COVID-19 患者中碳青霉烯类耐药鲍曼不动杆菌的三种药物联合治疗的早期启动。
Early initiation of three-drug combinations for the treatment of carbapenem-resistant A. baumannii among COVID-19 patients.
机构信息
Department of Practice, Science, and Health Outcomes Research, University of Maryland School of Pharmacy, 20 North Pine Street, Baltimore, MD, USA.
Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
出版信息
J Antimicrob Chemother. 2023 Apr 3;78(4):1034-1040. doi: 10.1093/jac/dkad042.
OBJECTIVES
We evaluated the clinical characteristics and outcomes of patients with COVID-19 who received three-drug combination regimens for treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections during a single-centre outbreak. Our objective was to describe the clinical outcomes and molecular characteristics and in vitro synergy of antibiotics against CRAB isolates.
MATERIALS AND METHODS
Patients with severe COVID-19 admitted between April and July 2020 with CRAB infections were retrospectively evaluated. Clinical success was defined as resolution of signs/symptoms of infection without need for additional antibiotics. Representative isolates underwent whole-genome sequencing (WGS) and in vitro synergy of two- or three-drug combinations was assessed by checkerboard and time-kill assays, respectively.
RESULTS
Eighteen patients with CRAB pneumonia or bacteraemia were included. Treatment regimens included high-dose ampicillin-sulbactam, meropenem, plus polymyxin B (SUL/MEM/PMB; 72%), SUL/PMB plus minocycline (MIN; 17%) or other combinations (12%). Clinical resolution was achieved in 50% of patients and 30-day mortality was 22% (4/18). Seven patients had recurrent infections, during which further antimicrobial resistance to SUL or PMB was not evident. PMB/SUL was the most active two-drug combination by checkerboard. Paired isolates collected before and after treatment with SUL/MEM/PMB did not demonstrate new gene mutations or differences in the activity of two- or three-drug combinations.
CONCLUSIONS
Use of three-drug regimens for severe CRAB infections among COVID-19 resulted in high rates of clinical response and low mortality relative to previous studies. The emergence of further antibiotic resistance was not detected phenotypically or through WGS analysis. Additional studies are needed to elucidate preferred antibiotic combinations linked to the molecular characteristics of infecting strains.
目的
我们评估了在单中心暴发期间，接受三联药物组合方案治疗耐碳青霉烯类鲍曼不动杆菌（CRAB）感染的 COVID-19 患者的临床特征和结局。我们的目的是描述针对 CRAB 分离株的抗生素的临床结果、分子特征和体外协同作用。
材料与方法
回顾性评估了 2020 年 4 月至 7 月期间因 CRAB 感染而住院的重症 COVID-19 患者。临床治愈定义为感染的体征/症状消退，无需额外使用抗生素。代表性分离株进行全基因组测序（WGS），通过棋盘法和时间杀伤法分别评估两药和三药组合的体外协同作用。
结果
共纳入 18 例 CRAB 肺炎或菌血症患者。治疗方案包括大剂量氨苄西林-舒巴坦、美罗培南和多黏菌素 B（SUL/MEM/PMB；72%）、SUL/PMB 加米诺环素（MIN；17%）或其他组合（12%）。50%的患者临床治愈，30 天死亡率为 22%（4/18）。7 例患者发生复发性感染，在此期间，SUL 或 PMB 未出现进一步的耐药性。棋盘法显示 PMB/SUL 是最有效的两药组合。用 SUL/MEM/PMB 治疗前后采集的配对分离株未显示新的基因突变或两药和三药组合活性的差异。
结论
与以往的研究相比，COVID-19 患者中使用三联药物方案治疗严重的 CRAB 感染可获得较高的临床反应率和较低的死亡率。表型或通过 WGS 分析均未检测到进一步的抗生素耐药性出现。需要进一步研究阐明与感染株分子特征相关的首选抗生素组合。
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