Mortality of metallo-β-lactamase-producing Enterobacterales bacteremias with combined ceftazidime–avibactam plus aztreonam vs. other active antibiotics: a multicenter target trial emulationResearch in context

Mortality of metallo-β-lactamase-producing Enterobacterales bacteremias with combined ceftazidime–avibactam plus aztreonam vs. other active antibiotics: a multicenter target trial emulationResearch in context

Summary: Background: Bacteremias caused by metallo-β-lactamase (MBL)-producing Enterobacterales are a critical challenge due to their limited treatment options. Although ceftazidime-avibactam (CAZAVI) combined with aztreonam (ATM) has shown in vitro efficacy, no prior studies have rigorously compar...

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Main Authors: Ivan Alfredo Huespe, Emilio Felipe Huaier Arriazu, Marisa Sanchez, Vanina Stanek, Javier Alberto Pollán, Susana Bauque, Débora Ávila Poletti, Verónica Monzón, Paola Novelli Poisson, María Virginia Boutet, Eleonora Cunto, Viviana Chediack, Melina Tatiana Beloso, Victoria Rucci, Marina Lagostena, Ricardo Cabrera, María José Gutiérrez, María Georgina Gómez, Sebastián Gabriel Arias, Clarisa Taffarel, Daniel Ivulich, Maria Isabel Garzón, Wanda Cornistein, Alicia Gira, Sonia Guadalupe Kriger, Leonora Duarte, Elisa Estenssoro, Matias Mirofsky, Maximiliano Gabriel Castro, Mariana Vaena, Yolleth Andrade Pino, Emilse Díaz Lobo, Luz Guadalupe Ibáñez, Maríangeles Visus, Gustavo Olaizola, Cecilia Domínguez, Marco Antonio Flores Montes, Alejandra Rodríguez, Claudia Vaustat, Ana Paula Amato, Joaquín Ignacio Coduri Anthonioz Blanc, Federico Rafael Galluccio, Macarena Vicino, Mauro David Arias, Damián Alejandro Violi, Sandra lucila Mosca, Debora Beltran, Lilian Benito Mori, Mayra Alejandra Brañez Merida, Yolanda Marine Cortez Aguayo, María Sol García, Oscar Garcia Messina, Adriel Armándola, Néstor Iván Carrizo, María Martha Filippi, Fernando Simil, Mariana Barnes, Esteban D'urbano, Florencia Masa, Santiago Moreno, Ramiro Larrea, Valentina Tissera Mondria, Juan Camilo Monterroza, Liliana Fernandez Canigia, Emiliano Cornu, Stefanía Fernández Molina, Justina Gatti, Sofia Cornejo, Pablo Pratesi, Rodrigo Almanza Raniero Tapia, Carlos Steer, Pedro Ivan Escobar, Evelyn Rocio Ruiz, Gisella Gregori, Adriana Romani, Pascual Valdez
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:The Lancet Regional Health. Americas
Subjects:
Bacteremia
Enterobacteriaceae
Metallo-beta-lactamase
Avibactam, ceftazidime drug combination
Aztreonam
Target trial emulation
Online Access:http://www.sciencedirect.com/science/article/pii/S2667193X25001851
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Summary:Summary: Background: Bacteremias caused by metallo-β-lactamase (MBL)-producing Enterobacterales are a critical challenge due to their limited treatment options. Although ceftazidime-avibactam (CAZAVI) combined with aztreonam (ATM) has shown in vitro efficacy, no prior studies have rigorously compared its clinical effectiveness to Other Active Antibiotics (OAAs). This study aims to evaluate the efficacy and safety of CAZAVI + ATM vs. OAAs in a large cohort of MBL bacteremia. Methods: A retrospective, multicenter, target trial emulation was conducted across 17 hospitals in Argentina between January 2016 and October 2024. Patients with confirmed MBL bacteremia who initiated active antibiotic treatment within 24 h of MBL identification and 96 h of blood sampling were included. Inverse probability of treatment weighting (IPTW) was used to reduce indication bias, and the analysis accounted for hospital clustering within Argentina's public, private, and social security health systems. The primary outcome was 30-day all-cause mortality, with secondary outcomes including clinical failure (relapse, complications, or death) and adverse events. Findings: Among 243 patients (93 receiving CAZAVI + ATM and 150 receiving OAAs), the 30-day mortality rate was 35% in the CAZAVI + ATM group vs. 47% in the OAA group (adjusted odds ratio [OR] 0·63, 95% CI 0·43–0·91, p < 0·01). Clinical failure occurred in 46% of the CAZAVI + ATM group and 53% of the OAA group (adjusted hazard ratio [HR] 0·65, 95% CI 0·44–0·97; p = 0·03). Adverse events were lower with CAZAVI + ATM (9·6% vs. 22·8%, p = 0·014). Interpretation: These findings suggest CAZAVI + ATM might be associated with lower mortality, reduced clinical failure, and fewer adverse events compared to OAAs in patients with MBL-type Enterobacterales bacteremia. Further prospective studies are warranted to confirm these observations. Funding: No specific funding was provided for this study.
ISSN:2667-193X

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