Post-antibiotic effect of levofloxacin and tobramycin alone or in combination with cefepime against Pseudomonas aeruginosa

Chemotherapy. 2009;55(6):446-50. doi: 10.1159/000265128. Epub 2009 Dec 8.


Background: Levofloxacin and tobramycin, alone and in combination with cefepime, were investigated for their in vitro activities and post-antibiotic effects (PAEs) on Pseudomonas aeruginosa.

Methods: The in vitro activities of tobramycin and levofloxacin in combination with cefepime were determined by microbroth chequerboard technique against six P. aeruginosa strains that were isolated from patients with bacteremia. The results were interpreted by fractional inhibitory concentration index. To determine the PAEs, P. aeruginosa strains in the logarithmic phase of growth were exposed for 1 h to antibiotics, alone and in combination. Recovery periods of test cultures were evaluated using viable counting after centrifugation.

Results: Three synergistic interactions were observed with cefepime-tobramycin and one with cefepime-levofloxacin combinations against tested strains.No antagonism was observed. Levofloxacin produced a PAE ranging from 1.9 to 4.5 h in a concentration-dependent manner. Similar PAEs were induced by tobramycin (ranging from 1.5 to 3.1 h). However, negative PAE values were obtained with cefepime. In combination, cefepime slightly reduced the PAE of tobramycin and levofloxacin against studied strains.

Conclusion: The finding of this study may have important clinical implications for the timing of doses during therapy with cefepime, levofloxacin and tobramycin alone and in combination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacology*
  • Bacteremia / drug therapy*
  • Bacteremia / microbiology
  • Cefepime
  • Cephalosporins / administration & dosage
  • Cephalosporins / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Drug Therapy, Combination
  • Humans
  • Levofloxacin
  • Microbial Sensitivity Tests
  • Ofloxacin / administration & dosage
  • Ofloxacin / pharmacology
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / isolation & purification
  • Time Factors
  • Tobramycin / administration & dosage
  • Tobramycin / pharmacology


  • Anti-Bacterial Agents
  • Cephalosporins
  • Levofloxacin
  • Cefepime
  • Ofloxacin
  • Tobramycin