Antimicrobial combinations in the therapy of infections due to gram-negative bacilli

Antimicrobial combinations are used most frequently to provide broad-spectrum coverage; however, they are also frequently employed to enhance antimicrobial activity (synergism). Although there is extensive in vitro documentation of synergism for many antibiotic combinations, a clear advantage for these combinations has been difficult to demonstrate in clinical studies. Several types of combinations have been useful in clinical medicine and frequently result in synergism. These include combinations of a cell wall-active agent with an aminoglycosidic aminocyclitol, combinations of a beta-lactamase inhibitor with a beta-lactam, and combinations of agents that inhibit sequential steps in a metabolic pathway. Given its spectrum of activity, aztreonam will often be used with clindamycin or a beta-lactam antibiotic. Combinations of beta-lactams may be synergistic via several mechanisms. However, these combinations also exhibit significant potential for antagonism when used against gram-negative bacilli and, therefore, require careful evaluation prior to clinical use.