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

Abstract 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.