C. difficile spores) and loss of secondary bile acids (which inhibit the growth of C. difficile, and may bind to and limit activity of toxins produced by C. difficile). These bile acid changes are also associated with reduced activity of the farnesoid X receptor pathway, which may exacerbate C. difficile colitis throughout its impact upon gut barrier function and host immune/inflammatory response. Furthermore, a key mechanism of efficacy of faecal microbiota transplant (FMT) in treating recurrent CDI has been shown to be restoration of gut microbiome bile metabolising functionality; ensuring the presence of this functionality among defined microbial communities (and other 'next generation' FMT products) designed to treat CDI may be critical to their success.
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Affiliation(s)
- Benjamin H. Mullish
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | - Jessica R. Allegretti
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, 850 Boylston Street, Suite 201, Chestnut Hill, MA 02467, USA
- Harvard Medical School, Harvard University, Boston, Massachusetts, USA
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21
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Imwattana K, Putsathit P, Knight DR, Kiratisin P, Riley TV. Molecular Characterization of, and Antimicrobial Resistance in, Clostridioides difficile from Thailand, 2017-2018. Microb Drug Resist 2021; 27:1505-1512. [PMID: 33956520 DOI: 10.1089/mdr.2020.0603] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Antimicrobial resistance (AMR) plays an important role in the pathogenesis and spread of Clostridioides difficile infection (CDI). Many antimicrobials, such as fluoroquinolones, have been associated with outbreaks of CDI globally. This study characterized AMR among clinical C. difficile strains in Thailand, where antimicrobial use remains inadequately regulated. Stool samples were screened for tcdB and positives were cultured. C. difficile isolates were characterized by toxin profiling and PCR ribotyping. Antimicrobial susceptibility testing was performed by agar incorporation, and whole-genome sequencing and AMR genotyping were performed on a subset of strains. There were 321 C. difficile strains isolated from 326 stool samples. The most common toxigenic ribotype (RT) was RT 017 (18%), followed by RTs 014 (12%) and 020 (7%). Resistance to clindamycin, erythromycin, moxifloxacin, and rifaximin was common, especially among RT 017 strains. AMR genotyping revealed a strong correlation between resistance genotype and phenotype for moxifloxacin and rifaximin. The presence of erm-class genes was associated with high-level clindamycin and erythromycin resistance. Point substitutions in the penicillin-binding proteins were not sufficient to confer meropenem resistance, but a Y721S substitution in PBP3 was associated with a 4.37-fold increase in meropenem minimal inhibitory concentration. No resistance to metronidazole, vancomycin, or fidaxomicin was observed.
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Affiliation(s)
- Korakrit Imwattana
- School of Biomedical Sciences, The University of Western Australia, Nedlands, Australia.,Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Papanin Putsathit
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, Australia
| | - Daniel R Knight
- School of Biomedical Sciences, The University of Western Australia, Nedlands, Australia.,Medical, Molecular and Forensic Sciences, Murdoch University, Murdoch, Australia
| | | | - Thomas V Riley
- School of Biomedical Sciences, The University of Western Australia, Nedlands, Australia.,School of Medical and Health Sciences, Edith Cowan University, Joondalup, Australia.,Medical, Molecular and Forensic Sciences, Murdoch University, Murdoch, Australia.,Department of Microbiology, PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Nedlands, Australia
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Clostridioides Difficile Infection : A comprehensive review for primary providers. ACTA ACUST UNITED AC 2021; 59:262-269. [PMID: 33713592 DOI: 10.2478/rjim-2021-0010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Indexed: 11/20/2022]
Abstract
Clostridioides Difficile infection (CDI) is an issue of great concern due to its rising incidence, recurrence, morbidity and impact on healthcare spending. Treatment guidelines have changed in the last few years, and new therapies are being considered. This is a practical review for the primary care practitioner of the latest guidelines for CDI diagnosis, treatment and emerging therapies.
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Comparison between the prophylactic effects of amoxicillin 24 and 48 hours pre-operatively on surgical site infections in Japanese patients with impacted mandibular third molars: A prospective cohort study. J Infect Chemother 2021; 27:845-851. [PMID: 33583740 DOI: 10.1016/j.jiac.2021.01.018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Revised: 01/25/2021] [Accepted: 01/28/2021] [Indexed: 01/04/2023]
Abstract
INTRODUCTION According to the guidelines, the dosage for mandibular wisdom tooth extraction (MWTE) varies within the administration period. There is a 24-fold difference between the minimum and maximum doses. If an appropriate antimicrobial can be administered without increasing incidence of surgical site infection (SSI), it may lead to a global action plan on antimicrobial resistance (AMR). Therefore, we prospectively surveyed incidence of SSI post-operatively and use of oral antibiotics (OA) for MWTE. METHODS Subjects were patients who underwent MWTE in our dental outpatient clinic from May 2019 to April 2020. Two groups were formed depending on type of administration period they received: 24 h and 48 h after surgery. The following information was collected: (1) patient factors (age, gender, body mass index, presence/absence of preoperative medication, diagnosis, impacted wisdom tooth status; (2) surgical factors (operative time, presence/absence of closure, presence/absence of hemostat, doctor career, type and frequency of painkiller); (3) relationship between administration period of OA and SSI occurrence; and (4) details of SSI. RESULTS Three hundred forty subjects were analyzed, all of which used amoxicillin. There were 106 cases in 24 h group and 234 cases in 48 h group. The total incidence of SSI was 1.1% (4/340 cases), with 0.9% (1/106 cases) in 24 h group and 1.3% (3/234 cases) in 48 h group; there was no difference between the two groups. CONCLUSION Our study suggests that amoxicillin (250 mg/dose every 8 h x 3 doses beginning 1 h before surgery) might be sufficient in preventing SSI in Japanese dental patients without SSI risk factors.
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Ghia CJ, Waghela S, Rambhad GS. Systematic Literature Review on Burden of Clostridioides difficile Infection in India. CLINICAL PATHOLOGY (THOUSAND OAKS, VENTURA COUNTY, CALIF.) 2021; 14:2632010X211013816. [PMID: 34104883 PMCID: PMC8170333 DOI: 10.1177/2632010x211013816] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 03/26/2021] [Indexed: 01/05/2023]
Abstract
BACKGROUND Owing to limited diagnostic facilities and surveillance protocols, there is a paucity on the prevalence data of Clostridioides difficile infections (CDIs) in developing countries such as India. OBJECTIVE The aims of these studies are (1) to determine the prevalence of CDI in India, (2) to understand the risk factors of CDI, and (3) to determine the impact of different diagnostic methods on reported CDI rates. METHOD A systematic literature search was conducted using PubMed and Google Scholar database to identify Indian studies reporting the prevalence of CDI. A total of 31 studies, published between 1990 and 2020 were included in the final analysis. A chi-square test was used to determine statistically significant association between prevalence rates, accuracy of different diagnosis methods, and antibiotic usage rates of CDI. RESULTS The prevalence of CDI was in the range of 3.4% to 18%, and the difference between regional prevalence of CDI was statistically significant (P < .001). The use of antibiotics, hospital stay, comorbidities, recent surgery, and the use of proton-pump inhibitors was considered as risk factors for the development of CDI. Compared to other regions, the rate of antibiotic usage was significantly higher in North India (P < .001). Among different diagnostic methods, C. difficile detection was significantly higher with enzyme-linked immunosorbent assay (18.02%) versus other multiple testing methods used (P < .001). CONCLUSION There is a significant burden of CDI across the country. Further surveillance studies are required to monitor changes in prevalence of CDI, risk factors, and accuracy of diagnosis methods for a better understanding of the disease burden in India.
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Affiliation(s)
- Canna J Ghia
- Medical and Scientific Affairs, Pfizer Limited,
Mumbai, India
| | - Shaumil Waghela
- Medical and Scientific Affairs, Pfizer Limited,
Mumbai, India
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25
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Kazakova SV, Baggs J, McDonald LC, Yi SH, Hatfield KM, Guh A, Reddy SC, Jernigan JA. Association Between Antibiotic Use and Hospital-onset Clostridioides difficile Infection in US Acute Care Hospitals, 2006-2012: An Ecologic Analysis. Clin Infect Dis 2020; 70:11-18. [PMID: 30820545 DOI: 10.1093/cid/ciz169] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2018] [Accepted: 02/25/2019] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Unnecessary antibiotic use (AU) contributes to increased rates of Clostridioides difficile infection (CDI). The impact of antibiotic restriction on hospital-onset CDI (HO-CDI) has not been assessed in a large group of US acute care hospitals (ACHs). METHODS We examined cross-sectional and temporal associations between rates of hospital-level AU and HO-CDI using data from 549 ACHs. HO-CDI was defined as a discharge with a secondary International Classification of Diseases, Ninth Revision, Clinical Modification code for CDI (008.45), and treatment with metronidazole or oral vancomycin > 3 days after admission. Analyses were performed using multivariable generalized estimating equation models adjusting for patient and hospital characteristics. RESULTS During 2006-2012, the unadjusted annual rates of HO-CDI and total AU were 7.3 per 10 000 patient-days (PD) (95% confidence interval [CI], 7.1-7.5) and 811 days of therapy (DOT)/1000 PD (95% CI, 803-820), respectively. In the cross-sectional analysis, for every 50 DOT/1000 PD increase in total AU, there was a 4.4% increase in HO-CDI. For every 10 DOT/1000 PD increase in use of third- and fourth-generation cephalosporins or carbapenems, there was a 2.1% and 2.9% increase in HO-CDI, respectively. In the time-series analysis, the 6 ACHs with a ≥30% decrease in total AU had a 33% decrease in HO-CDI (rate ratio, 0.67 [95% CI, .47-.96]); ACHs with a ≥20% decrease in fluoroquinolone or third- and fourth-generation cephalosporin use had a corresponding decrease in HO-CDI of 8% and 13%, respectively. CONCLUSIONS At an ecologic level, reductions in total AU, use of fluoroquinolones, and use of third- and fourth-generation cephalosporins were each associated with decreased HO-CDI rates.
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Affiliation(s)
- Sophia V Kazakova
- Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - James Baggs
- Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - L Clifford McDonald
- Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Sarah H Yi
- Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Kelly M Hatfield
- Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Alice Guh
- Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Sujan C Reddy
- Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - John A Jernigan
- Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
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Risk factors for Clostridioides difficile colonization among hospitalized adults: A meta-analysis and systematic review. Infect Control Hosp Epidemiol 2020; 42:565-572. [PMID: 33118886 DOI: 10.1017/ice.2020.1236] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVE To identify risk factors for asymptomatic Clostridioides difficile colonization among hospitalized adults utilizing a meta-analysis, which may enable early identification of colonized patients at risk of spreading C. difficile. DESIGN Meta-analysis and systematic review. METHODS We systematically searched MEDLINE, Scopus, Web of Science, and EMBASE from January 1, 1975, to February 15, 2020, for articles related to C. difficile colonization among hospitalized adults. Studies with multivariable analyses evaluating risk factors for asymptomatic colonization were eligible. RESULTS Among 5,506 studies identified in the search, 19 studies met the inclusion criteria. Included studies reported 20,334 adult patients of whom 1,588 were asymptomatically colonized with C. difficile. Factors associated with an increased risk of colonization were hospitalization in the previous 6 months (OR, 2.18; 95% CI, 1.86-2.56; P < .001), use of gastric acid suppression therapy within the previous 8 weeks (OR, 1.42; 95% CI, 1.17-1.73; P < .001), tube feeding (OR, 2.02; 95% CI, 1.06-3.85; P = .03), and corticosteroid use in the previous 8 weeks (OR, 1.58; 95% CI, 1.14-2.17; P = .006). Receipt of antibiotics in the previous 3 months (OR, 1.37; 95% CI, 0.94-2.01; P = .10) was not associated with statistically significant effects on risk of colonization. CONCLUSIONS C. difficile colonization was significantly associated with previous hospitalization, gastric acid suppression, tube feeding, and corticosteroid use. Recognition of these risk factors may assist in identifying asymptomatic carriers of C. difficile and taking appropriate measures to reduce transmission.
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Kwon HJ, Mohammed AE, Eltom KH, Albrahim JS, Alburae NA. Evaluation of antibiotic-induced behavioral changes in mice. Physiol Behav 2020; 223:113015. [PMID: 32553641 DOI: 10.1016/j.physbeh.2020.113015] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Revised: 06/03/2020] [Accepted: 06/12/2020] [Indexed: 12/20/2022]
Abstract
Gut microbiota (GM) plays a critical role in health maintenance. Previous reports connected GM with metabolic, immunologic and neurologic pathways. The main purpose of the current investigation was to study whether antibiotic-induced disturbances of GM affects psychological or behavioral conditions on mice as animal model. Mice were exposed to clindamycin or amoxicillin, and their behaviors were evaluated. Antibiotic-treated groups displayed reduced recognition memory and increased depression. No significant changes in the locomotor activity and anxiety were observed. Our data suggested that changes in GM composition by antibiotics may lead to the cognitive and behavioral deficit.
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Affiliation(s)
- Hye-Joo Kwon
- Biology Department, Faculty of Science, Princess Nourah bint Abdulrahman University, Riyadh 84428, Saudi Arabia; The University of Utah Asia Campus, Incheon, Korea
| | - Afrah E Mohammed
- Biology Department, Faculty of Science, Princess Nourah bint Abdulrahman University, Riyadh 84428, Saudi Arabia.
| | - Kamal H Eltom
- Unit of Animal Health and Safety of Animal Products, Institute for Studies and Promotion of Animal Exports, University of Khartoum, Shambat Postal Code 13314, Khartoum North, Sudan
| | - Jehan S Albrahim
- Biology Department, Faculty of Science, Princess Nourah bint Abdulrahman University, Riyadh 84428, Saudi Arabia
| | - Najla Ali Alburae
- Department of Biology, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia
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Temporal change of risk factors in hospital-acquired Clostridioides difficile infection using time-trend analysis. Infect Control Hosp Epidemiol 2020; 41:1048-1057. [PMID: 32468975 DOI: 10.1017/ice.2020.206] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
OBJECTIVE Given recent changes in the epidemiology of Clostridioides difficile infection (CDI) and prevention efforts, we investigated temporal changes over a period of 11 years (2006-2016) in incidence and risk factors for CDI. DESIGN Retrospective matched case-control study. SETTING/PATIENTS Pediatric and adult inpatients (n = 694,849) discharged from 3 hospitals (tertiary and quaternary care, community, and pediatric) in a large, academic health center in New York City. METHODS Risk factors were identified in cases and controls matched by length of stay at a ratio of 1:4. A Cochran-Armitage or Mann-Kendall test was used to investigate trends of incidence and risk factors. RESULTS Of 694,849 inpatients, 6,038 (0.87%) had CDI: 44% of these cases were hospital acquired (HA-CDI) and 56% were community acquired (CA-CDI). We observed temporal downward trends in HA-CDI (-0.03% per year) and upward trends in CA-CDI (+0.04% per year). Over time, antibiotics were administered to more patients (+3% per year); the use of high-risk antibiotics declined (-1.2% per year); and antibiotic duration increased in patients with HA-CDI (+4.4% per year). Fewer proton-pump inhibitors and more histamine-2 blockers were used (-3.8% and +7.3% per year, respectively; all Ptrend <.05). CONCLUSIONS Although the incidence of HA-CDI decreased over time, CA-CDI simultaneously increased. Continued efforts to assure judicious use of antibiotics in inpatient and community settings is clearly vital. Measuring the actual the level of exposure of an antibiotic (incidence density) should be used for ongoing surveillance and assessment.
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Impact of implementing a non-restrictive antibiotic stewardship program in an emergency department: a four-year quasi-experimental prospective study. Sci Rep 2020; 10:8194. [PMID: 32424172 PMCID: PMC7235006 DOI: 10.1038/s41598-020-65222-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Accepted: 04/27/2020] [Indexed: 11/08/2022] Open
Abstract
Antibiotic resistance is increasing worldwide. The implementation of antibiotic stewardship programmes (ASPs) is of utmost importance to optimize antibiotic use in order to prevent resistance development without harming patients. The emergency department (ED), cornerstone between hospital and community, represents a crucial setting for addressing ASP implementation; however, evidence data on ASP in ED are poor. In this study, a 4-year, non-restrictive, multi-faceted ASP was implemented in a general ED with the aim to evaluate its impact on antibiotic use and costs. Secondly, the study focused on assessing the impact on length of hospital stay (LOS), Clostridioides difficile infection (CDI) incidence rate, and mortality in the patients' group admitted from ED to medical wards. The ASP implementation was associated with a reduction of antibiotic use and costs. A mild but sustained LOS decrease in all medical wards and a significant downward trend of CDI incidence rate were observed, while mortality did not significantly change. In conclusion, the implementation of our ED-based ASP has demonstrated to be feasible and safe and might clinically benefit the hospital admitted patients' group. Further research is needed to identify the most suitable ASP design for ED and the key outcome measures to reliably assess its effectiveness.
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Nseir WB, Hussein SHH, Farah R, Mahamid MN, Khatib HH, Mograbi JM, Peretz A, Amara AE. Nonalcoholic fatty liver disease as a risk factor for Clostridium difficile-associated diarrhea. QJM 2020; 113:320-323. [PMID: 31688897 DOI: 10.1093/qjmed/hcz283] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Revised: 10/15/2019] [Indexed: 12/25/2022] Open
Abstract
AIMS Clostridium difficile is the most common cause of infectious nosocomial diarrhea among adults in developed countries. Nonalcoholic fatty liver disease (NAFLD) is considered the most common chronic liver disease and it is associated with bacterial infections. Our goal was to assess whether NAFLD considered a risk factor for C. difficile-associated diarrhea (CDAD). METHODS We conducted a retrospective study of patients admitted with CDAD at Baruch Padeh Medical Center, Poria, Israel during a period of four years. Data on demographic characteristics, clinical signs, underlying conditions, presence of fatty liver based on computed tomography/ultrasonography imaging and several risk factors for CDI were collected. The control group included patients with diarrhea who were negative for CDT and had been hospitalized during the same period. The controls were matched for age (±5 years) and gender. RESULTS Totally, 115/164 patients with CDAD met the inclusion criteria. The control group was consisted of 115 hospitalized patients with non-CDAD. The mean age of all the participants (230) was 69.57 ± 18 years. NAFLD was found in 76/115 (66%) patients with CDAD vs. 35/115 (30.4%) in the control group, P < 0.001. Moreover, we found significant associations between CDAD group and metabolic syndrome, prior use of antibiotic in the last 3 months, NAFLD and high serum levels of C-reactive protein. Multivariate analysis showed that NAFLD, odds ratio 1.51, 95% confidence interval 1.2-1.95, P = 0.05 was significantly associated with CDAD. CONCLUSIONS This retrospective study showed that NAFLD is a risk factor for CDAD. Moreover, metabolic syndrome and high serum levels of C-reactive protein were significantly associated with the risk of CDAD.
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Affiliation(s)
- W B Nseir
- Department of Internal Medicine A, Baruch Padeh Medical Center, Poriya
- The Azrieli Faculty of Medicine, Bar-Ilan University, Safed
| | - S H H Hussein
- Department of Internal Medicine A, Baruch Padeh Medical Center, Poriya
| | - R Farah
- The Azrieli Faculty of Medicine, Bar-Ilan University, Safed
- Department of Medicine B, Ziv Medical Center, Safed
| | - M N Mahamid
- The Azrieli Faculty of Medicine, Bar-Ilan University, Safed
- Gastroenterology Unit, Shaare Zedek Medical Center, Jerusalem
| | - H H Khatib
- Department of Internal Medicine A, Baruch Padeh Medical Center, Poriya
| | - J M Mograbi
- Department of Internal Medicine A, Baruch Padeh Medical Center, Poriya
| | - A Peretz
- The Azrieli Faculty of Medicine, Bar-Ilan University, Safed
- Microbiology Laboratory, Baruch Padeh Medical Center, Poriya, Israel
| | - A E Amara
- Department of Internal Medicine A, Baruch Padeh Medical Center, Poriya
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Baker SJ, Chu DI. Physical, Laboratory, Radiographic, and Endoscopic Workup for Clostridium difficile Colitis. Clin Colon Rectal Surg 2020; 33:82-86. [PMID: 32104160 DOI: 10.1055/s-0039-3400474] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Clostridium (reclassified as " Clostridioides ") difficile colitis is a common nosocomial infection associated with increased morbidity and mortality. Like many clinical encounters, a focused history and physical examination will help to guide initial management. Further laboratory testing will assist with diagnosis through stool studies, and blood tests, such as white blood cell counts and serum creatinine, can help to stratify patients into illness severity groups for treatment decisions. Radiographic evaluation can be helpful in patients with severe disease and concern for complicated colitis. Endoscopic evaluation should be carefully considered in patients with suspected mucosal injury secondary to infections and plays a role when an alternative diagnosis is suspected. Treatment options depend on the clinical presentation and can range from antibiotic therapy to emergent surgery to fecal transplantation for recurrent episodes. Care for these patients is often challenging, but through a systemic workup the appropriate treatment may be delivered.
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Affiliation(s)
- Samantha J Baker
- Department of General Surgery, University of Alabama at Birmingham, Birmingham, Alabama
| | - Daniel I Chu
- Department of Gastrointestinal Surgery, University of Alabama at Birmingham, Birmingham, Alabama
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32
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The damage response framework and infection prevention: From concept to bedside. Infect Control Hosp Epidemiol 2020; 41:337-341. [PMID: 31915082 DOI: 10.1017/ice.2019.354] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Hospital-acquired infections remain a common cause of morbidity and mortality despite advances in infection prevention through use of bundles, environmental cleaning, antimicrobial stewardship, and other best practices. Current prevention strategies and further hospital-acquired infection reduction are limited by lack of recognition of the role that host-microbe interactions play in susceptibility and by the inability to analyze multiple risk factors in real time to accurately predict the likelihood of a hospital-acquired infection before it occurs and to inform medical decision making. Herein, we examine the value of incorporating the damage-response framework and host attributes that determine susceptibility to infectious diseases known by the acronym MISTEACHING (ie, microbiome, immunity, sex, temperature, environment, age, chance, history, inoculum, nutrition, genetics) into infection prevention strategies using machine learning to drive decision support and patient-specific interventions.
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Puro N, Joseph R, Zengul FD, Cochran KJ, Camins BC, Ray M. Predictors of Hospital-Acquired Clostridioides difficile Infection: A Systematic Review. J Healthc Qual 2020; 42:127-135. [PMID: 31821178 DOI: 10.1097/jhq.0000000000000236] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Clostridioides difficile infections (CDIs) have been identified as a major health concern due to the high morbidity, mortality, and cost of treatment. The aim of this study was to review the extant literature and identify the various patient-related, medication-related, and organizational risk factors associated with developing hospital-acquired CDIs in adult patients in the United States. METHODS A systematic review of four (4) online databases, including Scopus, PubMed, CINAHL, and Cochrane Library, was conducted to identify empirical studies published from 2007 to 2017 pertaining to risk factors of developing hospital-acquired CDIs. FINDINGS Thirty-eight studies (38) were included in the review. Various patient-level and medication-related risk factors were identified including advanced patient age, comorbidities, length of hospital stay, previous hospitalizations, use of probiotic medications and proton pump inhibitors. The review also identified organizational factors such as room size, academic affiliation, and geographic location to be significantly associated with hospital-acquired CDIs. CONCLUSION Validation of the factors associated with high risk of developing hospital-acquired CDIs identified in this review can aid in the development of risk prediction models to identify patients who are at a higher risk of developing CDIs and developing quality improvement interventions that might improve patient outcomes by minimizing risk of infection.
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Archambault M, Rubin JE. Antimicrobial Resistance in Clostridium and Brachyspira spp. and Other Anaerobes. Microbiol Spectr 2020; 8:10.1128/microbiolspec.arba-0020-2017. [PMID: 31971162 PMCID: PMC10773235 DOI: 10.1128/microbiolspec.arba-0020-2017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2017] [Indexed: 01/26/2023] Open
Abstract
This article describes the antimicrobial resistance to date of the most frequently encountered anaerobic bacterial pathogens of animals. The different sections show that antimicrobial resistance can vary depending on the antimicrobial, the anaerobe, and the resistance mechanism. The variability in antimicrobial resistance patterns is also associated with other factors such as geographic region and local antimicrobial usage. On occasion, the same resistance gene was observed in many anaerobes, whereas some were limited to certain anaerobes. This article focuses on antimicrobial resistance data of veterinary origin.
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Affiliation(s)
- Marie Archambault
- Département de Pathologie et Microbiologie, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe, Québec J2S 2M2, Canada
| | - Joseph E Rubin
- Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatchewan S7N 5B4, Canada
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Razim A, Pacyga K, Martirosian G, Szuba A, Gamian A, Myc A, Górska S. Mapping Epitopes of a Novel Peptidoglycan Cross-Linking Enzyme Cwp22 Recognized by Human Sera Obtained from Patients with Clostridioides difficile Infection and Cord Blood. Microorganisms 2019; 7:microorganisms7110565. [PMID: 31739602 PMCID: PMC6920951 DOI: 10.3390/microorganisms7110565] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Revised: 11/12/2019] [Accepted: 11/13/2019] [Indexed: 01/05/2023] Open
Abstract
Clostridioides difficile (CD) cause a severe diarrhea which can lead to pseudomembranous colitis and even patient death. CD infection (CDI) is connected mainly with changes in intestinal microbiota as a consequence of antibiotic treatment. The growing resistance to antibiotics, justifies the search for new methods of combating CD. Despite of ongoing research on the immunity against the pathogen, there is still lack of any reliable vaccine. Most recently, Cwp22, that is a cross-linking enzyme involved in the production of CD peptidoglycan, seems to be a promising target to prevent CDI in high-risk patients. In this paper, the Cwp22 protein polypeptide-specific epitopes were mapped in silico and using PEPSCAN procedure. They were recognized not only by antibodies from CDI patients’ but also by umbilical cord blood sera. We identified three epitopes 54EFRVAT59, 201KVNGKM206 and 268WQEKNGKKYY277 of Cwp22 protein. Since Cwp22 protein has key functionality and the described above epitopes are also recognized by umbilical cord blood serum, we postulate that they could have important protective properties. In this paper, we propose Cwp22 protein as a good antigen candidate for CDI preventive vaccine. Our results open the possibility to use 54EFRVAT59, 201KVNGKM206 and 268WQEKNGKKYY277, epitopes as suitable anti-CD vaccine antigens.
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Affiliation(s)
- Agnieszka Razim
- Department of Immunology of Infectious Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland; (A.G.); (A.M.)
- Department of Microbiology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland;
- Correspondence: (A.R.); (S.G.)
| | - Katarzyna Pacyga
- Department of Microbiology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland;
| | - Gajane Martirosian
- Department of Medical Microbiology, School of Medicine in Katowice, Medical University of Silesia, 40-752 Katowice, Poland;
| | - Andrzej Szuba
- Division of Angiology, Wroclaw Medical University, 51-618 Wroclaw, Poland;
- Department of Internal Medicine, 4th Military Hospital in Wroclaw, 50-981 Wroclaw, Poland
| | - Andrzej Gamian
- Department of Immunology of Infectious Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland; (A.G.); (A.M.)
| | - Andrzej Myc
- Department of Immunology of Infectious Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland; (A.G.); (A.M.)
- MNIMBS, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-5648, USA
| | - Sabina Górska
- Department of Microbiology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland;
- Correspondence: (A.R.); (S.G.)
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Direct Measurement of Performance: A New Era in Antimicrobial Stewardship. Antibiotics (Basel) 2019; 8:antibiotics8030127. [PMID: 31450576 PMCID: PMC6784134 DOI: 10.3390/antibiotics8030127] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Revised: 08/20/2019] [Accepted: 08/21/2019] [Indexed: 01/23/2023] Open
Abstract
For decades, the performance of antimicrobial stewardship programs (ASPs) has been measured by incidence rates of hospital-onset Clostridioides difficile and other infections due to multidrug-resistant bacteria. However, these represent indirect and nonspecific ASP metrics. They are often confounded by factors beyond an ASP’s control, such as changes in diagnostic testing methods or algorithms and the potential of patient-to-patient transmission. Whereas these metrics remain useful for global assessment of healthcare systems, antimicrobial use represents a direct metric that separates the performance of an ASP from other safety and quality teams within an institution. The evolution of electronic medical records and healthcare informatics has made measurements of antimicrobial use a reality. The US Centers for Disease Control and Prevention’s initiative for reporting antimicrobial use and standardized antimicrobial administration ratio in hospitals is highly welcomed. Ultimately, ASPs should be evaluated based on what they do best and what they can control, that is, antimicrobial use within their own institution. This narrative review critically appraises existing stewardship metrics and advocates for adopting antimicrobial use as the primary performance measure. It proposes novel formulas to adjust antimicrobial use based on quality of care and microbiological burden at each institution to allow for meaningful inter-network and inter-facility comparisons.
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Maatman TK, Westfall-Snyder JA, Nicolas ME, Yee EJ, Ceppa EP, House MG, Nakeeb A, Schmidt CM, Zyromski NJ. The morbidity of C. difficile in necrotizing pancreatitis. Am J Surg 2019; 219:509-512. [PMID: 31427035 DOI: 10.1016/j.amjsurg.2019.08.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Revised: 08/09/2019] [Accepted: 08/12/2019] [Indexed: 12/22/2022]
Abstract
INTRODUCTION Necrotizing pancreatitis (NP) patients commonly require antibiotic treatment during the several month-long disease course. We hypothesized that Clostridium difficile infection (CDI) is common in NP and significantly impacts outcomes. MATERIALS AND METHODS Retrospective review of 704 NP patients treated at a single-institution (2005-2018). RESULTS 10% (67/704) of patients developed CDI a mean 78 days after NP onset. Patients developing CDI experienced increased total hospital days (CDI, 104; No CDI, 42; P < 0.001), readmission rates (CDI, 85%; No CDI, 64%; P = 0.006), and duration of NP (CDI, 248 days; No CDI, 183; P = 0.001). Risk factors for CDI included antibiotic use (OR, 96.2; 95% CI, 5.9-1556.2; P = 0.001) and any organ failure (OR, 2.0; 95% CI, 1.2-3.3, P = 0.008). Mortality was not affected by CDI (CDI, 10%; No CDI, 9%; P = 0.7). CONCLUSION Clostridium difficile infection is common in necrotizing pancreatitis and negatively impacts morbidity and disease recovery.
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Affiliation(s)
- Thomas K Maatman
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | | | - Megan E Nicolas
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Elliott J Yee
- Indiana University School of Medicine, Indianapolis, IN, USA
| | - Eugene P Ceppa
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Michael G House
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Attila Nakeeb
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - C Max Schmidt
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Nicholas J Zyromski
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
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Kitano H, Teishima J, Shigemura K, Ohge H, Fujisawa M, Matsubara A. Current status of countermeasures for infectious diseases and resistant microbes in the field of urology. Int J Urol 2019; 26:1090-1098. [PMID: 31382322 DOI: 10.1111/iju.14087] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Accepted: 07/17/2019] [Indexed: 12/12/2022]
Abstract
A worldwide increase in antimicrobial-resistant microbes due to the improper use of antimicrobial agents, along with a lack of progress in developing new antimicrobials, is becoming a societal problem. Although carbapenem-resistant Enterobacteriaceae, which are resistant to carbapenem antimicrobials, first appeared in 1993, treatment options remain limited. Mechanisms behind antimicrobial resistance involve changes to microbial outer membranes, drug efflux pump abnormalities, β-lactamase production and the creation of biofilms around cell bodies. Genetic information related to these forms of antimicrobial resistance exists on chromosomes and plasmids, and when located on the latter can easily be transmitted to other strains, no matter the species, which creates a risk of antimicrobial resistance spreading exceptionally rapidly. To prevent the spread of antimicrobial resistance, the World Health Organization in 2015 published an action plan on antimicrobial resistance, based on which World Health Organization member countries have laid out specific policies and targets. Urinary tract infections are a type of healthcare-associated infection, and the sexually transmitted disease pathogen, Neisseria gonorrhoeae, has been included in a list of microbes that pose a risk to human health published by the US Centers for Disease Control and Prevention. Urologists face numerous problems when attempting to use antimicrobials properly, which is one method of dealing with antimicrobial resistance. Therefore, this article describes the current state of resistant microbes associated with urinary tract infections and countermeasures for antimicrobial resistance, including new antimicrobials.
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Affiliation(s)
- Hiroyuki Kitano
- Department of Urology, Hiroshima University, Hiroshima City, Hiroshima, Japan.,Department of Infectious Diseases, Hiroshima University Hospital, Hiroshima City, Hiroshima, Japan
| | - Jun Teishima
- Department of Urology, Hiroshima University, Hiroshima City, Hiroshima, Japan
| | | | - Hiroki Ohge
- Department of Infectious Diseases, Hiroshima University Hospital, Hiroshima City, Hiroshima, Japan
| | - Masato Fujisawa
- Department of Urology, Kobe University, Kobe City, Hyogo, Japan
| | - Akio Matsubara
- Department of Urology, Hiroshima University, Hiroshima City, Hiroshima, Japan
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Estimating the Attributable Disease Burden and Effects of Interhospital Patient Sharing on Clostridium difficile Infections. Infect Control Hosp Epidemiol 2019; 40:656-661. [DOI: 10.1017/ice.2019.73] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
AbstractObjective:To estimate the burden of Clostridium difficile infections (CDIs) due to interfacility patient sharing at regional and hospital levels.Design:Retrospective observational study.Methods:We used data from the Healthcare Cost and Utilization Project California State Inpatient Database (2005–2011) to identify 26,878,498 admissions and 532,925 patient transfers. We constructed a weighted, directed network among the hospitals by defining an edge between 2 hospitals to be the monthly average number of patients discharged from one hospital and admitted to another on the same day. We then used a network autocorrelation model to study the effect of the patient sharing network on the monthly average number of CDI cases per hospital, and we estimated the proportion of CDI cases attributable to the network.Results:We found that 13% (95% confidence interval [CI], 7.6%–18%) of CDI cases were due to diffusion through the patient-sharing network. The network autocorrelation parameter was estimated at 5.0 (95% CI, 3.0–6.9). An increase in the number of patients transferred into and/or an increased CDI rate at the hospitals from which those patients originated led to an increase in the number of CDIs in the receiving hospital.Conclusions:A minority but substantial burden of CDI infections are attributable to hospital transfers. A hospital’s infection control may thus be nontrivially influenced by its neighboring hospitals. This work adds to the growing body of evidence that intervention strategies designed to minimize HAIs should be done at the regional rather than local level.
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Lee HY, Hsiao HL, Chia CY, Cheng CW, Tsai TC, Deng ST, Chen CL, Chiu CH. Risk factors and outcomes of Clostridium difficile infection in hospitalized patients. Biomed J 2019; 42:99-106. [PMID: 31130254 PMCID: PMC6541878 DOI: 10.1016/j.bj.2018.12.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2018] [Revised: 08/22/2018] [Accepted: 12/12/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The aim of this study was to identify risk factors for Clostridium difficile infection (CDI) and its attributable mortality and to propose methods to prevent CDI and improve patients' outcomes. METHODS CDI was defined as diarrheal patients with stool samples that were positive for C. difficile toxin. Clinical presentations of all patients with CDI and two times as many age- and sex-matched culture-negative controls at the Chang Gung Memorial Hospital in 2014 were identified and compared by multivariate, nonparametric, and Kaplan-Meier survival analysis. RESULTS There were no significant differences in ages, sex, or Charlson comorbidity indexes between the CDI group (n = 42) and the control group (n = 86). The multivariate analysis indicated that underlying peptic ulcer disease and previous use of gastric acid inhibitors or third-generation cephalosporins for at least 3 days were significantly more common in patients with CDI than in the controls. Charlson scores were associated with mortality due to CDI. Recommended treatment using oral vancomycin to treat patients with Charlson score ≥ 5 and oral metronidazole or vancomycin to treat those with moderate underlying disease (Charlson score ≥ 2 and ≤ 5) significantly increased survival in these patients (p = 0.001). CONCLUSIONS Oral vancomycin given to patients with high Charlson scores and oral metronidazole or vancomycin to patients with moderate Charlson scores decreased mortality due to CDI. Restricting the use of third-generation cephalosporins and gastric acid inhibitors is recommended to prevent CDI in hospitalized patients.
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Affiliation(s)
- Hao-Yuan Lee
- Department of Nursing, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan; Department of Pediatrics, Wei Gong Memorial Hospital, Miaoli, Taiwan; Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Hsuan-Ling Hsiao
- Department of Pharmacy, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chin-Yuan Chia
- Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Department of Pediatrics, Chang Gung Children's Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chun-Wen Cheng
- Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Tzu-Cheng Tsai
- Department of Pharmacy, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Shin-Tarng Deng
- Department of Pharmacy, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chyi-Liang Chen
- Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Cheng-Hsun Chiu
- Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Department of Pediatrics, Chang Gung Children's Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
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Sievers S, Metzendorf NG, Dittmann S, Troitzsch D, Gast V, Tröger SM, Wolff C, Zühlke D, Hirschfeld C, Schlüter R, Riedel K. Differential View on the Bile Acid Stress Response of Clostridioides difficile. Front Microbiol 2019; 10:258. [PMID: 30833939 PMCID: PMC6387971 DOI: 10.3389/fmicb.2019.00258] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Accepted: 01/31/2019] [Indexed: 12/16/2022] Open
Abstract
Clostridioides difficile is an intestinal human pathogen that uses the opportunity of a depleted microbiota to cause an infection. It is known, that the composition of the intestinal bile acid cocktail has a great impact on the susceptibility toward a C. difficile infection. However, the specific response of growing C. difficile cells to diverse bile acids on the molecular level has not been described yet. In this study, we recorded proteome signatures of shock and long-term (LT) stress with the four main bile acids cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), and lithocholic acid (LCA). A general overlapping response to all tested bile acids could be determined particularly in shock experiments which appears plausible in the light of their common steroid structure. However, during LT stress several proteins showed an altered abundance in the presence of only a single or a few of the bile acids indicating the existence of specific adaptation mechanisms. Our results point at a differential induction of the groEL and dnaKJgrpE chaperone systems, both belonging to the class I heat shock genes. Additionally, central metabolic pathways involving butyrate fermentation and the reductive Stickland fermentation of leucine were effected, although CA caused a proteome signature different from the other three bile acids. Furthermore, quantitative proteomics revealed a loss of flagellar proteins in LT stress with LCA. The absence of flagella could be substantiated by electron microscopy which also indicated less flagellated cells in the presence of DCA and CDCA and no influence on flagella formation by CA. Our data break down the bile acid stress response of C. difficile into a general and a specific adaptation. The latter cannot simply be divided into a response to primary and secondary bile acids, but rather reflects a complex and variable adaptation process enabling C. difficile to survive and to cause an infection in the intestinal tract.
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Affiliation(s)
- Susanne Sievers
- Institute of Microbiology, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
| | - Nicole G Metzendorf
- Institute of Microbiology, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
| | - Silvia Dittmann
- Institute of Microbiology, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
| | - Daniel Troitzsch
- Institute of Microbiology, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
| | - Viola Gast
- Institute of Microbiology, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
| | - Sophie Marlen Tröger
- Institute of Microbiology, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
| | - Christian Wolff
- Institute of Microbiology, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
| | - Daniela Zühlke
- Institute of Microbiology, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
| | - Claudia Hirschfeld
- Department of Microbial Proteomics, Institute of Microbiology, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
| | - Rabea Schlüter
- Imaging Center of the Department of Biology, University of Greifswald, Greifswald, Germany
| | - Katharina Riedel
- Institute of Microbiology, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany
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Chia BY, Teo JQM, Lee W, Liew YX, Ee RPL, Chlebicki MP, Oon LLE, Kwa ALH. Do antimicrobial stewardship programme interventions reduce the rate of and protect against Clostridium difficile infection? J Glob Antimicrob Resist 2019; 17:312-315. [PMID: 30682564 DOI: 10.1016/j.jgar.2019.01.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Revised: 01/10/2019] [Accepted: 01/11/2019] [Indexed: 12/29/2022] Open
Abstract
OBJECTIVES Antimicrobial stewardship programmes (ASPs) have often been recommended as a viable solution to minimise the incidence of Clostridium difficile infection (CDI), which can be life-threatening. This study aimed to evaluate whether ASP interventions have contributed to reducing CDI rates. METHODS A retrospective review of ASP interventions issued from January 2013 to April 2014 was performed using data from the ASP database of Singapore General Hospital, a 1600-bed tertiary-care hospital in Singapore. A total of 283 interventions satisfied the inclusion criteria, of which commonly audited antibiotics were piperacillin/tazobactam (41.3%) and carbapenems (54.8%). Comparisons were made at 30days post-intervention between those with accepted or rejected interventions. The primary outcome was CDI incidence; secondary outcomes included length of hospitalisation post-intervention, 30-day mortality and CDI recurrence rate. RESULTS Whilst the median duration of antibiotic therapy was reduced by 2days (6days vs. 4 days; P<0.001), acceptance of ASP interventions did not alter primary CDI incidence at 30days (P=0.644) post-intervention. However, reduced CDI recurrence rates were observed for patients positive for CDI in the accepted patient group compared with the rejected group (0% vs. 37.5%; P=0.03), with no difference in CDI 30-day mortality between the two groups. CONCLUSION Intervention acceptance did not contribute to a significant reduction in CDI incidence but may be associated with lower recurrence rates, although further studies are required.
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Affiliation(s)
- Bih Yee Chia
- Department of Pharmacy, Singapore General Hospital, Singapore; Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore
| | | | - Winnie Lee
- Department of Pharmacy, Singapore General Hospital, Singapore
| | - Yi Xin Liew
- Department of Pharmacy, Singapore General Hospital, Singapore
| | - Rachel Pui-Lai Ee
- Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore
| | | | | | - Andrea Lay-Hoon Kwa
- Department of Pharmacy, Singapore General Hospital, Singapore; Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore; Emerging Infectious Disease Program, Duke-National University of Singapore Medical School, Singapore.
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Jung S, Sexton ME, Owens S, Spell N, Fridkin S. Variability of Antibiotic Prescribing in a Large Healthcare Network Despite Adjusting for Patient-Mix: Reconsidering Targets for Improved Prescribing. Open Forum Infect Dis 2019; 6:ofz018. [PMID: 30815500 PMCID: PMC6386112 DOI: 10.1093/ofid/ofz018] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Revised: 12/11/2018] [Accepted: 01/10/2019] [Indexed: 12/20/2022] Open
Abstract
Background In the outpatient setting, the majority of antibiotic prescriptions are for acute respiratory infections (ARIs), but most of these infections are viral and antibiotics are unnecessary. We analyzed provider-specific antibiotic prescribing in a group of outpatient clinics affiliated with an academic medical center to inform future interventions to minimize unnecessary antibiotic use. Methods We conducted a cross-sectional study of patients who presented with an ARI to any of 15 The Emory Clinic (TEC) primary care clinic sites between October 2015 and September 2017. We performed multivariable logistic regression analysis to examine the impact of patient, provider, and clinic characteristics on antibiotic prescribing. We also compared provider-specific prescribing rates within and between clinic sites. Results A total of 53.4% of the 9600 patient encounters with a diagnosis of ARI resulted in an antibiotic prescription. The odds of an encounter resulting in an antibiotic prescription were independently associated with patient characteristics of white race (adjusted odds ratio [aOR] = 1.59; 95% confidence interval [CI], 1.47–1.73), older age (aOR = 1.32, 95% CI = 1.20–1.46 for patients 51 to 64 years; aOR = 1.32, 95% CI = 1.20–1.46 for patients ≥65 years), and comorbid condition presence (aOR = 1.19; 95% CI, 1.09–1.30). Of the 109 providers, 13 (12%) had a rate significantly higher than predicted by modeling. Conclusions Antibiotic prescribing for ARIs within TEC outpatient settings is higher than expected based on prescribing guidelines, with substantial variation in prescribing rates by site and provider. These data lay the foundation for quality improvement interventions to reduce unnecessary antibiotic prescribing.
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Affiliation(s)
- Sophia Jung
- Rollins School of Public Health, Emory University, Atlanta, Georgia
- Correspondence: S. Jung, MPH, Emory University, 1075 Trail Rd., Moscow, ID 83843 ()
| | - Mary Elizabeth Sexton
- Division of Infectious Diseases, Department of Medicine, Atlanta, Georgia
- Emory Antibiotic Resistance Center, Atlanta, Georgia
| | - Sallie Owens
- Emory University School of Medicine, Emory University, Atlanta, Georgia
| | - Nathan Spell
- Emory University School of Medicine, Emory University, Atlanta, Georgia
| | - Scott Fridkin
- Rollins School of Public Health, Emory University, Atlanta, Georgia
- Division of Infectious Diseases, Department of Medicine, Atlanta, Georgia
- Emory Antibiotic Resistance Center, Atlanta, Georgia
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Affiliation(s)
- Lin-Lin Zhou
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica; Chinese Academy of Sciences; Shanghai 201203 China
- University of the Chinese Academy of Sciences; Beijing 100049 China
| | - Cai-Guang Yang
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica; Chinese Academy of Sciences; Shanghai 201203 China
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Barai P, Hossain KM, Rahman SMM, Al Mazid MF, Gazi MS. Antidiarrheal Efficacy of Probiotic Bacteria in Castor Oil Induced Diarrheal Mice. Prev Nutr Food Sci 2018; 23:294-300. [PMID: 30675458 PMCID: PMC6342536 DOI: 10.3746/pnf.2018.23.4.294] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2018] [Accepted: 10/15/2018] [Indexed: 01/20/2023] Open
Abstract
Probiotics may offer a safe intervention for diarrheal diseases. The aim of the present study was the assessment of the antidiarrheal property of probiotic bacteria. For their antidiarrheal efficacy assessment, yogurt was prepared using the isolated bacteria from selective regional yogurt of Bangladesh, and mice model trails were conducted using castor oil induced diarrheal mice. The probiotic treatment was applied on three mice groups, each having 6 mice and their respective doses were 50 mL/kg body weight in treatment group (TG) 1, 100 mL/kg body weight in TG2, and 150 mL/kg body weight in TG3. A four week treatment of probiotic significantly (P<0.001) reduced the percentage (67.37%) of diarrhea in TG3 (150 mL yogurt/kg body weight). All the treatment groups showed a significant (P<0.001) increase in the latent periods, reduced the total fecal output, and frequency and fecal water content compared to the negative control group. Serum electrolytes (Na+ and K+) and total protein levels were higher in the TG3 compared to the negative control group. Further research regarding molecular characterization and identification of specific genes and proteins of interest may help to develop the next generation bacteriocins and antidiarrheal drugs.
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Affiliation(s)
- Pallob Barai
- Biotechnology and Genetic Engineering Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh
| | - Khondoker Moazzem Hossain
- Biotechnology and Genetic Engineering Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh
| | | | - Mohammad Faysal Al Mazid
- Biotechnology and Genetic Engineering Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh
| | - Mohammad Shamim Gazi
- Biotechnology and Genetic Engineering Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh
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Arrastia I, Arrieta A, Cossío FP. Application of 1,3-Dipolar Reactions between Azomethine Ylides and Alkenes to the Synthesis of Catalysts and Biologically Active Compounds. European J Org Chem 2018; 2018:5889-5904. [PMID: 30555273 PMCID: PMC6283252 DOI: 10.1002/ejoc.201800911] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Indexed: 12/19/2022]
Abstract
The (3+2) cycloaddition between azomethine ylides and alkenes is an efficient, convergent and stereocontrolled method for the synthesis of unnatural pyrrolidine and proline scaffolds. In this review, the application of this reaction to the synthesis of enantiopure organometallic ligands for asymmetric catalysis is presented first. These new EhuPhos ligands can participate in a second generation of 1,3-dipolar reactions that generate an offspring of unnatural proline derivatives that behave as efficient organocatalysts. These densely substituted unnatural l-proline derivatives exhibit distinct features, different to those described for natural l-proline and its derivatives. Finally, several examples of biologically active proline derivatives obtained by means of (3+2) cycloadditions involving azomethine ylides are presented. These applications show the character of privileged structures of these polysubstituted pyrrolidine rings.
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Affiliation(s)
- Iosune Arrastia
- Donostia International Physics Center (DIPC)Manuel Lardizabal Ibilbidea 420018San Sebastian/DonostiaSpain
| | - Ana Arrieta
- Department of Organic Chemistry I and Centro de Innovación en Química Avanzada (ORFEO‐CINQA)Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU)Manuel Lardizabal Ibilbidea 320018San Sebastian/DonostiaSpain
| | - Fernando P. Cossío
- Donostia International Physics Center (DIPC)Manuel Lardizabal Ibilbidea 420018San Sebastian/DonostiaSpain
- Department of Organic Chemistry I and Centro de Innovación en Química Avanzada (ORFEO‐CINQA)Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU)Manuel Lardizabal Ibilbidea 320018San Sebastian/DonostiaSpain
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ASID/ACIPC position statement - Infection control for patients with Clostridium difficile infection in healthcare facilities. Infect Dis Health 2018; 24:32-43. [PMID: 30691583 DOI: 10.1016/j.idh.2018.10.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Revised: 10/08/2018] [Accepted: 10/08/2018] [Indexed: 01/05/2023]
Abstract
BACKGROUND In 2011, the Australasian Society for Infectious Diseases (ASID) and the Australian Infection Control Association (AICA), now known as the Australasian College of Infection Prevention and Control (ACIPC), produced a position statement on infection control requirements for preventing and controlling Clostridium difficile infection (CDI) in healthcare settings. METHODS The statement updated in 2017 to reflect new literature available .The authors reviewed the 2011 position statement and critically appraised new literature published between 2011 and 2017 and relevant current infection control guidelines to identify where new evidence had become available or best practice had changed. RESULTS The position statement was updated incorporating the new findings. A draft version of the updated position statement was circulated for consultation to members of ASID and ACIPC. The authors responded to all comments received and updated the position statement. CONCLUSIONS This updated position statement emphasizes the importance of health service organizations having evidence-based infection prevention and control programs and comprehensive antimicrobial stewardship programs, to ensure the risk of C. difficile acquisition, transmission and infection is minimised.
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[Antibiotic prophylaxis in preterm premature rupture of membranes: CNGOF preterm premature rupture of membranes guidelines]. ACTA ACUST UNITED AC 2018; 46:1043-1053. [PMID: 30392988 DOI: 10.1016/j.gofs.2018.10.017] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2018] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To analyse benefits and risks of antibiotic prophylaxis in the management of preterm premature rupture of membranes. METHODS PubMed and Cochrane Central databases search. RESULTS Streptoccoccus agalactiae (group B streptococcus) and Escherichia coli are the two main bacteria identified in early neonatal sepsis (EL3). Antibiotic prophylaxis at admission is associated with significant prolongation of pregnancy (EL2), reduction in neonatal morbidity (EL1) without impact on neonatal mortality (EL2). Co-amoxiclav could be associated with an increased risk for neonatal necrotising enterocolitis (EL2). Antibiotic prophylaxis at admission in women with preterm premature rupture of the membranes is recommended (Grade A). Monotherapy with amoxicillin, third generation cephalosporin and erythromycin can be used as well as combination of erythromycin and amoxicillin (Professional consensus) for 7 days (GradeC). Shorter treatment is possible when initial vaginal culture is negative (Professional consensus). Co-amxiclav, aminoglycosides, glycopeptides, first and second generation cephalosporin, clindamycin and metronidazole are not recommended (Professional consensus). CONCLUSIONS Antibiotic prophylaxis against Streptoccoccus agalactiae (group B streptococcus) and E. coli is recommended in women with preterm premature of the membranes (Grade A). Monotherapy with amoxicillin, third generation cephalosporin or erythromycin, as well as combination of erythromycin and amoxicillin are recommended (Professional consensus).
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Nogueira T, David PHC, Pothier J. Antibiotics as both friends and foes of the human gut microbiome: The microbial community approach. Drug Dev Res 2018; 80:86-97. [PMID: 30370682 DOI: 10.1002/ddr.21466] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Revised: 08/14/2018] [Accepted: 08/15/2018] [Indexed: 12/28/2022]
Abstract
The exposure of the human gut to antibiotics can have a great impact on human health. Antibiotics pertain to the preservation of human health and are useful tools for fighting bacterial infections. They can be used for curing infections and can play a critical role in immunocompromised or chronic patients, or in fighting childhood severe malnutrition. Yet, the genomic and phylogenetic diversity of the human gut changes under antibiotic exposure. Antibiotics can also have severe side effects on human gut health, due to the spreading of potential antibiotic resistance genetic traits and to their correlation with virulence of some bacterial pathogens. They can shape, and even disrupt, the composition and functioning diversity of the human gut microbiome. Traditionally bacterial antibiotic resistances have been evaluated at clone or population level. However, the understanding of these two apparently disparate perspectives as both friends and foes may come from the study of microbiomes as a whole and from the evaluation of both positive and negative effects of antibiotics on microbial community dynamics and diversity. In this review we present some metagenomic tools and databases that enable the studying of antibiotic resistance in human gut metagenomes, promoting the development of personalized medicine strategies, new antimicrobial therapy protocols and patient follow-up.
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Affiliation(s)
- Teresa Nogueira
- cE3c - Centro de Ecologia, Evolução e Alterações Ambientais, Faculdade de Ciências, Universidade de Lisboa, Lisbon, Portugal
| | - Pedro H C David
- cE3c - Centro de Ecologia, Evolução e Alterações Ambientais, Faculdade de Ciências, Universidade de Lisboa, Lisbon, Portugal
| | - Joël Pothier
- Institut de Systématique, Evolution, Biodiversité (ISYEB), Sorbonne Université, Muséum National d'Histoire naturelle, CNRS, EPHE, CP, Paris, France
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