Chemotherapeutic efficacy of cefotaxime and failure of fosfomycin in murine Salmonella typhimurium infection.

Six clinical isolates and 1 reference strain of Salmonella typhimurium were sensitive to conventional antibiotics (ampicillin, chloramphenicol, cotrimoxazole), cefotaxime (CTX), and fosfomycin ( FOSFO ). All 7 strains carried a 55 megadalton plasmid ( Birnboim - Doly agarose gel electrophoresis technique) and were of comparable virulence for outbred NMRI mice (LD50 values = range of 1.7 X 10(5)-1.0 X 10(6) CFU; intraperitoneal route). CTX (5 mg/25 g mouse/day, divided into 2 doses; duration = 7 days) proved efficacious against 3 selected strains (No. H 8800, 14, and 20) of S. typhimurium (p less than 0.01). FOSFO (same therapeutic regimen) failed in this regard; following transitory improvement of diseased animals (days 2-4), the mortality of treated animals eventually approached that of untreated control animals. Administration of 15 mg FOSFO /mouse/day likewise failed to enhance murine survival. Reisolated S. typhimurium bacteria of these 3 assay strains still were susceptible to FOSFO . In vitro, CTX likewise surpassed FOSFO in bactericidal activity against the same 3 S. typhimurium strains on a weight-for-weight basis in various biological fluids (human midstream urine; human defibrinated blood; murine thioglycolate-induced macrophage-rich peritoneal exudate).