ly-163892 and Chronic-Disease

Two controlled clinical trials compared loracarbef (LY163892 with amoxicillin/clavulanate or amoxicillin in the treatment of acute exacerbations of chronic bronchitis. Collectively, of 1,057 patients enrolled, 390 qualified for analysis: group 1 comprised 200 patients treated with loracarbef (400 mg twice daily); group 2, 120 patients treated with amoxicillin/clavulanate (500 mg three times daily); and group 3, 70 patients treated with amoxicillin (500 mg three times daily). Symptomatic and bacteriologic outcomes were assessed at post-therapy (within 72 hours of therapy completion), and at late-posttherapy (10-14 days after therapy completion). These evaluations were combined to provide an "overall" evaluation that accounted for all unfavorable outcomes occurring at either the posttherapy or late-posttherapy visit. At the posttherapy evaluation, 93.0% of group 1 patients, 95.0% of group 2 patients, and 88.6% of group 3 patients demonstrated favorable clinical outcomes (cure or improvement). "Overall" favorable clinical outcomes were achieved in 88.0% of group 1 patients, 90.0% of group 2 patients, and 81.4% of group 3 patients. Bacteriologic results from the two studies could not be merged due to marked differences in how posttherapy bacteriologic results were assessed. The clinical significance of positive posttherapy sputum cultures was doubtful: 90% of patients with a positive sputum culture at the posttherapy visit who returned for the late-posttherapy visit had successful clinical outcomes documented at the late-posttherapy evaluation. Loracarbef was associated with a lower incidence of diarrhea and a higher incidence of headache as compared with amoxicillin/clavulanate. These results suggest that 400 mg loracarbef twice daily for 7 days is effective and safe in the treatment of acute exacerbations of chronic bronchitis.

Topics: Acute Disease; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Bronchitis; Cephalosporins; Chronic Disease; Clavulanic Acids; Diarrhea; Drug Therapy, Combination; Europe; Female; Headache; Humans; Incidence; Male; Middle Aged; Treatment Outcome; United States

To compare the efficacy and safety of five-day cefdinir treatment with seven-day loracarbef treatment in patients with acute exacerbations of chronic bronchitis, 586 patients were enrolled in a multicentre, randomised, double-blind trial. Patients received either five days of treatment with cefdinir (n = 291) at 300 mg twice daily or seven days of treatment with loracarbef (n = 295) at 400 mg twice daily. Microbiological assessments were done on sputum specimens obtained at admission and at the two post-therapy visits, if available. The clinical cure rates were 86% (138/160) and 85% (141/166) for the evaluable patients treated with cefdinir and loracarbef, respectively. Respiratory tract pathogens were isolated from 457 (78%) of 586 admission sputum specimens, with the predominant pathogens being Haemophilus parainfluenzae, H. influenzae, Moraxella catarrhalis and Staphylococcus aureus. The microbiological eradication rates at the test-of-cure visit were 88% (193/219 pathogens) and 90% (227/251 pathogens) for the evaluable patients treated with cefdinir and loracarbef, respectively. Adverse event rates while on treatment were 30% and 21% for cefdinir- and loracarbef-treated patients, respectively. These results indicate that a five-day regimen of cefdinir is effective and safe for the treatment of patients with acute exacerbations of chronic bronchitis.

Topics: Adolescent; Adult; Aged; Anti-Infective Agents; Bacterial Infections; Bronchitis; Cefdinir; Cephalosporins; Chronic Disease; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Prospective Studies; Sputum; Treatment Outcome

Two controlled clinical trials compared loracarbef (LY163892 with amoxicillin/clavulanate or amoxicillin in the treatment of acute exacerbations of chronic bronchitis. Collectively, of 1,057 patients enrolled, 390 qualified for analysis: group 1 comprised 200 patients treated with loracarbef (400 mg twice daily); group 2, 120 patients treated with amoxicillin/clavulanate (500 mg three times daily); and group 3, 70 patients treated with amoxicillin (500 mg three times daily). Symptomatic and bacteriologic outcomes were assessed at post-therapy (within 72 hours of therapy completion), and at late-posttherapy (10-14 days after therapy completion). These evaluations were combined to provide an "overall" evaluation that accounted for all unfavorable outcomes occurring at either the posttherapy or late-posttherapy visit. At the posttherapy evaluation, 93.0% of group 1 patients, 95.0% of group 2 patients, and 88.6% of group 3 patients demonstrated favorable clinical outcomes (cure or improvement). "Overall" favorable clinical outcomes were achieved in 88.0% of group 1 patients, 90.0% of group 2 patients, and 81.4% of group 3 patients. Bacteriologic results from the two studies could not be merged due to marked differences in how posttherapy bacteriologic results were assessed. The clinical significance of positive posttherapy sputum cultures was doubtful: 90% of patients with a positive sputum culture at the posttherapy visit who returned for the late-posttherapy visit had successful clinical outcomes documented at the late-posttherapy evaluation. Loracarbef was associated with a lower incidence of diarrhea and a higher incidence of headache as compared with amoxicillin/clavulanate. These results suggest that 400 mg loracarbef twice daily for 7 days is effective and safe in the treatment of acute exacerbations of chronic bronchitis.

Topics: Acute Disease; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Bronchitis; Cephalosporins; Chronic Disease; Clavulanic Acids; Diarrhea; Drug Therapy, Combination; Europe; Female; Headache; Humans; Incidence; Male; Middle Aged; Treatment Outcome; United States

Sputum and serum pharmacokinetics of loracarbef (LY163892) were performed in 19 patients with purulent bronchiectasis. Nine of the patients received 200 mg twice daily and ten patients, 400 mg twice daily, for a total of 14 days. beta-Lactamase activity was measurable in the lung secretions of all 19 patients at the start of therapy. Mean peak serum concentrations of 11.7 mg/L (S.E.M. 1.7) were recorded at 1 h after administration of 200 mg doses on day 2 of therapy and were 18.5 mg/L (S.E.M. 1.9) at 1.5 h in the 400 mg group. Loracarbef was shown to penetrate lung secretions even in the presence of beta-lactamase activity. Mean peak sputum concentrations were achieved between 2 and 4 h following dosing and were 0.2 mg/L (S.E.M. 0.05) in the 200 mg group and 0.4 mg/L (S.E.M. 0.08) in the 400 mg group. On days 7 and 14 of therapy, sputum loracarbef concentrations were similar 4 h after the morning dose (0.23 mg/L following 200 mg; 0.35 mg/L after 400 mg). These concentrations were approximately 2% of the peak serum concentration and penetration into lung secretions is similar to other beta-lactams.

Topics: Adult; Aged; Albumins; Anti-Bacterial Agents; beta-Lactamases; Bronchiectasis; Cephalosporins; Chronic Disease; Female; Humans; Lung; Male; Middle Aged; Serum Albumin; Sputum