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Multicenter Study
. 2020 Jan;39(1):169-177.
doi: 10.1007/s10096-019-03708-7. Epub 2019 Dec 7.

Five-year Pan-European, longitudinal surveillance of Clostridium difficile ribotype prevalence and antimicrobial resistance: the extended ClosER study

Jane Freeman  1   2 , Jonathan Vernon  3 , Sally Pilling  3 , Kirsti Morris  4 , Scott Nicolson  3 , Sharie Shearman  3 , Emma Clark  3 , Jose Alejandro Palacios-Fabrega  5 , Mark Wilcox  4   3 ; Pan-European Longitudinal Surveillance of Antibiotic Resistance among Prevalent Clostridium difficile Ribotypes’ Study Group
Affiliations
Multicenter Study

Five-year Pan-European, longitudinal surveillance of Clostridium difficile ribotype prevalence and antimicrobial resistance: the extended ClosER study

Jane Freeman et al. Eur J Clin Microbiol Infect Dis. 2020 Jan.

Abstract

Clostridium difficile infection (CDI) has been primarily treated with metronidazole or vancomycin. High recurrence rates, the emergence of epidemic PCR ribotypes (RTs) and the introduction of fidaxomicin in Europe in 2011 necessitate surveillance of antimicrobial resistance and CDI epidemiology. The ClosER study monitored antimicrobial susceptibility and geographical distribution of C. difficile RTs pre- and post-fidaxomicin introduction. From 2011 to 2016, 28 European countries submitted isolates or faecal samples for determination of PCR ribotype, toxin status and minimal inhibitory concentrations (MICs) of metronidazole, vancomycin, rifampicin, fidaxomicin, moxifloxacin, clindamycin, imipenem, chloramphenicol and tigecycline. RT diversity scores for each country were calculated and mean MIC results used to generate cumulative resistant scores (CRSs) for each isolate and country. From 40 sites, 3499 isolates were analysed, of which 95% (3338/3499) were toxin positive. The most common of the 264 RTs isolated was RT027 (mean prevalence 11.4%); however, RT prevalence varied greatly between countries and between years. The fidaxomicin geometric mean MIC for years 1-5 was 0.04 mg/L; only one fidaxomicin-resistant isolate (RT344) was submitted (MIC ≥ 4 mg/L). Metronidazole and vancomycin geometric mean MICs were 0.46 mg/L and 0.70 mg/L, respectively. Of prevalent RTs, RT027, RT017 and RT012 demonstrated resistance or reduced susceptibility to multiple antimicrobials. RT diversity was inversely correlated with mean CRS for individual countries (Pearson coefficient r = - 0.57). Overall, C. difficile RT prevalence remained stable in 2011-2016. Fidaxomicin susceptibility, including in RT027, was maintained post-introduction. Reduced ribotype diversity in individual countries was associated with increased antimicrobial resistance.

Keywords: Antimicrobial resistance; Antimicrobial susceptibility; Clostridium difficile; Ribotype prevalence; Surveillance.

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Conflict of interest statement

JF has received grants from Summit Therapeutics, Melinta and Morphochem.

MHW has received grants and consultancy fees from Abbott, Actelion, Alere, Astellas, bioMerieux, Cerexa, Cubist, Da Volterra, the European Tissue Symposium, MedImmune, Optimer, Pfizer, Qiagen, Sanofi-Pasteur, Summit, Synthetic Biologics and Valneva and consultancy fees from Astra Zeneca, Basilea, Durata, The Medicine Company, Merck, Nabriva, Pfizer, Roche and Seres.

JAPF is an employee of Astellas Pharma, Inc. and has a patent EP17167541.6 pending to Astellas Pharma Europe Ltd.

All other authors have no conflict of interest to declare.

Figures

Fig. 1
Fig. 1
Percentage prevalence by country of C. difficile PCR ribotypes in a year 1, b year 2, c year 3, d year 4 and e year 5 of the ClosER study. aNo submissions received from this country. Other = all other ribotypes with prevalence < 1%
Fig. 2
Fig. 2
Ribotype diversity by country during years 1–5 of the ClosER study
See this image and copyright information in PMC

References

    1. Baines S. D., O'Connor R., Freeman J., Fawley W. N., Harmanus C., Mastrantonio P., Kuijper E. J., Wilcox M. H. Emergence of reduced susceptibility to metronidazole in Clostridium difficile. Journal of Antimicrobial Chemotherapy. 2008;62(5):1046–1052. doi: 10.1093/jac/dkn313. - DOI - PubMed
    1. Barbut F., Mastrantonio P., Delmée M., Brazier J., Kuijper E., Poxton I. Prospective study of Clostridium difficile infections in Europe with phenotypic and genotypic characterisation of the isolates. Clinical Microbiology and Infection. 2007;13(11):1048–1057. doi: 10.1111/j.1469-0691.2007.01824.x. - DOI - PubMed
    1. Bauer MP, Notermans DW, van Benthem BH, Brazier JS, Wilcox MH, Rupnik DL, Monnet JT, Van Dissel JT, Kuijper EJ. Clostridium difficile infection in Europe: a hospital-based survey. Lancet. 2011;377:63–73. doi: 10.1016/S0140-6736(10)61266-4. - DOI - PubMed
    1. Clinical and Laboratory Standards Institute . Methods for antimicrobial susceptibility testing of anaerobic bacteria. 8. Wayne: CLSI; 2012. - PubMed
    1. Cornely OA, Crook DW, Esposito R, Poirier A, Somero MS, Weiss K, Sears P, Gorbach S. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. Lancet Infect Dis. 2012;12:281–289. doi: 10.1016/S1473-3099(11)70374-7. - DOI - PubMed

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