Clinical, microbiological and genomic characterization of Gram-negative bacteria with dual carbapenemases as identified by rapid molecular testing.

Objective: Dual carbapenemase-producing organisms (DCPOs) are an emerging threat that expands the spectrum of antimicrobial resistance. There is limited literature on the clinical and genetic epidemiology of DCPOs. Methods: DCPO isolates were identified by Xpert® Carba-R PCR testing of routine diagnostic cultures performed from 2018 to 2021 at a New York City health system. WGS was performed by Illumina and/or PacBio. Medical records of patients were reviewed for clinical and epidemiological data. Results: Twenty-six DCPO isolates were obtained from 13 patients. Klebsiella pneumoniae (n = 22) was most frequent, followed by Pseudomonas aeruginosa (n = 2), Escherichia coli (n = 1) and Enterobacter cloacae (n = 1). The most common DCPO combination was blaNDM/blaOXA-48-like (n = 16). Notably, 1.05% (24/2290) of carbapenem-resistant Enterobacterales isolates were identified as DCPOs. The susceptibility profiles matched the identified resistance genes, except for a K. pneumoniae (blaKPC/blaOXA-48-like) isolate that was phenotypically susceptible to meropenem. Eleven patients were hospitalized within the year prior to admission, and received antibiotic(s) 1 month prior. Seven patients were originally from outside the USA. Hypertension, kidney disease and diabetes were frequent comorbidities. Death in two cases was attributed to DCPO infection. WGS of eight isolates showed that carbapenemases were located on distinct plasmids, except for one K. pneumoniae isolate where NDM and KPC carbapenemases were located on a single IncC-type plasmid backbone. Conclusions: Here we characterized a series of DCPOs from New York City. Foreign travel, prior hospitalization, antibiotic usage and comorbidities were common among DCPO cases. All carbapenemases were encoded on plasmids, which may facilitate horizontal transfer.

Correlation between Identification of ß-Lactamase Resistance Genes and Antimicrobial Susceptibility Profiles in Gram-Negative Bacteria: a Laboratory Data Analysis.

We reported the frequency of resistance gene detection in Gram-negative blood culture isolates and correlated these findings with corresponding antibiograms. Data were obtained from 1045 isolates tested on the GenMark Dx ePlex Blood Culture Identification Gram-Negative Panels at the Mount Sinai Hospital Clinical Microbiology Laboratory in New York from March 2019 to February 2021. Susceptibilities were performed using Vitek 2 (bioMérieux Clinical Diagnostics) or Microscan (Beckman Coulter Inc.). blaCTX-M was detected in 26.4% Klebsiella pneumoniae, 23.5% Escherichia coli, and 16.4% Proteus mirabilis isolates. As would be expected, both blaCTX-M and blaCTX-M negative isolates were likely to be susceptible to newer agents while blaCTX-M positive isolates were more likely to be resistant to earlier generations of beta-lactam antibiotics. 3/204 blaCTX-M-positive isolates were found to be ceftriaxone-susceptible. Conversely, 2.8% ceftriaxone nonsusceptible strains were negative for all ß-lactamase genes on the ePlex BCID-GN panel, including blaCTX-M. The prevalence of CTX-M-producing Enterobacterales remains high in the United States. A small number of blaCTX-M-positive isolates were susceptible to ceftriaxone, and a small number of ceftriaxone nonsusceptible isolates were negative for blaCTX-M. Further studies are needed to determine the optimal management when an isolate is phenotypically susceptible to ceftriaxone, but blaCTX-M is detected. IMPORTANCE There is limited literature on corresponding results obtained from rapid molecular diagnostics with the antibiotic susceptibility profile. We reported a correlation between the results obtained from ePlex and the antibiograms against a large collection of Gram-negative bacteria. We reported that there can be a discrepancy in a small number of cases, but the clinical significance of that is unknown.