Department of Medical Affairs, Cubist Pharmaceuticals, Lexington, MA, USA.
Antimicrob Agents Chemother. 2013 Mar;57(3):1192-200. doi: 10.1128/AAC.02192-12. Epub 2012 Dec 17.
Patients with underlying renal disease may be vulnerable to vancomycin-mediated nephrotoxicity and Staphylococcus aureus bacteremia treatment failure. In light of recent data demonstrating the successful use of β-lactam plus daptomycin in very difficult cases of S. aureus bacteremia, we examined safety and clinical outcomes for patients who received daptomycin with or without concomitant β-lactams. We identified 106 patients who received daptomycin for S. aureus bacteremia, had mild or moderate renal insufficiency according to FDA criteria, and enrolled in the Cubicin Outcomes Registry and Experience (CORE), a multicenter registry, from 2005 to 2009. Daptomycin treatment success was 81%. Overall treatment efficacy was slightly enhanced with the addition of a β-lactam (87% versus 78%; P = 0.336), but this trend was most pronounced for bacteremia associated with endocarditis or bone/joint infection or bacteremia from an unknown source (90% versus 57%; P = 0.061). Factors associated with reduced daptomycin efficacy (by logistic regression) were an unknown source of bacteremia (odds ratio [OR] = 7.59; 95% confidence interval [CI] = 1.55 to 37.2), moderate renal impairment (OR = 9.11; 95% CI = 1.46 to 56.8), and prior vancomycin failure (OR = 11.2; 95% CI = 1.95 to 64.5). Two patients experienced an increase in creatine phosphokinase (CPK) that resolved after stopping daptomycin. No patients developed worsening renal insufficiency related to daptomycin. In conclusion, daptomycin appeared to be effective and well tolerated in patients with S. aureus bacteremia and mild to moderate renal insufficiency. Daptomycin treatment efficacy might be enhanced with β-lactam combination therapy in primary endovascular and bone/joint infections. Additional studies will be necessary to confirm these findings.
患有基础肾脏疾病的患者可能容易发生万古霉素介导的肾毒性和金黄色葡萄球菌菌血症治疗失败。鉴于最近的数据表明,β-内酰胺联合达托霉素在非常困难的金黄色葡萄球菌菌血症病例中取得了成功,我们检查了接受达托霉素联合或不联合β-内酰胺治疗的患者的安全性和临床结局。我们确定了 106 名根据 FDA 标准患有轻度或中度肾功能不全的金黄色葡萄球菌菌血症患者,他们参加了 Cubicin Outcomes Registry and Experience(CORE),这是一项多中心注册研究,时间为 2005 年至 2009 年。达托霉素治疗成功率为 81%。总体治疗效果略有提高,β-内酰胺的加入(87%对 78%;P=0.336),但对于与心内膜炎或骨/关节感染或不明来源菌血症相关的菌血症,这种趋势更为明显(90%对 57%;P=0.061)。通过逻辑回归与降低达托霉素疗效相关的因素是菌血症的不明来源(比值比[OR] = 7.59;95%置信区间[CI] = 1.55 至 37.2),中度肾功能不全(OR = 9.11;95%CI = 1.46 至 56.8),以及万古霉素治疗失败(OR = 11.2;95%CI = 1.95 至 64.5)。有 2 名患者的肌酸磷酸激酶(CPK)升高,停用达托霉素后恢复正常。没有患者因达托霉素而出现肾功能不全加重。总之,达托霉素在金黄色葡萄球菌菌血症和轻度至中度肾功能不全患者中似乎是有效且耐受良好的。β-内酰胺联合治疗可能会增强达托霉素治疗原发性血管内和骨/关节感染的疗效。需要进一步的研究来证实这些发现。