Loracarbef (LY163892) versus cefaclor in the treatment of bacterial skin and skin-structure infections in an adult population.

Loracarbef (LY163892), a member of the class of beta-lactam antibiotics known as carbacephems, is characterized by a high level of chemical stability and a broad spectrum of antibacterial activity that persists in the presence of beta-lactamase. The efficacy and safety of loracarbef, 200 mg (twice daily), and cefaclor, 250 mg (three times daily) (one patient received 178 mg of cefaclor suspension, three times daily), were compared in a randomized, double-blind, multicenter trial conducted in adults with skin and skin-structure infections due predominantly to Staphylococcus aureus. Examination within 72 hours after the completion of therapy indicated a favorable clinical response in 84 (93.3%) of the 90 loracarbef-treated patients evaluable for efficacy and in 79 (95.2%) of the 83 evaluable patients treated with cefaclor. Pathogens were eradicated in 83 (92.2%) of the patients in the loracarbef group and 74 (89.2%) of those in the cefaclor group. Only four adverse events--headache/migraine, diarrhea, abdominal pain, and nausea--occurred in greater than 2% of the total study population. The overall incidence of adverse events in the 201 loracarbef-treated and 192 cefaclor-treated patients evaluated for safety was 19.9% and 24.5%, respectively. Adverse events that required hospitalization or discontinuation of treatment occurred in four patients in the cefaclor group but in none of those treated with loracarbef. There were no statistically significant differences in the clinical or bacteriologic response or the incidence of side effects between the two treatment groups. These findings indicate that loracarbef given twice daily is comparable in safety and efficacy to cefaclor given three times daily in the treatment of adults with skin and skin-structure infections.

Loracarbef (LY163892) versus amoxicillin/clavulanate in the treatment of acute purulent bacterial bronchitis.

In this single-blind study, 488 patients with acute bronchitis were randomly assigned to receive 400 mg of loracarbef twice daily or 500/125 mg of amoxicillin/clavulanate three times daily for seven days. Treatment efficacy was evaluated in 98 patients treated with loracarbef and in 99 treated with amoxicillin-clavulanate in whom pretreatment positive cultures of pathogens susceptible to both study drugs were found. Streptococcus pneumoniae, Haemophilus influenzae, Moraxella (Branhamella) catarrhalis, and Klebsiella pneumoniae were isolated in pure or mixed cultures in 64% of the evaluable patients; S pneumoniae was found in 26%. Among the evaluable patients, the rate of favorable clinical responses (cure and improvement) in the loracarbef group (96 of 98 patients; 98.0%) was similar to that in the amoxicillin/clavulanate group (96 of 99 patients; 97.0%); the favorable bacteriologic response rates were also similar (93.7% vs 92.9%, respectively). Eight patients in the loracarbef group and nine in the amoxicillin/clavulanate group discontinued treatment because of adverse events. The events were presumed to be drug related in five of the loracarbef group and in seven of the amoxicillin/clavulanate group. During therapy, diarrhea was the most frequently reported event in both groups. However, it occurred in only 8.2% of the loracarbef-treated patients compared with 22.5% of the amoxicillin/clavulanate patients (P less than 0.001). It is concluded that both loracarbef and amoxicillin/clavulanate are safe and effective in the treatment of acute purulent bacterial bronchitis.

Loracarbef (LY163892) versus amoxicillin/clavulanate in the treatment of acute bacterial exacerbations of chronic bronchitis.

In this single-blind study, 579 patients with chronic bronchitis were randomly assigned to receive 400 mg of loracarbef twice daily or 500/125 mg of amoxicillin/clavulanate thrice daily for seven days. Treatment efficacy was evaluated in 129 of the loracarbef-treated patients and 120 amoxicillin/clavulanate-treated patients in whom pretreatment positive cultures of pathogens susceptible to both antibiotics were isolated. Three organisms predominated in either pure or mixed cultures in 57.0% of the evaluable patients: Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella (Branhamella) catarrhalis; H influenzae was isolated in 25.0% of the patients with single pathogens. Among the evaluable patients, favorable clinical responses (cure or improvement) were noted in 93.8% of the loracarbef-treated patients and in 95.0% of the amoxicillin/clavulanate-treated patients. A favorable bacteriologic response (pathogen eliminated or presumed eliminated) was found in 82.2% of loracarbef-treated patients and 90.0% of amoxicillin/clavulanate-treated patients. Six patients in the loracarbef group and 14 in the amoxicillin/clavulanate group discontinued treatment because of adverse events. The events were judged to be drug related in four loracarbef-treated patients and in 11 amoxicillin/clavulanate-treated patients. The incidence of diarrhea and other gastrointestinal symptoms was significantly more frequent in the amoxicillin/clavulanate group (13.5% and 5.6%) than in the loracarbef group (4.5% and 1.7%), while the incidence of severe headaches was significantly more frequent in the loracarbef than the amoxicillin/clavulanate group (7.2% vs 3.1%). It is concluded that loracarbef and amoxicillin/clavulanate are safe and effective in the treatment of acute bacterial exacerbations of chronic bronchitis.

Comparative study of cephalexin hydrochloride and cephalexin monohydrate in the treatment of skin and soft tissue infections.

In two prospective, randomized multicenter double-blind studies with a dosage of either 250 mg given four times a day (study A) or 500 mg given two times a day (study B), the comparative efficacy and safety of cephalexin hydrochloride (LY061188; Keftab) and cephalexin monohydrate (Keflex) for treatment of skin and soft tissue infections were determined. In study A, 97 patients received cephalexin hydrochloride and 101 patients received cephalexin monohydrate. In study B, 75 patients received cephalexin hydrochloride and 70 patients received cephalexin monohydrate. Diagnoses included abscesses, cellulitis, wound infections, and infected dermatitis, and were comparable in the different treatment groups. Pathogens were isolated from 82% of patients enrolled; the majority of isolates were of Staphylococcus aureus, Streptococcus pyogenes, other staphylococcal species, and a few gram-negative bacteria. In study A, 68 of 71 (95.7%) evaluable patients who received cephalexin hydrochloride responded satisfactorily; 73 of 81 (90%) patients who received cephalexin monohydrate also responded satisfactorily. In study B, 56 of 58 (96.5%) evaluable patients who received cephalexin hydrochloride responded satisfactorily; 47 of 50 (94%) patients who received cephalexin monohydrate also responded satisfactorily. An adverse clinical event leading to discontinuation of the treatment drug developed in 17 of 343 (4.95%) patients in both studies. No differences were noted between the two drugs. Skin eruptions, pruritus, and mild gastrointestinal symptoms were the common adverse effects. These data suggest that cephalexin hydrochloride, a new formulation of cephalexin, is a safe and effective antimicrobial agent for treatment of a variety of skin and subcutaneous infections in a dosage of either 250 mg four times a day or 500 mg twice a day.