Antibiotic synergism and antimicrobial combinations in clinical infections

The clinical benefits of antimicrobial combinations in certain situations have been appreciated for over 30 years. Combinations of cell wall-active agents with aminoglycosides, of beta-lactams with inhibitors of beta-lactamase, and of drugs that inhibit separate steps along a critical metabolic pathway may produce an enhanced bactericidal effect. The concept that combination therapy may be advantageous when resistance to a single agent develops rapidly has been applied in the treatment of tuberculosis and in the design of regimens employing rifampin, a drug with excellent antimicrobial activity but against which resistance frequently develops. By permitting successful treatment of fungal infections with a smaller total dose of amphotericin B, combination therapy may reduce the risk of nephrotoxicity. Despite the drawbacks inherent in the use of multiple drugs, antimicrobial combinations continue to play an important role in clinical therapeutics.