Antimicrobial Susceptibility of Clostridioides difficile in Spain: Multicenter Retrospective Cohort Study

<b>Background/Objetives</b>: The objective of this study was to determine the in vitro susceptibility profiles of clinical <i>Clostridioides difficile</i> isolates to metronidazole (MTZ), vancomycin (VAN), fidaxomicin (FDX), tigecycline (TGC), and eravacycline (ERV) in a multicenter Spanish cohort, and to evaluate their association with clinical factors. <b>Methods</b>: Strains were obtained from prospectively included patients in the ICD-ANCRAID-SEICV cohort (ClinicalTrials.gov ID: NCT04801862) in Andalucía and the Valencian Community between 1 January 2020 and 30 April 2023. Antimicrobial susceptibility testing was performed using E-test for MTZ, VAN, TGC, and ERV, and agar dilution for FDX. <b>Results</b>: The results were interpreted following EUCAST clinical breakpoints and ECOFF criteria. A total of 107 patients were included (median age 70 years; 65.4% women). Nearly half of the cases were community-acquired, 30% nosocomial, and the remainder healthcare-associated. Most infections were non-severe, and 32.7% experienced recurrence. Overall resistance levels were low: VAN and TGC each showed resistance in 2.8% of isolates, followed by MTZ (1.9%). Only one isolate was resistant to FDX (0.9%), and none to ERV. MIC90 values were low for all agents. Some resistant isolates displayed co-resistance and were recovered from patients with prior antibiotic exposure. Among the seven patients carrying resistant strains, most were women, and the cases were predominantly community-acquired. Clinical characteristics, including age, comorbidity, infection origin, and severity, did not differ from those with susceptible isolates. All patients achieved clinical cure without recurrent infection. No association was found between elevated MIC values and recurrence or greater severity. <b>Conclusions:</b> FDX and ERV demonstrated excellent in vitro activity. Resistance to MTZ, VAN, and TGC was uncommon but detectable. Findings highlight the need for continued antimicrobial resistance surveillance and evaluation of its potential clinical impact.