Cai Bingxuan, Cai Yiying, Liew Yi Xin, Chua Nathalie Grace, Teo Jocelyn Qi-Min, Lim Tze-Peng, Kurup Asok, Ee Pui Lai Rachel, Tan Thuan Tong, Lee Winnie, Kwa Andrea Lay-Hoon
Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore.
Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore Department of Pharmacy, Singapore General Hospital, Singapore.
Antimicrob Agents Chemother. 2016 Jun 20;60(7):4013-22. doi: 10.1128/AAC.03064-15. Print 2016 Jul.
Polymyxins have emerged as a last-resort treatment of extensively drug-resistant (XDR) Gram-negative Bacillus (GNB) infections, which present a growing threat. Individualized polymyxin-based antibiotic combinations selected on the basis of the results of in vitro combination testing may be required to optimize therapy. A retrospective cohort study of hospitalized patients receiving polymyxins for XDR GNB infections from 2009 to 2014 was conducted to compare the treatment outcomes between patients receiving polymyxin monotherapy (MT), nonvalidated polymyxin combination therapy (NVCT), and in vitro combination testing-validated polymyxin combination therapy (VCT). The primary and secondary outcomes were infection-related mortality and microbiological eradication, respectively. Adverse drug reactions (ADRs) between treatment groups were assessed. A total of 291 patients (patients receiving MT, n = 58; patients receiving NVCT, n = 203; patients receiving VCT, n = 30) were included. The overall infection-related mortality rate was 23.0% (67 patients). In the multivariable analysis, treatment of XDR GNB infections with MT (adjusted odds ratio [aOR], 8.49; 95% confidence interval [CI], 1.56 to 46.05) and NVCT (aOR, 5.75; 95% CI, 1.25 to 25.73) was associated with an increased risk of infection-related mortality compared to that with treatment with VCT. A higher Acute Physiological and Chronic Health Evaluation II (APACHE II) score (aOR, 1.14; 95% CI 1.07 to 1.21) and a higher Charlson comorbidity index (aOR, 1.28; 95% CI, 1.11 to 1.47) were also independently associated with an increased risk of infection-related mortality. No increase in the incidence of ADRs was observed in the VCT group. The use of an individualized antibiotic combination which was selected on the basis of the results of in vitro combination testing was associated with significantly lower rates of infection-related mortality in patients with XDR GNB infections. Future prospective randomized studies will be required to validate these findings.
多黏菌素已成为治疗广泛耐药（XDR）革兰氏阴性杆菌（GNB）感染的最后手段，此类感染构成的威胁日益增大。可能需要根据体外联合试验结果选择个体化的基于多黏菌素的抗生素联合用药方案，以优化治疗。我们开展了一项回顾性队列研究，纳入2009年至2014年因XDR GNB感染接受多黏菌素治疗的住院患者，比较接受多黏菌素单药治疗（MT）、未经验证的多黏菌素联合治疗（NVCT）和经体外联合试验验证的多黏菌素联合治疗（VCT）的患者的治疗结局。主要结局和次要结局分别为感染相关死亡率和微生物清除情况。评估了各治疗组之间的药物不良反应（ADR）。共纳入291例患者（接受MT的患者，n = 58；接受NVCT的患者，n = 203；接受VCT的患者，n = 30）。总体感染相关死亡率为23.0%（67例患者）。在多变量分析中，与接受VCT治疗相比，MT（校正比值比[aOR]，8.49；95%置信区间[CI]，1.56至46.05）和NVCT（aOR，5.75；95% CI，1.25至25.73）治疗XDR GNB感染与感染相关死亡率风险增加相关。较高的急性生理与慢性健康状况评分系统II（APACHE II）评分（aOR，1.14；95% CI 1.07至1.21）和较高的查尔森合并症指数（aOR，1.28；95% CI，1.11至1.47）也与感染相关死亡率风险增加独立相关。VCT组未观察到ADR发生率增加。根据体外联合试验结果选择个体化抗生素联合用药与XDR GNB感染患者较低的感染相关死亡率相关。未来需要进行前瞻性随机研究来验证这些发现。
