Ryder Jonathan H, Tong Steven Y C, Gallagher Jason C, McDonald Emily G, Thevarajan Irani, Lee Todd C, Cortés-Penfield Nicolás W
Department of Internal Medicine, Division of Infectious Diseases, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Victorian Infectious Diseases Service, Royal Melbourne Hospital, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Open Forum Infect Dis. 2022 Oct 31;9(11):ofac583. doi: 10.1093/ofid/ofac583. eCollection 2022 Nov.
Based primarily on in vitro and animal models, with little data directly addressing patient outcomes, current guidelines recommend treating staphylococcal prosthetic valve endocarditis (PVE) with antibiotic combinations including gentamicin and rifampin. Here, we synthesize the clinical data on adjunctive rifampin and gentamicin in staphylococcal PVE.
We conducted a systematic review and meta-analysis of PubMed- and Cochrane-indexed studies reporting outcomes of staphylococcal PVE treated with adjunctive rifampin, gentamicin, both agents, or neither (ie, glycopeptide or β-lactam monotherapy). We recorded outcomes including mortality, relapsed infection, length of stay, nephrotoxicity, hepatotoxicity, and important drug-drug interactions (DDIs).
Four relevant studies were identified. Two studies (n = 117) suggested that adding gentamicin to rifampin-containing regimens did not reduce clinical failure (odds ratio [OR], 0.98 [95% confidence interval {CI}, .39-2.46]), and 2 studies (n = 201) suggested that adding rifampin to gentamicin-containing regimens did not reduce clinical failure (OR, 1.29 [95% CI, .71-2.33]). Neither gentamicin nor rifampin was associated with reduced infection relapse; 1 study found that rifampin treatment was associated with longer hospitalizations (mean, 31.3 vs 42.3 days; < .001). Comparative safety outcomes were rarely reported, but 1 study found rifampin to be associated with hepatoxicity, nephrotoxicity, and DDIs, leading to treatment discontinuation in 31% of patients.
The existing clinical data do not suggest a benefit of either adjunctive gentamicin or rifampin in staphylococcal PVE. Given that other studies also suggest these agents add nephrotoxicity, hepatoxicity, and risk of DDIs without benefit in staphylococcal endovascular infections, we suggest that recommendations for gentamicin and rifampin in PVE be downgraded and primarily be used within the context of clinical trials.
目前的指南主要基于体外和动物模型，直接涉及患者预后的数据很少，推荐使用包括庆大霉素和利福平在内的抗生素联合治疗葡萄球菌人工瓣膜心内膜炎（PVE）。在此，我们综合了关于葡萄球菌PVE中辅助使用利福平和庆大霉素的临床数据。
我们对PubMed和Cochrane索引的研究进行了系统评价和荟萃分析，这些研究报告了使用辅助性利福平、庆大霉素、两种药物或不使用（即糖肽类或β-内酰胺类单药治疗）治疗葡萄球菌PVE的结果。我们记录了包括死亡率、感染复发、住院时间、肾毒性、肝毒性和重要药物相互作用（DDIs）等结果。
共确定了四项相关研究。两项研究（n = 117）表明，在含利福平的治疗方案中添加庆大霉素并不能降低临床失败率（优势比[OR]，0.98[95%置信区间{CI}，0.39 - 2.46]），两项研究（n = 201）表明，在含庆大霉素的治疗方案中添加利福平并不能降低临床失败率（OR，1.29[95%CI，0.71 - 2.33]）。庆大霉素和利福平均与感染复发率降低无关；一项研究发现利福平治疗与更长的住院时间相关（平均，31.3天对42.3天；P < 0.001）。很少有关于比较安全性结果的报告，但一项研究发现利福平与肝毒性、肾毒性和DDIs相关，导致31%的患者停药。
现有临床数据未表明辅助使用庆大霉素或利福平对葡萄球菌PVE有益。鉴于其他研究也表明这些药物会增加肾毒性、肝毒性和DDIs风险，而对葡萄球菌血管内感染无益处，我们建议降低PVE中庆大霉素和利福平的推荐级别，主要在临床试验中使用。
