Clostridioides difficile resistance to antibiotics, including post-COVID-19 data

ABSTRACTIntroduction Updating data on Clostridioides difficile antibiotic resistance is important for treatment improvement of C. difficile infections (CDIs).Areas covered Results from 20 countries were included. The mean resistance to 2 mg/l vancomycin, 2 mg/l metronidazole, 4 mg/l moxifloxacin, and 4 mg/l clindamycin was 4.7% (0 to ≥ 26% in two studies), 2.6% (0 to ≥ 40% in 3 studies), 34.9% (6.6->80%), and 61.0% (30->90%), respectively. Resistance to erythromycin (>60–88%), rifampin (>23–55.0%), imipenem (0.6 to > 78% in a clone), tigecycline (0-<5.0%), and fidaxomicin (0–2%) was also found. Resistance to ≥ 5 antibiotics of different classes was reported in some countries. High resistance and multidrug resistance were observed in hypervirulent and epidemic strains. Although only 1% of COVID-19 patients had CDIs, the proportion might be underestimated.Expert opinion C. difficile antimicrobial susceptibility varied by country/region, study period, and circulating ribotypes. For CDI treatment, fidaxomicin (preferably) or vancomycin is recommended, while metronidazole is suitable for mild infections. New approaches, including biotherapeutics (Rebyota), strains, antibiotics (ridinilazole and ibezapolstat), and monoclonal antibodies/cocktails merit further evaluation. Because of the resistance rate variations, C. difficile antibiotic susceptibility should be regularly monitored. Post-COVID-19 resistance should be separately presented. Some discrepancies between vancomycin and metronidazole results need to be clarified.Plain Language SummaryClostridioides difficile can cause mild to dangerous diarrhea in people following antibiotic use. Many antibacterial agents can cause diseases. However, treatment is limited to three antibiotics. The study of resistance to them is important for improving the treatment of infections. The study of resistance to other antibiotics helps to understand the spread and risks of infections. We discussed data about C. difficile antibiotic resistance from 20 countries according to recent publications. For the treatment of C. difficileinfections, fidaxomicin is the drug of choice with 0–2% resistance to it. Resistance to the two other antibiotics used to treat infections is less than 5% of isolates. Much higher resistance was found to antibiotics that can cause C. difficile infections such as ciprofloxacin, clindamycin, ceftriaxone, erythromycin, and others. The resistance varies according to the country, patients' groups, years of study, and circulating strains. The resistance was high in hypervirulent and epidemic strains. In some studies, there was resistance to 5 and 6 antibiotics of different classes. Antibiotic use and incidence of infections during the COVID-19 pandemic varied. However, the evolution of C. difficile infection during the pandemic has yet to be determined.KEYWORDS: AntibioticresistanceClostridioides difficileClostridium difficilehypervirulentmultidrug resistanceribotypestreatment Article highlights Recent data about C. difficile antibiotic resistance (AMR) in 20 countries was discussed.The drug of choice to treat C. difficile infections (CDIs) is fidaxomicin, with vancomycin as an alternative, and metronidazole for mild infections. The mean (>2 mg/l) vancomycin and metronidazole resistance rates were 4.7% and 2.6%, respectively, while fidaxomicin resistance (>1 mg/l, 0-2%) was absent or low.AMR to most antibiotics that can cause CDIs was high and widely variable. Imipenem resistance (up to 78.1% at >4 mg/l in a clone) was also found. Resistance to 5-6 antibiotics of different classes was detected in some countries and was prevalent in the imipenem-resistant RT017 and 'hypervirulent' RT027 strain.Although both antibiotic use and CDI incidence during the COVID-19 pandemic varied widely, the evolution of C. difficile AMR has yet to be determined.Newer biotherapeutics (Rebyota), strains or antibiotics (ridinilazole and ibezapolstat), and monoclonal antibodies/cocktails are promising. Phage therapy and vaccines are also interesting directions for future development.Declaration of interestThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants (unmentioned above) or patents received or pending, or royalties.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Supplementary materialSupplemental data for this article can be accessed online at https://doi.org/10.1080/17512433.2023.2252331Additional informationFundingThis work was supported by Medical University of Sofia, Bulgaria, under Grant/Contract No. [D-136/14.06.2022], project No. 7305/17.11.2021