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The activity of latamoxef (LMOX) and tobramycin (TOB) alone and in combination against four clinical isolates of Pseudomonas aeruginosa was examined in vitro and in intraperitoneal infection mice. In in vitro Checker board studies, the combination of LMOX and TOB produced synergism against all isolates tested, and the broth dilution method or higher inoculum size tended to enhance the synergistic activity of these antibiotics. In experimental infection mice with above four P. aeruginosa, a excellent synergistic effect was also observed with the fixed combination of LMOX and TOB in the ratio of 10: 1. In in vivo experiments using P. aeruginosa PS-24, the combination therapy of LMOX and TOB was more effective than a single therapy in reducing bacterial counts in peritoneal cavity of mice, and its synergistic activity appeared to be independent of the challenge dose or the dosing schedule. In addition, the combination of these antibiotics was found to be synergistic in a wide range of combination ratios (LMOX: TOB=5: 1-320: 1). In neutropenic mice induced by cyclophosphamide, the combination therapy of LMOX and TOB also revealed synergistic activity against intraperitoneal infection with P. aeruginosa PS-24.
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