亚胺培南/西司他丁/瑞来巴坦治疗由亚胺培南不敏感病原体引起的医院获得性/呼吸机相关性细菌性肺炎：RESTORE-IMI 2临床研究的亚组分析和分离株分子特征分析

摘要(中文译文)

※ 中文译文由 AI 辅助生成,仅供学术参考,请以英文原文为准。

对于由碳青霉烯类耐药病原体引起的医院获得性和呼吸机相关性细菌性肺炎（HABP/VABP）患者，需要额外的治疗选择。本亚组分析考察了RESTORE-IMI 2研究中接受亚胺培南/西司他丁/雷利巴坦（IMI/REL）治疗的受试者的临床和微生物学结局，按基线下呼吸道（LRT）分离株对亚胺培南的敏感性进行分层。同时评估了治疗期间对IMI/REL非敏感性的出现情况。基线LRT标本在筛选前≤48小时内采集，由中心实验室鉴定，并根据临床和实验室标准协会的折点判定敏感性。接受IMI/REL治疗、基线LRT病原体至少1株对亚胺培南非敏感但对亚胺培南/REL敏感的受试者的结局，与携带亚胺培南敏感病原体的受试者进行了比较。同时评估了对亚胺培南/REL非敏感性的出现，并对分离株进行了分子学特征分析。在微生物学改良意向治疗人群中，共有215名受试者接受了IMI/REL治疗，其中112名感染了亚胺培南敏感病原体，18名感染了亚胺培南非敏感但亚胺培南/REL敏感病原体，这18名受试者被纳入本分析。在这18名受试者中，88.9%在重症监护病房，83.3%携带一种革兰阴性基线病原体。对于因亚胺培南非敏感病原体与亚胺培南敏感病原体所致HABP/VABP而接受IMI/REL治疗的受试者，第28天全因死亡率分别为22.2%和18.8%（校正差异：7.3 [-8.8至31.1]）。在总共192株分离株中，59株革兰阴性分离株（对亚胺培南非敏感的基线分离株及来自同一受试者的同种后续分离株）通过多重聚合酶链反应和测序技术进行了特征分析。在112名具有指定亚胺培南敏感基线病原体的受试者中，有3名受试者的分离株出现了对亚胺培南/REL的非敏感性（两株为铜绿假单胞菌，一株为肺炎克雷伯菌）。在接受IMI/REL治疗的受试者中，无论基线病原体对亚胺培南的敏感性如何，第28天全因死亡率相似。治疗期间对亚胺培南/REL非敏感性的出现率较低。ClinicalTrials.gov（NCT02493764）。

Abstract

Additional treatment options are needed for patients with hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) caused by carbapenem-resistant pathogens. This subgroup analysis examined clinical and microbiologic outcomes in participants from RESTORE-IMI 2 treated with imipenem/cilastatin/relebactam (IMI/REL), stratified by baseline lower respiratory tract (LRT) isolate susceptibility to imipenem. Emergence of nonsusceptibility to IMI/REL during treatment was also evaluated. Baseline LRT specimens were obtained ≤48 hours before screening, identified at a central laboratory, and susceptibility determined per the Clinical and Laboratory Standards Institute breakpoints. Outcomes for participants who received IMI/REL, with ≥1 imipenem-nonsusceptible, imipenem/REL-susceptible baseline LRT pathogen were compared with participants with imipenem-susceptible pathogens. Emergence of nonsusceptibility to imipenem/REL was also assessed, and isolates were characterized molecularly. In total, 215 participants in the microbiologic-modified intent-to-treat population received IMI/REL, of whom 112 were infected with imipenem-susceptible pathogens and 18 with imipenem-nonsusceptible, imipenem/REL-susceptible pathogens and were included in this analysis. Of these 18 participants, 88.9% were in the intensive care unit and 83.3% had one gram-negative baseline pathogen. Day 28 all-cause mortality was 22.2% and 18.8% (adjusted difference: 7.3 [-8.8 to 31.1]) for participants who received IMI/REL for the treatment of HABP/VABP caused by imipenem-nonsusceptible versus imipenem-susceptible pathogens, respectively. Of a total of 192 isolates, 59 gram-negative isolates (baseline isolates that were nonsusceptible to imipenem and subsequent isolates of the same species from the same participants) were characterized using multiplex polymerase chain reaction and sequencing techniques. Emergence of nonsusceptibility to imipenem/REL occurred in isolates from three of the 112 participants with indicated imipenem-susceptible baseline pathogens (two isolates of Pseudomonas aeruginosa and one isolate of Klebsiella pneumoniae). Day 28 all-cause mortality was similar among participants treated with IMI/REL, regardless of baseline pathogen susceptibility to imipenem. Emergence of nonsusceptibility to imipenem/REL on treatment was low. ClinicalTrials.gov (NCT02493764).

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