Combination Therapy Restricts Emergence of Resistance

When antibiotic resistance mutations are so protective that safe doses cannot maintain drug concentrations above MPC with a single agent, combination therapy can close the mutant selection window. In this dosing strategy, two or more compounds are sought that act independently: A resistance mutation against one does not affect the other. (This is called the absence of cross resistance.) In addition, the compounds should not interfere with each other. When the concentrations of the two compounds both exceed their respective MIC, the pathogen needs to acquire two concurrent mutations for growth. Because obtaining two concurrent resistance mutations is expected to occur rarely with bacteria, drug combinations will restrict emergence of resist....²²¹