多黏菌素单药治疗与联合治疗耐碳青霉烯类微生物的比较
Colistin Monotherapy versus Combination Therapy for Carbapenem-Resistant Organisms.
作者信息
Kaye Keith S, Marchaim Dror, Thamlikitkul Visanu, Carmeli Yehuda, Chiu Cheng-Hsun, Daikos George, Dhar Sorabh, Durante-Mangoni Emanuele, Gikas Achilles, Kotanidou Anastasia, Paul Mical, Roilides Emmanuelle, Rybak Michael, Samarkos Michael, Sims Matthew, Tancheva Dora, Tsiodras Sotirios, Kett Daniel, Patel Gopi, Calfee David, Leibovici Leonard, Power Laura, Munoz-Price Sylvia, Stevenson Kurt, Susick Laura, Latack Katie, Daniel Jolene, Chiou Christine, Divine George W, Ghazyaran Varduhi, Pogue Jason M
机构信息
Division of Allergy, Immunology, and Infectious Diseases, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ.
Division of Infectious Diseases, Assaf Harofeh Medical Center, Be'er Ya'akov, Israel.
出版信息
NEJM Evid. 2023 Jan;2(1). doi: 10.1056/evidoa2200131. Epub 2022 Dec 6.
BACKGROUND
Pneumonia and bloodstream infections (BSI) due to extensively drug-resistant (XDR) , XDR , and carbapenem-resistant Enterobacterales (CRE) are associated with high mortality rates, and therapeutic options remain limited. This trial assessed whether combination therapy with colistin and meropenem was superior to colistin monotherapy for the treatment of these infections.
METHODS
The OVERCOME (Colistin Monotherapy versus Combination Therapy) trial was an international, randomized, double-blind, placebo-controlled trial. We randomly assigned participants to receive colistin (5 mg/kg once followed by 1.67 mg/kg every 8 hours) in combination with either meropenem (1000 mg every 8 hours) or matching placebo for the treatment of pneumonia and/or BSI caused by XDR A. , XDR , or CRE. The primary outcome was 28-day mortality, and secondary outcomes included clinical failure and microbiologic cure.
RESULTS
Between 2012 and 2020, a total of 464 participants were randomly assigned to treatment, and 423 eligible patients comprised the modified intention-to-treat population. was the predominant trial pathogen (78%) and pneumonia the most common index infection (70%). Most patients were in the intensive care unit at the time of enrollment (69%). There was no difference in mortality (43 vs. 37%; P=0.17), clinical failure (65 vs. 58%; difference, 6.8 percentage points; 95% confidence interval [CI], -3.1 to 16.6), microbiologic cure (65 vs. 60%; difference, 4.8 percentage points; 95% CI, -5.6 to 15.2), or adverse events (acute kidney injury, 52 vs. 49% [P=0.55]; hypersensitivity reaction, 1 vs. 3% [P=0.22]; and neurotoxicity, 5 vs. 2% [P=0.29]) between patients receiving monotherapy and combination therapy, respectively.
CONCLUSIONS
Combination therapy with colistin and meropenem was not superior to colistin monotherapy for the treatment of pneumonia or BSI caused by these pathogens. (Funded by the National Institute of Allergy and Infectious Diseases, Division of Microbiology and Infectious Diseases protocol 10-0065; ClinicalTrials.gov number, NCT01597973.).
背景
由广泛耐药（XDR）、耐碳青霉烯类肠杆菌科细菌（CRE）引起的肺炎和血流感染（BSI）与高死亡率相关，且治疗选择仍然有限。本试验评估了黏菌素和美罗培南联合治疗是否优于黏菌素单药治疗这些感染。
方法
“克服（黏菌素单药治疗与联合治疗）”试验是一项国际、随机、双盲、安慰剂对照试验。我们将参与者随机分配接受黏菌素（5mg/kg静脉滴注一次，随后每8小时1.67mg/kg）联合美罗培南（每8小时1000mg）或匹配的安慰剂，以治疗由XDR嗜麦芽窄食单胞菌、XDR或CRE引起的肺炎和/或BSI。主要结局为28天死亡率，次要结局包括临床失败和微生物学治愈。
结果
2012年至2020年期间，共有464名参与者被随机分配接受治疗，423名符合条件的患者组成了改良意向性分析人群。嗜麦芽窄食单胞菌是主要试验病原体（78%），肺炎是最常见的索引感染（70%）。大多数患者在入组时处于重症监护病房（69%）。单药治疗组和联合治疗组在死亡率（43%对37%；P=0.17）、临床失败（65%对58%；差异6.8个百分点；95%置信区间[CI]，-3.1至16.6）、微生物学治愈（65%对60%；差异4.8个百分点；95%CI，-5.6至15.2）或不良事件（急性肾损伤，52%对49%[P=0.55]；超敏反应，1%对3%[P=0.22]；神经毒性，5%对2%[P=0.29]）方面均无差异。
结论
对于治疗由这些病原体引起的肺炎或BSI，黏菌素和美罗培南联合治疗并不优于黏菌素单药治疗。（由美国国立过敏与传染病研究所微生物学和传染病司资助，协议编号10-0065；ClinicalTrials.gov编号，NCT01597973。）
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