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.
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.
Potel
G
G
Laboratoire d'Antibiologie, Faculté de Médecine, Nantes, France.
Caillon
J
J
Fantin
B
B
Raza
J
J
Le Gallou
F
F
Lepage
J Y
JY
Le Conte
P
P
Bugnon
D
D
Baron
D
D
Drugeon
H
H
D000583:Amikacin / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D000818:Animals; D004334:Drug Administration Schedule; D004697:Endocarditis, Bacterial / Q000188:drug therapy*; D004756:Enterobacteriaceae Infections / Q000188:drug therapy*; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D006801:Humans; D007262:Infusions, Intravenous; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D012706:Serratia marcescens / Q000187:drug effects; D014031:Tobramycin / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology
D005839:Gentamicins; D000583:Amikacin; D014031:Tobramycin