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新型β-内酰胺酶增强剂研究用抗生素头孢吡肟/齐他培南(WCK 5222)治疗产 NDM 广泛耐药铜绿假单胞菌感染所致腹腔感染相关性脓毒症患者的同情用药:一例报告。

Compassionate use of a novel β-lactam enhancer-based investigational antibiotic cefepime/zidebactam (WCK 5222) for the treatment of extensively-drug-resistant NDM-expressing Pseudomonas aeruginosa infection in an intra-abdominal infection-induced sepsis patient: a case report.

机构信息

Institute of Critical Care medicine, Medanta, Lucknow, India.

Department of Pulmonary Medicine, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, India.

出版信息

Ann Clin Microbiol Antimicrob. 2023 Jul 5;22(1):55. doi: 10.1186/s12941-023-00606-x.


DOI:10.1186/s12941-023-00606-x
PMID:37408075
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10324185/
Abstract

Infections in critically-ill patients caused by extensively-drug-resistant (XDR)-Pseudomonas aeruginosa are challenging to manage due to paucity of effective treatment options. Cefepime/zidebactam, which is currently in global Phase 3 clinical development (Clinical Trials Identifier: NCT04979806, registered on July 28, 2021) is a novel mechanism of action based β-lactam/ β-lactam-enhancer combination with a promising activity against a broad-range of Gram-negative pathogens including XDR P. aeruginosa. We present a case report of an intra-abdominal infection-induced sepsis patient infected with XDR P. aeruginosa and successfully treated with cefepime/zidebactam under compassionate use. The 50 year old female patient with past-history of bariatric surgery and recent elective abdominoplasty and liposuction developed secondary pneumonia and failed a prolonged course of polymyxins. The organism repeatedly isolated from the patient was a New-Delhi metallo β-lactamase-producing XDR P. aeruginosa resistant to ceftazidime/avibactam, imipenem/relebactam and ceftolozane/tazobactam, susceptible only to cefepime/zidebactam. As polymyxins failed to rescue the patient, cefepime/zidebactam was administered under compassionate grounds leading to discharge of patient in stable condition. The present case highlights the prevailing precarious scenario of antimicrobial resistance and the need for novel antibiotics to tackle infections caused by XDR phenotype pathogens.

摘要

由于缺乏有效的治疗选择,重症患者中由广泛耐药(XDR)铜绿假单胞菌引起的感染难以治疗。头孢吡肟/齐他培南,目前正在进行全球 3 期临床开发(临床试验标识符:NCT04979806,于 2021 年 7 月 28 日注册),是一种新的作用机制的β-内酰胺/β-内酰胺增强剂组合,对包括 XDR 铜绿假单胞菌在内的广泛革兰氏阴性病原体具有有前途的活性。我们报告了一例腹腔感染诱导性败血症患者的病例报告,该患者感染了 XDR 铜绿假单胞菌,在同情用药下成功接受头孢吡肟/齐他培南治疗。这名 50 岁女性患者有减肥手术史,最近接受了腹部整形术和脂肪抽吸术,继发肺炎,并经历了延长的多粘菌素疗程失败。从患者中反复分离出的病原体是一种新德里金属β-内酰胺酶产生的 XDR 铜绿假单胞菌,对头孢他啶/阿维巴坦、亚胺培南/雷巴他定和头孢洛扎/他唑巴坦耐药,仅对头孢吡肟/齐他培南敏感。由于多粘菌素未能挽救患者,根据同情用药原则给予头孢吡肟/齐他培南治疗,使患者病情稳定出院。本病例突出了抗菌药物耐药性的普遍危险局面,需要新型抗生素来应对 XDR 表型病原体引起的感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd35/10324185/8e6fe3158217/12941_2023_606_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd35/10324185/8e6fe3158217/12941_2023_606_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd35/10324185/8e6fe3158217/12941_2023_606_Fig1_HTML.jpg

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本文引用的文献

[1]
Antimicrobial activity of cefepime/zidebactam (WCK 5222), a β-lactam/β-lactam enhancer combination, against clinical isolates of Gram-negative bacteria collected worldwide (2018-19).

J Antimicrob Chemother. 2022-9-30

[2]
New Drugs for the Treatment of Infections with Limited Treatment Options: A Narrative Review.

Antibiotics (Basel). 2022-4-26

[3]
Activity of Ceftolozane-Tazobactam, Imipenem-Relebactam, Ceftazidime-Avibactam, and Comparators against Pseudomonas aeruginosa Isolates Collected in United States Hospitals According to Results from the SMART Surveillance Program, 2018 to 2020.

Antimicrob Agents Chemother. 2022-5-17

[4]
Comparative in vivo activity of human-simulated plasma and epithelial lining fluid exposures of WCK 5222 (cefepime/zidebactam) against KPC- and OXA-48-like-producing Klebsiella pneumoniae in the neutropenic murine pneumonia model.

J Antimicrob Chemother. 2021-8-12

[5]
Pseudomonas aeruginosa epidemic high-risk clones and their association with horizontally-acquired β-lactamases: 2020 update.

Int J Antimicrob Agents. 2020-12

[6]
Activity of Cefiderocol, a Siderophore Cephalosporin, against Multidrug-Resistant Gram-Negative Bacteria.

Antimicrob Agents Chemother. 2020-11-17

[7]
Activity of WCK 5222 (Cefepime-Zidebactam) against Worldwide Collected Gram-Negative Bacilli Not Susceptible to Carbapenems.

Antimicrob Agents Chemother. 2020-11-17

[8]
Effective inhibition of PBPs by cefepime and zidebactam in the presence of VIM-1 drives potent bactericidal activity against MBL-expressing Pseudomonas aeruginosa.

J Antimicrob Chemother. 2020-6-1

[9]
Efficacy of human-simulated bronchopulmonary exposures of cefepime, zidebactam and the combination (WCK 5222) against MDR Pseudomonas aeruginosa in a neutropenic murine pneumonia model.

J Antimicrob Chemother. 2020-1-1

[10]
A large-scale whole-genome comparison shows that experimental evolution in response to antibiotics predicts changes in naturally evolved clinical .

Antimicrob Agents Chemother. 2019-9-9

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