Rapid valve sterilization with meropenem plus ceftolozane/tazobactam combination therapy for Pseudomonas aeruginosa

Valliammai Alaguvel1, Anuj K Khetarpal1, Allen Jankeel1

  • 1Department of Pediatrics, University of California Irvine School of Medicine, Irvine, CA 92697, USA.

PubMed
Abstract

Insights

This study shows that combining meropenem and ceftolozane/tazobactam effectively treated Pseudomonas aeruginosa prosthetic valve endocarditis. The combination demonstrated synergy in human blood and biofilm, offering a promising alternative for challenging infections.

Area of Science:

  • Infectious Diseases
  • Pharmacology
  • Microbiology

Background:

  • * Pseudomonas aeruginosa infective endocarditis (IE) is a severe condition with high treatment failure and mortality rates.
  • * Current therapies, including antipseudomonal β-lactams with aminoglycosides or fluoroquinolones, often lack efficacy and cause adverse effects.

Purpose of the Study:

  • * To report a case of P. aeruginosa prosthetic valve endocarditis successfully treated with meropenem and ceftolozane/tazobactam.
  • * To investigate the synergistic effects of this antibiotic combination in various in vitro and ex vivo models.

Main Methods:

  • * Case report of P. aeruginosa prosthetic valve endocarditis.
  • * In vitro assays: checkerboard, time-kill, human whole blood killing, and biofilm assays.
  • * Ex vivo model: simulated endocardial vegetation (SEV) model.

Main Results:

  • * Meropenem plus ceftolozane/tazobactam achieved microbiological clearance and facilitated cardiac surgery.
  • * Synergy was observed in human whole blood and biofilm assays, and modestly in the SEV model.
  • * Additivity was noted in checkerboard assays; synergy was absent in standard time-kill assays.

Conclusions:

  • * The combination of meropenem and ceftolozane/tazobactam shows promising synergistic activity in conditions mimicking the human body.
  • * This combination may offer a safer alternative for treating P. aeruginosa IE and stabilizing patients before surgery.
  • * Further clinical trials are warranted to confirm efficacy and safety in severe Pseudomonas infections.

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