Influence of dosage interval on the therapeutic response to gentamicin in mice infected with Klebsiella pneumoniae

Chemotherapy. 1987;33(1):68-76. doi: 10.1159/000238477.

Abstract

Without treatment all mice died after receiving 10(3) Klebsiella pneumoniae by intraperitoneal injection. Nevertheless, it was possible to delay treatment for 12 h and still observe a therapeutic response from im gentamicin (5 mg/kg). This gave initial serum concentrations comparable to clinical levels, which fell rapidly (t 1/2 = 15 min) to reach the limit of detection by 90 min. Courses were given of 3 or 6 doses spaced at different intervals. Irrespective of dosage interval there was a marked fall in bacteraemia with each of the first two doses. Between doses separated by 8 or even 12 h there was no evidence of bacterial multiplication but this was obvious by 24 h. Both the bacteraemic responses and the lengths of survival were best with the 12-hour dosage interval. These results are consistent with other reports of the persistence of antibiotic effects despite undetectable serum concentrations and the compatibility of a substantial dosage interval with a successful therapeutic outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Administration Schedule
  • Female
  • Gentamicins / administration & dosage
  • Gentamicins / blood
  • Gentamicins / therapeutic use*
  • Klebsiella Infections / blood
  • Klebsiella Infections / drug therapy*
  • Klebsiella Infections / microbiology
  • Klebsiella pneumoniae
  • Mice
  • Sepsis / drug therapy
  • Sepsis / microbiology
  • Time Factors

Substances

  • Gentamicins