Brinkman Cassandra 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 Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
Antimicrob Agents Chemother. 2017 Jan 24;61(2). doi: 10.1128/AAC.01822-16. Print 2017 Feb.
Staphylococcal prosthetic joint infections (PJIs) are associated with biofilm formation, making them difficult to treat; if managed with debridement and implant retention, rifampin-based therapy is usually employed. Rifampin resistance potentially challenges PJI treatment. In investigating the effects of rifampin monotherapy on methicillin-resistant Staphylococcus aureus (MRSA) foreign-body osteomyelitis in rats, we previously demonstrated that rifampin resistance was selected but that it disappeared 14 days following rifampin monotherapy (1) and that rifampin resistance occurred less frequently following two rounds than following one round of rifampin monotherapy (2). Here, we compared rifampin monotherapy followed by rifampin-vancomycin combination therapy to rifampin-vancomycin combination therapy alone in experimental MRSA foreign-body osteomyelitis. Animals treated with rifampin monotherapy followed by rifampin-vancomycin combination therapy had decreased quantities of bacteria 14 days following treatment completion (P = 0.034) compared to those in animals treated with combination therapy alone. Additionally, some isolates recovered from animals treated with combination therapy alone, although still susceptible to rifampin, had higher MIC, minimum biofilm-inhibitory concentration (MBIC), and minimum biofilm-bactericidal concentration (MBBC) values than those of the inoculating strain. This suggests that rifampin may remain a feasible treatment option in foreign-body-associated orthopedic infections following the selection of rifampin resistance.
葡萄球菌人工关节感染（PJI）与生物膜形成有关，使其难以治疗；若采用清创术和保留植入物的方法进行处理，通常会采用基于利福平的治疗。利福平耐药性可能会对PJI治疗构成挑战。在研究利福平单一疗法对大鼠耐甲氧西林金黄色葡萄球菌（MRSA）异物性骨髓炎的影响时，我们之前证明了利福平耐药性会被选择出来，但在利福平单一疗法14天后它会消失（1），并且两轮利福平单一疗法后利福平耐药性的发生频率低于一轮治疗后（2）。在此，我们在实验性MRSA异物性骨髓炎中比较了先进行利福平单一疗法然后进行利福平 -万古霉素联合疗法与单纯利福平 -万古霉素联合疗法的效果。与仅接受联合疗法治疗的动物相比，先接受利福平单一疗法然后接受利福平 -万古霉素联合疗法治疗的动物在治疗完成14天后细菌数量减少（P = 0.034）。此外，从仅接受联合疗法治疗的动物中分离出的一些菌株，尽管仍对利福平敏感，但与接种菌株相比，其最低抑菌浓度（MIC）、最低生物膜抑制浓度（MBIC）和最低生物膜杀菌浓度（MBBC）值更高。这表明在选择利福平耐药性后，利福平可能仍是异物相关骨科感染的一种可行治疗选择。
