Ceftazidime-Avibactam as Early Empiric Therapy for Gram-Negative Nosocomial Infections: A Risk-Stratified Empiric Use...

International evidence supports early initiation of ceftazidime-avibactam (CAZ-AVI) in carbapenem-resistant Enterobacterales (CRE) infections, with superior outcomes when therapy is initiated within 72 h. The applicability of this principle to the United Arab Emirates (UAE) requires contextualization against local antimicrobial resistance epidemiology.

This consensus narrative review integrates two evidence streams: (1) national AMR surveillance data from the UAE National Antimicrobial Resistance Surveillance Report 2024-encompassing 195,108 non-duplicate isolates from 318 surveillance sites across all seven Emirates-providing phenotypic susceptibility and resistance rates for key gram-negative pathogens; and (2) a structured review of the published international evidence base on CAZ-AVI clinical efficacy, outcome data, and timing, identified through PubMed searches using the terms "ceftazidime-avibactam", "empiric therapy", "carbapenem-resistant Enterobacterales", and "nosocomial infections". The risk-stratification framework was developed through expert consensus by the authoring group, informed by the integrated evidence synthesis and structured around established clinical risk factors for carbapenem-resistant gram-negative infection.

National carbapenem resistance among Enterobacterales remains low (imipenem 3.4%R; meropenem 1.4%R), with Klebsiella pneumoniae exhibiting the highest carbapenem non-susceptibility (imipenem 5.8% NS; meropenem 2.8% NS). Direct CAZ-AVI susceptibility testing data were available only for Pseudomonas aeruginosa at the emirate level, showing consistently high susceptibility (88-93% across Abu Dhabi, Dubai, and the Northern Emirates); dedicated CAZ-AVI susceptibility data for Klebsiella pneumoniae and Escherichia coli were not reported in any emirate-level antibiogram, representing a significant national surveillance gap. The absence of carbapenemase genotype data (OXA-48 versus NDM/MBL) in the national surveillance dataset is identified as a further critical gap.

CAZ-AVI is not supported as a universal empiric therapy for all nosocomial pneumonia in the UAE. A risk-stratified approach is proposed: standard anti-pseudomonal beta-lactams for general nosocomial infections, and early CAZ-AVI for pre-defined high-risk CRE-suspected patients, where the timing benefit is operationally justified primarily by the international outcome evidence, given that UAE-specific CAZ-AVI phenotypic data are currently available only for P. aeruginosa. Investment in carbapenemase molecular surveillance and expanded CAZ-AVI susceptibility reporting is recommended as a national priority to enable precise empiric prescribing.