Antibiotic combinations: should they be tested?

When antibiotic combinations are used to provide a broader spectrum of antimicrobial activity or in an attempt to prevent the emergence of resistant organisms, it is rarely necessary or practical to perform tests of drug interactions in vitro. In vitro testing of combinations may be useful when combinations are used in an attempt to attain synergistic interactions. In some cases, screening methods can be used as substitutes for formal synergy testing. This paper examines the mechanisms of antibiotic interaction leading to synergism or antagonism, surveys attempts to correlate in vitro observations with efficacy in animal models, and reviews clinical data providing evidence for or against a useful role of synergistic antibiotic interactions in the treatment of human infections.