Serum bactericidal activity of trovafloxacin, in combination with cefepime or amikacin, in healthy volunteers

Abstract

To investigate the phamacokinetics and serum bactericidal activities (SBAs) of trovafloxacin, cefepime and amikacin alone and trovafloxacin in combination with cefepime or amikacin, so that the most favorable combination with trovafloxacin can be determined. In this open, randomized, crossover study, 12 healthy volunteers (six females, six males; mean age +/- SD, 25.1 +/- 2.6 years) received an infusion of either 300 mg of alatrovafloxacin or 2000 mg of cefepime or 6 mg/kg body weight amikacin alone, or 300 mg of alatrovafloxacin plus 2000 mg of cefepime or plus 6 mg/kg body weight amikacin. The SBAs against Pseudomonas aeruginosa, Staphylococcus aureus (11 strains each), Citrobacter freundii and Acinetobacter spp. (10 strains each) 1, 10 and 24 h after drug administration were measured by a standard microdilution method. Concentrations of trovafloxacin, cefepime and amikacin in serum and urine were analyzed before and up to 10 and 12 h, respectively, after drug infusion. Significant synergistic effects on SBA were observed with the combination of trovafloxacin and cefepime against P. aeruginosa, S. aureus and Acinetobacter spp. 1 h after drug administration, and against Citrobacter freundii 1, 10 and 24 h after drug administration. The combination of trovafloxacin and amikacin showed significant synergistic effects against P. aeruginosa, S. aureus and C. freundii 1 h after drug administration. The combination of trovafloxacin and cefepime was, in general, more active than the combination of trovafloxacin and amikacin. No significant differences in the serum concentrations of trovafloxacin were observed between single and combined administration. However, the maximal concentration of cefepime was significantly lower when it was used in combination with trovafloxacin. Our study suggests a favorable interaction between trovafloxacin and cefepime. This combination showed more synergistic bactericidal activity against most of the test strains compared to the combination of trovafloxacin and amikacin. However, for P. aeruginosa, the bactericidal activity of cepefime alone was higher than that of the combination with trovafloxacin.