Powerful Bactericidal Activity of Moxifloxacin in Human Leprosy

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.Fluoroquinolones have proven to be active against Mycobacterium leprae in rodents (10,13,18,20,31) and in clinical trials (9,19,26) in leprosy patients. The first studies of fluoroquinolones in M. leprae-infected mice found that ciprofloxacin was inactive while pefloxacin and ofloxacin were bactericidal (18,20). We (13) tested several fluoroquinolones against M. leprae in mice, finding some, namely WIN5727, temafloxacin, and particularly sparfloxacin, to be superior to pefloxacin and ofloxacin. Furthermore, in the heavily infected, neonatally thymectomized Lewis rat, the combination of rifampin and ofloxacin was more regularly sterilizing than the combinations of both rifampin plus dapsone and rifampin plus clofazimine (10), rifampin, dapsone, and clofazimine being the three components of the widely implemented WHO-recommended regimens for treatment of multibacillary (MB) leprosy (36, 37). Clinical trials of pefloxacin and ofloxacin treatments in leprosy have demonstrated encouraging clinical responses and the clearance of viable M. leprae within 2 months (9,19,26), this rate of clearance being higher than those with dapsone and clofazimine (several months [32]), similar to those with minocycline (8, 12) and clarithromycin (3), but much lower than that with rifampin (29,32,34).Moxifloxacin against Mycobacterium tuberculosis (6, 14, 23, 25) has been found to be more bactericidal in vitro than other quinolones and similar in bactericidal activity to rifampin. Also, moxifloxacin has been demonstrated in a murine model of tuberculosis to add to the sterilizing activities of isoniazid, rifampin, and pyrazinamide (27) and to provide significant bactericidal activity in the first few days of treatment of human tuberculosis, both as monotherapy (17,24,28) and as multidrug therapy (2, 15). As a result, trials with moxifloxacin treatment of active pulmonary tuberculosis are currently in progress, using it to both replace established agents and shorten the course of effective therapy of active pulmonary tuberculosis.In a murine model of leprosy, moxifloxacin has been demonstrated to be more bactericidal than ofloxacin and, in that regard, as potent as rifampin (5). Because the 1-year WHO regimen (37) for MB leprosy is still quite lengthy, some studies have foun...

Comparison of Effectiveness between Rifampicin Ofloxin-Minocycline Regimen and Multidrug Therapy-World Health Organization in Multibacillary Leprosy Patients

“…9 The ROM regimen has a higher price with less side effects (nausea and vomiting), with once in a month drug consumption, making it more simple for the patients compare to MDT-WHO regimen which needs to be consumed every day with more side effects (skin hyperpigmentation, hemolytic anemia, methemoglobinemia, hypersensitivity reaction), but given freely. 10 Based on those considerations, occupations might be considered as an influencing factor in choosing leprosy medication regimen, therefore a further study needs to be conducted to prove this.…”

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

“…Early bactericidal activity trials were developed to test various antibiotics [27,78,79,[91][92][93][94]. Other studies were developed to test the drugs in small samples of patients.…”

Quinolones for mycobacterial infections

“…A small clinical study from the Philippines [7] investigated eight patients with multibacillary leprosy who were given moxifloxacin 400 mg once daily. In all eight patients, a single 400 mg dose of moxifloxacin resulted in significant killing (P < 0.006) of M. leprae, ranging from 82% to 99%, with a mean of 91%.…”