Cefpirome, alone and in combination with gentamicin for enterococcal pyelonephritis in the rodent model

Abstract

The in vitro and in vivo activity of cefpirome (CF) against Enterococcus faecalis GK strain was examined. The ratio of minimal inhibitory to bactericidal concentration (MIC/MBC) values in μg/ml were (a) ampicillin 0.8/1.5; (b) gentamicin 2/25; (c) vancomycin, 0.8/50; and (d) CF, 8/32. A time-kill study using 10 7 organisms per milliliter showed a drop of 3 logs 10 at 4 hr in the tube containing cefpirome (10 μg/ml) as well as the tube containing cefpirome (5 μg/ml) plus gentamicin (GM) (2 μg/ml), as compared to the control and the tube containing GM at 4 μg/ml. At 8 and 24 hr, however, regrowth to control levels occurred. Of this enterococcal strain consisting of 10 8 organisms, 1 ml was then injected intravenously by tail vein into 150 male Wistar rats weighing 120 g each. Eleven day after injection, 10 rats were killed and the remaining ones were randomized into four treatment groups: (a) untreated control; (b) BM, 0.9 mg; (c) CF, 10 mg; and (d) CF + GM. The rats received the injections intramuscularly twice daily. At least 10 rats from each group were killed for quantitative kidney cultures at 1, 2, and 4 weeks after start of therapy. At the end of 4 weeks of therapy, the results were significantly better in the combination group compared to the other three groups.