Benefit from high intrarenal levels of gentamicin in the treatment of E. coli pyelonephritis.

The importance of high intrarenal levels of gentamicin on the outcome of experimental pyelonephritis was studied in rats receiving either a short course (three days) of gentamicin (G) alone or combined with a longer course (14 days) of ampicillin (A), cephalothin (C), or trimethoprim (T), or two weeks of therapy with ampicillin, cephalothin, trimethoprim and gentamicin given alone. While ampicillin, cephalothin and trimethoprim were undetectable in the medulla within six hours of cessation of therapy, gentamicin was still detectable in levels six folds above the MIC up to six months after treatment had ceased. Six months after the end of treatment, the percentage of sterile left kidneys in animals treated with ampicillin (50%), cephalothin (15%), trimethoprim (20%) was lower than the percentage of animals receiving 14 days of gentamicin (100%), or the combinations AG:89%, CG:67% and TG:60%, P less than 0.01. Following three days of gentamicin, 50% of the left kidneys were sterilized. When compared to ampicillin, cephalothin or trimethoprim alone, combined therapies significantly reduced the number of CFU in the kidneys P less than 0.01. These combinations were almost as effective as two weeks of therapy with gentamicin. Short-term therapy (three days) with an aminoglycoside which concentrates in the renal parenchyma, combined with an antibiotic which will accumulate in other parts of the nephron, may result in "pharmacological synergy". This new approach to therapy of pyelonephritis may be promising.