Synergistic antibacterial activity between L-norvalyl-L-1-aminoethylphosphonic acid and nocardicin A

Abstract

The phosphonopeptide L- norvalyl -L-1- aminoethylphosphonic acid [ Nva -Ala(P)] has been studied in combination with 12 beta-lactam antibiotics for activity against Pseudomonas aeruginosa. Nocardicin A was found to give the most potent synergistic combination with Nva -Ala(P). This interaction was widely observed in clinical isolates of P. aeruginosa in vitro and in a mouse septicemia model. Synergy was also observed in vitro and in vivo in several other species, including Proteus mirabilis, indole-positive Proteus spp., and Serratia marcescens. The interaction between Nva -Ala(P) and nocardicin A involved a strongly bacteriolytic mechanism. In addition, the individual components were complementary to one another in their action against organisms not showing synergy. These properties resulted in a broad spectrum of activity of the combination Nva -Ala(P) plus nocardicin A when used to treat experimental gram-negative bacterial infections.