624. Combination versus Monotherapy for Gram-Negative Bloodstream Infections: Matching by Predicted Prognosis
Session: Oral Abstract Session: Bacteremia and Endocarditis
Thursday, October 8, 2015: 3:00 PM
Room: 32--ABC
Background: The utility of combination antimicrobial therapy for treatment of gram-negative bloodstream infection (GN BSI) remains unclear. Prior studies have yielded contradictory results mostly due to differences in acute severity of illness, source of infection, and major comorbidities. The Bloodstream Infection Mortality Risk Score (BSIMRS) predicts prognosis of GN BSI with high discrimination based on the above variables. This retrospective, quasi-experimental cohort study examined the impact of empirical combination therapy (CT) as compared to monotherapy (MT) for GN BSI after matching by predicted prognosis using BSIMRS.

Methods: Hospitalized adults with first episodes of GN BSI from 2010-2013 at Palmetto Health Hospitals in Columbia, SC, USA were identified. Patients receiving empirical CT with beta-lactam plus aminoglycoside or fluoroquinolone were matched to patients receiving beta-lactam MT. Patients were matched by exact BSIMRS, age (± 10 years), sex, and beta-lactam type (anti-pseudomonal or non-pseudomonal). Multivariate Cox proportional hazards regression with propensity score adjustment was used to examine 28-day mortality overall and within predefined BSIMRS categories (< 5 and ≥ 5).

Results: Among 830 unique patients with GN BSI, 190 matched pairs of patients receiving CT and MT were included in the study (N=380, BSIMRS <5 in 212 [56%], BSIMRS ≥ 5 in 168 [44%]). The median age was 66 years, 204 (54%) were female, and 246 (65%) received anti-pseudomonal beta-lactams. Overall, mortality in patients who received CT and MT was 13% and 15%, respectively (P=0.51). After stratification by BSIMRS, mortality in both CT and MT was 1.1% in patients with BSIMRS < 5 (P=0.98) and 27% and 32%, respectively, in patients with BSIMRS ≥ 5 (P=0.47). After adjusting for the propensity to receive CT, risk of mortality was not significantly different for CT compared to MT (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.51-1.60). This finding persisted for both subgroups (BSIMRS < 5, HR 0.96, 95% CI 0.04-24.28; BSIMRS ≥ 5, HR 0.83, 95% CI 0.46-1.48).

Conclusion: There is no survival benefit from CT over MT for patients with GN BSI regardless of BSIMRS. Future studies will focus on the impact of CT in niched subgroups, e.g. patients with very high BSIMRS or with risk factors for antimicrobial resistance.

Julie Ann Justo, PharmD, MS, BCPS, AAHIVP1, P. Brandon Bookstaver, PharmD, FCCP, BCPS (AQ-ID), AAHIVP1, Joseph Kohn, PharmD, BCPS2, Helmut Albrecht, MD3 and Majdi Al-Hasan, MD3, (1)Department of Clinical Pharmacy and Outcomes Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, (2)Palmetto Health Richland, Columbia, SC, (3)Department of Medicine, Division of Infectious Diseases, University of South Carolina School of Medicine, Columbia, SC


J. A. Justo, Cempra Pharmaceuticals: Scientific Advisor , Consulting fee

P. B. Bookstaver, Forest Labs: Grant Investigator and Scientific Advisor , Consulting fee

J. Kohn, None

H. Albrecht, None

M. Al-Hasan, None

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