Clinical trial of fusidic acid for lepromatous leprosy

Abstract

Fusidic acid was assessed for antileprosy activity in nine lepromatous leprosy patients. Patients received fusidic acid at either 500 mg/day for 12 weeks or 750 mg/day for 4 weeks followed by 500 mg/day for 8 weeks. All patients showed time-dependent clinical improvement and decreases in bacillary morphological index, radiorespirometric activity and PCR signal, and in serum phenolic glycolipid I. Fusidic acid appears to be a weakly bactericidal antileprosy agent which may have a role in the multidrug treatment of leprosy pending an evaluation of lepra-reaction-suppressive activity. 64 ,ug/ml (11, 18, 23) and, when combined with ethambutol, against some Mycobacterium avium complex strains (18).Fusidic acid is active against Mycobacterium leprae both in axenic medium and in macrophage culture as determined in the BACTEC 460 system (50% inhibition at 1.25 to 2.5 ,ug/ml) (9). An earlier attempt to detect antileprosy activity of fusidic acid in the mouse footpad was unsuccessful (7), possibly because of poor absorption of this compound in mice (14).On the basis of the in vitro activity against M. leprae and human pharmacokinetic properties, a clinical trial of filmcoated sodium fusidate (Fucidin; Leo Pharmaceutical) was conducted with lepromatous leprosy patients. In addition to clinical response, morphological index (MI), and mouse footpad infectivity, patient response was also monitored by measurement of serum phenolic glycolipid I antigen as well as radiorespirometry (10) The patients were hospitalized and received either (i) 500 mg of fusidic acid daily for 8 weeks (patients 1 to 5) or (ii) 750 mg of fusidic acid daily for 4 weeks followed by 500 mg daily for 4 weeks (patients 6 to 9). For all patients, this treatment was followed by an additional 4 weeks of administration of 500 mg of fusidic acid daily as outpatients in order to evaluate the clinical response further.The degree of clinical improvement was assessed according to previously described criteria (3). Serum and 6-mm skin punch biopsy samples were collected just prior to initiation of treatment and at 2-week intervals for 8 weeks. Part of each biopsy sample was processed for mouse footpad assay, radiorespirometry, and MI. The remaining portion was processed separately for PCR. The BI was determined from skin slit smears from at least six sites.The procedure of Cho et al. (6) for measuring phenolic glycolipid I antigen levels was followed. Scoring was based on the relative intensity of color development from the reaction of peroxidase with 4-chloro-1-naphthol.The infectivity for mice of 5, 50, 500, or 5,000 acid-fast bacilli (AFB) from skin biopsy homogenates was determined as previously described (3

Transmission of Leprosy: A Study of Skin and Nasal Secretions of Household Contacts of Leprosy Patients Using PCR

“…Earlier studies have shown that PCR positivity associated with M. leprae from skin biopsies from patients receiving successful anti-leprosy therapy was reduced significantly as early as 2 months after initiating therapy. 11,18 Similarly, in our study, successful treatment of MB patients for 1 year showed reductions in PCR reactivity from both sites sampled, suggesting that neither nasal secretions nor skin are likely portals of exit for M. leprae from patients receiving appropriate therapy. Earlier time points, ranging from 1 to 3 months, showed minor reductions in PCR positivity rates from both skin washings and nasal secretions.…”

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

“…The rationale for testing CLARI, MINO, OFLO, and SPFX in clinical trials derived from their promising bactericidal effects in mice. Fusidic acid probably is the only drug which was said to be inactive against M. leprae in mice but exhibited a weak bactericidal activity against M. leprae in a human trial (7); nevertheless, its inactivity in mice has not been documented by the investigator and has yet to be confirmed by others. On the other hand, because the pharmacokinetics of the drugs and the pathogenesis of M. leprae infection in mice are quite different from those in patients, the potential lead of a new drug or a new treatment identified in the mouse footpad system must be evaluated in clinical trials before moving toward field application.…”

Detection of gene mutations related with drug resistance inMycobacterium lepraefrom leprosy patients using Touch-Down (TD) PCR

“…Because of the cumbersome nature of this drug screening method, comprehensive estimates of drug resistance in leprosy have been difficult to obtain. A widely used indirect measure of drug‐resistant M. leprae is the radiometric analysis [3,4]. This method also has many disadvantages with regard to time, expense, and characterization of resistant mechanism for anti‐leprosy drug.…”