Treatment of staphylococcal pyelonephritis in rats with N-formimidoyl thienamycin.

The therapeutic efficacy of N-formimidoyl thienamycin alone or coadministered with MK0791, an inhibitor of renal dehydropeptidase-I, compared to methicillin in experimental pyelonephritis in rats was investigated. Pyelonephritis was produced with a methicillin-sensitive strain (2776) and a methicillin-resistant strain (Berman) of Staphylococcus aureus. N-formimidoyl thienamycin alone or coadministered with the inhibitor was significantly better than methicillin when treating methicillin-sensitive or methicillin-resistant infection. There was a trend suggesting that N-formimidoyl thienamycin coadministered with MK0791 was overall the best agent. These studies show that N-formimidoyl thienamycin is efficacious in the treatment of S. aureus pyelonephritis in the rat regardless of methicillin sensitivity, and this agent plus the dehydropeptidase inhibitor should be considered in the treatment of such infections.