Trimethoprim and methenamine hippurate. A new theoretical combination for the treatment of urinary tract infections.
The antibacterial interaction of methenamine hippurate (MH) and trimethoprim (TMP) was tested in vitro in 3 different media: urine, brain-heart broth and Mueller-Hinton broth. MH and TMP were found to have a synergistic interaction in chequer-board titration against 11/11 bacteria in urine. Low concentrations of MH (1/2 MIC) had an additive or synergistic effect with TMP against 14/14 bacteria in brain-heart broth and 20/26 bacteria in Mueller-Hinton broth. In addition, the growth of bacteria in urine from healthy subjects treated with TMP (200 mg), MH (1000 mg) or a combination of TMP + MH (200 + 1000 mg) twice a day for 5 days was compared. A synergistic or additive effect of TMP and MH was found against 14/16 strains. Antagonistic interaction was not found in any of the tests. Preliminary pharmacokinetic studies with TMP and MH showed no marked interaction between the drugs. The hydrolysis of MH to formaldehyde was inversely related to urinary pH, and at pH 5 most of the formaldehyde released from MH in urine was generated within 3 h. The results suggest that the combination of TMP and MH may be more efficient than TMP alone in the treatment of urinary tract infections.
D000328:Adult; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004927:Escherichia coli Infections / Q000188:drug therapy; D005260:Female; D006626:Hippurates / Q000008:administration & dosage*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007710:Klebsiella Infections / Q000188:drug therapy; D008709:Methenamine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011512:Proteus Infections / Q000188:drug therapy; D013290:Streptococcal Infections / Q000188:drug therapy; D014295:Trimethoprim / Q000008:administration & dosage*; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000382:microbiology / Q000652:urine
D006626:Hippurates; D014295:Trimethoprim; D008709:Methenamine; C011481:methenamine hippurate