In vitro studies with combinations of sulfamoxole and trimethoprim (co-trifamole)

Chequerboard studies with sulfamoxole and trimethoprim against urinary pathogens showed that the combination was never antagonistic but usually showed little or no synergistic effect. An exception was with the inherently sulphonamide-resistant Strep. faecalis in which marked synergism (F.I.C. Index less than 0.3) was shown with all strains tested. This synergism is thought to be clinically relevant. Experiments were undertaken with a new in vitro test system to establish whether the combination of sulfamoxole with trimethoprim will prevent the emergence of bacterial resistance. Using concentrations of the drugs attained in the blood during treatment, it was shown that trimethoprim monotherapy was likely to result in the emergence of trimethoprim-resistant pathogens, whereas treatment with sulfamoxole and trimethoprim resulted in the elimination of the test bacteria without the emergence of resistance. Using urinary concentrations of drugs, the "urinary' pathogen was shown to be eliminated by trimethoprim alone or in combination with sulfamoxole, without the emergence of resistant bacteria. This would not necessarily preclude the emergence of resistant bacteria in commensal sites exposed to lesser, sun-inhibitory drug concentrations.