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DRUG INFORMATION ROUNDS

Single Versus Combined Antibiotic Therapy for Gram-Negative Infections

at time of writing, Infectious Diseases Specialty Resident, Department of Pharmacy, University of North Carolina Hospitals; Clinical Instructor, School of Pharmacy, University of North Carolina, Chapel Hill, NC; now, Clinical Assistant Professor, School of Pharmacy, Temple University, Philadelphia, PA

Ralph H Raasch, PharmD FCCP BCPS

Associate Professor of Pharmacy, School of Pharmacy, University of North Carolina Hospitals

John C Rublein, PharmD BCPS

Clinical Specialist, Department of Pharmacy, University of North Carolina Hospitals

Reprints: Olga M Klibanov PharmD, Department of Pharmacy Practice, School of Pharmacy, Temple University, 3307 N. Broad St., Philadelphia, PA 19140-5101, fax 215/707-8326, klibanov{at}temple.edu

OBJECTIVE: To evaluate the available clinical data regarding single versus combination antimicrobial therapy for treatment of gram-negative infections, focusing on the more recent data in predominantly nonneutropenic hosts. In vitro and in vivo data regarding various antimicrobial combinations are also discussed.

DATA SOURCES: Clinical trials, review articles, and meta-analyses were identified from a MEDLINE search (1960–July 2003). Special attention was given to clinical outcome trials performed since 1989. Search terms included gram-negative infections, drug synergism, Pseudomonas aeruginosa, monotherapy, combination therapy, carbapenems, ß-lactams, cefepime, aminoglycosides, and fluoroquinolones.

DATA SYNTHESIS: Although most of the studies were not randomized, double-blind, or controlled, the most recent literature indicates that monotherapy with agents that are active against isolated organisms, including P. aeruginosa, may be appropriate for most patients. Efficacy outcomes, including mortality, did not significantly differ in most studies comparing single and combination therapies. Some trials suggest that combination therapy may be preferred in neutropenic patients and those with pseudomonal infections.

CONCLUSIONS: Hospitalized patients with gram-negative infections are often treated with combination antimicrobial agents; however, some of the recently available data, although limited, suggest that administration of monotherapy is a feasible alternative in certain patient populations.

Key Words: combination therapy, gram-negative infections, monotherapy

Published Online, December 19, 2003. www.theannals.com, DOI 10.1345/aph.1D132

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