Molecular Epidemiology of Ceftriaxone-Nonsusceptible Enterobacterales Isolates in an Academic Medical Center in the United States

BACKGROUND: Knowledge of whether Enterobacterales are not susceptible to ceftriaxone without understanding the underlying resistance mechanisms may not be sufficient to direct appropriate treatment decisions. As an example, extended-spectrum β-lactamase (ESBL)–producing organisms almost uniformly display nonsusceptibility to ceftriaxone. Regardless of susceptibility to piperacillin-tazobactam or cefepime, carbapenem antibiotics are the treatment of choice for invasive infections. No such guidance exists for ceftriaxone-nonsusceptible organisms with mechanisms other than ESBL production. We sought to investigate the molecular epidemiology of ceftriaxone-nonsusceptible Enterobacterales. METHODS: All consecutive Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, or Proteus mirabilis clinical isolates with ceftriaxone minimum inhibitory concentrations (MICs) of ≥2 mcg/mL from unique patients at a United States hospital over an 8-month period were evaluated for β-lactamase genes using a DNA microarray–based assay. RESULTS: Of 1929 isolates, 482 (25%) had ceftriaxone MICs of ≥2 mcg/mL and were not resistant to any carbapenem antibiotics. Of the 482 isolates, ESBL (bla(CTX-M), bla(SHV), bla(TEM)) and/or plasmid-mediated ampC (p-ampC) genes were identified in 376 (78%). ESBL genes were identified in 310 (82.4%), p-ampC genes in 2 (0.5%), and both ESBL and p-ampC genes in 64 (17.0%) of the 376 organisms. There were 211 (56%), 120 (32%), 41 (11%), and 4 (1%) isolates with 1, 2, 3, or ≥4 ESBL or p-ampC genes. The most common ESBL genes were of the bla(CTX-M-1) group (includes bla(CTX-M-15)), and the most common p-ampC gene was bla(CMY-2). CONCLUSIONS: There is considerable diversity in the molecular epidemiology of ceftriaxone-nonsusceptible Enterobacterales. An understanding of this diversity can improve antibiotic decision-making.