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In December 1992, Derouin et al. (3) confirmed the efficacy and synergistic effect of the clarithromycin-minocycline combination on experimental toxoplasmosis, as previously reported by Araujo et al. (1). In this study, the survival rate of mice varied between 93 and 100% depending on the dose of each drug. Since the conventional regimens, pyrimethaminesulfadiazine and pyrimethamine-clindamycin, are associated with a high rate of treatment-limiting adverse events (2, 4), the clarithromycin-minocycline combination was used as salvage therapy for a few patients who could not tolerate these regimens. We report this preliminary experience with the clarithromycin-minocycline combination in humans. Eight AIDS patients were treated for toxoplasmosis with this combination, because at least two of the three main drugs caused previous treatment-limiting adverse events. They were six men and two women with a mean age of 28 to 38 years and a mean CD4 count of 18 6 15 cells/mm. All patients had toxoplasmosis diagnosed after suggestive contrast-enhancing lesions were found at the initial CT scan (n 5 7), before any anti Toxoplasma gondii treatment was started, or after detection of T. gondii in broncho-alveolar lavage (patient 8). All showed a favorable response to anti-T. gondii therapy. Six patients (patients 1 to 6) were assessable for acute therapy (Table 1). The combination of clarithromycin and minocycline was given as first-line therapy to two patients who had a relapse of toxoplasmosis (patients 1 and 6) and after 17 6 7 days of standard therapy to the four others. Clarithromycin was administered at a dose of 0.75 to 2 g/day and minocycline at a dose of 200 mg/day. The mean duration of acute therapy with the combination was 9 6 4 weeks. During acute therapy, no other potentially active therapy for toxoplasmosis was given, except to one patient (patient 6), who was concomitantly given pyrimethamine at 75 mg/day. When the combination was started, five patients had neurological and CT scan signs of progressive cerebral toxoplasmosis and one patient (patient 4) had neurological signs and a CT scan done 2 weeks earlier that had suggested cerebral toxoplasmosis. Two patients (patients 1 and 2) with partial neurological and CT scan responses died at weeks 8 and 12, of causes unrelated to toxoplasmosis: human immunodeficiency virus encephalitis for one, and shock related to Clostridium difficile colitis for the other. The four other patients had complete clinical resolution, with minimal radiological sequelae in three and complete CT scan response in one. However, in three of them, the presumed benefit of clarithromycin-minocycline could be due to the earlier standard therapy. The clarithromycin-minocycline combination had to be discontinued only once (patient 2), due to a fivefold increase in serum transaminase levels in a patient who had concomitant potentially hepatotoxic drugs for tuberculosis. Maintenance therapy was assessed for six patients (patients

Clarithromycin-minocycline combination as salvage therapy for toxoplasmosis in patients infected with human immunodeficiency virus