Enhanced activity of novobiocin against gram negative bacilli in acid media.

One hundred eighty three clinical isolates of gram negative bacteria representing agenera were tested for susceptibility to novobiocin in media at pH 5E, 5.5, 6.0, 7.4 and 8.0. In all instances, there was markedly greater activity in the more acidic media; this correlated with decreasing ionization of an acid group having a pK of 5.06. The isolates of E. coli and Proteus were the most susceptible to novobiocin. and Enterobacter isolates were the most resistant of those tested. At pH 5.0, 172 (92*4) of the isolates were inhibited by concentrations achievable in the urine of patients under treatment (a 50 /tg/ml); at pH 5.5, 140 strains (75%) were inhibited by such concentrations. The data presented suggest that a clinical trial of the effect of novobiocin plus acidification in the treatment of urinary tract infections may be warranted, particularly when alternative therapy requires the use of relatively toxic drugs.