Acute exacerbations of complicated/severe bronchitis: Ciprofloxacin 750 MG BID vs. clarithromycin 500 MG BID

Purpose: In a community-based, randomized trial, the efficacy and safety of ciprofloxacin (CIP, 750mg) and clarithromycin (CLARI, 500mg), each given for 10d BID, were compared for the treatment of patients with acute exacerbations of complicated/severe bronchitis (AECB). Methods: Patients >40 yrs old with complicated/severe AECB episodes were enrolled (i.e., failed previous antibiotic treatment within prior 2-4 wks; regional susceptibility data showing high number of previous resistant pathogens; at least 3 AECB episodes within the past year; and/or at least 3 co-morbid conditions). Each patient had a baseline medical history and symptom evaluation, plus assessments for clinical and microbiologic response at the end of therapy and at follow-up (3-5 wks post-therapy). Results: Four hundred-five US-based physicians enrolled 2180 patients. Most patients were Caucasian (83%), current or previous smokers (81%) and had a mean age of 62 yrs. A history of at least 3 AECB episodes in the prior year were reported by 54% of CIP- and 53% of CLARI-treated patients. Dyspnea, increased sputum purulence and volume, increased cough frequency and severity were present in >85% of patients in both antibiotic groups. Cardiac co-morbidities were present in >22% of patients. Approx. 36% of patients had a positive pretherapy culture, including: Haemophilus spp (28%), M catarrhalis (18%), Enterobacteriaceae (18%), S aureus (17%), and S pneumoniae (7%). Beta-lactamase production was reported for 85% of M catarrhalis and 38% of H influenzae isolates. Thirty-five percent of pneumococcal isolates (n= 56) showed intermediate level penicillin-resistance of which 3% and 15% were resistant to CIP and CLARI, respectively. Among 705 patients with a pretherapy pathogen, clinical success rates at the end of therapy were 94% for CIP vs 89% for CLARI (P=0.026 ). Overall bacteriologic eradication rates for CIP/CLARI were 98%/95%, respectively. Specific eradication rates for particular organisms were: Haemophilus spp (n= 102/116) , 99%/93.1%; M catarrhalis (n= 72/70), 99%/100%; S pneumoniae (n= 32/24), 91%/92% and Enterobacteriaceae (n= 73/63) 100%/ 95%. Drug-related events occurred in 12% of CIP- and 10% of CLARI-treated patients. Conclusions: CIP 750mg BID had a statistically significantly higher clinical cure rate vs CLARI in the treatment of patients with bacteriologically proven complicated/severe AECB. Clinical Implications: CIP offers considerable clinical benefits for the treatment of severe/complicated AECB, and should be considered as a first line choice for these patients.