Multiple combination bactericidal antibiotic testing for patients with cystic fibrosis infected with multiresistant strains of Pseudomonas aeruginosa

Am J Respir Crit Care Med. 2000 Dec;162(6):2241-5. doi: 10.1164/ajrccm.162.6.2005018.


We developed a rapid in vitro antibiotic susceptibility test to screen double- and triple-antibiotic combinations for bactericidal activity against 75 multiresistant Pseudomonas aeruginosa isolates referred from 44 cystic fibrosis (CF) patients. When used alone, the most effective intravenous antibiotic, meropenem, was bactericidal against only 44% of the isolates. High-dose tobramycin (200 microg/ml; concentrations achievable by aerosol administration) was bactericidal against 72% of isolates. Adding a second antibiotic significantly improved bactericidal activity. The most effective double-antibiotic combinations contained high-dose tobramycin plus meropenem, piperacillin/tazobactam, or ciprofloxacin, and were bactericidal against 88 to 94% of the isolates. Excluding high-dose tobramycin, the most effective intravenous double-antibiotic combinations contained meropenem plus ciprofloxacin, tobramycin (4 microg/ml), or cefipime, and were bactericidal against 85%, 71%, and 70% of isolates, respectively. Adding a third antibiotic did not significantly improve inhibition in vitro. We conclude that double-antibiotic combinations containing meropenem or high-dose tobramycin show the best bactericidal activity in vitro against multiresistant strains of P. aeruginosa. Addition of a third antibiotic to these double-antibiotic combinations may be unnecessary.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoglycosides
  • Anti-Bacterial Agents / antagonists & inhibitors
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Infective Agents / antagonists & inhibitors
  • Anti-Infective Agents / pharmacology*
  • Cystic Fibrosis / complications
  • Cystic Fibrosis / microbiology*
  • Dose-Response Relationship, Drug
  • Drug Resistance, Multiple*
  • Drug Therapy, Combination / antagonists & inhibitors
  • Drug Therapy, Combination / pharmacology*
  • Fluoroquinolones
  • Humans
  • Lactams
  • Microbial Sensitivity Tests / methods
  • Microbial Sensitivity Tests / statistics & numerical data
  • Pseudomonas Infections / microbiology*
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / isolation & purification
  • Time Factors


  • Aminoglycosides
  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Fluoroquinolones
  • Lactams