Distinct molecular epidemiology and outcomes of carbapenem-resistant gram-negative infections in Lebanon: insights from the MDRO network.

BACKGROUND: This study provides the first prospective, genomically validated dataset integrated into the global MultiDrug-Resistant Organism (MDRO) Network from the Middle East and North Africa region. To address the substantial gap in antimicrobial resistance (AMR) data, the American University of Beirut Medical Center (AUBMC) investigated carbapenem-resistant Enterobacterales (CRE), Acinetobacter baumannii (CRAB), and Pseudomonas aeruginosa (CRPA). METHODS: Consecutive, hospitalized patients whose clinical cultures were positive for CRE, CRAB, or CRPA were prospectively enrolled between June 2018 and November 2019. Data on demographics, hospitalization, outcomes, and antimicrobial susceptibility were collected. Whole-genome sequencing (WGS) characterized the isolates. The primary outcome was the Desirability of Outcome Ranking (DOOR). RESULTS: Ninety-four patients were included: 35 with CRE, 19 with CRAB, and 40 with CRPA. Overall, 30% of patients survived without adverse events, whereas 33% experienced two or more adverse events. Patients with CRAB had the poorest prognosis, with only 5% surviving without complications, and a significantly different DOOR distribution versus CRE or CRPA (p = 0.023). Adjusted DOOR probabilities confirmed the poorer outcomes associated with CRAB: when compared with CRE or CRPA, a randomly selected CRAB patient had only a 37.7% (95% CI, 24.9-52.6%) and 38.8% (95% CI, 26.5-52.7%) probability of achieving a more desirable outcome, respectively. WGS identified blaNDM-5 (24%) and blaOXA-48 (24%) as the most common genes in CRE, blaOXA-23 in all CRAB strains, and blaVIM-2 in 88% of CRPA strains. The dominant clones were CG383 K. pneumoniae (CRE), CG2 (CRAB), and CG111 (CRPA). CONCLUSIONS: MDRO infections in Lebanon have distinct molecular patterns compared to the US, Chinese, South American, and Australian cohorts, as well as poor outcomes, especially with CRAB. Ongoing surveillance, strengthening regional collaboration, and future clinical trials are essential to guide diagnostic and therapeutic strategies in settings with increasing AMR. TRIAL REGISTRY: ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT03646227. DATE OF REGISTRATION: 15-08-2018.

Duke Scholars

Author Vance Garrison Fowler Jr. Medicine, Infectious Diseases