Zasowski Evan J, Trinh Trang D, Atwan Safana M, Merzlyakova Marina, Langf Abdalhamid M, Bhatia Sahil, Rybak Michael J
Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan.
Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas.
Open Forum Infect Dis. 2019 Apr 3;6(4):ofz079. doi: 10.1093/ofid/ofz079. eCollection 2019 Apr.
Data suggest that vancomycin + β-lactam combinations improve clearance of methicillin-resistant (MRSA) bloodstream infections (BSIs). However, it is unclear which specific β-lactams confer benefit. This analysis evaluates the impact of concomitant empiric cefepime on outcomes of MRSA BSIs treated with vancomycin.
Retrospective cohort study of adults with MRSA BSI from 2006 to 2017. Vancomycin + cefepime therapy was defined as ≥24 hours of cefepime during the first 72 hours of vancomycin. The primary outcome was microbiologic failure, defined as BSI duration ≥7 days and/or 60-day recurrence. Multivariable logistic regression was used to evaluate the association between vancomycin + cefepime therapy and binary outcomes. Cause-specific and subdistribution hazard models were used to evaluate the association between vancomycin + cefepime and BSI clearance.
Three hundred fifty-eight patients were included, 129 vancomycin and 229 vancomycin + cefepime. Vancomycin + cefepime therapy was independently associated with reduced microbiologic failure (adjusted odds ratio [aOR], 0.488; 95% confidence interval [CI], 0.271-0.741). This was driven by a reduction in the incidence of BSI durations ≥7 days (vancomycin + cefepime aOR, 0.354; 95% CI, 0.202-0.621). Vancomycin + cefepime had no association with 30-day mortality (aOR, 0.952; 95% CI, 0.435-2.425). Vancomycin + cefepime was associated with faster BSI clearance in both cause-specific (HR, 1.408; 95% CI, 1.125-1.762) and subdistribution hazard models (HR, 1.264; 95% CI, 1.040-1.536).
Concomitant empiric cefepime improved MRSA BSI clearance and may be useful as the β-lactam component of synergistic vancomycin + β-lactam regimens when empiric or directed gram-negative coverage is desired.
数据表明，万古霉素与β-内酰胺类药物联合使用可提高耐甲氧西林金黄色葡萄球菌（MRSA）血流感染（BSI）的清除率。然而，尚不清楚哪种特定的β-内酰胺类药物具有益处。本分析评估了经验性联用头孢吡肟对万古霉素治疗的MRSA BSI结局的影响。
对2006年至2017年患有MRSA BSI的成年人进行回顾性队列研究。万古霉素+头孢吡肟治疗定义为在万古霉素治疗的前72小时内使用头孢吡肟≥24小时。主要结局为微生物学治疗失败，定义为BSI持续时间≥7天和/或60天复发。采用多变量logistic回归评估万古霉素+头孢吡肟治疗与二元结局之间的关联。使用特定病因和亚分布风险模型评估万古霉素+头孢吡肟与BSI清除之间的关联。
共纳入358例患者，其中129例接受万古霉素治疗，229例接受万古霉素+头孢吡肟治疗。万古霉素+头孢吡肟治疗与微生物学治疗失败的降低独立相关（调整后的比值比[aOR]为0.488；95%置信区间[CI]为0.271-0.741）。这是由于BSI持续时间≥7天的发生率降低所致（万古霉素+头孢吡肟aOR为0.354；95%CI为0.202-0.621）。万古霉素+头孢吡肟与30天死亡率无关（aOR为0.952；95%CI为0.435-2.425）。在特定病因风险模型（风险比[HR]为1.408；95%CI为1.125-1.762）和亚分布风险模型（HR为1.264；95%CI为1.040-1.536）中，万古霉素+头孢吡肟均与更快的BSI清除相关。
经验性联用头孢吡肟可改善MRSA BSI的清除，当需要经验性或针对性的革兰氏阴性菌覆盖时，可作为协同性万古霉素+β-内酰胺类治疗方案中的β-内酰胺类药物使用。
