Grüneberg R N
Curr Med Res Opin. 1982;8(2):128-33. doi: 10.1185/03007998209109768.
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.
用磺胺甲恶唑和甲氧苄啶对尿路病原体进行的棋盘格研究表明，这两种药物联合使用从未产生拮抗作用，但通常显示出很少或没有协同效应。一个例外是对固有耐磺胺类药物的粪肠球菌，在所测试的所有菌株中均显示出明显的协同作用（F.I.C.指数小于0.3）。这种协同作用被认为具有临床相关性。采用一种新的体外测试系统进行了实验，以确定磺胺甲恶唑与甲氧苄啶联合使用是否能防止细菌耐药性的出现。使用治疗期间血液中达到的药物浓度，结果表明单用甲氧苄啶治疗可能会导致产生对甲氧苄啶耐药的病原体，而用磺胺甲恶唑和甲氧苄啶治疗则可消除测试细菌且不会出现耐药性。使用尿液中的药物浓度，结果表明单用甲氧苄啶或与磺胺甲恶唑联合使用均可消除“尿路”病原体，且不会出现耐药菌。但这不一定能排除在接触较低、抑制性药物浓度的共生部位出现耐药菌的可能性。
