Diversity of resistance mechanisms in carbapenem-resistant Enterobacteriaceae at a health care system in Northern California, from 2013 to 2016

Abstract

The mechanism of resistance in carbapenem-resistant Enterobacteriaceae (CRE) has therapeutic implications. We comprehensively characterized emerging mechanisms of resistance in CRE between 2013 and 2016 at a health system in Northern California. A total of 38.7% (24/62) of CRE isolates were carbapenemase gene-positive, comprising 25.0% (6/24) bla OXA-48 like , 20.8% (5/24) bla KPC , 20.8% (5/24) bla NDM , 20.8% (5/24) bla SME , 8.3% (2/24) bla IMP , and 4.2% (1/24) bla VIM. Between carbapenemases and porin loss, the resistance mechanism was identified in 95.2% (59/62) of CRE isolates. Isolates expressing bla KPC were 100% susceptible to ceftazidimeavibactam, meropenem-vaborbactam, and imipenem-relebactam; bla OXA-48 like-positive isolates were 100% susceptible to ceftazidime-avibactam; and metallo β-lactamase-positive isolates were nearly all nonsusceptible to above antibiotics. Carbapenemase gene-negative CRE were 100% (38/38), 92.1% (35/38), 89.5% (34/38), and 31.6% (12/38) susceptible to ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, and ceftolozane-tazobactam, respectively. None

Emerging Transcriptional and Genomic Mechanisms Mediating Carbapenem and Polymyxin Resistance in Enterobacteriaceae : a Systematic Review of Current Reports

“…The loss of both major outer membrane proteins, OmpK35 and OmpK36, in E. coli and K. aerogenes was seen in some clinical isolates to mediate high-level carbapenem resistance ( 51 – 53 ). However, in K. pneumoniae , Salmonella enterica serotype Typhimurium, and other Enterobacteriaceae species, including Enterobacter cloacae complex ( E. asburiae and E. cloacae ) and Raoultella ornithinolytica , porin deficiency reduces the susceptibility of isolates to carbapenem but does not confer clinical resistance, and β-lactamase activity is required ( 56 , 57 ). The transformation of porin-deficient isolates with an NDM-harboring plasmid revealed a synergistic effect mediating high-level carbapenem resistance ( 51 ).…”

Infections Due to Carbapenem-Resistant Bacteria in Patients With Hematologic Malignancies

“…However, the way GN bacteria resist carbapenems may play a role in the antibiotic combination synergies. Clinical trials and studies on therapeutic efficacy should integrate epidemiological data regarding the existing diversity of resistance mechanisms and profiles in CR Enterobacteriaceae (Senchyna et al, 2018).…”

<p>A Clinical Review and Critical Evaluation of Imipenem-Relebactam: Evidence to Date</p>

“…MIC 50 and MIC 90 are the Minimum Inhibitory Concentrations for 50% and 90% of Isolates, Respectively. Imipenem Susceptibility is Based on FDA-Approved MIC Breakpoints as Follows: Enterobacterales, Susceptible (S) ≤1 µg/mL, Intermediate (I) 2 µg/mL, Resistant (R) ≥4 µg/mL; P. aeruginosa , S ≤2 µg/mL, I 4 µg/mL, R ≥8 µg/mL; A. baumannii , S <2 µg/mL, I 4 µg/mL, R >8 µg/mL; Anaerobic Bacteria, S ≤4 µg/mL, I 8 µg/mL, R ≥16 µg/mL Organism Number of Isolates I-R MIC (μg/mL) Percent Susceptible MIC 50 MIC 90 Enterobacterales Non- proteeae Enterobacterales 6 3143 0.12 0.5 99.1 CRE 6 130 0.5 2 78.5 CRE 29 62 NR NR 71 CRE 26 96 0.5 1 100 CRE 27 200 ≤0.25 0.5 NR OXA-48-like CRE 30 20 4 ≥32 15 KPC Enterobacterales 23 110 0.25 1 90.9 Colistin-resistant Enterobacterales 27 97 ≤0.25 ...…”