No abstract

The diuretic amiloride has been under recent investigation as adjunctive therapy for pulmonary disease in children with cystic fibrosis (CF). In preliminary studies, the antimicrobial activity of this agent alone or combined with beta-lactam agents against reference strains of Pseudomonas aeruginosa and P. cepacia was poor; however, amiloride was markedly synergistic with tobramycin against P. cepacia. The purpose of this study was to determine the extent of amiloride-tobramycin synergy against CF respiratory isolates of P. aeruginosa, P. cepacia, and P. maltophilia. The MICs of tobramycin and amiloride alone against the Pseudomonas test strains were determined by agar dilution. Synergy was determined by combining each of four subinhibitory concentrations of amiloride (at least fourfold below the MIC) with doubling dilutions of tobramycin and comparing the MIC of tobramycin alone and in combination for each strain. At the highest concentration tested, the drug combination synergistically inhibited 50% of the P. cepacia strains tested; the combination was synergistic against fewer isolates of P. aeruginosa and P. maltophilia. Only P. cepacia was inhibited by tobramycin combined with amiloride at achievable airway concentrations. We conclude that the combination of tobramycin and amiloride may be potentially useful in the treatment of P. cepacia infections in children with CF.

1. Human renal renin has been purified 200 000-fold from cadaver kidney cortex by a method which employs affinity chromatography on aminohexyl pepstatin. 2. The product of this purification has a specific activity of 400 Goldblatt units/mg when compared with Haas human renin standard. 3. This product appears as a single band on sodium dodecyl sulphate gel and polyacrylamide-disc gel electrophoresis. Renin enzymatic activity was recovered after elution from a polyacrylamide-disc gel run at pH 7·8. 4. Yield with this method was 1%.