Direct RNA-based detection of CTX-M β-lactamases in human blood samples

Int J Med Microbiol. 2015 May;305(3):370-7. doi: 10.1016/j.ijmm.2015.02.005. Epub 2015 Feb 20.

Abstract

Bloodstream infections with ESBL-producers are associated with increased mortality, which is due to delayed appropriate treatment resulting in clinical failure. Current routine diagnostics for detection of bloodstream infections consists of blood culture followed by species identification and susceptibility testing. In attempts to improve and accelerate diagnostic procedures, PCR-based methods have been developed. These methods focus on species identification covering only a limited number of ESBL coding genes. Therefore, they fail to cover the steadily further evolving genetic diversity of clinically relevant β-lactamases. We have recently designed a fast and novel RNA targeting method to detect and specify CTX-M alleles from bacterial cultures, based on an amplification-pyrosequencing approach. We further developed this assay towards a diagnostic tool for clinical use and evaluated its sensitivity and specificity when applied directly to human blood samples. An optimized protocol for mRNA isolation allows detection of specific CTX-M groups from as little as 100 CFU/mL blood via reverse transcription, amplification, and pyrosequencing directly from human EDTA blood samples as well as from pre-incubated human blood cultures with a turnaround time for test results of <7 h.

Keywords: Blood culture; Degenerate primers; EDTA blood; Extended-spectrum beta-lactamases (ESBL); Pyrosequencing; qRT-PCR.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteremia / diagnosis*
  • Bacteremia / microbiology
  • Bacteria / enzymology*
  • Bacteria / genetics
  • Bacteria / isolation & purification
  • Blood / microbiology*
  • Humans
  • Polymerase Chain Reaction / methods*
  • RNA, Bacterial / analysis*
  • RNA, Bacterial / genetics
  • RNA, Messenger / analysis*
  • RNA, Messenger / genetics
  • Sensitivity and Specificity
  • Time Factors
  • beta-Lactamases / genetics*

Substances

  • RNA, Bacterial
  • RNA, Messenger
  • beta-Lactamases