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.
