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  • Title: In vitro and in vivo antibacterial activity of FR-31564, a phosphonic acid antimicrobial agent.
    Author: Neu HC, Kamimura T.
    Journal: Antimicrob Agents Chemother; 1981 Jun; 19(6):1013-23. PubMed ID: 7271270.
    Abstract:
    The in vitro and in vivo activity of FR-31564 [sodium hydrogen 3-(N-hydroxyformamido)propylphosphate] against gram-positive and -negative aerobic and anaerobic bacteria was investigated and compared with that of fosfomycin, cephalexin, carbenicillin, and trimethoprim-sulfamethoxazole. The in vitro activity of FR-31564 was markedly enhanced when combined with glucose 6-phosphate or fructose 6-phosphate, but not when combined with ribose phosphate, adenosine monophosphate, or glycerol phosphate. In vitro activity of FR-31564 also was enhanced by human or horse blood, but not by human serum. The type of medium had a great effect on the minimal inhibitory concentration, with the lowest minimal inhibitory concentrations achieved on nutrient agar, 8- to 16-fold less than with Mueller-Hinton, heart infusion, or Trypticase soy agars. FR-31564 was more active than fosfomycin, cephalexin, carbenicillin, or trimethoprimsulfamethoxazole against Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, Enterobacter cloacae, E. aerogenes, and Citrobacter. It was less active than fosfomycin against Serratia marcescens and Proteus mirabilis and did not inhibit gram-positive cocci or anaerobic species. FR-31564 inhibited a number of E. coli, K. pneumoniae, and some Pseudomonas aeruginosa strains resistant to the other agents. In the presence and absence of human blood FR-31564 showed bactericidal activity, and P. aeruginosa exposed to FR-31564 for 3 h showed a 6-h lag in regrowth. FR-31564 administered by the subcutaneous route was more active in protecting mice challenged with P. aeruginosa than was fosfomycin, carbenicillin, or cefoperazone. It was as active by the oral route in protecting mice challenged with E. coli as was fosfomycin, ampicillin, cephalexin, or trimethoprimsulfamethoxazole.
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