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

1998 ◽  
Vol 42 (5) ◽  
pp. 1115-1120 ◽  
Author(s):  
Baohong Ji ◽  
Samba Sow ◽  
Evelyne Perani ◽  
Christian Lienhardt ◽  
Vimala Diderot ◽  
...  

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.

1996 ◽  
Vol 40 (9) ◽  
pp. 2137-2141 ◽  
Author(s):  
B Ji ◽  
P Jamet ◽  
E G Perani ◽  
S Sow ◽  
C Lienhardt ◽  
...  

Fifty patients with newly diagnosed lepromatous leprosy were allocated randomly to one of five groups and treated with either a month-long standard regimen of multidrug therapy (MDT) for multibacillary leprosy, a single dose of 600 mg of rifampin, a month-long regimen with the dapsone (DDS) and clofazimine (CLO) components of the standard MDT, or a single dose of 2,000 mg of clarithromycin (CLARI) plus 200 mg of minocycline (MINO), with or without the addition of 800 mg of ofloxacin (OFLO). At the end of 1 month, clinical improvement accompanied by significant decreases of morphological indexes in skin smears was observed in about half of the patients of each group. A significant bactericidal effect was demonstrated in the great majority of patients in all five groups by inoculating the footpads of mice with organisms recovered from biopsy samples obtained before and after treatment. Rifampin proved to be a bactericidal drug against Mycobacterium leprae more potent than any combination of the other drugs. A single dose of CLARI-MINO, with or without OFLO, displayed a degree of bactericidal activity similar to that of a regimen daily of doses of DDS-CLO for 1 month, suggesting that it may be possible to replace the DDS and CLO components of the MDT with a monthly dose of CLARI-MINO, with or without OFLO. However, gastrointestinal adverse events were quite frequent among patients treated with CLARI-MINO, with or without OFLO, and may be attributed to the higher dosage of CLARI or MINO or to the combination of CLARI-MINO plus OFLO. In future trials, therefore, we propose to reduce the dosages of the drugs to 1,000 mg of CLARI, 100 mg of MINO, and 400 mg of OFLO.


2008 ◽  
Vol 52 (9) ◽  
pp. 3113-3117 ◽  
Author(s):  
Fe Eleanor F. Pardillo ◽  
Jasmin Burgos ◽  
Tranquilino T. Fajardo ◽  
Eduardo Dela Cruz ◽  
Rodolfo M. Abalos ◽  
...  

ABSTRACT In a clinical trial of moxifloxacin in eight multibacillary leprosy patients, moxifloxacin proved highly effective. In all trial patients, a single 400-mg dose of moxifloxacin resulted in significant killing (P ≤ 0.006) of Mycobacterium leprae, ranging from 82% to 99%, with a mean of 91%. In all instances, no viable bacilli were detected with an additional 3 weeks of daily therapy, this observed rapid bactericidal activity being matched previously only by rifampin. On moxifloxacin therapy, skin lesions cleared exceedingly rapidly with definite improvement observed consistently after eight doses and progressive resolution continuing for the 56 days of the trial. Side effects, toxicities, and laboratory abnormalities were mild, not requiring discontinuation of therapy.


2011 ◽  
Vol 80 (2) ◽  
pp. 742-752 ◽  
Author(s):  
Mehervani Chaduvula ◽  
A. Murtaza ◽  
Namita Misra ◽  
N. P. Shankar Narayan ◽  
V. Ramesh ◽  
...  

ABSTRACTLsr2 protein ofMycobacterium lepraewas shown earlier to elicit B and T cell responses in leprosy patients (20, 28). Lymphoproliferation toM. lepraeand Lsr2 antigens was observed in >70% of tuberculoid (T) patients and in 16 and 34% of lepromatous (L) patients, respectively. We focused on theM. lepraenonresponders in the lepromatous group using 22 synthetic Lsr2 peptides (end-to-end peptides A to F and overlapping peptides p1 to p16) inin vitroT cell responses. A total of 125 leprosy and 13 tuberculosis patients and 19 healthy controls from the area of endemicity (here, healthy controls, or HC) were investigated. The highest responses were observed (67 to 100%) in HC for all peptides except p1 to p3, and the lowest was observed in tuberculosis patients. Significant differences in lymphoproliferation were observed in T, L, and HC groups (analysis of variance [ANOVA],P= 0.000 to 0.015) for all end-to-end peptides except B and for p5 and p7 to p10. Hierarchical recognition between lepromatous and tuberculoid leprosy was noted for p8 (P< 0.05) and between the HC and L groups for p7 to p10, p15, and p16 (P< 0.005 toP< 0.02). Significant lymphoproliferation was observed to peptides A to F and p1 to p9, p11, p12, p15, p16 (P= 0.000 to 0.001) with 40% responding to peptides C and p16 in L patients. Lepromatous patients also showed significantly higher levels of a gamma interferon (IFN-γ) response to peptide C than to other peptides (P< 0.05). Major histocompatibility complex (MHC) class II bias for peptide recognition was not observed. These studies indicate that Lsr2 has multiple T cell epitopes that inducein vitroT cell responses in the highly infective lepromatous leprosy patients.


1997 ◽  
Vol 41 (9) ◽  
pp. 1953-1956 ◽  
Author(s):  
B Ji ◽  
P Jamet ◽  
S Sow ◽  
E G Perani ◽  
I Traore ◽  
...  

Fifty-one lepromatous leprosy patients, all of whom had relapsed after previous dapsone (DDS) monotherapy, were treated between 1990 and 1991 with 600 mg of rifampin (RMP) plus 400 mg of ofloxacin (OFLO) daily for 4 weeks, and the great majority of the patients were followed up at least once a year after completion of the treatment. After only 173 patient-years of follow-up, 5 relapses had been detected; the overall relapse rate was 10.0% (confidence limits, 1.7 and 18.3%), or 2.9 relapses (confidence limits, 0.4 and 5.4) per 100 patient-years. The unacceptably high relapse rate indicated that 4 weeks of treatment with daily RMP-OFLO was unable to reduce the number of viable Mycobacterium leprae organisms to a negligible level. In addition, the M. leprae from one of the relapses were proved to have multiple resistance to DDS, RMP, and OFLO. To avoid further relapses, the follow-up was terminated and the great majority of the patients were retreated with the standard 2-year multidrug therapy from 1994. No further relapse has been diagnosed since the beginning of retreatment.


2004 ◽  
Vol 46 (5) ◽  
pp. 275-277 ◽  
Author(s):  
Om Parkash ◽  
Hari Bhan Singh ◽  
Subha Rai ◽  
Archna Pandey ◽  
Vishwa Mohan Katoch ◽  
...  

We have searched for Mycobacterium leprae DNA for 36kDa protein in urine using a M. leprae specific PCR technique. A limited number of 16 patients (of which 11 belonged to lepromatous leprosy and five to tuberculoid leprosy) and eight healthy individuals were included for the present study. The number of urine samples positive by PCR were 36.4% (4/11) in lepromatous patients and 40% (2/5) in tuberculoid patients. None of the samples from healthy individuals was positive. To our knowledge, the results indicate, for the first time, the presence of M. leprae DNA in urine from leprosy patients. Another important finding obtained out of the study is that amongst treated patients 66.6% (4/6) were positive whereas amongst untreated only 20% (2/10) were positive. From the present indicative data it appears that treatment improves the PCR results with urine as a sample. Thus, the approach could prove to be useful for monitoring the treatment response of individual patients and needs to be further evaluated with a large number of patients.


2005 ◽  
Vol 100 (7) ◽  
pp. 703-707 ◽  
Author(s):  
Nora M Cardona-Castro ◽  
Sandra Restrepo-Jaramillo ◽  
Myriam Gil de la Ossa ◽  
Patrick J Brennan

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