Katip Wasan, Lee Shaun Wen Huey, Kasatpibal Nongyao, Rayanakorn Ajaree
Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand.
Epidemiological and Innovative Research Group for Infectious Diseases (EIRGID), Chiang Mai University, Chiang Mai, Thailand.
Br J Clin Pharmacol. 2025 Apr;91(4):1250-1262. doi: 10.1111/bcp.16362. Epub 2024 Dec 8.
Evidence on the optimal targets of vancomycin for treating other Gram-positive infections apart from methicillin-resistant Staphylococcus aureus (MRSA) is lacking. This review aims to identify the recommended vancomycin therapeutic level for favourable clinical outcomes among patients infected with vancomycin-sensitive enterococcal infections.
Analytical studies describing the vancomycin levels of vancomycin-sensitive enterococcal infections among adult population were searched. The primary outcome was 30-day all-cause mortality, and the secondary outcomes were clinical failure and nephrotoxicity. Study characteristics were extracted and pooled using random-effects meta-analysis. The study quality was assessed using the Joanna Briggs Institute critical appraisal tool.
A total of nine retrospective cohorts studies involving 1013 patients with vancomycin-sensitive enterococci were included. The meta-analysis found that high area under the curve to minimum inhibitory concentration ratio (AUC/MIC) of vancomycin ≥ 389 mgh/L significantly lowered the 30-day mortality (odds ratio [OR], 0.44, 95% confidence interval [CI], 0.26-0.75). Analysis of the target AUC/MIC showed that high vancomycin AUC/MIC (≥ 389-400 mgh/L) significantly reduced clinical failure rate (OR 0.59, 95% CI 0.37-0.94). The mortality and treatment failure rates did not differ significantly between those with high or low trough levels. Higher vancomycin AUC/MIC and trough levels were significantly associated with increased nephrotoxicity (OR 3.11, 95% CI 1.65-5.89; OR 2.95, 95% CI 1.60-5.44, respectively).
The use of a higher vancomycin AUC/MIC concentration can be effective to reduce 30-day mortality and clinical failure but this needs to take into consideration the risk of nephrotoxicity. Well-conducted prospective studies are warranted due to the scarcity of evidence.
除耐甲氧西林金黄色葡萄球菌（MRSA）外，缺乏关于万古霉素治疗其他革兰氏阳性感染最佳靶点的证据。本综述旨在确定万古霉素敏感肠球菌感染患者中有利于临床结局的推荐万古霉素治疗水平。
检索描述成年人群中万古霉素敏感肠球菌感染的万古霉素水平的分析性研究。主要结局是30天全因死亡率，次要结局是临床失败和肾毒性。使用随机效应荟萃分析提取并汇总研究特征。使用乔安娜·布里格斯研究所的批判性评价工具评估研究质量。
共纳入9项涉及1013例万古霉素敏感肠球菌患者的回顾性队列研究。荟萃分析发现，万古霉素曲线下面积与最低抑菌浓度比值（AUC/MIC）≥389mgh/L可显著降低30天死亡率（优势比[OR]，0.44，95%置信区间[CI]，0.26 - 0.75）。对目标AUC/MIC的分析表明，高万古霉素AUC/MIC（≥389 - 400mgh/L）可显著降低临床失败率（OR 0.59，95%CI 0.37 - 0.94）。高谷浓度和低谷浓度患者的死亡率和治疗失败率无显著差异。较高的万古霉素AUC/MIC和谷浓度与肾毒性增加显著相关（分别为OR 3.11，95%CI 1.65 - 5.89；OR 2.95，95%CI 1.60 - 5.44）。
使用较高的万古霉素AUC/MIC浓度可有效降低30天死亡率和临床失败率，但这需要考虑肾毒性风险。由于证据不足，有必要开展高质量的前瞻性研究。
