Brinkman Cassandra L, Tyner Harmony L, Schmidt-Malan Suzannah M, Mandrekar Jayawant N, Patel Robin
Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Antimicrob Agents Chemother. 2015 Aug;59(8):4481-8. doi: 10.1128/AAC.05078-14. Epub 2015 May 18.
Orthopedic foreign body-associated infections are often treated with rifampin-based combination antimicrobial therapy. We previously observed that rifampin-resistant and methicillin-resistant Staphylococcus aureus (MRSA) isolates were present 2 days after cessation of rifampin therapy in experimental foreign body osteomyelitis. Unexpectedly, only rifampin-susceptible isolates were detected 14 days after the completion of treatment. We studied two rifampin-resistant isolates recovered 2 days after treatment and one rifampin-susceptible isolate recovered 14 days after treatment. Growing these isolates alone in vitro or in vivo demonstrated no fitness defects; however, in mixed culture, rifampin-susceptible bacteria outcompeted rifampin-resistant bacteria. In vivo, two courses of rifampin treatment (25 mg/kg of body weight every 12 h for 21 days) yielded a greater decrease in bacterial quantity in the bones of treated animals 14 days following treatment than that in animals receiving a single course of treatment (P = 0.0398). In infections established with equal numbers of rifampin-resistant and rifampin-susceptible bacteria, one course of rifampin treatment did not affect bacterial quantities. Rifampin-resistant and rifampin-susceptible isolates were recovered both 2 days and 14 days following treatment completion; however, the proportion of animals with rifampin-resistant isolates was lower at 14 days than that at 2 days following treatment completion (P = 0.024). In untreated animals infected with equal numbers of rifampin-resistant and rifampin-susceptible bacteria for 4 weeks, rifampin-susceptible isolates were exclusively recovered, indicating the outcompetition of rifampin-resistant by rifampin-susceptible isolates. The data presented imply that although there is no apparent fitness defect in rifampin-resistant bacteria when grown alone, they are outcompeted by rifampin-susceptible bacteria when the two are present together. The findings also suggest that selected rifampin resistance may not persist in initially rifampin-susceptible infections following the discontinuation of rifampin.
骨科异物相关感染通常采用基于利福平的联合抗菌治疗。我们之前观察到，在实验性异物性骨髓炎中，利福平治疗停止2天后就出现了耐利福平和耐甲氧西林金黄色葡萄球菌（MRSA）分离株。出乎意料的是，治疗结束14天后仅检测到对利福平敏感的分离株。我们研究了治疗2天后分离出的两株耐利福平菌株和治疗14天后分离出的一株对利福平敏感的菌株。单独在体外或体内培养这些菌株未显示出适应性缺陷；然而，在混合培养中，对利福平敏感的细菌胜过了耐利福平的细菌。在体内，两个疗程的利福平治疗（每12小时25mg/kg体重，共21天）在治疗后14天使治疗动物骨骼中的细菌数量比接受一个疗程治疗的动物有更大程度的减少（P = 0.0398）。在用等量的耐利福平菌和对利福平敏感的细菌建立的感染中，一个疗程的利福平治疗不影响细菌数量。治疗结束2天和14天后均回收了耐利福平菌和对利福平敏感的分离株；然而，治疗结束14天时携带耐利福平分离株的动物比例低于治疗结束2天时（P = 0.024）。在未经治疗的动物中，用等量的耐利福平菌和对利福平敏感的细菌感染4周后，仅回收了对利福平敏感的分离株，这表明对利福平敏感的分离株胜过了耐利福平的分离株。所呈现的数据表明，虽然耐利福平细菌单独生长时没有明显的适应性缺陷，但当两者同时存在时，它们会被对利福平敏感的细菌胜过。这些发现还表明，在利福平停用后，最初对利福平敏感的感染中，所选的利福平耐药性可能不会持续存在。
