Management of infections caused by gram-negative bacilli: the role of antimicrobial combinations

Treatment with antimicrobial combinations is generally used to provide broad-spectrum coverage and/or to enhance antimicrobial activity (synergism). Extensive in vitro documentation of synergism exists for many such combinations, but an obvious benefit has been difficult to demonstrate clinically. Several types of therapeutically useful combinations often result in synergism; these combinations include a cell wall-active agent with an aminoglycosidic aminocyclitol, a beta-lactamase inhibitor with a beta-lactam antibiotic, and agents that inhibit sequential steps in a metabolic pathway. Combinations of beta-lactam antibiotics may be synergistic by means of several mechanisms, but such combinations have significant potential for antagonism when used against gram-negative bacilli and, thus, must be evaluated closely before clinical use.