Prevention of emergence of bacterial resistance with the combination of sulphamethoxazole and trimethoprim.

An in vitro technique is described for testing the proposition that combining two antibiotics prevents the emergence of bacterial resistance to either. The model was applied to testing the combination of sulphamethoxazole and trimethoprim (co-trimoxazole). Under the test conditions when a doubly sensitive organism was exposed to sulphamethoxazole or trimethoprim alone, resistance to sulphamethoxazole or trimethoprim readily emerged. When exposed to both drugs together, the doubly sensitive organism was eliminated from the cultures without emergence of bacterial resistance to either drug. A sulphamethoxazole-resistant organism exposed to trimethoprim alone or to sulphamethoxazole plus trimethoprim developed trimethoprim resistance with equal facility. The experiments show that the use of sulphamethoxazole-trimethoprim prevents the emergence of bacterial resistance among doubly-sensitive strains.