{"title":"Ceftazidime-avibactam plus aztreonam for extensively drug-resistant gram-negative infections in critically ill patients","authors":"Debasish Biswal , Aayush Chawla , Pankhuri Kumari , Sandeep Mangla , Ripenmeet Salhotra","doi":"10.1016/j.jcrc.2025.155207","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Extensively drug-resistant (XDR) gram-negative pathogens represent a critical therapeutic challenge in intensive care units, with mortality rates exceeding 50 %. The synergistic combination of ceftazidime-avibactam with aztreonam offers a novel therapeutic approach, particularly in carbapenemase-producing Enterobacterales.</div></div><div><h3>Methods</h3><div>This prospective observational study analysed 24 critically ill adult ICU patients with confirmed XDR gram-negative infections from October 2024 to April 2025. Comprehensive antimicrobial susceptibility testing, carbapenemase detection, and <em>E</em>- strip based synergy testing of ceftazidime-avibactam (CZA) with aztreonam (ATM), cefepime-enmetazobactam (FEP-ENM) testing were performed. Primary outcomes included clinical response, microbiological clearance, and 30-day mortality. Statistical analysis included descriptive statistics, Fisher's exact test, Mann-Whitney <em>U</em> test, logistic regression analysis and Kaplan-Meier survival analysis.</div></div><div><h3>Results</h3><div>Twenty-four XDR isolates were analysed: <em>Klebsiella pneumoniae</em> (<em>n</em> = 18, 75 %) and <em>Escherichia coli</em> (<em>n</em> = 6, 25 %). All demonstrated resistance to individual agents (CZA; MIC >16 μg/ml), (ATM; MIC >256 μg/mL) and FEP-ENM (zone size <6 mm). Carbapenemase detection revealed NDM in 91.7 % (22/24), with NDM + OXA-48 co- production in 66.7 % (16/24). Synergy was demonstrated in 62.5 % (15/24) cases with significant MIC reduction (median 0.5 μg/mL, IQR 0.25–1.0). Clinical improvement occurred in 31.3 % (5/16) of synergy-positive versus 12.5 % (1/8) of synergy-negative cases (<em>p</em> = 0.631). Microbiological clearance was achieved exclusively in synergy- positive cases (18.8 % vs 0 %, <em>p</em> = 0.534). Independent predictors of mortality included septic shock presentation (OR 3.5, 95 % CI 0.7–17.8, <em>p</em> = 0.134).</div></div><div><h3>Conclusion</h3><div>Ceftazidime-avibactam plus aztreonam combination demonstrated significant in vitro synergy against XDR pathogens with promising trends toward improved clinical outcomes in critically ill patients, representing a crucial salvage therapy option warranting larger randomized controlled trials.</div></div>","PeriodicalId":15451,"journal":{"name":"Journal of critical care","volume":"90 ","pages":"Article 155207"},"PeriodicalIF":2.9000,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of critical care","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0883944125001947","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Extensively drug-resistant (XDR) gram-negative pathogens represent a critical therapeutic challenge in intensive care units, with mortality rates exceeding 50 %. The synergistic combination of ceftazidime-avibactam with aztreonam offers a novel therapeutic approach, particularly in carbapenemase-producing Enterobacterales.
Methods
This prospective observational study analysed 24 critically ill adult ICU patients with confirmed XDR gram-negative infections from October 2024 to April 2025. Comprehensive antimicrobial susceptibility testing, carbapenemase detection, and E- strip based synergy testing of ceftazidime-avibactam (CZA) with aztreonam (ATM), cefepime-enmetazobactam (FEP-ENM) testing were performed. Primary outcomes included clinical response, microbiological clearance, and 30-day mortality. Statistical analysis included descriptive statistics, Fisher's exact test, Mann-Whitney U test, logistic regression analysis and Kaplan-Meier survival analysis.
Results
Twenty-four XDR isolates were analysed: Klebsiella pneumoniae (n = 18, 75 %) and Escherichia coli (n = 6, 25 %). All demonstrated resistance to individual agents (CZA; MIC >16 μg/ml), (ATM; MIC >256 μg/mL) and FEP-ENM (zone size <6 mm). Carbapenemase detection revealed NDM in 91.7 % (22/24), with NDM + OXA-48 co- production in 66.7 % (16/24). Synergy was demonstrated in 62.5 % (15/24) cases with significant MIC reduction (median 0.5 μg/mL, IQR 0.25–1.0). Clinical improvement occurred in 31.3 % (5/16) of synergy-positive versus 12.5 % (1/8) of synergy-negative cases (p = 0.631). Microbiological clearance was achieved exclusively in synergy- positive cases (18.8 % vs 0 %, p = 0.534). Independent predictors of mortality included septic shock presentation (OR 3.5, 95 % CI 0.7–17.8, p = 0.134).
Conclusion
Ceftazidime-avibactam plus aztreonam combination demonstrated significant in vitro synergy against XDR pathogens with promising trends toward improved clinical outcomes in critically ill patients, representing a crucial salvage therapy option warranting larger randomized controlled trials.
期刊介绍:
The Journal of Critical Care, the official publication of the World Federation of Societies of Intensive and Critical Care Medicine (WFSICCM), is a leading international, peer-reviewed journal providing original research, review articles, tutorials, and invited articles for physicians and allied health professionals involved in treating the critically ill. The Journal aims to improve patient care by furthering understanding of health systems research and its integration into clinical practice.
The Journal will include articles which discuss:
All aspects of health services research in critical care
System based practice in anesthesiology, perioperative and critical care medicine
The interface between anesthesiology, critical care medicine and pain
Integrating intraoperative management in preparation for postoperative critical care management and recovery
Optimizing patient management, i.e., exploring the interface between evidence-based principles or clinical insight into management and care of complex patients
The team approach in the OR and ICU
System-based research
Medical ethics
Technology in medicine
Seminars discussing current, state of the art, and sometimes controversial topics in anesthesiology, critical care medicine, and professional education
Residency Education.