Co-Colonization of Non-difficile Clostridial Species in Antibiotic-Associated Diarrhea Caused by Clostridioides difficile

<b>Background/Objectives</b>: Antibiotic-associated diarrhea (AAD) is a public health problem that develops in the hospital setting. The most common causative agent of AAD is <i>Clostridioides difficile</i> infection (CDI), although other non-<i>difficile</i> Clostridia (NDC) might also be present. NDC include members of the RIC group such as <i>Clostridium ramosum</i> [<i>T. ramosa</i>], <i>Clostridium innocuum</i> and <i>Clostridium clostridioforme</i> [<i>E. clostridioformis</i>]. The co-colonization of NDC and CDI in patients with AAD has not been fully analyzed. <b>Methods</b>: We compared clinical and laboratory data of patients with <i>C. difficile</i> infection (CDI) plus NDC against patients with only CDI. This study was a retrospective, case-control study. Hospitalized confirmed CDI cases were analyzed. CDI detection was performed using a 2-step diagnostic algorithm, including glutamate dehydrogenase (GDH) with toxin A/toxin B assays and molecular detection of the <i>tpi</i> gene. Stool samples were cultured and colonies morphologically compatible with any Clostridia were identified with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Fisher's exact test and odds ratio (OR) were calculated to determine the degree of correlation between the variables and the study groups. <b>Results</b>: In the CDI + NDC group (<i>n</i> = 7), positive culture was observed for <i>C. ramosum</i> [<i>T. ramosa</i>] (<i>n</i> = 3), <i>C. innocuum</i> (<i>n</i> = 3), and <i>C. butyricum</i> (<i>n</i> = 1). According to our results, CDI + NDC patients received more days of antibiotic therapy, took more days to reduce diarrhea, had a significant increase in the number of days to suppress diarrhea, and previous hospitalizations were more frequently reported. <b>Conclusions</b>: In conclusion, the positive culture of NDC species such as <i>C. innocuum</i> or <i>C. ramosum</i> in patients with AAD caused by CDI correlates with treatment extension and/or failure.