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Community-acquired pneumonia occurs 3 to 4 million times per year in the United States, accounting for about 500,000 hospitalizations annually. Empiric treatment is usually instituted because of a lack of early organism-specific diagnostic tests. This study compared empiric therapy with ofloxacin to standard antibiotic regimens (usually a beta-lactam with or without a macrolide) for patients hospitalized for community-acquired pneumonia. Therapy was administered to 298 patients (146 receiving ofloxacin and 152 receiving standard therapy); 227 patients (ofloxacin, 109; standard treatment, 118) were evaluable for treatment efficacy. The most common pyogenic respiratory pathogens were Haemophilus influenzae (30 isolates) and Streptococcus pneumoniae (24 isolates). There was evidence of infection with either Mycoplasma pneumoniae (38 patients), Chlamydia pneumoniae (40 patients), or a Legionella sp. (8 patients) in a total of 79 patients (35%). The clinical success rates were similar in both groups among evaluable patients (92%, ofloxacin; 87%, standard therapy) and among patients with atypical respiratory pathogens (88%, ofloxacin; 81%, standard therapy). The mean numbers (+/- the standard deviations) of intravenous doses of antibiotics were 7.5 +/- 8.0 in the ofloxacin group and 18.4 +/- 18.5 in the standard therapy group (P < 0.001); the mean number of oral doses of ofloxacin per patient was 19.7 +/- 11.2, compared with 30.2 +/- 16.0 oral antibiotic doses in the standard therapy group (P < 0.001). All treatments were well tolerated and associated with no significant clinical or laboratory abnormalities. The findings of this study indicate that ofloxacin is active against traditional bacterial pathogens as well as the major atypical respiratory pathogens. When given as monotherapy for the empiric treatment of community-acquired pneumonia, ofloxacin is as effective as standard antimicrobial therapy.

The pharmacokinetics of 1-oxa-beta-lactam (LY127935), a new semisynthetic beta-lactam antibiotic, was studied in four healthy adult volunteers (mean age of 27 years, mean body surface area +/- standard error [SE] of 1.87 +/- 0.08 m(2), and mean creatinine clearance +/- SE of 116 +/- 12 ml/min per 1.73 m(2)). Immediately after completion of a 1-g, 20-min intravenous (i.v.) infusion, the mean serum level +/- SE was 70.7 +/- 8.5 mug/ml. After a 1-g intramuscular (i.m.) injection, peak serum levels occurred from 30 min to 1 h, and the mean peak serum level +/- SE was 52.3 +/- 1.6 mug/ml. Beginning at 1 h, the serum concentrations after i.m. administration were higher than those after i.v. administration. At 8 h, the mean serum level +/- SE was 3.8 +/- 0.6 mug/ml after completion of the i.v. infusion and 4.8 +/- 0.7 mug/ml after the i.m. injection. The mean serum half-lives for the beta phase i.v. and i.m. administration were similar (2.3 +/- 0.7 h and 2.4 +/- 0.2 h, respectively). The mean apparent volume of distribution +/- SE was 16.6 +/- 1.9 liters per 1.73 m(2). The mean serum clearance +/- SE of LY127935 was 85.4 +/- 12.7 ml/min per 1.73 m(2), and the mean renal clearance +/- SE was 54.5 +/- 4.4 ml/min per 1.73 m.(2) Urine concentrations of LY127935 were at least 140 mug/ml in each volunteer during the first 12 h after i.m. or i.v. administration. The mean percentages of the dose recovered in the urine +/- SE within 2 h after i.v. or i.m. administration were similar (30 +/- 4 and 34 +/- 11, respectively). Only 67 +/- 3% and 75 +/- 13% were recovered in the urine within 24 h after i.v. and i.m. administration, respectively.

Cefazolin (CZ), cephalothin (CF), cefoxitin (CX), and cefamandole (CM) were evaluated in therapy of Staphylococcus aureus infection produced in perforated table tennis balls placed intraperitoneally in rabbits. Four weeks after placement of two balls in each rabbit, a beta-lactamase producing strain of S. aureus was injected into one of the balls. Twenty-four hours later therapy was initiated with 40 mg of CZ or 80 mg of CF, CX, or CM per kg intramuscularly every 6 h. After 24 h of treatment, the mean log(10) colony-forming units per ml were 7.1 for CZ, 6.7 for CF, 6.5 for CX, and 7.2 for CM. After 72 h the mean log(10) colony-forming units per ml were 5.0 for CZ, 4.1 for CF, 3.6 for CX, and 5.6 for CM. After 8 days, the titers were 1.6/ml for CZ, 1.0 for CF, 1.9 for CX, and 3.6 for CM. CZ serum levels were about double CF and CX levels and about two-thirds of CM levels. In sterile ball fluid CZ and CM levels were more than double CF or CX concentrations. Concentrations of all four antibiotics were lower in infected balls.