Molecular Epidemiology of Ceftriaxone Non-Susceptible 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 non-susceptibility 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 non-susceptible organisms with mechanisms other than ESBL production. We sought to investigate the molecular epidemiology of ceftriaxone non-susceptible Enterobacterales.

METHODS

All consecutive Escherichia coli, Klebsiellapneumoniae, Klebsiella oxytoca, or Proteus mirabilis clinical isolates with ceftriaxone 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 (blaCTX-M, blaSHV, blaTEM) 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 or more ESBL or p-ampC genes. The most common ESBL genes were of the blaCTX-M-1 group (includes blaCTX-M-15) and the most common p-ampC gene was the blaCMY-2.

CONCLUSIONS

There is considerable diversity in the molecular epidemiology of ceftriaxone non-susceptible Enterobacterales. An understanding of this diversity can improve antibiotic decision-making.