Clarithromycin was administered to nine previously untreated lepromatous leprosy patients. Patients received two 1,500-mg doses on the first day, followed by 7 days of no treatment, in order to evaluate the potential efficacy of intermittent therapy. Patients then received 1,000 mg daily for 2 weeks followed by 500 mg daily for 9 weeks. The efficacy of therapy was monitored clinically, by changes in morphological index, mouse footpad infectivity, and radiorespirometric activity of Mycobacterium leprae obtained from serial biopsies and by serum levels of phenolic glycolipid I. Clarithromycin was well tolerated, with only minor side effects noted in two patients. Most patients showed reductions in morphological index and radiorespirometry 1 week after the first two doses. Within 3 weeks of starting treatment (total of 17 g of clarithromycin), biopsy-derived M. leprae specimens from all patients had a morphological index of zero, were noninfectious for mice, and had less than 1% of the radiorespirometric activity of pretreatment specimens. Reductions in serum phenolic glycolipid I levels were observed for most patients at 3 weeks. Significant clinical improvement was evident after 4 weeks of treatment. All analyses indicate that clarithromycin is rapidly bactericidal for M. leprae in humans.Clarithromycin is a new semi-synthetic macrolide with activity, pharmacokinetics, and gastric tolerance superior to those of erythromycin. Clarithromycin has demonstrated exceptional activity against Mycobacterium leprae both in vitro (3, 4) and in vivo (5, 7, 8, 11); its activity surpasses that of other macrolides (5,8) and approximates that of rifampin (5, 7).A recent clinical trial of 500 mg of clarithromycin daily against leprosy showed good activity as determined by loss of infectivity of biopsy-derived M. leprae for mice (10). Because of the exceptional tolerance of clarithromycin and increased half-life at increasing dosage (3) and considering the current use of intermittent rifampin therapy in leprosy, we evaluated the effect of both a single day's dose and a higher daily dose of clarithromycin for nine lepromatous leprosy patients and monitored efficacy by a number of rapid assays in addition to the mouse footpad assay. MATERUILS AND METHODSPatients and treatment. Nine male, previously untreated patients with multibacillary leprosy were recruited; all patients had at least one lesion with a bacteriologic index (BI) of >4+ and a morphologic index (MI) of >1% and of sufficient size so that five 6-mm skin punch biopsy specimens could be taken. By clinical evaluation, patients 1 to 3 were classified as borderline lepromatous and patients 4 to 9 were classified as polar lepromatous. Patients ranged from 14 to 56 (median, 31) years in age. Patients had neither a recent history nor signs or symptoms of lepra reactions upon admission. Examination procedures on admission and during the trial were as previously described (1).Patients, who were hospitalized at the Research Institute for Tropical Medicine, Manila, Philippines, for...

Nine previously untreated patients with lepromatous leprosy were treated with 200 mg of sparfloxacin daily for 12 weeks to determine whether this drug is bactericidal for Mycobacterium leprae in humans. The efficacy of therapy was monitored both clinically and by measuring changes in morphological index, mouse footpad infectivity, and the radiorespirometric activity of M. leprae organisms obtained from serial biopsy specimens and also by determining titers of phenolic glycolipid-I in serum. Most patients showed clinical improvement within 2 weeks of treatment; this was accompanied by significant reductions in the morphological index, mouse footpad infectivity, and bacillary radiorespirometric activity. After 4 weeks of treatment, all patients had a morphological index of zero and specimens from most patients were noninfectious for mice, while the median decrease in radiorespirometric activity was >99%v. Overall results by the rapid radiorespirometric assay paralleled those of the mouse footpad and morphological index assays. Sparfloxacin given at 200 mg once daily appears to be rapidly bactericidal in humans, with activity similar to that observed in a previous clinical trial with 400 mg of ofloxacin.Among the fluoroquinolones, only ofloxacin and pefloxacin have been subjected to clinical trials in patients with leprosy (11), and both have displayed potent bactericidal activity. Sparfloxacin is a new fluoroquinolone with superior activity against most gram-positive bacteria (14) and Mycobacterium tuberculosis (16). The recent development of radiorespirometric assays for rapidly assessing the drug susceptibility of Mycobacterium leprae in vitro (5) made possible a comparative study of 20 fluoroquinolones (7). Sparfloxacin (AT-4140) was found to be the most active clinically relevant quinolone; its in vitro activity surpassed those of both pefloxacin and ofloxacin. Comparative studies (versus ofloxacin) in both nude mice (10, 20) and healthy immune-competent mice (6, 9) confirmed the in vitro observations. Considering its favorable plasma half-life of 17 h (13) and efficacy against other intracellular infections, sparfloxacin was chosen for a clinical trial in the treatment of patients with leprosy.A dosage of 200 mg of sparfloxacin given once daily was chosen on the basis of in vitro radiorespirometry (7), activity in the mouse footpad model (6), human pharmacokinetics (13), and the recommendation of the manufacturer.In addition to clinical response, morphological index (MI) and mouse footpad infectivity, this trial was monitored by measuring phenolic glycolipid-I (PGL-I) antigen levels in serum and radiorespirometric determination of the oxidation of palmitic acid by biopsy-derived M. leprae. Serum and biopsy specimens were collected just prior to the initiation of treatment and at 2-week intervals for 8 weeks. BI was determined from skin slit smears from at least six sites. MI (the percentage of solid-staining bacilli) was determined from slides prepared from homogenates of biopsy specimens. MATERIALS AND METHO...