Antibiotic Resistance Genotype, Phenotype, and Clinical Outcomes in Patients with Gram-Negative Infections at Rabin Medical Center in Israel

Background. Antibiotic resistance contributes to morbidity and mortality. A better understanding of how genetic and phenotypic resistance impacts clinical outcomes is needed. We performed whole-genome sequencing on five medically important pathogens (Acinetobacter baumannii, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) seen in Israel to investigate determinants of resistance and impact on outcomes.Methods. 168 isolates from 162 patients with gram-negative infections admitted to Beilinson Hospital at Rabin Medical Center (May 2019-June 2020) were included for final analysis. Genomes were analyzed for resistance determinants and correlated with microbiologic and clinical data.Results. 30-day mortality was 21.0% (34/162). 29 patients had carbapenem-resistant isolates (29/168, 17.2%), while 63 patients had multidrug-resistant isolates (63/168, 37.5%). Albumin levels were associated with mortality and length of stay while arrival from a healthcare facility and prior chemotherapy predicted having a multidrug-resistant isolate. Sequencing revealed possible patient-to-patient transmission events. blaCTX-M-15 was associated with multidrug-resistant in E. coli (OR = 3.888, P = 0.023) on multivariate analysis. blaOXA-72 copy number was associated with carbapenem-resistance in A. baumannii (P = 0.003) and meropenem minimum inhibitory concentration (P = 0.005), yet carbapenem-resistant isolates retained sensitivity to cefiderocol and sulbactam-durlobactam. RJX84154 was associated with multidrug-resistance across all pathogens (P = 0.0018) and in E. coli (P = 0.0024).Conclusions. Low albumin levels were associated with 30-day mortality and length of stay in this hospitalized patient population in Israel. blaCTX-M-15 was correlated with multidrug-resistance in E. coli, and blaOXA-72 depth predicts meropenem minimum inhibitory concentration in A. baumannii. RJX84154 may play a role in multidrug-resistance.