2433. Oral Vancomycin Plus Intravenous Metronidazole for Severe Clostridioides difficile Infection in Critically Ill Patients

BACKGROUND: Molecular strain 027/NAP1/BI (NAP1) is a common cause of Clostridioides difficile infections (CDI). Despite high morbidity and mortality, optimal therapy remains elusive. There is also a paucity of data regarding optimal treatment of critically ill patients with severe CDI. We aimed to determine the impact of combination therapy (intravenous metronidazole [IV MTZ] plus oral vancomycin [PO VAN]) on clinical outcomes in critically ill patients with severe CDI, including those with NAP1 CDI. METHODS: Retrospective cohort of adult patients admitted to an intensive care unit (ICU) from April 2016 to October 2018 with a positive C. difficile PCR and an order for PO VAN. Patients with an order for IV MTZ for at least 72 hours formed the combination therapy group. A subset of patients had stool samples collected for NAP1 identification via GeneXpert C. difficile Epi molecular assay. The primary outcome was 30-day in-hospital mortality. A subgroup was matched using Acute Physiology and Chronic Health Evaluation (APACHE) II Scores. Cox regression was conducted to identify variables associated with time to mortality. RESULTS: 138 patients were included; 60 (43.5%) received IV MTZ. Patients with IV MTZ had a higher median WBC count at diagnosis (20.9 vs 15.9, P = 0.0002) and were more likely to receive a higher dose of PO VAN (31.7% vs 12.9%, P = 0.008). 42 patients had NAP1 testing, 11 were positive (26.2%). There was no difference in probability of receiving IV MTZ based on APACHE II, however, NAP1+ were more likely to receive IV MTZ (50% vs 16.7%, P = 0.049). Clinical success was higher in the monotherapy group (46.8% vs 16.7%, P = 0.002). There was no difference in mortality (20% vs 14.1%, P = 0.368). In a subgroup of patients matched by APACHE II (n = 96), mortality remained non-significantly different (18.8% vs 14.6%, P = 0.785). Adjusted for IV MTZ, APACHE II (aHR = 1.06, 95% CI 1–1.12) and number of severity criteria (aHR = 2.08, 95% CI 1.40 – 2.97) were associated with mortality. There was no difference in mortality (9.1% vs 3.2% P = 0.459) or clinical success (18.2% vs 33.7%, P = 0.283) among NAP1+ vs. NAP- patients. CONCLUSION: Our data questions the utility of IV MTZ with PO VAN for ICU patients with severe CDI, including NAP1 infections. There remains a possibility for confounding by indication in our analysis. DISCLOSURES: All authors: No reported disclosures.