An Antibiotic Stewardship Program Blueprint for Optimizing Verigene BC-GN within an Institution: a Tale of Two Cities

Antimicrob Agents Chemother. 2018 Apr 26;62(5):e02538-17. doi: 10.1128/AAC.02538-17. Print 2018 May.

Abstract

Rapid diagnostic tests (RDTs) have revolutionized the management of Gram-negative bacteremia by allowing antimicrobial stewardship teams the ability to escalate therapy and improve patient outcomes through timely organism identification and detection of certain resistance determinants. However, given the complex nature of Gram-negative resistance, stewardship teams are left without clear direction for how to respond when resistance determinants are absent, as the safety of de-escalation in this setting is unknown. The primary purpose of this analysis was to determine the negative predictive values (NPVs) of resistance marker absence for predicting susceptibility in target bug-drug scenarios at two geographically distinct institutions. A total of 1,046 Gram-negative bloodstream isolates that were analyzed with the Verigene BC-GN platform were assessed. Except for Pseudomonas aeruginosa, the absence of resistance determinants as reported by the RDT largely predicted susceptibility to target antibiotics at both institutions. NPVs for ceftriaxone susceptibility in Escherichia coli and Klebsiella pneumoniae in the absence of either CTX-M or a carbapenemase gene were 98% and 93 to 94%, respectively. Similar results were seen with other target bug-drug scenarios, with NPVs of 94 to 100% demonstrated at both institutions, with the exception of P. aeruginosa, for which NPVs were poor, likely due to the more complex nature of resistance in this pathogen. The results of this study show that clinicians at both institutions should have confidence in de-escalation in the absence of resistance determinant detection by Verigene BC-GN testing, and the methodology described within this article can serve as a blueprint for other stewardship programs to employ at their institutions to optimize management of Gram-negative bacteremia.

Keywords: Gram negative; Verigene; bacteremia; film array; rapid diagnostic; stewardship.

MeSH terms

  • Antimicrobial Stewardship / methods*
  • Bacteremia / drug therapy
  • Bacteremia / microbiology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Escherichia coli / drug effects
  • Escherichia coli / pathogenicity
  • Gram-Negative Bacteria / drug effects
  • Gram-Negative Bacteria / metabolism
  • Gram-Negative Bacteria / pathogenicity
  • Gram-Negative Bacterial Infections / drug therapy
  • Gram-Negative Bacterial Infections / microbiology
  • Humans
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / pathogenicity
  • beta-Lactamases / genetics
  • beta-Lactamases / metabolism

Substances

  • Bacterial Proteins
  • beta-Lactamases
  • carbapenemase