Direct β-Lactam Inactivation Method: a New Low-Cost Assay for Rapid Detection of Carbapenemase- or Extended-Spectrum-β-Lactamase-Producing Enterobacterales Directly from Positive Blood Culture Bottles

J Clin Microbiol. 2019 Dec 23;58(1):e01178-19. doi: 10.1128/JCM.01178-19. Print 2019 Dec 23.

Abstract

We validate and evaluate a new phenotypic assay, named the direct β-lactam inactivation method (dBLIM), for the rapid and simultaneous detection of carbapenemase or extended-spectrum-cephalosporinase activity directly from Enterobacterales (EB)-positive blood cultures (BCs). It originates from the carbapenem inactivation method (CIM), an inexpensive and highly sensitive assay for carbapenemase activity detection. dBLIM cutoff values to detect extended-spectrum β-lactamase (ESBL) and carbapenemase activities resulted in diameters of ≤12 mm for a 5-μg-cefotaxime disk and for a 10-μg-meropenem disk. dBLIM assessment was determined with both aerobic and anaerobic BC bottles spiked with 422 characterized EB strains, classifiable into the following 4 phenotypic groups: (i) ESBL/AmpC-type β-lactamase (ACBL)/carbapenemase (CARB)-nonproducing (np-ESBL/ACBL/CARB) EB (n = 116), (ii) ESBL-producing EB (n = 111), (iii) AmpC-β-lactamase-producing EB (n = 33), and (iv) carbapenemase-producing EB (n = 162). No false-positive results were obtained in any of the np-ESBL/ACBL/CARB EB, ESBL, and AmpC groups, demonstrating an overall assay specificity of 100%. There were no significant discrepancies in dBLIM performance between aerobic and anaerobic BCs across all groups, except with VIM-type carbapenemase-expressing EB. Interestingly, among BCs spiked with blaVIM-harboring EB, the sensitivity rates of the assay in anaerobic and aerobic bottles were 53.6% and 100%, respectively. In contrast, dBLIM performance was deemed excellent for the KPC, OXA-48, and NDM carbapenemase producers regardless of the type of bottle being tested, with a sensitivity rate ranging between 99% and 100%. Concerning the detection of the extended-spectrum cephalosporinases of the ESBL-producing and AmpC types, dBLIM sensitivities was 100% and 84 to 87%, respectively. dBLIM may be a cost-effective and highly robust phenotypic screening method for the reliable detection of carbapenemases or extended-spectrum cephalosporinases directly from BCs on the same day of bottle positivity detection.

Keywords: CIM test; ESBL detection; blood culture; carbapenemase detection.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / biosynthesis
  • Bacterial Proteins / genetics*
  • Carbapenem-Resistant Enterobacteriaceae / classification*
  • Carbapenem-Resistant Enterobacteriaceae / drug effects*
  • Carbapenem-Resistant Enterobacteriaceae / genetics
  • Carbapenem-Resistant Enterobacteriaceae / isolation & purification
  • Enterobacteriaceae Infections / diagnosis*
  • Enterobacteriaceae Infections / microbiology*
  • Humans
  • Microbial Sensitivity Tests*
  • Reproducibility of Results
  • beta-Lactam Resistance
  • beta-Lactamases / biosynthesis
  • beta-Lactamases / genetics*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • beta-Lactamases
  • carbapenemase