The therapeutic effect of cefozopran (SCE-2787), a new semisynthetic parenteral cephalosporin, against experimental infections in mice was examined. Cefozopran was more effective than cefpiramide and was as effective as ceftazidime and cefpirome against acute respiratory tract infections caused by Kiebsiella pneumoniae DT-S. In the model of chronic respiratory tract infection caused by K. pneumoniae 27, cefozopran was as effective as ceftazidime. The therapeutic effect of cefozopran against urinary tract infections caused by Pseudomonas aeruginosa P9 was superior to that of cefpirome and was equal to those of ceftazidime and cefclidin. In addition, cefozopran was more effective than ceftazidime and was as effective as flomoxef in a thigh muscle infection caused by methicillin-sensitive Staphylococcus aureus 308A-1. Against thigh muscle infections caused by methicillin-resistant S. aureus N133, cefozopran was the most effective agent. The potent therapeutic effect of cefozopran in those experimental infections in mice suggests that it would be effective against respiratory tract, urinary tract, and soft tissue infections caused by a variety of gram-positive and gram-negative bacteria in humans.The search for new drugs effective as antibacterial agents requires the thorough evaluation of drugs not only in vitro but also in vivo (i.e., in the control and management of experimental infections). Systemic infections induced by an intraperitoneal injection of a bacterial suspension have been commonly used for the evaluation of new antibiotics. Such infections, however, are not always representative of infectious diseases in humans. It is therefore important to evaluate antibiotics by using animal models of infection which more closely mimic the actual situation in humans.This paper deals with the in vivo evaluation of cefozo- (Fig. 1), cefpirome, and cefclidin were prepared in the Research and Develop-* Corresponding author. ment Division of Takeda Chemical Industries, Ltd. Ceftazidime (Nippon Glaxo Co., Ltd., Tokyo, Japan), cefpiramide (Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan), and flomoxef (Shionogi & Co., Ltd., Osaka, Japan) were obtained commercially. MICs of each antibiotic were determined by an agar dilution method using an inoculum of ca.104 CFU and are shown in each table.Experimental infections and antibiotic treatment. (i) Respiratory tract infection. Acute respiratory tract infection caused by K pneumoniae DT-S was induced as described previously (19). Briefly, K pneumoniae DT-S was grown overnight at 37°C in brain heart infusion broth (Difco Laboratories, Detroit, Mich.), and cells were collected by centrifugation, washed with phosphate-buffered saline (Dulbecco formula [modified] without magnesium and calcium; Flow Laboratories, Inc., McLean, Va.), and suspended in the same buffered saline to give a suspension of ca. 109 CFU/ml. The bacterial suspension was placed in a nebulizer (Vaponefrin pocket nebulizer; USV Pharmaceutical Co., Tuckahoe, N.Y.) and aerosolized at a pressure of 1.2 kg/cm2 for ...