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Aminoglycosides are usually considered to be concentration-dependent antibiotics and to have similar pharmacodynamic and pharmacokinetic properties. To verify the equivalent activity of the aminoglycosides on a susceptible strain, we tested the killing rate of three aminoglycosides (gentamicin, tobramycin, and amikacin) on one strain of Serratia marcescens both in vitro and in vivo by using a rabbit model of left-ventricle endocarditis. Despite, similar MICs, the time-kill curve of gentamicin was consistently better than those of amikacin and tobramycin, whatever the concentration of each antibiotic used (1, 2, 4, 8, 16, or 32 mg/liter), after a 5-h incubation. The in vivo bacterial reduction in the vegetations was measured 24 h after administration of an intravenous 48-mg/kg bolus of each antibiotic or at the end of a 24-h continuous intravenous infusion of the same dose. Gentamicin was significantly more effective when administered as a bolus than when administered as a continuous infusion (2.8 +/- 0.2 versus 6.4 +/- 1.5 log10 CFU/g of vegetation, respectively; P less than 0.01), whereas amikacin was more effective as a continuous infusion than as a bolus injection (3.6 +/- 2.0 versus 7.5 +/- 1.3 log10 CFU/g of vegetation, respectively; P less than 0.01). Tobramycin was not very effective, whatever the dosage tested (approximately 6.5 to 7 log10 CFU/g). These results suggest that concentration-dependent bactericidal activities, both in vitro and in vivo, may vary greatly among aminoglycosides despite similar MICs.

antimicrobial agents and chemotherapy

Impact of dosage schedule on the efficacy of gentamicin, tobramycin, or amikacin in an experimental model of Serratia marcescens endocarditis: in vitro-in vivo correlation