一项比较亚胺培南/西司他丁/雷巴他定与癌症合并发热性中性粒细胞减少症患者标准治疗中革兰氏阴性覆盖的随机非劣效性研究。

A randomized non-inferiority study comparing imipenem/cilastatin/relebactam with standard-of-care Gram-negative coverage in cancer patients with febrile neutropenia.

机构信息

Department of Infectious Diseases, Infection Control and Employee Health, Unit 1460, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.

Department of Hospital Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

出版信息

J Antimicrob Chemother. 2024 Oct 1;79(10):2543-2553. doi: 10.1093/jac/dkae254.

DOI:10.1093/jac/dkae254

PMID:39092963

Abstract

BACKGROUND

Antibiotic overuse leads to the emergence of antibiotic resistance that threatens immunocompromised cancer patients. Infections caused by MDR Gram-negative pathogens are difficult to treat and associated with high mortality. Hence, empirical therapy with standard-of-care (SOC) antibiotics could be suboptimal in these vulnerable patients. New antibiotics covering potential resistant pathogens may be considered.

METHODS

We conducted a randomized non-inferiority study comparing safety and efficacy of imipenem/cilastatin/relebactam (IPM/REL), a β-lactam/β-lactamase inhibitor combination, with SOC antibiotics (cefepime, piperacillin/tazobactam or meropenem) in cancer patients with febrile neutropenia. Patients received at least 48 h of IV antibiotics and were assessed at end-of-IV (EOIV) therapy, test of cure (TOC; Days 21-28), and late follow-up (LFU; Days 35-42).

RESULTS

A total of 100 patients were enrolled (49 IPM/REL and 50 SOC). Demographics and rates of documented microbiological infections were similar in both groups. In the SOC arm, 86% of antibiotics consisted of cefepime. Patients on IPM/REL had a higher favourable clinical response at EOIV than those on SOC (90% versus 74%; P = 0.042); however, responses were similar at TOC and LFU. Microbiological eradication was comparable at all three timepoints. Study drug-related adverse events and adverse events leading to drug discontinuation were similar in both groups, with no study drug-related mortality.

CONCLUSIONS

Our results suggest that compared with SOC antibiotics, predominantly cefepime, IPM/REL for empirical coverage of febrile neutropenia in cancer patients is generally safe and could be associated with a better clinical outcome at EOIV. The current SOC consisting mainly of agents that do not cover for ESBL-producing and carbapenem-resistant Enterobacterales bacteria should be reconsidered.

摘要

背景

抗生素的过度使用导致了抗生素耐药性的出现，这对免疫功能低下的癌症患者构成了威胁。多重耐药革兰氏阴性病原体引起的感染难以治疗，死亡率高。因此，在这些脆弱的患者中，标准治疗（SOC）抗生素的经验性治疗可能并不理想。可能需要考虑覆盖潜在耐药病原体的新抗生素。

方法

我们进行了一项随机非劣效性研究，比较了在发热性中性粒细胞减少症的癌症患者中，使用碳青霉烯类/β-内酰胺酶抑制剂复合制剂亚胺培南/西司他丁/雷巴他定（IPM/REL）与 SOC 抗生素（头孢吡肟、哌拉西林/他唑巴坦或美罗培南）的安全性和疗效。患者接受至少 48 小时的静脉内抗生素治疗，并在结束静脉内（EOIV）治疗时、治疗结束时（TOC；第 21-28 天）和晚期随访（LFU；第 35-42 天）进行评估。

结果

共纳入 100 例患者（49 例 IPM/REL 和 50 例 SOC）。两组患者的人口统计学特征和记录的微生物感染率相似。在 SOC 组中，86%的抗生素为头孢吡肟。在 EOIV 时，接受 IPM/REL 治疗的患者比接受 SOC 治疗的患者有更高的有利临床反应（90%比 74%；P=0.042）；然而，在 TOC 和 LFU 时反应相似。所有三个时间点的微生物清除率相似。在所有三个时间点，研究药物相关的不良事件和导致药物停药的不良事件在两组之间相似，没有研究药物相关的死亡。