Combination therapy as a tool to prevent emergence of bacterial resistance

Emergence of resistance is an ever increasing problem. One of the methods by which emergence of resistance may possibly be prevented, or at least delayed, is the use of combination therapy. Since the emergence of resistant mutants is a direct result of selective pressure by antimicrobial therapy, the chance of mutants resistant to two antimicrobials in the parent population being present is a product of mutation frequencies, provided that resistance mechanisms are independent. Comparative studies in in vitro pharmacokinetic models and in vivo indicate that emergence of resistance is less common when combination therapy is used. This is particularly true for microorganisms known to develop resistance relatively quickly, such as Pseudomonas aeruginosa, and resistance mechanisms which occur at a relatively high frequency.