Objective: To evaluate the costs, consequences, effectiveness, and safety of ciprofloxacin vs standard antibiotic care in patients with an initial acute exacerbation of chronic bronchitis (AECB) as well as recurrent AECBs over a 1-year period.
Design: Randomized, multicenter, parallel-group, open-label study.
Setting: Outpatient general practice.
Patients: A total of 240 patients, 18 years or older with chronic bronchitis, with a history of frequent exacerbations (three or more in the past year) presenting with a type 1 or 2 AECB (two or more of increased dyspnea, increased sputum volume, or sputum purulence).
Main outcome measures: The assessment included AECB symptoms, antibiotics prescribed, concomitant medications, adverse events, hospitalizations, emergency department visits, outpatient resources such as diagnostic tests, procedures, and patient and caregiver out-of-pocket expenses. Patients completed the Nottingham Health Profile, St. George's Respiratory Questionnaire, and the Health Utilities Index. The parameters were recorded with each AECB and at regular quarterly intervals for 1 year. These variables were compared between the ciprofloxacin-treated group and the usual-care-treated group.
Results: Patients receiving ciprofloxacin experienced a median of two AECBs per patient compared to a median of three AECBs per patient receiving usual care. The mean annualized total number of AECB-symptom days was 42.9+/-2.8 in the ciprofloxacin arm compared to 45.6+/-3.0 days in the usual-care arm (p=0.50). The overall duration of the average AECB was 15.2+/-0.6 days for the ciprofloxacin arm compared to 16.3+/-0.6 days for the usual-care arm. Treatment with ciprofloxacin tended to accelerate the resolution of all AECBs compared to usual care (relative risk=1.20; 95% confidence interval [CI], 0.91 to 1.58; p=0.19). Treatment assignment did not affect the interexacerbation period but a history of severe bronchitis, prolonged chronic bronchitis, and an increased number of AECBs in the past year were associated with shorter exacerbations-free periods. There was a slight, but not statistically significant, improvement in all quality of life measures with ciprofloxacin over usual care. The only factors predictive of hospitalization were duration of chronic bronchitis (odds ratio=4.6; 95% CI, 1.6, 13.0) and severity of chronic bronchitis (odds ratio=4.3; 95% CI, 0.8, 24.6). The incremental cost difference of $578 Canadian in favor of usual care was not significant (95% CI, -$778, $1,932). The cost for the ciprofloxacin arm over the usual care arm was $18,588 Canadian per quality-adjusted life year gained. When the simple base case analysis was expanded to examine the effect of risk stratification, the presence of moderate or severe bronchitis and at least four AECBs in the previous year changed the economic and clinical analysis to one favorable to ciprofloxacin with the ciprofloxacin-treated group having a better clinical outcome at lower cost ("win-win" scenario).
Conclusions: Treatment with ciprofloxacin tended to accelerate the resolution of all AECBs compared to usual care; however, the difference was not statistically significant. Further, usual care was found to be more reflective of best available care rather than usual first-line agents such as amoxicillin, tetracycline, or trimethoprim-sulfamethoxazole as originally expected. Despite the similar antimicrobial activities and broad-spectrum coverage of both ciprofloxacin and usual care, the trends in clinical outcomes and all quality of life measurements favor ciprofloxacin. In patients suffering from an AECB with a history of moderate to severe chronic bronchitis and at least four AECBs in the previous year, ciprofloxacin treatment offered substantial clinical and economic benefits. In these patients, ciprofloxacin may be the preferred first antimicrobial choice.