ly-163892 and Bronchitis

Acute bronchitis, an illness frequently encountered by primary-care physicians, is an inflammation of the tracheobronchial tree that results from a respiratory tract infection. It is characterized by persistent cough and sputum production and is occasionally accompanied by fever and/or chest pain. Acute bronchitis may have a viral or bacterial origin and is often treated with antibiotics. Four clinical trials were conducted to compare high and low doses of loracarbef, a new oral beta-lactam antibiotic, with three agents commonly used to treat acute bronchitis: amoxicillin/clavulanate, cefaclor, and amoxicillin. Results of these studies indicated that loracarbef, 400 and 200 mg twice daily, had clinical and bacteriologic efficacy against the common respiratory pathogens Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella (Branhamella) catarrhalis that was comparable with that of the comparative agents. Loracarbef was as well tolerated as cefaclor and amoxicillin; moreover, it produced a significantly lower incidence of diarrhea than did amoxicillin/clavulanate. Loracarbef may be considered a safe and effective alternative agent for the treatment of patients with acute bronchitis.

Topics: Acute Disease; Bronchitis; Cephalosporins; Clinical Trials as Topic; Drug Resistance, Microbial; Europe; Gastrointestinal Diseases; Humans; Respiratory Tract Infections; United States

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

The effect on the oropharyngeal and intestinal microflora and the efficacy and tolerance of loracarbef (200 mg b.i.d. for 7 days) versus amoxicillin (500 mg t.i.d. for 7 days) were compared in 80 patients with bronchitis. The oropharyngeal samples of 18% of patients in the amoxicillin group and 5% of patients in the loracarbef group revealed a new Gram-negative species around days 8-10. The presence of other aerobic bacteria than found at baseline in the faeces occurred in 38% of patients treated with amoxicillin compared with 31% in the loracarbef group on days 8-10. After treatment, no loracarbef- or amoxicillin-resistant aerobic Gram-negative bacteria were found in faecal samples in the loracarbef group, while amoxicillin- or loracarbef-resistant (E. coli) strains appeared in 35% of patients receiving amoxicillin (p < 0.001). Treatment success occurred by days 8-10 in all 40 patients receiving loracarbef, compared with 90% in the amoxicillin group, on days 21-28, in 93% and 90% respectively. The results of this study indicate that the use of loracarbef leads to minor changes in the normal oropharyngeal and intestinal microflora compared with amoxicillin, while almost no resistant Gram-negative bacteria emerge after treatment with loracarbef.

Topics: Acute Disease; Adolescent; Adult; Amoxicillin; Bacteria, Anaerobic; Bronchitis; Cephalosporins; Enterococcus faecalis; Female; Gram-Negative Aerobic Bacteria; Humans; Intestines; Male; Microbial Sensitivity Tests; Oropharynx; Yeasts