488. Oral Vancomycin Plus Intravenous Metronidazole for Severe Clostridium difficile Infection in Critically Ill Patients

Abstract

BackgroundThere remains a paucity of data regarding optimal treatment of patients with severe Clostridium difficile infection (CDI) in the intensive care unit (ICU). Based on expert opinion, the 2018 SHEA-IDSA CDI Clinical Practice Guidelines recommend combination therapy (oral vancomycin [PO VAN] plus intravenous metronidazole [IV MDZ]) in fulminant CDI only. A 2015 study suggested a mortality benefit with combination therapy of PO VAN plus IV MDZ for ICU patients regardless of severity. The objective of this study was to determine the impact of combination therapy on clinical outcomes in ICU patients with severe CDI, compared with PO VAN monotherapy.MethodsSingle-center, retrospective, cohort of adult patients admitted to an ICU between April 2016 and April 2018 with a positive C. difficile nucleic acid amplification test and an order for PO VAN were screened for inclusion. Patients were excluded if they had life-threatening intra-abdominal complications, including toxic megacolon/emergent colectomy. The primary outcome was 30-day in-hospital all-cause mortality. In a subgroup analysis, patients were matched using Acute Physiology and Chronic Health Evaluation (APACHE) II scores. Logistic regression was conducted to identify clinical variables associated with mortality.ResultsOne hundred one patients were included; 47 received combination therapy with IV MDZ. Baseline characteristics were similar across groups, except patients in the IV MDZ group had a higher median white blood cell (WBC) count at diagnosis (18.4 vs. 13.9, P = 0.023) and were more likely to receive a higher dose (500 mg) of PO VAN (36.2% vs. 7.4%, P < 0.0001). Thirty-day mortality was 14.9% in the combination group vs. 7.4% in the monotherapy group, (P = 0.338). APACHE II Score was the only variable independently associated with 30-day mortality (OR = 1.13, 95% CI 1.03 – 1.24). There was no difference in probability of receiving IV MDZ based on APACHE II score. In a subgroup of patients matched by APACHE II score (n = 76), mortality remained nonsignificantly different (15.8% vs. 9.7%, P = 0.480).ConclusionOur data question the utility of IV MDZ in addition to PO VAN for ICU patients with severe CDI. There remains a possibility for confounding by indication in this retrospective analysis.Disclosures E. Heil, ALK-Abelló: Grant Investigator, Research grant. K. Claeys, Nabriva: Scientific Advisor, Consulting fee. Melinta: Scientific Advisor, Consulting fee.