Bactericidal Activity of a Single-Dose Combination of Ofloxacin plus Minocycline, with or without Rifampin, against Mycobacterium leprae in Mice and in Lepromatous Patients

Abstract

To develop a fully supervisable, monthly administered regimen for treatment of leprosy, the bactericidal effect of a single-dose combination of ofloxacin (OFLO) and minocycline (MINO), with or without rifampin (RMP), against Mycobacterium leprae was studied in the mouse footpad system and in previously untreated lepromatous leprosy patients. Bactericidal activity was measured by the proportional bactericidal method. In mouse experiments, the activity of a single dose of the combination OFLO-MINO was dosage related; the higher dosage of the combination displayed bactericidal activity which was significantly inferior to that of a single dose of RMP, whereas the lower dosage did not exhibit a bactericidal effect. In the clinical trial, 20 patients with previously untreated lepromatous leprosy were treated with a single dose consisting of either 600 mg of RMP plus 400 mg of OFLO and 100 mg of MINO or 400 mg of OFLO plus 100 mg of MINO. The OFLO-MINO combination exhibited definite bactericidal activity in 7 of 10 patients but was less bactericidal than the RMP-OFLO-MINO combination. Both combinations were well tolerated. Because of these promising results, a test of the efficacy of multiple doses of ROM in a larger clinical trial appears justified.

Update on the epidemiology, diagnosis, and treatment of leprosy

“…They can be administered to patients presenting with an intolerance, resistance, or clinical failure to first-line agents. Patients presenting with rifampicin-resistant leprosy need to take those antibiotics daily, and treatment duration must be extended to 24 months because of a lower bactericidal activity compared with rifampicin [33,59].…”

Considerations on clinical trials of leprosy treatment: need of novel drug combinations

“…In vitro experiments demonstrated that fusidic acid is highly bactericidal [97]; but in a Phase II trial, it was only weakly bactericidal [93]. Likewise, Ji et al observed bactericidal activity in mice after 1 month of MDT (99.95%) were similar to that with a single dose of RFM, clarithromycin, OFL and MIN (99.4%) [74]. However, single-dose ROM treatment has been insufficient in humans [87].…”

“…Either no information on the comparable characteristics of the volunteer participants at intake was included, or the study groups were significantly different upon enrollment in some of the key end points evaluated. The study by Ji et al is a case in point: the mean patient MI in the group receiving ROM was significantly smaller than the one receiving OFL-MIN (p = 0.001) [74].…”

“…Screening of antibiotics known to be safe and well tolerated for their in vitro bactericidal effect against M. leprae [73,74], such as some fluoroquinolones, tetracyclines and macrolides, made possible the formulation of new regimens that have been tested in several trials (Table 3). Franzblau and White compared the in vitro activities of 20 fluoroquinolones against M. leprae and reported that OFL had excellent bactericidal activity, whereas pefloxacin and temofloxacin could have potential for treating clinical leprosy [73].…”

Performance of PCR-reverse blot hybridization assay for detection of rifampicin-resistant Mycobacterium leprae

“…Leprosy is a chronic infectious disease caused by Mycobacterium leprae and mainly affects the skin and peripheral nerves. In addition, Leprosy is a major global health problem in several countries of Asia, Latin America, and Africa (Ji et al, 1998;Maeda et al, 2001). Leprosy is effectively controlled by a multidrug therapy (MDT) regimen of dapsone, rifampicin, and clofazimine.…”