A highly multiplexed melt-curve assay for detecting the most prevalent carbapenemase, ESBL, and AmpC genes

Diagn Microbiol Infect Dis. 2020 Aug;97(4):115076. doi: 10.1016/j.diagmicrobio.2020.115076. Epub 2020 May 8.

Abstract

Resistance to third-generation cephalosporins and carbapenems in Gram-negative bacteria is chiefly mediated by beta-lactamases including extended-spectrum beta-lactamase (ESBL), AmpC, and carbapenemase enzymes. Routine phenotypic detection methods do not provide timely results, and there is a lack of comprehensive molecular panels covering all important markers. An ESBL/carbapenemase high-resolution melt analysis (HRM) assay (SHV, TEM, CTX-M ESBL families, and NDM, IMP, KPC, VIM and OXA-48-like carbapenemases) and an AmpC HRM assay (16S rDNA control, FOX, MOX, ACC, EBC, CIT, and DHA) were designed and evaluated on 111 Gram-negative isolates with mixed resistance patterns. The sensitivity for carbapenemase, ESBL, and AmpC genes was 96.7% (95% confidence interval [CI]: 82.8-99.9%), 93.6% (95% CI: 85.7-97.9%), and 93.8% (95% CI: 82.8-98.7%), respectively, with a specificity of 100% (95% CI: 95.6-100%), 93.9% (95% CI: 79.8-99.3%), and 93.7% (95% CI: 84.5-98.2%). The HRM assays enable the simultaneous detection of the 14 most important ESBL, carbapenemase, and AmpC genes and could be used as a molecular surveillance tool or to hasten detection of antimicrobial resistance for treatment management.

Keywords: Antimicrobial resistance; Carbapenemase; ESBL; High resolution melt analysis.

Publication types

  • Evaluation Study

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / genetics*
  • Carbapenems / pharmacology
  • Cephalosporins / pharmacology
  • Drug Resistance, Bacterial / genetics*
  • Gram-Negative Bacteria / classification
  • Gram-Negative Bacteria / genetics
  • Gram-Negative Bacteria / isolation & purification
  • Gram-Negative Bacterial Infections / diagnosis
  • Humans
  • Molecular Diagnostic Techniques / methods*
  • Multiplex Polymerase Chain Reaction / methods*
  • Sensitivity and Specificity
  • beta-Lactamases / genetics*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Carbapenems
  • Cephalosporins
  • beta-Lactamases