{"title":"头孢他啶-阿维巴坦加阿曲南治疗重症患者广泛耐药革兰氏阴性感染","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":"{\"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}","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
摘要
广泛耐药(XDR)革兰氏阴性病原体是重症监护病房的一个关键治疗挑战,死亡率超过50%。头孢他啶-阿维巴坦与氨曲南的协同组合提供了一种新的治疗方法,特别是在产生碳青霉烯酶的肠杆菌中。方法本前瞻性观察研究分析2024年10月至2025年4月24例确诊为XDR革兰氏阴性感染的重症成人ICU患者。对头孢他啶-阿维巴坦(CZA)与氨曲南(ATM)、头孢吡肟-恩美唑巴坦(FEP-ENM)进行综合药敏试验、碳青霉烯酶检测及E条协同试验。主要结局包括临床反应、微生物清除率和30天死亡率。统计分析包括描述性统计、Fisher精确检验、Mann-Whitney U检验、logistic回归分析和Kaplan-Meier生存分析。结果共检出24株XDR:肺炎克雷伯菌(18株,75%)和大肠埃希菌(6株,25%)。所有人都表现出对单个药物的耐药性(CZA;MIC 16 μg/ml), (ATM;MIC >256 μg/mL)和FEP-ENM(区大小>; 6 mm)。碳青霉烯酶检测结果显示NDM占91.7% (22/24),NDM + OXA-48共产生占66.7%(16/24)。62.5%(15/24)的病例显示协同作用,MIC显著降低(中位数0.5 μg/mL, IQR 0.25-1.0)。31.3%(5/16)的协同阳性患者临床改善,12.5%(1/8)的协同阴性患者临床改善(p = 0.631)。微生物清除率仅在协同作用阳性病例中实现(18.8% vs 0%, p = 0.534)。死亡率的独立预测因素包括感染性休克表现(OR 3.5, 95% CI 0.7-17.8, p = 0.134)。结论头孢他啶-阿维巴坦+阿曲南联合治疗对XDR病原体具有显著的体外协同作用,有望改善危重患者的临床结果,是一种重要的挽救性治疗选择,需要更大规模的随机对照试验。
Ceftazidime-avibactam plus aztreonam for extensively drug-resistant gram-negative infections in critically ill patients
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.