Institute of Medical Microbiology and Infection Control, Hospital of Goethe-University, Paul-Ehrlich-Str. 40, 60596 Frankfurt/Main, Germany.
Int J Antimicrob Agents. 2010 Dec;36(6):562-5. doi: 10.1016/j.ijantimicag.2010.08.007. Epub 2010 Oct 13.
Trimethoprim/sulfamethoxazole (SXT), alone and in combination with rifampicin (RIF), is a therapeutic option against Staphylococcus aureus, including strains expressing meticillin resistance. However, the antimicrobial activity of SXT is antagonised by thymidine, which can be present in infected and/or inflamed tissues such as the airways of cystic fibrosis (CF) patients. In this study, thymidine concentrations in CF sputa were determined and the antimicrobial activities of SXT, 5-iodo-2'-deoxyuridine (IdUrd) and RIF alone and in combination against S. aureus were analysed. Thymidine concentrations in the sputa of ten different CF patients varied from <100 μg/L to 38845 μg/L. The abolished antimicrobial activity of SXT against 22 S. aureus strains in the presence of thymidine was restored by combination with IdUrd. In contrast, SXT combined with RIF in the presence of thymidine did not show a synergistic effect and, furthermore, allowed the emergence of RIF-resistant bacteria. Adding RIF to the combination of SXT and IdUrd did not improve antimicrobial activity against S. aureus. In conclusion, the combination of SXT and RIF as a therapeutic option against S. aureus infections in chronic inflamed tissues should be judged critically.
甲氧苄啶/磺胺甲恶唑（SXT）单独使用和与利福平（RIF）联合使用是治疗金黄色葡萄球菌的一种选择，包括表达耐甲氧西林的菌株。然而，SXT 的抗菌活性受到胸苷的拮抗，胸苷可能存在于感染和/或炎症组织中，如囊性纤维化（CF）患者的气道。在本研究中，测定了 CF 痰液中的胸苷浓度，并分析了 SXT、5-碘-2'-脱氧尿苷（IdUrd）和 RIF 单独和联合使用对金黄色葡萄球菌的抗菌活性。10 名不同 CF 患者痰液中的胸苷浓度从<100μg/L 到 38845μg/L 不等。在胸苷存在的情况下，SXT 对 22 株金黄色葡萄球菌的抗菌活性被 IdUrd 联合所恢复。相比之下，SXT 与 RIF 联合在胸苷存在时并未显示协同作用，并且还导致了 RIF 耐药菌的出现。将 RIF 添加到 SXT 和 IdUrd 的联合用药中并没有改善对金黄色葡萄球菌的抗菌活性。总之，对于慢性炎症组织中金黄色葡萄球菌感染的治疗选择，应审慎评估 SXT 和 RIF 的联合使用。
