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

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.