Journal of critical care · 2025
Ceftazidime-avibactam plus aztreonam for extensively drug-resistant gram-negative infections in critically ill patients.
Наблюдательное исследованиеПисьмо в редакциюНазвание и аннотация: Перевод в очереди
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Biswal Debasish, Chawla Aayush, Kumari Pankhuri, Mangla Sandeep, Salhotra Ripenmeet
Аннотация
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.
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.