Experimental pneumococcus infection in mice: correlation of bactericidal activity in vitro with the effect in vivo for gentamicin, netilmicin and tobramycin.
An experimental model in mice, incorporating the intraperitoneal inoculation of a Streptococcus pneumoniae type 3, was used to evaluate the effect in vivo after single-dose administration of the three aminoglycosides, gentamicin, tobramycin and netilmicin, and to correlate this effect with their in vitro activity against the pathogen, in particular the bactericidal rate. The minimal inhibitory concentrations (MIC's), which were equal to the minimal bactericidal concentrations (MBC's), were 12.5 micrograms/ml for netilmicin, and 25 micrograms/ml for the two other aminoglycosides, respectively. All three antibiotics showed excellent bactericidal activities even at concentrations 1/4 times the MIC's, but the bactericidal rate was clearly lower for tobramycin than for the two other aminoglycosides. The effect in vivo measured as the 50% effective dose (ED50) closely reflected the relative bactericidal activities of the drugs. Of the pharmacokinetic parameters investigated on dosages equal to the ED50's for the three drugs, the best to correlate with the bactericidal rates in vitro were the peak serum concentrations.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005839:Gentamicins / Q000008:administration & dosage* / Q000378:metabolism; D066298:In Vitro Techniques; D008657:Metabolic Clearance Rate; D051379:Mice; D008826:Microbial Sensitivity Tests; D009428:Netilmicin / Q000008:administration & dosage* / Q000378:metabolism; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy*; D013296:Streptococcus pneumoniae / Q000472:pathogenicity; D014031:Tobramycin / Q000008:administration & dosage* / Q000378:metabolism
D005839:Gentamicins; D009428:Netilmicin; D014031:Tobramycin