The therapeutic response of cephalosporin-treated E. coli pyelonephritis of the rat, in relation to variations of the infection model.

In the E. coli pyelonephritis, induced in female Wistar rats by retrograde infection (high pressure reflux), we investigated the influence of 1) the time of commencement of therapy, 2) the renal bacterial counts, i.e. the inflammatory activity of the pyelonephritis after endovesical instillation of cultures with different bacterial concentrations, and 3) the level of infection resistance of the experimental animal strain on the therapeutic response of the model infection with single doses of cefoxitin (150 mg/ml) and cefotaxime (5 mg/ml). Early commencement of therapy post inoculation was therapeutically advantageous provided the intrarenal multiplication of the infective organisms was not delayed or the initial bacterial concentrations were not too high. The mild form of pyelonephritis with lower renal bacterial concentrations and poor inflammatory activity after endovesical instillation of a low inoculum (10(4) cfu/ml) was less amenable to treatment than the inflammatory active pyelonephritis with high renal bacterial counts, using a high inoculum (10(7) cfu/ml). High renal bacterial counts after retrograde inoculation of an E. coli culture of 10(8) cfu/ml resulted in significant reduction of bacterial counts 48, 72 and 96 h post infectionem, with i.m. application of cefoxitin 12 h prior. For Wistar rat strain Bor:WIST, which showed a stronger infection resistance with lower renal bacterial concentrations and a stronger tendency to spontaneous healing, application of a single dose of cefotaxime (5 mg/ml) was therapeutically ineffective, whereas, in contrast, with Han: WIST rats the acute phase of E. coli pyelonephritis could be treated effectively.