Antimicrobial susceptibility in Clostridioides difficile varies according to European region and isolate source

Author:

Freeman Jane123,Viprey Virginie1,Ewin Duncan1,Spittal William1,Clark Emma12,Vernon Jon1,Fawley Warren24,Davis Georgina1,Tkalec Valerija56,Wilcox Mark123ORCID,Rupnik Maja356,Davies Kerrie123ORCID, ,Bonten Marc,Davies Kerrie A,Wilcox Mark H,Kuijper Ed,Rupnik Maja,Wingen-Heimann Sebastian,Tacconelli Evelina,Vilken Tuba,Petrosillo Nicola

Affiliation:

1. Healthcare Associated Infections Research Group, Leeds Institute of Medical Research, University of Leeds , Leeds , UK

2. Department of Microbiology, Leeds Teaching Hospitals NHS Trust, Leeds , UK

3. European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Study Group for Clostridioides difficile (ESGCD), Basel, Switzerland

4. C. difficile Ribotyping Network for England and Wales , UK Health Security Agency, Leeds , UK

5. National Laboratory for Health, Environment and Food (NLZOH), Centre for Medical Microbiology , Maribor , Slovenia

6. Faculty of Medicine, University of Maribor , Maribor , Slovenia

Abstract

Abstract Objectives Clostridioides difficile epidemiology is evolving with country-associated emerging and resistant ribotypes (RT). Antimicrobial susceptibility testing of C. difficile isolated from clinical and animal samples collected across Europe in 2018 was performed to provide antimicrobial resistance data and according to C. difficile RTs and source. Methods Samples were cultured for C. difficile and isolates PCR ribotyped. Metronidazole, vancomycin, fidaxomicin, moxifloxacin, clindamycin, imipenem, tigecycline, linezolid, rifampicin and meropenem minimum inhibitory concentrations (MICs) for 280 clinical and 126 animal isolates were determined by Wilkins–Chalgren agar dilution. Results Fidaxomicin was the most active antimicrobial (all isolates geometric mean MIC = 0.03 mg/L) with no evidence of reduced susceptibility. Metronidazole MICs were elevated among RT027 (1.87 mg/L) and RT181 clinical isolates (1.03 mg/L). RT027 and RT181 had elevated geometric mean moxifloxacin MICs (14.49 mg/L, 16.88 mg/L); clindamycin (7.5 mg/L, 9.1 mg/L) and rifampicin (0.6 mg/L, 21.5 mg/L). Five isolates (RT002, RT010 and RT016) were metronidazole resistant (MIC = 8 mg/L) and 10 (RT027; RT198) had intermediate resistance (4 mg/L). Metronidazole MICs were not elevated in animal isolates. Increased geometric mean vancomycin MICs were observed among RT078, mostly isolated from animals, but there was no resistance (MIC ≥ 4 mg/L). Clinical and animal isolates of multiple RTs showed resistance to moxifloxacin and clindamycin. No resistance to imipenem or meropenem was observed. Conclusion Increased antimicrobial resistance was detected in eastern Europe and mostly associated with RT027 and related emerging RT181, while clinical isolates from northern and western Europe had the lowest general levels of resistance.

Funder

Innovative Medicines Initiative

European Federation of Pharmaceutical Industries and Associations

Publisher

Oxford University Press (OUP)

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