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BACKGROUND: The new Centers for Disease Control and Prevention treatment guidelines for Chlamydia trachomatis include two recently available drugs, azithromycin and ofloxacin. The best choice for initial therapy remains controversial. OBJECTIVES: We wanted to perform a cost-effectiveness analysis of five different antibiotic regimens for the treatment of uncomplicated Chlamydia trachomatis cervicitis. METHODS: Using information gathered from a MEDLINE search of the English language literature from 1966 to 1994, employing the key words "cervicitis," "C. trachomatis," "erythromycin," "tetracycline," "doxycycline," "ofloxacin," and "azithromycin," we developed a decision analysis model specific for a nonpregnant woman with uncomplicated Chlamydia trachomatis cervicitis. Options in this model included an initially cured infection, a failed initial cure resulting in persistent cervicitis, or pelvic inflammatory disease treated either on an inpatient or outpatient basis. Probability estimates for each option were derived from previously published reports. A cost-effectiveness analysis was performed for three end points: cost per cure with initial therapy, cost per case of pelvic inflammatory disease averted, and cost per hospitalization averted. Sensitivity analyses were done by varying the cure rates for each antibiotic and the complication rates for failed therapy. The costs incurred for treatment were also varied. RESULTS: Using the high estimate for initial cure rates, doxycycline and tetracycline were the most cost-effective agents. Azithromycin was the next most cost-effective agent, followed by ofloxacin and erythromycin. To achieve an equivalent final cost, the probability of initial cure with azithromycin must exceed that of doxycycline by 3 percentage points. As the cost of azithromycin decreases, the difference in initial cure rates between the two drugs to achieve an equivalent final cost becomes smaller. CONCLUSIONS: Doxycycline remains the drug of choice in the treatment of Chlamydia trachomatis cervicitis. The results favor the use of azithromycin rather than doxycycline when there is concern for compliance to the standard doxycycline regimen. A lower cost for azithromycin could favor its use as the drug of choice.