In vitro and in vivo antibacterial activities of FR-31564, a new phosphonic acid antibiotic

FR-31564, a new phosphonic acid antibiotic, was active against most Gram-negative bacteria except Serratia marcescens and glucose-nonfermenting Gram-negative rods excluding Pseudomonas aeruginosa. The antibacterial activity in vitro of FR-31564 was stronger than that of fosfomycin especially against Escherichia coli, Klebsiella pneumoniae, Enterobacter species and P. aeruginosa. FR-31564 also was active against Gram-negative bacteria resistant to beta-lactam antibiotics and against gentamicin-resistant strains of P. aeruginosa. The antibacterial activity in vitro of FR-31564, like that of fosfomycin, was enhanced when 10% rabbit blood was added to the nutrient agar. The therapeutic efficacy of FR-31564 in experimental infections in mice was superior to that of fosfomycin in infections due to most Gram-negative bacteria used, and was similar to that of gentamicin in infections due to Citrobacter freundii, Proteus rettgeri and Proteus inconstans B. The protective effect of FR-31564, particularly in the P. aeruginosa infection, was superior to that of other control drugs including gentamicin.