Sparfloxacin vs ofloxacin in the treatment of acute bacterial exacerbations of chronic bronchitis: a multicenter, double-blind, randomized, comparative study. Sparfloxacin Multicenter ABECB Study Group.

STUDY OBJECTIVE: Comparison of efficacy and safety of sparfloxacin vs ofloxacin for treatment of acute bacterial exacerbations of chronic bronchitis (ABECB). DESIGN: Multicenter, double-blind, randomized study. SETTING: Sixty-eight private offices and outpatient clinics in the United States and Canada. PATIENTS: Seven hundred ninety-eight adults with ABECB, as confirmed by the acute onset of new (or worsened from the immediate premorbid state) cough and sputum production. INTERVENTIONS: Randomization 1:1 to sparfloxacin, 400 mg on day 1, then 200 mg once daily, or ofloxacin, 400 mg twice daily, with matching comparator placebos, given concurrently for 10 consecutive days. RESULTS: The primary efficacy parameter was overall response in the bacteriologically evaluable population. Overall success rates in this population were 85.3% and 89.3% for sparfloxacin and ofloxacin, respectively. The two-sided 95% confidence interval was -9.9, 1.9, indicating that sparfloxacin was statistically equivalent to ofloxacin. The all-treated population analysis was similar to that in the evaluable population. Bacterial eradication rates were similar in both treatment groups for Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Chlamydia pneumoniae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Enterobacter cloacae, and Staphylococcus aureus. The frequency of adverse events overall was comparable in the two treatment groups. The sparfloxacin group had a lower frequency of digestive and nervous system adverse events, but a higher frequency of photosensitivity reactions than the ofloxacin group. CONCLUSIONS: Once-daily oral treatment with 200 mg sparfloxacin (after initial 400 mg dose) is as effective as twice-daily treatment with 400 mg ofloxacin in patients with ABECB.

Multinational multicenter controlled trial comparing ceftibuten with cefaclor for the treatment of acute otitis media. Members of the Ceftibuten Otitis Media International Study Group.

A randomized, controlled, single blind clinical trial was conducted in children with acute otitis media to evaluate the safety and efficacy of a 10-day course of therapy with ceftibuten 9 mg/kg taken as a single daily dose, up to a maximum daily dose of 400 mg, compared with cefaclor 40 mg/kg/day in three divided doses, up to a maximum of 1 g/day. Patients were evaluated any time from 1 to 3 days after completion of therapy (posttreatment follow-up). A total of 154 patients (106 ceftibuten, 48 cefaclor) were evaluable for efficacy. Clinical success as determined by resolution (cure) or improvement of signs and symptoms of infection were seen in 89 and 88% of patients treated with ceftibuten and cefaclor, respectively, at the posttreatment follow-up visit. At the extended follow-up visit (any time from 2 to 4 weeks after completion of therapy), clinical success was sustained in 88 and 82% of the ceftibuten-treated and cefaclor-treated patients, respectively. A total of 391 patients (264 ceftibuten, 127 cefaclor) were included in the safety analysis. Treatment-related adverse experiences occurred in 8% of ceftibuten-treated patients and 14% of cefaclor-treated patients. All were mild or moderate and the majority were gastrointestinal. There were no deaths or serious adverse events. The results of this study suggest that ceftibuten is an effective and well-tolerated alternative to other antibiotic therapies for the treatment of children with acute otitis media.

Comparison of 5-day, short-course gatifloxacin therapy with 7-day gatifloxacin therapy and 10-day clarithromycin therapy for acute exacerbation of chronic bronchitis.

BACKGROUND: The ideal duration of antibiotic therapy for acute exacerbation of chronic bronchitis (AECB) remains controversial. OBJECTIVE: This study compared short-course, 5-day gatifloxacin treatment with standard 10-day clarithromycin treatment in patients with AECB; 7-day gatifloxacin therapy was a secondary comparator. METHODS: This was a multicenter, prospective, randomized, double-blind study in which adult outpatients with AECB were randomized to 1 of 3 treatment groups: 5 days of gatifloxacin, 7 days of gatifloxacin, or 10 days of clarithromycin. Clinical cure and microbiologic eradication rates were determined 7 to 14 days after the completion of antibiotic treatment. RESULTS: A total of 527 patients with AECB were enrolled and treated with study drug (174, gatifloxacin 5-day; 175, gatifloxacin 7-day; 178, clarithromycin 10-day). Most patients (82%) had type 1 (severe) exacerbations, and a bacterial pathogen was isolated from pretreatmer, sputum samples in 59% of patients. The overall clinical cure rates among clinically evaluable patients were comparable between groups: 89% (135/151 patients) in the gatifloxacin 5-day group; 88% (136/154) in the gatifloxacin 7-day group; and 89% (145/163) in the clarithromycin 10-day group. The 95% CIs for the differences in response rates were -6.1 to 7.0 for gatifloxacin 5-day versus clarithromycin, -8.9 to 5.0 for gatifloxacin 7-day versus clarithromycin, and -5.5 to 8.0 for gatifloxacin 5-day versus 7-day. These observations did not appear to be affected by use of corticosteroids or smoking status, type of exacerbation, or duration of current episode. The microbiologic eradication rate among microbiologically evaluable pathogens was >90% in all treatment groups. No clinically meaningful differences were noted in the incidence of drug-related adverse events. CONCLUSION: Short-course, 5-day gatifloxacin therapy in patients with AECB resulted in clinical cure and microbiologic eradication rates comparable to those of standard 7- and 10-day therapies.

Effectiveness of short-course therapy (5 days) with grepafloxacin in the treatment of acute bacterial exacerbations of chronic bronchitis.

Three hundred eighty-nine patients were enrolled in a double-masked, multicenter, randomized clinical trial comparing the clinical and bacteriologic efficacies and safety of a 5-day course (n = 195) versus a 10-day course (n = 194) of grepafloxacin 400 mg once daily in the treatment of acute bacterial exacerbations of chronic bronchitis (ABECB). Patients in the 5-day treatment group received placebo on days 6 through 10. Bacteriologic assessments were based on cultures of sputum specimens obtained before and, when possible, during and after treatment. Organisms were isolated from the pretreatment sputum specimens of 332 of 388 (86%) patients, the primary pathogens being Haemophilus parainfluenzae, Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus (29%, 19%, 4%, 5%, and 5% of isolates, respectively). Among isolates tested for beta-lactamase production, results were positive in 25% of H influenzae isolates and 90% of M catarrhalis isolates. Forty-two percent of S pneumoniae isolates demonstrated reduced susceptibility (intermediate or high-level resistance) to penicillin. A satisfactory clinical outcome (cure or improvement) was achieved in 83% (128 of 155) and 81% (122 of 150) of clinically evaluable patients treated with grepafloxacin for 5 or 10 days, respectively. Pathogens were eradicated or presumed eradicated in 77% (106 of 138) and 80% (98 of 123) of bacteriologically evaluable patients treated with grepafloxacin for 5 or 10 days, respectively. The 2 treatment groups were equivalent with respect to both clinical and bacteriologic efficacy, and no statistically significant differences in the incidence of drug-related adverse events were seen between the 2 groups. Substantial symptom relief was evident with both treatment regimens by the first during-treatment measurement, which occurred between days 3 through 5. These results indicate that treatment with 400 mg grepafloxacin once daily for 5 days is as well tolerated and effective as treatment for 10 days in patients with ABECB. The lower cost compared with a 10-day regimen and the increased likelihood that patients will complete the entire shorter, once-daily regimen make the 5-day grepafloxacin regimen a useful therapeutic option in the treatment of ABECB.

Short-course moxifloxacin therapy for treatment of acute bacterial exacerbations of chronic bronchitis. The Bronchitis Study Group.

Chronic bronchitis is common among adults and infectious exacerbations contribute considerably to morbidity and mortality. We aimed to compare the safety and efficacy of moxifloxacin to clarithromycin for the treatment of patients with acute bacterial exacerbations of chronic bronchitis (ABECB) using a prospective, randomized, double-blind, parallel group trial. Between November 21, 1996 and April 7, 1998, 936 patients with acute exacerbations of chronic bronchitis (AECB) were enrolled at 56 centers across the United States of which 491 (52%) had ABECB (i.e. pretherapy pathogen). Patients were randomized to either oral moxifloxacin 400 mg administer once daily, for either 5 or 10 days, or clarithromycin 500 mg bid for 10 days. For the purpose of study blinding, the patients taking moxifloxacin received placebo to maintain uniform dosing. The main outcome measures were bacteriological response at the end of therapy (post-therapy days 0-6) and follow-up (7-17 days post-therapy) visits, as well as overall clinical response, clinical response at the end of therapy and clinical response at follow-up. Two patient populations were analyzed: efficacy-valid (i.e., those with a pretherapy pathogen) and intent-to-treat (i.e., all subjects that took drug). In 420 efficacy valid patients with a pretherapy organism, overall clinical resolution was 89% for 5 days moxifloxacin vs. 91% for 10 day moxifloxacin vs. 91% for 10 day clarithromycin. Bacteriological eradication rates at the end of therapy were 94% and 95% for 5-day moxifloxacin and 10-day moxifloxacin, respectively, and 91% for the clarithromycin group. Eradication rates at follow-up were 89% and 91% for 5-day moxifloxacin and 10-day moxifloxacin respectively, and 85% for the clarithromycin group. Among 926 intent-to-treat patients (312 5-day moxifloxacin, 302 10-day moxifloxacin and 312 clarithromycin), drug-related events were reported for 26%, 30% and 35%, respectively. Moxifloxacin 400 mg once daily, as a 5 or 10 day regimen, was found to be clinically and bacteriologically equivalent to 10 day clarithromycin for the treatment of ABECB. Given its favorable safety and tolerability profile, moxifloxacin administered once daily for 5 days may be as effective and a more convenient treatment than a standard course of clarithromycin for patients with ABECB.

The safety and efficacy of short course (5-day) moxifloxacin vs. azithromycin in the treatment of patients with acute exacerbation of chronic bronchitis.

Chronic bronchitis is common among adults and infectious exacerbations contribute considerably to morbidity and mortality. We aimed to compare the safety and efficacy of moxifloxacin to azithromycin for the treatment of patients with acute exacerbations of chronic bronchitis (AECB) of suspected bacterial origin. Between October 1998 and April 1999, 567 patients with AECB were enrolled at 37 centers across the United States and Canada of which 280 (49%) had acute bacterial exacerbation of chronic bronchitis (i.e. pretherapy pathogen). Patients were randomized to either oral moxifloxacin 400 mg administered once daily for 5 days or azithromycin for 5 days (500 mg qd x 1, then 250 mg qd x 4). For the purpose of study blinding, all patients received encapsulated tablets. The main outcome measure was clinical response at the test-of-cure visit (14-21 days post-therapy). Secondary measures included bacteriologic response and a time-course of bacteriological eradication (one center only). Three patient populations were analysed for efficacy: clinically-valid, microbiologically-valid (i.e. those with a pretherapy pathogen), and intent-to-treat (i.e. received at least one dose of study drug). For the efficacy-valid group, clinical response at the test-of-cure visit was 88% for patients in each treatment group. In 237 microbiologically-valid patients, corresponding clinical resolution rates were 88% for 5-day moxifloxacin vs. 86% for 5-day azithromycin. Bacteriological eradication rates at the end of therapy were 95% for 5-day moxifloxacin and 94% for the azithromycin group. Corresponding eradication rates at the test-of-cure visit were 89% and 86%, respectively. Of note, eradication rates at test-of-cure for Haem. philos influenzae and H. parainfluenzae for moxifloxacin were 97% and 88% compared to 83% and 62% respectively for azithromycin. Among 567 intent-to-treat patients (283 moxifloxacin and 284 azithromycin), drug-related events were reported for 22% and 17%, respectively. Diarrhea and nausea were the most common drug-related events reported in each treatment group. Moxifloxacin 400 mg once daily for 5 days was found to be clinically and bacteriologically equivalent to 5-day azithromycin for the treatment of AECB of proven bacterial etiology. Given its excellent in-vitro activity, especially against antibiotic-resistant respiratory pathogens, and its acceptable safety profile, moxifloxacin should be considered an effective alternative therapy for patients with AECB of suspected bacterial origin.

Comparison of the effectiveness of levofloxacin and amoxicillin-clavulanate for the treatment of acute sinusitis in adults.

In this comparative trial, outpatients with acute sinusitis were randomly assigned to receive levofloxacin (500 mg orally once daily) or amoxicillin-clavulanate (500/125 mg orally 3 times daily) for 10 to 14 days. The success rates (cured and improved) 2 to 5 days after the end of treatment were 88.4% for the 267 clinically evaluable patients who received levofloxacin and 87.3% for the 268 clinically evaluable patients who received amoxicillin-clavulanate. Drug-related adverse events occurred in a smaller percentage of patients in the levofloxacin treatment group (7.4%) than in the amoxicillin-clavulanate treatment group (21.2%). The most common of these were nausea, diarrhea, vaginitis, and abdominal pain for levofloxacin-treated patients and diarrhea, vaginitis, nausea, genital moniliasis, abdominal pain, vomiting, and flatulence for amoxicillin-clavulanate-treated patients. The results of this study show that once-daily administration of levofloxacin is as effective and better tolerated than amoxicillin-clavulanate administered 3 times daily for treating acute sinusitis in adult outpatients.

Effects of amlodipine on exercise tolerance, quality of life, and left ventricular function in patients with heart failure from left ventricular systolic dysfunction.

BACKGROUND: A preliminary study suggested that the long-acting late-generation calcium-channel blocker amlodipine has favorable effects on exercise tolerance and is safe to use in heart failure, in contrast to earlier generation agents. The goal of 2 multicenter studies was to assess the effect of adjunctive therapy with amlodipine in addition to standard therapy on exercise capacity, quality of life, left ventricular function, and safety parameters in patients with heart failure and left ventricular systolic dysfunction. METHODS: Two large multicenter trials examining the effects of amlodipine on these parameters over a 12-week period of therapy were undertaken in patients with mild to moderate heart failure and left ventricular systolic dysfunction. A total of 437 patients with stable heart failure were studied in a randomized, double-blind, placebo-controlled prospective design. RESULTS: Amlodipine at a dose of 10 mg/day in addition to standard therapy in such patients was associated with no significant difference in change in exercise tolerance on a Naughton protocol compared with placebo in each trial. Among all patients taking amlodipine, exercise time increased 53 +/- 9 (SE) seconds; exercise time for those taking placebo increased 66 +/- 9 seconds (P = not significant). There were no significant differences in changes of quality of life parameters between amlodipine- and placebo-treated patients, and there were no significant differences in symptom scores or New York Heart Association classification between groups. Left ventricular function (measured as ejection fraction) improved 3. 4% +/- 0.5% in amlodipine-treated patients and 1.5% +/- 0.5% in placebo-treated patients (P =.007). There was no statistically significant excess of important adverse events (episodes of worsening heart failure in 10% amlodipine-treated vs 6.3% of placebo-treated patients) or differences in need for changes in background medication between groups. CONCLUSIONS: The addition of 10 mg of amlodipine per day to standard therapy in patients with heart failure is associated with no significant improvement in exercise time compared with placebo therapy over a 12-week period, and there was no increased incidence of adverse events. These data suggest that the addition of amlodipine to standard therapy in heart failure will not result in additional efficacy per se beyond standard therapy.