Zeller Valérie, Durand Frédérick, Kitzis Marie-Dominique, Lhotellier Luc, Ziza Jean-Marc, Mamoudy Patrick, Desplaces Nicole
Service de Chirurgie Osseuse et Traumatologique, Groupe Hospitalier Diaconesses-Croix Saint-Simon, Paris, France.
Antimicrob Agents Chemother. 2009 Mar;53(3):883-7. doi: 10.1128/AAC.00389-08. Epub 2008 Dec 15.
Cefazolin has been used for many years to treat bone and joint infections. Because of its time-dependent antimicrobial activity, continuous infusion would potentially be beneficial. We report on the feasibility, safety, and efficacy of prolonged continuous intravenous cefazolin therapy in a cohort of 100 patients, their serum cefazolin levels, and the concomitant bone cefazolin concentrations in 8 of them. This retrospective cohort study included all the patients treated for bone or joint infection with a continuous cefazolin infusion administered over a 12-h period twice daily for >or=2 weeks. Drug monitoring was performed at least twice for all the patients. Serum and bone cefazolin concentrations were determined by standardized disk diffusion microbiological assays. The absence of clinical, biological, and radiological signs of infection after 2 years of follow-up and the same criteria after 1 year of follow-up defined cures and probable cures, respectively. The median treatment duration was 42 days, and the median daily cefazolin dose was 6 g. Half of the patients received parenteral antibiotic therapy on an outpatient basis. Two moderate-grade adverse events were observed. The median serum cefazolin concentrations were 63 microg/ml (range, 13 to 203 microg/ml) and 57 microg/ml (range, 29 to 128 microg/ml) on days 2 to 10 and days 11 to 21, respectively. The median bone cefazolin concentration reached 13.5 microg/g (range, 3.5 to 29 microg/g). The median bone concentration/serum concentration ratio was 0.25 (range, 0.06 to 0.41). Among 88 patients with a median follow-up of 25 months (range, 12 to 53 months), 52 were considered cured and 29 were considered probably cured. Thus, the treatment of bone and joint infections with a prolonged continuous intravenous cefazolin infusion was feasible, effective, well-tolerated, safe, and convenient, making it a strong candidate for home therapy.
头孢唑林已被用于治疗骨与关节感染多年。由于其具有时间依赖性抗菌活性，持续输注可能有益。我们报告了100例患者接受长时间持续静脉输注头孢唑林治疗的可行性、安全性和有效性，以及他们的血清头孢唑林水平和其中8例患者的骨组织头孢唑林浓度。这项回顾性队列研究纳入了所有因骨或关节感染接受治疗的患者，他们接受头孢唑林持续输注，每日两次，每次12小时，持续≥2周。对所有患者至少进行了两次药物监测。血清和骨组织中的头孢唑林浓度通过标准化纸片扩散微生物学测定法测定。随访2年时无感染的临床、生物学和放射学迹象，随访1年时符合相同标准分别定义为治愈和可能治愈。中位治疗持续时间为42天，头孢唑林每日中位剂量为6g。一半的患者在门诊接受了肠外抗生素治疗。观察到两例中度不良事件。在第2至10天和第11至21天，血清头孢唑林浓度中位数分别为63μg/ml（范围13至203μg/ml）和57μg/ml（范围29至128μg/ml）。骨组织头孢唑林浓度中位数达到13.5μg/g（范围3.5至29μg/g）。骨组织浓度/血清浓度中位数比值为0.25（范围0.06至0.41）。在88例中位随访25个月（范围12至53个月）的患者中，52例被认为治愈，29例被认为可能治愈。因此，长时间持续静脉输注头孢唑林治疗骨与关节感染是可行、有效、耐受性良好、安全且方便的，使其成为家庭治疗的有力候选方法。
