Single versus combined antibiotic therapy for gram-negative infections

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.

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, beta-lactams, cefepime, aminoglycosides, and fluoroquinolones.

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.

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.