TY - JOUR
T1 - Molecular Epidemiology of Ceftriaxone-Nonsusceptible Enterobacterales Isolates in an Academic Medical Center in the United States
AU - Tamma, Pranita D.
AU - Sharara, Sima L.
AU - Pana, Zoi D.
AU - Amoah, Joe
AU - Fisher, Stephanie L.
AU - Tekle, Tsigereda
AU - Doi, Yohei
AU - Simner, Patricia J.
N1 - Funding Information:
Financialsupport.This work was supported by funding from the National Institutes of Health K23-AI127935 awarded to P.D.T.; R01-AI104895, R21-AI123747, R21-AI135522 to Y.D.; and an R21-AI130608 awarded to P.J.S.
Funding Information:
Potential conflicts of interest. Y.D. has received grants from Accelerate Diagnostics and The Medicines Company and personal fees from Meiji, Achaogen, Allergan, Curetis, The Medicines Company, Roche, Gilead, Pfizer, Tetraphase, Merck, Astellas, and Recida. P.J.S. has received grants and personal fees from Accelerate Diagnostics, grants from BD Diagnostics, Inc., grants from bioMerieux, Inc., grants from Check-Points Diagnostics, grants from BV, grants from Hardy Diagnostics, personal fees from Roche Diagnostics, and personal fees from Opgen Inc. outside the submitted work. All other authors declare no competing interests. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - 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 (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 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 blaCMY-2. Conclusions: There is considerable diversity in the molecular epidemiology of ceftriaxone-nonsusceptible Enterobacterales. An understanding of this diversity can improve antibiotic decision-making.
AB - 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 (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 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 blaCMY-2. Conclusions: There is considerable diversity in the molecular epidemiology of ceftriaxone-nonsusceptible Enterobacterales. An understanding of this diversity can improve antibiotic decision-making.
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U2 - 10.1093/ofid/ofz353
DO - 10.1093/ofid/ofz353
M3 - Article
AN - SCOPUS:85081199608
VL - 6
JO - Open Forum Infectious Diseases
JF - Open Forum Infectious Diseases
SN - 2328-8957
IS - 8
M1 - ofz353
ER -