Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.
Antimicrob Agents Chemother. 2013 Sep;57(9):4190-6. doi: 10.1128/AAC.00526-13. Epub 2013 Jun 17.
Enterococci are among the leading pathogens isolated in hospital-acquired infections. Current antimicrobial options for vancomycin-resistant enterococci (VRE) are limited. Prior data suggest that daptomycin at >6 mg/kg of body weight/day may be used to treat enterococcal infections. We retrospectively evaluated the effectiveness and safety of high-dose daptomycin (HD-daptomycin) therapy (>6 mg/kg) in a multicenter cohort of adult patients with enterococcal infections to describe the characteristics and outcomes. Two hundred forty-five patients were evaluated. Enterococcus faecium was identified in 175 (71%), followed by Enterococcus faecalis in 49 (20%) and Enterococcus spp. in 21 (9%); overall, 204 (83%) isolates were VRE. Enterococcal infections included bacteremia (173, 71%) and intra-abdominal (35, 14%) and bone and joint (25, 10%) infections. The median dosage and duration of HD-daptomycin were 8.2 mg/kg/day (interquartile range [IQR], 7.7 to 9.7) and 10 days (IQR, 6 to 15), respectively. The overall clinical success rate was 89% (193/218), and microbiological eradication was observed in 93% (177/191) of patients. The median time to clearance of blood cultures on HD-daptomycin was 3 days (IQR, 2 to 5). The 30-day all-cause mortality rate was 27%, and 5 (2%) patients developed daptomycin-nonsusceptible enterococcal strains while on HD-daptomycin. Seven patients (3%) had creatine phosphokinase (CPK) elevation, yet no HD-daptomycin regimen was discontinued due to an elevated CPK and all patients were asymptomatic. Overall, there was a high frequency of clinical success and microbiological eradication in patients treated with HD-daptomycin for enterococcal infections, even in patients with complicated and difficult-to-treat infections. No adverse event-related discontinuation of HD-daptomycin was noted. HD-daptomycin may be an option for the treatment of enterococcal infections.
肠球菌是医院获得性感染中分离的主要病原体之一。目前，治疗耐万古霉素肠球菌（VRE）的抗菌药物选择有限。先前的数据表明，每日超过 6 毫克/公斤体重的达托霉素可能用于治疗肠球菌感染。我们回顾性评估了高剂量达托霉素（HD-daptomycin）（>6 毫克/公斤）治疗肠球菌感染的有效性和安全性，在一个多中心队列的成人患者中描述其特征和结局。评估了 245 例患者。175 例（71%）鉴定为屎肠球菌，49 例（20%）为粪肠球菌，21 例（9%）为其他肠球菌；204 例（83%）分离株为 VRE。肠球菌感染包括菌血症（173 例，71%）、腹腔内（35 例，14%）和骨骼关节（25 例，10%）感染。HD-daptomycin 的中位剂量和疗程分别为 8.2 毫克/公斤/天（四分位距 [IQR]，7.7 至 9.7）和 10 天（IQR，6 至 15）。总的临床成功率为 89%（193/218），177 例（93%）患者的微生物学清除率。HD-daptomycin 清除血培养物的中位时间为 3 天（IQR，2 至 5）。30 天全因死亡率为 27%，5 例（2%）患者在接受 HD-daptomycin 治疗时出现达托霉素不敏感肠球菌株。7 例（3%）患者肌酸磷酸激酶（CPK）升高，但没有因 CPK 升高而停用 HD-daptomycin 方案，所有患者均无症状。总体而言，接受 HD-daptomycin 治疗的肠球菌感染患者有很高的临床成功率和微生物学清除率，即使是在复杂和治疗困难的感染患者中。没有观察到与不良事件相关的 HD-daptomycin 停药。HD-daptomycin 可能是治疗肠球菌感染的一种选择。
