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Association Between Minimum Inhibitory Concentration, Beta-lactamase Genes and Mortality for Patients Treated With

A Henderson1,2, D L Paterson1, M D Chatfield1

  • 1University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia.

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
|October 27, 2020
PubMed
Abstract

Insights

Piperacillin/tazobactam non-susceptibility strongly predicted mortality in the MERINO trial. Excluding these strains reduced the observed mortality difference between piperacillin/tazobactam and meropenem.

Area of Science:

  • Infectious Diseases
  • Clinical Microbiology
  • Pharmacology

Background:

  • The MERINO trial evaluated piperacillin/tazobactam versus meropenem for treating ceftriaxone-nonsusceptible Enterobacterales.
  • Understanding the impact of antimicrobial resistance, specifically minimum inhibitory concentrations (MICs) and resistance genes, on patient outcomes is critical.

Purpose of the Study:

  • To assess the association between piperacillin/tazobactam and meropenem MICs, beta-lactam resistance genes, and 30-day mortality within the MERINO trial.
  • To re-evaluate treatment outcomes based on antimicrobial susceptibility profiles.

Main Methods:

  • Blood isolates underwent broth microdilution and whole genome sequencing.
  • Multivariate logistic regression was used to analyze 30-day mortality, controlling for confounders.
  • Absolute risk increase in mortality was calculated for different patient populations.

Main Results:

  • Piperacillin/tazobactam non-susceptibility (MIC >16 mg/L) was a significant predictor of 30-day mortality (OR 14.9).
  • The absolute risk increase for 30-day mortality with piperacillin/tazobactam versus meropenem was 9% (primary analysis).
  • Isolates with coharbored extended-spectrum beta-lactamase (ESBL) and OXA-1 genes showed the highest mortality risk increase (14%).

Conclusions:

  • Excluding piperacillin/tazobactam non-susceptible strains diminished the observed mortality difference between the treatment arms.
  • Meropenem is recommended for definitive treatment of ceftriaxone-nonsusceptible E. coli and Klebsiella due to susceptibility testing reliability and resistance gene prevalence.
Keywords:
bloodstream infectionextended spectrum beta-lactamasemeropenempiperacillin-tazobactam

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