黏菌素与美罗培南联合治疗对耐碳青霉烯类革兰阴性菌所致肺炎或血流感染患者预后的影响
The Impact of Synergistic Therapy Between Colistin and Meropenem on Outcomes of Patients With Pneumonia or Bloodstream Infection Due to Carbapenem-Resistant Gram-Negative Pathogens.
作者信息
Huralska Mariya, Pogue Jason M, Rybak Michael, Abdul-Mutakabbir Jacinda C, Stamper Kyle, Marchaim Dror, Thamlikitkul Visanu, Carmeli Yehuda, Chiu Cheng-Hsun, Daikos George, Dhar Sorabh, Durante-Mangoni Emanuele, Gikas Achilles, Kotanidou Anastasia, Paul Mical, Roilides Emmanuel, Samarkos Michael, Sims Matthew, Tancheva Dora, Tsiodras Sotirios, Kett Daniel H, Patel Gopi, Calfee David P, Leibovici Leonard, Power Laura, Munoz-Price Silvia, Shaikh Hamadullah, Susick Laura, Latack Katie, Chiou Christine, Divine George, Ghazyaran Varduhi, Kaye Keith S
机构信息
Division of Infectious Diseases, Department of Medicine, Rutgers Robert Wood Johnson Medical School United States.
Department of Clinical Pharmacy, University of Michigan College of Pharmacy United States.
出版信息
Clin Infect Dis. 2025 Jul 19. doi: 10.1093/cid/ciaf398.
BACKGROUND
Colistin, a last-line treatment for carbapenem-resistant Gram-negative bacilli (CRGNB), is frequently used in combination with meropenem because these agents often demonstrate in vitro synergy. Using data from the OVERCOME trial comparing colistin + meropenem to colistin + placebo for treatment of pneumonia or bloodstream infection due to CRGNB, we evaluated the impact of synergistic therapy on outcomes.
METHODS
In vitro synergy testing between colistin and meropenem was conducted using 24-hour time-kill analysis; synergy was defined as >2-log reduction in colony-forming units/ml compared to the most active single agent. Patients receiving synergistic combination therapy were compared to patients receiving functional colistin monotherapy (colistin alone or combination therapy without synergy). Outcomes included mortality, clinical failure and microbiologic cure. Adjusted analyses controlled for variables on which randomization was stratified and confounders.
RESULTS
146 subjects receiving synergistic combination therapy and 261 subjects receiving functional monotherapy were included. Most had pneumonia (70%), CR Acinetobacter baumannii infection (79%) and were in intensive care (69%). A. baumannii was more common in those receiving synergistic combination therapy than functional monotherapy (p<0.001). Mortality rates were similar (38.3%, 41.4%, respectively). In adjusted analyses, synergistic combination therapy was associated with significantly lower clinical failure rates (55.3%, 64.3%, adjusted odds ratio [aOR] 0.62, p=0.049), with consistent findings in pneumonia (62.6%, 71.8%, aOR 0.55, p=0.04) and A. baumannii subgroups (57.4%, 69.4%, aOR 0.60, p=0.06). Microbiologic cure rates were similar.
CONCLUSIONS
Colistin-based, synergistic combination treatment with meropenem (compared to non-synergistic colistin-based therapy), was associated with decreased clinical failure, particularly in patients with pneumonia and A. baumannii.
背景
黏菌素是耐碳青霉烯类革兰阴性杆菌（CRGNB）感染的最后一线治疗药物，因其与美罗培南常显示出体外协同作用，故常与美罗培南联合使用。利用来自OVERCOME试验的数据，比较黏菌素+美罗培南与黏菌素+安慰剂治疗CRGNB所致肺炎或血流感染的疗效，我们评估了协同治疗对结局的影响。
方法
采用24小时杀菌分析对黏菌素和美罗培南进行体外协同试验；协同作用定义为与最有效的单一药物相比，菌落形成单位/毫升减少>2个对数。将接受协同联合治疗的患者与接受功能性黏菌素单药治疗（单独使用黏菌素或无协同作用的联合治疗）的患者进行比较。结局包括死亡率、临床失败和微生物学治愈。校正分析控制了随机分层变量和混杂因素。
结果
纳入146例接受协同联合治疗的受试者和261例接受功能性单药治疗的受试者。大多数患者患有肺炎（70%）、CR鲍曼不动杆菌感染（79%）且在重症监护室（69%）。鲍曼不动杆菌在接受协同联合治疗的患者中比功能性单药治疗的患者更常见（p<0.001）。死亡率相似（分别为38.3%和41.4%）。在校正分析中，协同联合治疗与显著更低的临床失败率相关（分别为55.3%和64.3%，校正比值比[aOR]为0.62，p=0.049），在肺炎（分别为62.6%和71.8%，aOR为0.55，p=0.04）和鲍曼不动杆菌亚组（分别为57.4%和69.4%，aOR为0.60，p=0.06）中结果一致。微生物学治愈率相似。
结论
基于黏菌素的美罗培南协同联合治疗（与非协同的基于黏菌素的治疗相比）与临床失败率降低相关，尤其是在肺炎和鲍曼不动杆菌感染患者中。
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