Clostridioides difficile infection: are the three currently used antibiotic treatment options equal from pharmacological and microbiological points of view?

Recently, the recommendations for the treatment of Clostridioides difficile infection (CDI) have been updated. However, in addition to the clinical efficacy data, the drug of choice should ideally represent optimal antimicrobial stewardship, with an emphasis on rapid restoration of the gut microbiota to minimize the risk of infection relapses. Oral administration of metronidazole results in low concentration in stool, and interaction with fecal microbiota reduces its antimicrobial bioactivity. Reported elevated minimum inhibitory concentrations of metronidazole in epidemic C. difficile ribotypes and the emergence of plasmid-mediated resistance to metronidazole represent additional potential risks for clinical failure. If metronidazole is the only CDI treatment option, antimicrobial susceptibility testing on agar containing heme should be performed in C. difficile isolate. Compared with metronidazole, oral vancomycin and fidaxomicin reach very high concentrations in the stool, and therefore can quickly reduce C. difficile shedding. Health care facilities with higher CDI incidence and/or occurrence of epidemic ribotypes should not use metronidazole because prolonged C. difficile shedding can increase the risk for further C. difficile transmission. Only fidaxomicin has a narrow spectrum of antimicrobial activity, which might be, together with persistence on spores, the main contributing factor to reduce the recurrent CDI rates.