Cycloserine as an alternative urinary tract infection therapy: susceptibilities of 500 urinary pathogens to standard and alternative therapy antimicrobials

Abstract

Cycloserine has been used previously in some areas of the world for the treatment of urinary tract infections. The emergence of multi-resistant strains of Enterobacteriaceae and the lack of new agents in the development pipeline has prompted a need to review the activity of older agents. Susceptibility testing of cycloserine has traditionally been problematic owing to testing in standard media, containing competitive alanine, thus presenting falsely elevated minimum inhibitory concentrations (MICs). This study tests urinary coliforms against cycloserine in both standard and minimal media. Susceptibilities were performed on 500 "wild type" UTI coliforms using Mueller-Hinton broth in the range 0.008-128 μg/ml in accordance with ISO guidelines. Cycloserine was also tested in Minimal Salts medium + 2 % 1 M glucose + 0.2 % 1 M magnesium sulphate. MICs were recorded after 18 h of incubation at 35 °C and interpreted with EUCAST breakpoints (where available). Cycloserine MIC50 for the "wild type" coliforms was 32 μg/ml in Mueller-Hinton broth compared with 2 μg/ml in Minimal Salts. Eighty-seven per cent of "wild type" UTI coliforms show cycloserine MICs < = 8 μg/ml in Minimal Salts. The epidemiological cut-off values for cycloserine for E. coli in this study were 64 μg/ml using Mueller-Hinton broth and 8 μg/ml using Minimal Salts medium. Ninety-four per cent of trimethoprim-resistant and 82 % of third generation cephalosporin-resistant E. coli had MICs in Minimal Salts ≤ 8 μg/ml. Cycloserine is still licensed in some countries for the treatment of urinary infections and the data presented here suggest that it may play a role in the management of infections resistant to trimethoprim and third generation cephalosporins.