The study by Laine and colleagues [1] provides compelling evidence for the superior efficacy of fluconazole compared with ketoconazole in the treatment of candida esophagitis in patients with AIDS but fails to address the considerable differences in cost.

We constructed two flow diagrams to analyze the differences in cost incurred during treatment of candida esophagitis in 100 patients assigned to either fluconazole or ketoconazole therapy (Figure 1). At our hospital pharmacy, the cost to the patient for a 100-mg tablet of fluconazole is $7.24, whereas a 200-mg tablet of ketoconazole costs $2.46, an approximate threefold difference. Based on the data provided by Laine and coworkers, the clinical cure rates for therapy with ketoconazole and fluconazole are 65% and 85%, respectively. In our analysis, patients who did not respond to their initial regimen were crossed over to treatment with the second agent. In crossover therapy, we assumed that the probability for clinical cure with each agent would remain constant, despite failure to respond to the initial drug. However, no data are available with which to estimate response. The study by Laine and colleagues does show that the efficacy of fluconazole is not affected by previous antifungal therapy. The efficacy of ketoconazole, on the contrary, is diminished by recent antifungal therapy. Duration of therapy was calculated based on the therapeutic regimens, 3 and 8 weeks, as outlined by Laine and colleagues. To estimate cost, we assumed clinical cure to occur after the minimum therapeutic course and clinical failure to result after the maximal therapeutic regimen.

View larger version (24K): [in this window] [in a new window]   Figure 1. Cost comparison of initiating therapy for candida esophagitis with ketoconazole or fluconazole.

In the flow diagram, the cost quoted in each box applies only to its respective box. We calculated that the total cost for treating 100 patients initially with fluconazole is $20 210, whereas initial treatment of 100 patients with ketoconazole, followed by treatment of only nonresponders with fluconazole, costs $14 768. In other words, equivalent clinical cure rates can be achieved with reduced cost when therapy for candida esophagitis is instituted with ketoconazole as the first-line agent. Given the recurrent nature of candida esophagitis, several courses of therapy are often required in the lifetime of an individual patient; thus, minimizing the cost per patient is an integral aspect of effective management.