Do antibiotic combinations prevent the emergence of resistant organisms?

Abstract

Antibiotic combinations are often used in the therapy of infectious diseases to broaden the antibacterial spectrum and to enhance antimicrobial activity. Another potential reason for combination therapy is to reduce or prevent the emergence of resistant organisms during therapy. Antituberculous chemotherapy provides a classic example in which drug combinations have successfully prevented the emergence of drug-resistant organisms and improved clinical outcome. The purpose of this brief report is to review the success of combination therapy in preventing resistance in more common bacterial infections.The emergence of resistance during single-drug therapy is a well-documented clinical phenomenon, especially with the broad-spectrum ß-lactams against gram-negative bacilli. As with Mycobacterium tuberculosis, the resistant organisms are generally thought to be naturally occurring mutants selected by drug exposure. Because mutation frequencies appear to vary from 10-6 to 10-8, it is not surprising that emergence of resistant organisms observed clinically occurs primarily at sites of high organism density, such as the respiratory and urinary tracts.