Cosgrove Sara E, Vigliani Gloria A, Fowler Vance G, Abrutyn Elias, Corey G Ralph, Levine Donald P, Rupp Mark E, Chambers Henry F, Karchmer Adolf W, Boucher Helen W
Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Clin Infect Dis. 2009 Mar 15;48(6):713-21. doi: 10.1086/597031.
The safety of adding initial low-dose gentamicin to antistaphylococcal penicillins or vancomycin for treatment of suspected Staphylococcus aureus native valve endocarditis is unknown. This study evaluated the association between this practice and nephrotoxicity.
We performed a prospective cohort study of safety data from a randomized, controlled trial of therapy for S. aureus bacteremia and native valve infective endocarditis involving 236 patients from 44 hospitals in 4 countries. Patients either received standard therapy (antistaphylococcal penicillin or vancomycin) plus initial low-dose gentamicin (n=116) or received daptomycin monotherapy (n = 120). We measured renal adverse events and clinically significant decreased creatinine clearance in patients (1) in the original randomized study arms and (2) who received any initial low-dose gentamicin either, as a study medication or <or= days before enrollment.
Renal adverse events occurred in 8 (7%) of 120 daptomycin recipients, 10 (19%) of 53 vancomycin recipients, and 11 (17%) of 63 antistaphylococcal penicillin recipients. Decreased creatinine clearance occurred in 9 (8%) of 113 of evaluable daptomycin recipients, 10 (22%) of 46 vancomycin recipients, and 16 (25%) of 63 antistaphylococcal penicillin recipients. An additional 21 patients received initial low-dose gentamicin <or=2 days before study enrollment. A total of 22% of patients who received initial low-dose gentamicin versus 8% of patients who did not receive initial low-dose gentamicin experienced decreased creatinine clearance (P = 005 ). Independent predictors of a clinically significant decrease in creatinine clearance were age >or=65 years and receipt of any initial low-dose gentamicin.
Initial low-dose gentamicin as part of therapy for S. aureus bacteremia and native valve infective endocarditis is nephrotoxic and should not be used routinely, given the minimal existing data supporting its benefit.
在治疗疑似金黄色葡萄球菌自体瓣膜心内膜炎时,在抗葡萄球菌青霉素或万古霉素基础上加用初始低剂量庆大霉素的安全性尚不清楚。本研究评估了这种治疗方法与肾毒性之间的关联。
我们对一项针对金黄色葡萄球菌菌血症和自体瓣膜感染性心内膜炎治疗的随机对照试验的安全性数据进行了前瞻性队列研究,该试验涉及4个国家44家医院的236例患者。患者要么接受标准治疗(抗葡萄球菌青霉素或万古霉素)加初始低剂量庆大霉素(n = 116),要么接受达托霉素单药治疗(n = 120)。我们测量了患者的肾脏不良事件以及具有临床意义的肌酐清除率下降情况,这些患者包括:(1)原始随机研究组中的患者;(2)在入组前作为研究用药或在≤2天内接受过任何初始低剂量庆大霉素治疗的患者。
120例接受达托霉素治疗的患者中有8例(7%)发生肾脏不良事件,53例接受万古霉素治疗的患者中有10例(19%)发生,63例接受抗葡萄球菌青霉素治疗的患者中有11例(17%)发生。在113例可评估的接受达托霉素治疗的患者中有9例(8%)肌酐清除率下降,46例接受万古霉素治疗的患者中有10例(22%),63例接受抗葡萄球菌青霉素治疗的患者中有16例(25%)。另外有21例患者在入组研究前≤2天接受了初始低剂量庆大霉素治疗。接受初始低剂量庆大霉素治疗的患者中有22%出现肌酐清除率下降,而未接受初始低剂量庆大霉素治疗的患者中这一比例为8%(P = 0.05)。肌酐清除率出现具有临床意义下降的独立预测因素为年龄≥65岁以及接受过任何初始低剂量庆大霉素治疗。
作为金黄色葡萄球菌菌血症和自体瓣膜感染性心内膜炎治疗一部分的初始低剂量庆大霉素具有肾毒性,鉴于现有支持其益处的数据极少,不应常规使用。