#Clostridiodes difficile in #COVID19 Patients, #Detroit, #Michigan, #USA, March–April 2020 (Emerg Infect Dis., summary)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Summary, edited.]

Volume 26, Number 9—September 2020 | Letter

Clostridiodes difficile in COVID-19 Patients, Detroit, Michigan, USA, March–April 2020

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To the Editor: Sandhu et al. (1) reported 9 patients who were co-infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Clostridioides difficile. C. difficile infection (CDI) can be a co-occurrence or result of antimicrobial drug overuse and is potentially a complication of coronavirus disease (COVID-19). We report a 52-year-old man with hypertension who had fever, respiratory symptoms, abdominal pain, and diarrhea for 3 days. At admission to Saint Michael’s Medical Center (Newark, New Jersey, USA), he had a temperature of 101.8°F but was otherwise hemodynamically stable. He had an elevated absolute lymphocyte count (700 cells/μL), indicating lymphopenia. He tested positive for SARS-CoV-2 RNA by reverse transcription PCR and had elevated inflammatory markers on blood profile. He tested positive for C. difficile toxin and antigen at admission. He did not use antimicrobial drugs or proton pump inhibitors and had no known contacts with persons with diarrhea. He was mechanically ventilated and received oral vancomycin, intravenous metronidazole, and vasopressors. He died of respiratory failure and septic shock. In comparison to the patients described by Sandhu et al., the patient we report was younger and did not have a history of antimicrobial use.

(…)

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Keywords: SARS-CoV-2; COVID-19; Bacterial infection; USA; Michigan.

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Use of #ribaxamase (SYN-004), a β-lactamase, to prevent #Clostridium difficile #infection in β-lactam-treated patients: a double-blind, phase 2b, randomised placebo-controlled trial (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Use of ribaxamase (SYN-004), a β-lactamase, to prevent Clostridium difficile infection in β-lactam-treated patients: a double-blind, phase 2b, randomised placebo-controlled trial

John F Kokai-Kun, PhD, Tracey Roberts, BSN, Olivia Coughlin, PhD, Chenxiong Le, PhD, Heidi Whalen, MHS, Ralph Stevenson, PhD, Vincent J Wacher, PhD, Joseph Sliman, MD

Published: March 15, 2019 / DOI: https://doi.org/10.1016/S1473-3099(18)30731-X

 

Summary

Background

Infections with Clostridium difficile are a health threat, yet no products are currently licensed for prevention of primary C difficile infections. Intravenous β-lactam antibiotics are considered to confer a high risk of C difficile infection because of their biliary excretion into the gastrointestinal tract and disruption of the gut microbiome. ribaxamase (SYN-004) is an orally administered β-lactamase that was designed to be given with intravenous β-lactam antibiotics to degrade excess antibiotics in the upper gastrointestinal tract before they disrupt the gut microbiome and lead to C difficile infection. We therefore aimed to determine whether administration of ribaxamase could prevent C difficile infection in patients being treated with intravenous ceftriaxone for a lower respiratory tract infection, thereby supporting continued clinical development.

Methods

In this parallel-group, double-blind, multicentre, phase 2b, randomised placebo-controlled trial, we recruited patients who had been admitted to a hospital with a lower respiratory tract infection with a pneumonia index score of 90–130 and who were expected to be treated with ceftriaxone for at least 5 days. Patients were recruited from 54 clinical sites in the USA, Canada, Bulgaria, Hungary, Poland, Romania, and Serbia. We randomly assigned patients older than 50 years to groups (1:1) in blocks of four by use of an interactive web portal; these groups were assigned to receive either 150 mg ribaxamase or placebo four times per day during, and for 72 h after, treatment with ceftriaxone. All patients, clinical investigators, study staff, and sponsor personnel were masked to the study drug assignments. The primary endpoint was the incidence ofC difficile infection, as diagnosed by the local laboratory, in patients who received at least one treatment dose, and this outcome was assessed during treatment and for 4 weeks after treatment. This study is registered with ClinicalTrials.gov, number NCT02563106.

Findings

Between Nov 16, 2015, and Nov 10, 2016, we screened 433 patients for inclusion in the study. Of these patients, 20 (5%) patients were excluded from the study (16 [4%] patients did not meet inclusion criteria; four [1%] patients because of dosing restrictions). We enrolled and randomly assigned 413 patients to groups, of whom 207 patients were assigned to receive ceftriaxone plus ribaxamase and 206 patients were assigned to receive ceftriaxone plus placebo. However, one (<1%) patient in the ribaxamase group withdrew consent and was not treated with ribaxamase. During the study and within the 4 weeks after antibiotic treatment, two (1·0%) patients in the ribaxamase group and seven (3·4%) patients in the placebo group were diagnosed with an infection with C difficile (risk reduction 2·4%, 95% CI −0·6 to 5·9; one-sided p=0·045). Adverse events were similar between groups but more deaths were reported in the ribaxamase group (11 deaths vs five deaths in the placebo group). This disparity was due to the higher incidence of deaths attributed to cardiac-associated causes in the ribaxamase group (six deaths vs one death in the placebo group).

Interpretation

In patients treated with intravenous ceftriaxone for lower respiratory tract infections, oral ribaxamase reduced the incidence of C difficileinfections compared with placebo. The imbalance in deaths between the groups appeared to be related to the underlying health of the patients. Ribaxamase has the potential to prevent C difficileinfection in patients treated with intravenous β-lactam antibiotics, and our findings support continued clinical development of ribaxamase to prevent C difficile infection.

Funding

Synthetic Biologics.

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Keywords: Antibiotics; Clostridium difficile; Ceftriaxone; Ribaxamase.

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The first #isolation of #Clostridium difficile RT078/ST11 from #pigs in #China (PLoS One, abstract)

[Source: PLoS One, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

The first isolation of Clostridium difficile RT078/ST11 from pigs in China

Li-Juan Zhang, Ling Yang, Xi-Xi Gu, Pin-Xian Chen, Jia-Li Fu, Hong-Xia Jiang

Published: February 26, 2019 / DOI: https://doi.org/10.1371/journal.pone.0212965

 

Abstract

We investigated the molecular characteristics and antimicrobial susceptibility of Clostridium difficile isolated from animals in China. We obtained 538 rectal swabs from pigs, chickens and ducks in 5 provinces during 2015 and 2016. C. difficile isolates were characterized by detection of toxin genes, multilocus sequence typing and ribotyping. And antimicrobial susceptibility testing was performed using the agar dilution method. Out of 538 samples, 44 (8.2%) were C. difficile positive with high prevalence in pigs (n = 31). Among these, 39 (88.6%) were toxigenic including 14 (31.8%) that were A+B+CDT+ and 13 (29.5%) A+B+. The remaining 12 (27.3%) were A-B+. We identified 7 ST types and 6 PCR ribotypes. The most predominant type was ST11/RT078 with toxin profile A+B+CDT+ and all were isolated from piglets with diarrhea. ST109 isolates possessed two different toxigenic profiles (A-B-CDT- and A-B+CDT-) and although it was not the most prevalent sequence type, but it was widely distributed between chickens, ducks and pigs in the 5 provinces. All C. difficile isolates were fully susceptible to vancomycin, metronidazole, fidaxomicin, amoxicillin/clavulanate and meropenem but retained resistance to 4 or 5 of the remaining antibiotics, especially cefotaxime, tetracycline, ciprofloxacin, cefoxitin. The RT078/ST11 isolates were simultaneously resistant to cefotaxime, tetracycline, cefoxitin, ciprofloxacin and imipenem. This is the first report of the molecular epidemiology of C. difficile isolated from food animals in China. We identified the epidemic strain RT078/ST11 as the predominate isolate among the animals we screened in our study.

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Citation: Zhang L-J, Yang L, Gu X-X, Chen P-X, Fu J-L, Jiang H-X (2019) The first isolation of Clostridium difficile RT078/ST11 from pigs in China. PLoS ONE 14(2): e0212965. https://doi.org/10.1371/journal.pone.0212965

Editor: Pradeep Dudeja, University of Illinois at Chicago, UNITED STATES

Received: November 2, 2018; Accepted: February 12, 2019; Published: February 26, 2019

Copyright: © 2019 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper.

Funding: This work was supported by the National Natural Science Foundation of China (31272602) (H-XJ) and Graduate Student Oversea Study Program of South China Agriculture University (2017LHPY029) (LY). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

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Keywords: Antibiotics; Drugs Resistance; Clostridium difficile; Pigs; China.

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#Cadazolid for the #treatment of #Clostridium difficile #infection: results of two double-blind, placebo-controlled, non-inferiority, randomised phase 3 trials (Lancet, abstract)

[Source: The Lancet, full page: (LINK). Abstract, edited.]

Cadazolid for the treatment of Clostridium difficile infection: results of two double-blind, placebo-controlled, non-inferiority, randomised phase 3 trials

Dale N Gerding, MD, Prof Oliver A Cornely, MD, Simon Grill, PhD, Hilke Kracker, PhD, Anne Claire Marrast, MD, Prof Carl Erik Nord, PhD, et al.

Published: January 29, 2019 / DOI: https://doi.org/10.1016/S1473-3099(18)30614-5

 

Summary

Background

Cadazolid is a novel quinoxolidinone antibiotic developed for treating Clostridium difficile infection. We aimed to investigate the safety and efficacy of cadazolid compared with vancomycin in patients with C difficile infection.

Methods

IMPACT 1 and IMPACT 2 were identically designed, multicentre, double-blind, placebo-controlled, non-inferiority, randomised phase 3 trials. IMPACT 1 was done in Australia, Brazil, Canada, France, Germany, Italy, the Netherlands, Peru, Poland, Romania, Spain, and the USA, and IMPACT 2 was done in Argentina, Belgium, Brazil, Canada, Chile, Croatia, Czech Republic, Greece, Hungary, Israel, Romania, Slovakia, South Korea, the UK, and the USA. Patients (aged 18 years or older) with mild-to-moderate or severe C difficileinfection (diarrhoea with positive glutamate dehydrogenase and toxin A or B enzyme immunoassays) were randomly assigned (1:1) with a randomisation list stratified by centre and C difficile infection episode type (block size of four), and allocation was masked to investigators and participants. Patients received either oral cadazolid 250 mg twice daily with vancomycin-matching placebo capsule four times daily or oral vancomycin 125 mg four times a day with cadazolid-matching placebo suspension twice daily for 10 days, with 30 days of follow-up. The primary efficacy outcome was non-inferiority (margin −10%) of cadazolid versus vancomycin for clinical cure in the modified intention-to-treat and per-protocol populations. Clinical cure was defined as resolution of diarrhoea with no additional treatment for C difficile infection. These trials are registered with ClinicalTrials.gov, numbers NCT01987895 (IMPACT 1) and NCT01983683 (IMPACT 2).

Findings

Between March 28, 2014, and March 24, 2017, for IMPACT 1, and Dec 13, 2013, and May 2, 2017, for IMPACT 2, 1263 participants were randomly assigned to receive cadazolid (306 in IMPACT 1 and 298 in IMPACT 2) or vancomycin (326 in IMPACT 1 and 311 in IMPACT 2). In the modified intention-to-treat population in IMPACT 1, 253 (84%) of 302 had clinical cure in the cadazolid group versus 271 (85%) of 318 in the vancomycin group. In IMPACT 2, 235 (81%) of 290 versus 258 (86%) of 301 had clinical cure. In the per-protocol population, 247 (88%) of 282 versus 264 (92%) of 288 had clinical cure in IMPACT 1 and 214 (87%) of 247 versus 237 (92%) of 259 in IMPACT 2. Non-inferiority for clinical cure to vancomycin was shown in IMPACT 1 but not in IMPACT 2 (IMPACT 1 treatment difference: −1·4 [95% CI −7·2 to 4·3] for modified intention to treat and −4·1 [–9·2 to 1·0] for per protocol; IMPACT 2: −4·7 [–10·7 to 1·3] for modified intention to treat and −4·9 [–10·4 to 0·6] for per protocol). The safety and tolerability profiles of the two antibiotics were similar.

Interpretation

Cadazolid was safe and well tolerated but did not achieve its primary endpoint of non-inferiority to vancomycin for clinical cure in one of two phase 3 C difficile infection trials. Therefore, further commercial development of cadazolid for C difficile infection is unlikely.

Funding

Actelion Pharmaceuticals.

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Keywords: Antibiotics; Vancomycin; Cadazolid; Clostridium difficile.

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Comparative efficacy of #treatments for #Clostridium difficile #infection: a systematic review and network meta-analysis (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Comparative efficacy of treatments for Clostridium difficile infection: a systematic review and network meta-analysis

Tumas Beinortas, MBBCh†, Nicholas E Burr, MBBS†, Prof Mark H Wilcox, MD

†Contributed equally

Published: 16 July 2018 / DOI: https://doi.org/10.1016/S1473-3099(18)30285-8

© 2018 Elsevier Ltd. All rights reserved.

 

Summary

Background

Several new treatments for Clostridium difficile infections have been investigated. We aimed to compare and rank treatments for non-multiply recurrent infections with C difficile in adults.

Methods

We did a random effects network meta-analysis within a frequentist setting to obtain direct and indirect comparisons of trials. We searched MEDLINE, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for published and unpublished trials from the creation of these databases until June 30, 2017. We included randomised controlled trials of treatments for non-multiply recurrent infections with confirmed C difficile in adults (at least 18 years) that reported both primary cure and recurrence rates, and we used the Cochrane Risk of Bias tool to appraise trial methods. For our analysis, we extracted the total numbers of patients with primary cure and recurrence from published and unpublished reports. The primary outcome was sustained symptomatic cure, defined as the number of patients with resolution of diarrhoea minus the number with recurrence or death.

Findings

Of 23 004 studies screened, 24 trials, which comprised 5361 patients and 13 different treatments, were included in the analysis. The overall quality of evidence was rated as moderate to low. For sustained symptomatic cure, fidaxomicin (odds ratio 0·67, 95% CI 0·55–0·82) and teicoplanin (0·37, 0·14–0·94) were significantly better than vancomycin. Teicoplanin (0·27, 0·10–0·70), ridinilazole (0·41, 0·19–0·88), fidaxomicin (0·49, 0·35–0·68), surotomycin (0·66, 0·45–0·97), and vancomycin (0·73, 0·56–0·95) were better than metronidazole. Bacitracin was inferior to teicoplanin (0·22, 0·06–0·77) and fidaxomicin (0·40, 0·17–0·94), and tolevamer was inferior to all drugs except for LFF571 (0·50, 0·18–1·39) and bacitracin (0·67, 0·28–1·58). Global heterogeneity of the entire network was low (Cochran’s Q=15·70; p=0·47).

Interpretation

Among the treatments for non-multiply recurrent infections by C difficile, the highest quality evidence indicates that fidaxomicin provides a sustained symptomatic cure most frequently. Fidaxomicin is a better treatment option than vancomycin for all patients except those with severe infections with C difficile and could be considered as a first-line therapy. Metronidazole should not be recommended for treatment of C difficile.

Funding

None.

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Keywords: Clostridium difficile; Antibiotics; Fidaxomicin; Vancomycin; Metronidazole.

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#Effectiveness of targeted enhanced terminal #room #disinfection on #hospital-wide acquisition and #infection with #MDR organisms and #Clostridium difficile: … (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Effectiveness of targeted enhanced terminal room disinfection on hospital-wide acquisition and infection with multidrug-resistant organisms and Clostridium difficile: a secondary analysis of a multicentre cluster randomised controlled trial with crossover design (BETR Disinfection)

Deverick J Anderson, MD, Rebekah W Moehring, MD, Prof David J Weber, MD, Sarah S Lewis, MD, Luke F Chen, MBBS, J Conrad Schwab, MD, Paul Becherer, MD, Michael Blocker, MD, Patricia F Triplett, MD, Lauren P Knelson, MSPH, Yuliya Lokhnygina, PhD, Prof William A Rutala, PhD, Prof Daniel J Sexton, MD for the CDC Prevention Epicenters Program

Published: 04 June 2018 / DOI: https://doi.org/10.1016/S1473-3099(18)30278-0

© 2018 Elsevier Ltd. All rights reserved.

 

Summary

Background

The hospital environment is a source of pathogen transmission. The effect of enhanced disinfection strategies on the hospital-wide incidence of infection has not been investigated in a multicentre, randomised controlled trial. We aimed to assess the effectiveness of four disinfection strategies on hospital-wide incidence of multidrug-resistant organisms and Clostridium difficile in the Benefits of Enhanced Terminal Room (BETR) Disinfection study.

Methods

We did a prespecified secondary analysis of the results from the BETR Disinfection study, a pragmatic, multicentre, crossover cluster-randomised trial that assessed four different strategies for terminal room disinfection in nine hospitals in the southeastern USA. Rooms from which a patient with a specific infection or colonisation (due to the target organisms C difficile, meticillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci (VRE), or multidrug-resistant Acinetobacter spp) was discharged were terminally disinfected with one of four strategies: standard disinfection (quaternary ammonium disinfectant, except for C difficile, for which 10% hypochlorite [bleach] was used; reference); standard disinfection and disinfecting ultraviolet light (UV-C), except for C difficile, for which bleach and UV-C was used (UV strategy); 10% hypochlorite (bleach strategy); and bleach and UV-C (bleach and UV strategy). We randomly assigned the sequence of strategies for each hospital (1:1:1:1), and each strategy was used for 7 months, including a 1-month wash-in period and 6 months of data collection. The prespecified secondary outcomes were hospital-wide, hospital-acquired incidence of all target organisms (calculated as number of patients with hospital-acquired infection with a target organism per 10 000 patient days), and hospital-wide, hospital-acquired incidence of each target organism separately. BETR Disinfection is registered with ClinicalTrials.gov, number NCT01579370.

Findings

Between April, 2012, and July, 2014, there were 271 740 unique patients with 375 918 admissions. 314 610 admissions met all inclusion criteria (n=73 071 in the reference study period, n=81 621 in the UV study period, n=78 760 in the bleach study period, and n=81 158 in the bleach and UV study period). 2681 incidenct cases of hospital-acquired infection or colonisation occurred during the study. There was no significant difference in the hospital-wide risk of target organism acquisition between standard disinfection and the three enhanced terminal disinfection strategies for all target multidrug-resistant organisms (UV study period relative risk [RR] 0·89, 95% CI 0·79–1·00; p=0·052; bleach study period 0·92, 0·79–1·08; p=0·32; bleach and UV study period 0·99, 0·89–1·11; p=0·89). The decrease in risk in the UV study period was driven by decreases in risk of acquisition of C difficile (RR 0·89, 95% CI 0·80–0·99; p=0·031) and VRE (0·56, 0·31–0·996; p=0·048).

Interpretation

Enhanced terminal room disinfection with UV in a targeted subset of high-risk rooms led to a decrease in hospital-wide incidence of C difficile and VRE. Enhanced disinfection overcomes limitations of standard disinfection strategies and is a potential strategy to reduce the risk of acquisition of multidrug-resistant organisms and C difficile.

Funding

US Centers for Disease Control and Prevention.

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Keywords: Antibiotics; Drugs Resistance; Clostridium difficile; Nosocomial Outbreaks.

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#Antimicrobial susceptibility and ribotypes of #Clostridium difficile isolates from a Phase 2 clinical trial of #ridinilazole (SMT19969) and #vancomycin (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Antimicrobial susceptibility and ribotypes of Clostridium difficile isolates from a Phase 2 clinical trial of ridinilazole (SMT19969) and vancomycin

David R Snydman, Laura A McDermott, Cheleste M Thorpe, Justin Chang, Jenna Wick, Seth T Walk, Richard J Vickers

Journal of Antimicrobial Chemotherapy, dky135, https://doi.org/10.1093/jac/dky135

Published: 30 April 2018

 

Abstract

Objectives

We evaluated the antimicrobial susceptibility and ribotypes of Clostridium difficile isolates from participants in a Phase 2 study of ridinilazole, a novel targeted-spectrum agent for treatment of C. difficile infection.

Methods

Participants received ridinilazole (200 mg twice daily) or vancomycin (125 mg four times daily) for 10 days (ClinicalTrials.gov: NCT02092935). The MICs of ridinilazole and comparators for C. difficile isolates from stool samples were determined by agar dilution. Toxin gene profiling was performed by multiplex PCR and ribotype identification by capillary electrophoresis.

Results

Eighty-nine isolates were recovered from 88/100 participants (one participant had two strains at baseline). The median colony count (cfu/g stool) was 1.9 × 104 (range: 2.5 × 102–7.0 × 106). Twelve participants (three received ridinilazole and nine received vancomycin) experienced recurrence, confirmed by immunoassays for free toxin in stool samples. The ribotype of eight out of nine isolates obtained at recurrence matched those of the initial isolates. All isolates, including those obtained at recurrence, were susceptible to ridinilazole within the expected range [median (range) MIC: 0.12 (0.06–0.5) mg/L]. The median (range) vancomycin MIC was 1 (0.5–4.0) mg/L. At baseline, 13.6% and 13.3% of samples in the ridinilazole and vancomycin groups were positive for VRE, increasing to 23.7% and 29.7% by day 40, respectively. Common ribotypes included 014-20 (14 isolates), 027 (13), 106 (7), 002 (7), 078-126 (4), 001 (4), 087 (3) and 198 (3). Toxin gene profiling of nearly all baseline isolates (98.9%) revealed a binary toxin gene (cdtA/cdtB) prevalence of 35%.

Conclusions

Ridinilazole potently inhibited recovered C. difficile isolates. Recurrence was not associated with altered susceptibility.

Issue Section: ORIGINAL RESEARCH

© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

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Keywords: Antibiotics; Clostridium difficile; Vancomycin; Ridinilazole.

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#NYC House #Mice (Mus musculus) as Potential #Reservoirs for Pathogenic #Bacteria and #Antimicrobial Resistance Determinants (mBio, abstract)

[Source: mBio, full page: (LINK). Abstract, edited.]

New York City House Mice (Mus musculus) as Potential Reservoirs for Pathogenic Bacteria and Antimicrobial Resistance Determinants

Simon H. Williams a,  Xiaoyu Che a,  Ashley Paulick b, Cheng Guo a, Bohyun Lee a, Dorothy Muller a, Anne-Catrin Uhlemann c, Franklin D. Lowy c, Robert M. Corrigan d, W. Ian Lipkin a

a Center for Infection and Immunity, Columbia University, New York, New York, USA; b Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA; c Division of Infectious Diseases, Department of Medicine, Columbia University, New York, New York, USA; d RMC Pest Management Consulting, Briarcliff Manor, New York, USA

Claire M. Fraser, Editor

Author Affiliations: University of Maryland, School of Medicine

Address correspondence to W. Ian Lipkin, wil2001@cumc.columbia.edu.

 

ABSTRACT

House mice (Mus musculus) thrive in large urban centers worldwide. Nonetheless, little is known about the role that they may play in contributing to environmental contamination with potentially pathogenic bacteria. Here, we describe the fecal microbiome of house mice with emphasis on detection of pathogenic bacteria and antimicrobial resistance genes by molecular methods. Four hundred sixteen mice were collected from predominantly residential buildings in seven sites across New York City over a period of 13 months. 16S rRNA sequencing identified Bacteroidetes as dominant and revealed high levels of Proteobacteria. A targeted PCR screen of 11 bacteria, as indicated by 16S rRNA analyses, found that mice are carriers of several gastrointestinal disease-causing agents, including Shigella, Salmonella, Clostridium difficile, and diarrheagenic Escherichia coli. Furthermore, genes mediating antimicrobial resistance to fluoroquinolones (qnrB) and β-lactam drugs (blaSHV and blaACT/MIR) were widely distributed. Culture and molecular strain typing of C. difficile revealed that mice harbor ribotypes associated with human disease, and screening of kidney samples demonstrated genetic evidence of pathogenic Leptospira species. In concert, these findings support the need for further research into the role of house mice as potential reservoirs for human pathogens and antimicrobial resistance in the built environment.

 

IMPORTANCE

Mice are commensal pests often found in close proximity to humans, especially in urban centers. We surveyed mice from seven sites across New York City and found multiple pathogenic bacteria associated with febrile and gastrointestinal disease as well as an array of antimicrobial resistance genes.

KEYWORDS: antimicrobial resistance –  bacteriome –  mice –  New York City

 

FOOTNOTES

Citation Williams SH, Che X, Paulick A, Guo C, Lee B, Muller D, Uhlemann A-C, Lowy FD, Corrigan RM, Lipkin WI. 2018. New York City house mice (Mus musculus) as potential reservoirs for pathogenic bacteria and antimicrobial resistance determinants. mBio 9:e00624-18. https://doi.org/10.1128/mBio.00624-18.

For a companion article on this topic, see https://doi.org/10.1128/mBio.01354-17.

Received 19 March 2018  – Accepted 22 March 2018  – Published 17 April 2018

Copyright © 2018 Williams et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

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Keywords: USA; New York City; House Mice; Antibiotics; Drugs Resistance; Clostridium difficile; Leptospira spp.; Shigella spp.; Salmonella spp.; E. Coli.

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Extended-pulsed #fidaxomicin versus #vancomycin for #Clostridium difficile infection in patients 60 years and older (EXTEND): a randomised, controlled, open-label, phase 3b/4 trial (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients 60 years and older (EXTEND): a randomised, controlled, open-label, phase 3b/4 trial

Prof Benoit Guery, MD, Prof Francesco Menichetti, MD, Veli-Jukka Anttila, MD, Nicholas Adomakoh, MBBS, ProfJose Maria Aguado, MD, Karen Bisnauthsing, BSc, Areti Georgopali, MD, Simon D Goldenberg, MD, Andreas Karas, MD, Gbenga Kazeem, PhD, Chris Longshaw, PhD, Jose Alejandro Palacios-Fabrega, PhD, Prof Oliver A Cornely, MD, Maria J G T Vehreschild, MD for the EXTEND Clinical Study Group††Members listed in the appendix

Published: 19 December 2017 / DOI: http://dx.doi.org/10.1016/S1473-3099(17)30751-X

© 2017 Elsevier Ltd. All rights reserved.

 

Summary

Background

Clostridium difficile infection causes severe complications and frequently recurs. An extended-pulsed fidaxomicin regimen might facilitate sustained clinical cure by prolonging C difficile suppression and supporting gut microbiota recovery. We aimed to compare clinical outcomes of extended-pulsed fidaxomicin with standard vancomycin.

Methods

In this randomised, controlled, open-label, superiority study, we recruited hospitalised adults aged 60 years and older with confirmed C difficile infection at 86 European hospitals. Patients were randomly assigned (1:1) using an interactive web response system to receive extended-pulsed fidaxomicin (200 mg oral tablets, twice daily on days 1–5, then once daily on alternate days on days 7–25) or vancomycin (125 mg oral capsules, four times daily on days 1–10), stratified by baseline C difficile infection severity, cancer presence, age (≥75 years vs <75 years), and number of previous C difficile infection occurrences. The primary endpoint was sustained clinical cure 30 days after end of treatment (day 55 for extended-pulsed fidaxomicin and day 40 for vancomycin), assessed in all randomised patients who met the inclusion criteria and received at least one dose of study medication (modified full analysis set). Adverse events were assessed in all patients who received at least one dose of study drug. The study is registered with ClinicalTrials.gov, number NCT02254967.

Findings

Between Nov 6, 2014, and May 5, 2016, 364 patients were enrolled and randomly assigned to receive extended-pulsed fidaxomicin or vancomycin. 362 patients received at least one dose of study medication (181 in each group). 124 (70%) of 177 patients in the modified full analysis set receiving extended-pulsed fidaxomicin achieved sustained clinical cure 30 days after end of treatment, compared with 106 (59%) of 179 patients receiving vancomycin (difference 11% [95% CI 1·0–20·7], p=0·030; odds ratio 1·62 [95% CI 1·04–2·54]). Incidence of treatment-emergent adverse events did not differ between extended-pulsed fidaxomicin (121 [67%] of 181) and vancomycin (128 [71%] of 181) treatment arms. One death in the vancomycin arm was considered by the investigator to be related to study drug.

Interpretation

Extended-pulsed fidaxomicin was superior to standard-dose vancomycin for sustained cure of C difficile infection, and, to our knowledge, extended-pulsed fidaxomicin recurrence rates in this study are the lowest observed in a randomised clinical trial of antibiotic treatment for C difficile infection.

Funding

Astellas Pharma, Inc.

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Keywords: Antibiotics; Drugs Resistance; Clostridium difficile; Fidaxomicin; Vancomycin.

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#Surveillance of #antibiotic #resistance among common #Clostridium difficile ribotypes in #HK (Sci Rep., abstract)

[Source: Scientific Reports, full page: (LINK). Abstract, edited.]

Surveillance of antibiotic resistance among common Clostridium difficile ribotypes in Hong Kong

Viola C. Y. Chow, Thomas N. Y. Kwong, Erica W. M. So, Yolanda I. I. Ho, Sunny H. Wong,
Raymond W. M. Lai & Raphael C. Y. Chan

Scientific Reports 7, Article number: 17218 (2017) / doi:10.1038/s41598-017-17523-7

Received: 14 August 2017 – Accepted: 27 November 2017 – Published online: 08 December 2017

 

Abstract

Incidence of Clostridium difficile infection (CDI) is rapidly increasing and it poses a major health burden globally. However, data regarding the epidemiology of CDI in Asia are limited. We aimed to characterize the antimicrobial susceptibility patterns of common ribotypes of toxigenic C. difficile in Hong Kong. Fifty-three PCR ribotypes were identified among 284 toxigenic C. difficile clinical isolates. The five most prevalent ribotypes were 002 (13%), 017 (12%), 014 (10%), 012 (9.2%), and 020 (9.5%). All tested C. difficile strains remained susceptible to metronidazole, vancomycin, meropenem and piperacillin/tazobactam, but highly resistant to cephalosporins. Of the fluoroquinolones, highest resistance to ciprofloxacin was observed (99%), followed by levofloxacin (43%) and moxifloxacin (23%). The two newly emerged PCR ribotypes, 017 and 002, demonstrated high levels of co-resistance towards clindamycin, tetracycline, erythromycin and moxifloxacin. PCR ribotypes 017 and 002 with multi-drug resistance are rapidly emerging and continuous surveillance is important to monitor the epidemiology of C. difficile to prevent outbreaks of CDI.

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Keywords: Antibiotics; Drugs Resistance; Clostridium difficile; HK.

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