title: 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.
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001433:Bacteriolysis; D004357:Drug Synergism; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D007769:Lactams; D051379:Mice; D008826:Microbial Sensitivity Tests; D011513:Proteus mirabilis / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D018805:Sepsis / Q000188:drug therapy
chemical_list: D000900:Anti-Bacterial Agents; D007769:Lactams; C006437:alafosfalin; C027318:nocardicin; D000409:Alanine