title: Influence of dosage interval on the therapeutic response to gentamicin in mice infected with Klebsiella pneumoniae.
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.
mesh_terms: D000818:Animals; D004334:Drug Administration Schedule; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D007710:Klebsiella Infections / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D007711:Klebsiella pneumoniae; D051379:Mice; D018805:Sepsis / Q000188:drug therapy / Q000382:microbiology; D013997:Time Factors
chemical_list: D005839:Gentamicins