Antibiotic Usage and Healthcare-Associated Clostridioides difficile in Patients with and Without COVID-19: A Tertiary Hospital Experience

<b>Background/Objectives</b>: Data about the relationship between COVID-19 and healthcare-associated <i>Clostridioides difficile</i> infection (HA-CDI) occurrence are still controversial. This study examines antibiotics associated with CDI in patients with and without COVID-19 infection. <b>Methods</b>: A prospective cohort study was conducted at the University Clinical Center Belgrade, Serbia, from January 2019 to December 2021. Patients with the first episode of HA-CDI without and with COVID-19 were included. Results of bacteriology analyses, demographic and clinical data, and data on antibiotic usage and daily defined doses (DDD) were collected by the hospital Infection Control Team. <b>Results</b>: Out of 547 HA-CDI cases, 341 (62.3%) had COVID-19 infection. HA-CDI patients with COVID-19 were significantly younger (<i>p</i> = 0.017) with fewer comorbidities (<0.001). Two or more antibiotics in therapy were more frequently used by those patients (<i>p</i> = 0.03). COVID-19 patients were treated significantly more by third- and fourth-generation cephalosporins, fluoroquinolones (<i>p</i> < 0.001) and macrolides (<i>p</i> = 0.01). Ceftriaxone had a higher median DDD in COVID-19 patients (6.00, range 1.00-20.00) compared to non-COVID-19 patients (4.00, range 1.00-14.00), (<i>p</i> = 0.007). Conversely, meropenem showed a lower median DDD in COVID-19 patients. Multivariate analysis identified the use of fourth-generation cephalosporins and fluoroquinolones as independent risk factors for HA-CDI in COVID-19 patients. <b>Conclusions</b>: Patients with HA-CDI and COVID-19 more frequently received two or more antibiotics before the onset of HAI-CDI. The third and fourth generations of cephalosporins, fluoroquinolones and macrolides were administered significantly more often in these patients. More frequent administration of ceftriaxone was observed, but the lower DDD associated with meropenem needed additional analysis.