Influence of Dosage Interval on the Therapeutic Response to Gentamicin in Mice Infected with Klebsiella pneumoniae

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Abstract
Without treatment all mice died after receiving 103 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 (t1/2 = 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.