ETIOLOGY, SUSCEPTIBILITY, AND TREATMENT OF ACUTE BACTERIAL EXACERBATIONS OF COMPLICATED CHRONIC-BRONCHITIS IN THE PRIMARY-CARE SETTING - CIPROFLOXACIN 750 MG BID VERSUS CLARITHROMYCIN 500 MG BID

Although controversial, antimicrobial therapy for the treatment of acu te exacerbations of chronic bronchitis (AECB) appears beneficial in pa tients with a history of repeated infections, those who have co: morbi d illnesses, and those with marked airway obstruction. In a community- based, open, randomized trial, the efficacy and safety of ciprofloxaci n (CIP) 750 mg and clarithromycin (CLA) 500 mg, each given twice daily for 10 days, were compared in 2180 patients with AECB (1083 CIP, 1097 CLA). Patients were >40 years of age and had complicated/severe AECB episodes defined as at least three episodes within the past year, at l east three comorbid conditions, previous failed antibiotic treatment f or AECB within the previous 2 to 4 weeks, or community susceptibility data indicating a high number of resistant pathogens. Significant bact erial isolates (>10(5) colony-forming units per milliliter) from homog enized sputa were identified. Susceptibility to a range of antimicrobi als was determined by the microbroth dilution technique. The majority of patients were white (83%) and were current or previous smokers (81% ). Mean patient age was 62 years. A history of at least three AECB epi sodes in the previous year was reported by 54% of CIP-treated patients and 53% of CLA-treated patients. Of 777 primary isolates positively i dentified and cultured from 673 patients, the bacterial pathogens isol ated and their incidence included Haemophilus species, 28%; Moraxella catarrhalis, 18%; Enterobacteriaceae, 18%; Staphylococcus aureus, 17%; Streptococcus pneumoniae, 7%; and Pseudomonas aeruginosa, 4%. Beta-la ctamase production was found in 38% of Haemophilus influenzae, 10% of Haemophilus para-influenzae, and 85% of M catarrhalis isolates. Thirty -four percent of S pneumoniae isolates were resistant to penicillin (m inimum inhibitory concentration greater than or equal to 0.12 mg/L). A mong the 673 patients who were valid for clinical assessment and had a pretherapy pathogen isolated, clinical success and overall bacteriolo gic eradication rates at the end of therapy were 93% and 98% for CTP v ersus 90% and 96% for CLA. The differences between CIP and CLA did nor reach statistical significance. Superinfections were reported signifi cantly more frequently in CLA-treated (3%) versus CIP-treated patients (1%). Eradication rates for specific organisms for CIP and CLA, respe ctively, were Haemophilus species, 99% and 93%; M catarrhalis, 99% and 100%; S pneumoniae, 91% and 92%; and Enterobacteriaceae, 100% and 95% . Drug-related adverse events occurred in 12% of CLP-treated patients and 10% of CLA-treated patients. CIP 750 mg BID had a higher (but not statistically significant) clinical and bacteriologic cure rate than C LA 500 mg BID, in the treatment of patients with bacteriologically pro ven complicated/severe AECB. The causative bacterial pathogens of AECB appear to be evolving, with a predominance of gram-negative and other resistant organisms observed. Thus antibiotic therapy for at-risk pat ients with AECB should include agents that have activity against gram- negative pathogens.