Influence of acetohydroxamic acid on experimental Corynebacterium renale pyelonephritis

The role of Corynebacterium renale urease in the establishment of pyelonephritis was studied by the oral administration of acetohydroxamic acid (AHA), a urease inhibitor, to experimentally infected rats. The bacteria were introduced by surgical insertion of a zinc disc containing 1 X 10(6) colony-forming units of C-renale into the urinary bladder whereas sterile discs were implanted in the bladders of the control animals. Daily administration of AHA via the drinking water did not halt the development of pyelonephritis. Larger doses, given by gavage, did accomplish this goal; that is, the pH of the urine was lowered, the number of colony-forming units of C. renale in the kidney was reduced drastically, and pyelonephritic lesions were observed in the kidney by light-microscopic examination. All experimental rats developed cystitis in varying degrees of severity. About 70% of the intact AHA given by gavage was excreted in the urine 24 h after administration of this compound. Rats implanted with a urease-negative mutant of C. renale displayed no signs of pyelonephritis but did develop cystitis.