488. Oral Vancomycin plus Intravenous Metronidazole for Severe Clostridium difficile Infection in Critically Ill Patients
Session: Poster Abstract Session: Healthcare Epidemiology: Updates in C. difficile
Thursday, October 4, 2018
Room: S Poster Hall
Background: There 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 to PO VAN monotherapy.

Methods: Single-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.

Results: 101 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 non-significantly different (15.8% vs 9.7%, P = 0.480).

Conclusion: Our data questions 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.

Ana Vega, PharmD1, Teri Hopkins, PharmD, BCPS2, Emily Heil, PharmD, BCPS-AQID1, Jennifer Johnson, PhD3, Surbhi Leekha, MBBS, MPH4 and Kimberly Claeys, PharmD, BCPS1, (1)Pharmacy Practice and Science, University of Maryland School of Pharmacy, Baltimore, MD, (2)South Texas Veterans Health Care System (STVHCS), San Antonio, TX, (3)University of Maryland, Baltimore, MD, (4)Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD


A. Vega, None

T. Hopkins, None

E. Heil, ALK-Abelló: Grant Investigator , Research grant .

J. Johnson, None

S. Leekha, None

K. Claeys, Nabriva: Scientific Advisor , Consulting fee . Melinta: Scientific Advisor , Consulting fee .

Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 3rd with the exception of research findings presented at the IDWeek press conferences.