Rapid Molecular Diagnostics to Inform Empiric Use of Ceftazidime/Avibactam and Ceftolozane/Tazobactam Against Pseudomonas aeruginosa: PRIMERS IV

Clin Infect Dis. 2019 May 17;68(11):1823-1830. doi: 10.1093/cid/ciy801.

Abstract

Background: Overcoming β-lactam resistance in pathogens such as Pseudomonas aeruginosa is a major clinical challenge. Rapid molecular diagnostics (RMDs) have the potential to inform selection of empiric therapy in patients infected by P. aeruginosa.

Methods: In this study, we used a heterogeneous collection of 197 P. aeruginosa that included multidrug-resistant isolates to determine whether 2 representative RMDs (Acuitas Resistome test and VERIGENE gram-negative blood culture test) could identify susceptibility to 2 newer β-lactam/β-lactamase inhibitor (BL-BLI) combinations, ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (TOL/TAZO).

Results: We found that the studied RMD platforms were able to correctly identify BL-BLI susceptibility (susceptibility sensitivity, 100%; 95% confidence interval [CI], 97%, 100%) for both BLs-BLIs. However, their ability to detect resistance to these BLs-BLIs was lower (resistance sensitivity, 66%; 95% CI, 52%, 78% for TOL/TAZO and 33%; 95% CI, 20%, 49% for CZA).

Conclusions: The diagnostic platforms studied showed the most potential in scenarios where a resistance gene was detected or in scenarios where a resistance gene was not detected and the prevalence of resistance to TOL/TAZO or CZA is known to be low. Clinicians need to be mindful of the benefits and risks that result from empiric treatment decisions that are based on resistance gene detection in P. aeruginosa, acknowledging that such decisions are impacted by the prevalence of resistance, which varies temporally and geographically.

Keywords: Pseudomonas aeruginosa; antimicrobial resistance; ceftazidime/avibactam; ceftolozane/tazobactam.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Azabicyclo Compounds / therapeutic use*
  • Ceftazidime / therapeutic use*
  • Cephalosporins / therapeutic use*
  • Drug Combinations
  • Drug Resistance, Multiple, Bacterial*
  • Genotype
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Diagnostic Techniques / methods
  • Molecular Diagnostic Techniques / standards*
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / drug effects
  • Sensitivity and Specificity
  • Tazobactam / therapeutic use*
  • beta-Lactam Resistance
  • beta-Lactamase Inhibitors / pharmacology
  • beta-Lactamase Inhibitors / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Azabicyclo Compounds
  • Cephalosporins
  • Drug Combinations
  • avibactam, ceftazidime drug combination
  • beta-Lactamase Inhibitors
  • ceftolozane, tazobactam drug combination
  • Ceftazidime
  • Tazobactam