| Summary: | Oral vancomycin and metronidazole, though they are the therapeutic choice for <i>Clostridioides difficile</i> infections (CDIs), also markedly disturb microbiota, leading to a prolonged loss of colonization resistance to <i>C. difficile</i> after therapy; as a result, their use is associated with a high treatment failure rate and high recurrent rate. An alternative for CDIs therapy contains the delivery of beneficial (probiotic) microorganisms into the intestinal tract to restore the microbial balance. Recently, mixture regimens containing <i>Lactobacillus</i> species, <i>Saccharomyces boulardii</i>, or <i>Clostridium butyricum</i> have been extensively studied for the prophylaxis of CDIs. Fecal microbiota transplantation (FMT), the transfer of (processed) fecal material from healthy donors to patients for treating CDIs, combined with vancomycin was recommended as the primary therapy for multiple recurrent CDIs (rCDIs). Either probiotics or FMT have been utilized extensively in preventing or treating CDIs, aiming at less disturbance in the microbiota to prevent rCDIs after therapy cessation. Otherwise, many newly developed therapeutic agents have been developed and aim to preserve microbiota during CDI treatment to prevent disease recurrence and might be useful in clinical patients with rCDIs in the future.
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