Orthopaedic Hospital Research Center, Orthopaedic Hospital Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Antimicrob Agents Chemother. 2012 May;56(5):2590-7. doi: 10.1128/AAC.06291-11. Epub 2012 Feb 27.
Vancomycin is widely used for intravenous prophylaxis against surgical implant infections. However, it is unclear whether alternative antibiotics used to treat methicillin-resistant Staphylococcus aureus (MRSA) infections are effective as prophylactic agents. The aim of this study was to compare the efficacies of vancomycin, daptomycin, and tigecycline as prophylactic therapy against a methicillin-sensitive S. aureus (MSSA) or MRSA surgical implant infection in mice. MSSA or MRSA was inoculated into the knee joints of mice in the presence of a surgically placed medical-grade metallic implant. The efficacies of low- versus high-dose vancomycin (10 versus 110 mg/kg), daptomycin (1 versus 10 mg/kg), and tigecycline (1 versus 10 mg/kg) intravenous prophylaxis were compared using in vivo bioluminescence imaging, ex vivo bacterial counts, and biofilm formation. High-dose vancomycin, daptomycin, and tigecycline resulted in similar reductions in bacterial burden and biofilm formation. In contrast, low-dose daptomycin and tigecycline were more effective than low-dose vancomycin against the implant infection. In this mouse model of surgical implant MSSA or MRSA infection, daptomycin and tigecycline prophylaxis were effective over a broader dosage range than vancomycin. Future studies in humans will be required to determine whether these broader effective dose ranges for daptomycin and tigecycline in mice translate to improved efficacy in preventing surgical implant infections in clinical practice.
万古霉素被广泛用于预防手术植入物感染的静脉内预防。然而，用于治疗耐甲氧西林金黄色葡萄球菌（MRSA）感染的替代抗生素是否作为预防性药物有效尚不清楚。本研究的目的是比较万古霉素、达托霉素和替加环素作为预防性治疗对小鼠耐甲氧西林金黄色葡萄球菌（MSSA）或 MRSA 手术植入物感染的疗效。在存在手术放置的医用级金属植入物的情况下，将 MSSA 或 MRSA 接种到小鼠膝关节中。使用体内生物发光成像、体外细菌计数和生物膜形成来比较低剂量与高剂量万古霉素（10 与 110mg/kg）、达托霉素（1 与 10mg/kg）和替加环素（1 与 10mg/kg）静脉内预防的疗效。高剂量万古霉素、达托霉素和替加环素导致细菌负荷和生物膜形成的相似减少。相比之下，低剂量达托霉素和替加环素对植入物感染的疗效优于低剂量万古霉素。在这种 MSSA 或 MRSA 手术植入物感染的小鼠模型中，达托霉素和替加环素预防的有效剂量范围比万古霉素更广。需要在人类中进行进一步的研究，以确定在小鼠中达托霉素和替加环素的这些更广泛的有效剂量范围是否转化为在临床实践中预防手术植入物感染的疗效提高。
