Effect of Clarithromycin Regimen for Mycobacterium avium Complex Pulmonary Disease

Abstract

We have investigated the efficacy of a clarithromycin-containing four-drug regimen for Mycobacterium avium complex (MAC) pulmonary disease in 46 patients without acquired immunodeficiency syndrome (AIDS). The patients were 14 males and 32 females with a mean age of 60.9 +/- 11.5 yr. Patients received 10 mg/kg/d of clarithromycin plus ethambutol, rifampin, and initial kanamycin and subsequent quinolone for 24 mo. Seven patients (15.2%) were dropped in the first 6 mo. Among 39 patients who received more than 6 mo of therapy, 28 patients (71.8%) converted their sputa to negative: 26 of 31 patients (83.9%) infected with clarithromycin-susceptible strains and two of eight patients (25.0%) with resistant or intermediate strains. The timing of sputum conversion was 3.6 +/- 1.9 mo, with a range of 2 to 9 mo. The conversion rate was significantly lower in patients who were infected with clarithromycin-resistant or intermediate strains, who had had prior therapy (55.0% versus 89.5%), or who were acid-fast bacilli (AFB) smear-positive at entry (60.7% versus 100%). The age and sex of patients, the species of pathogen (M. avium or M. intracellulare), type and extent of the disease, and the use of kanamycin did not significantly affect the conversion rate. Although the regimen was efficacious for newly treated patients, frequent adverse reactions and a low conversion rate of sputum in retreated patients are problems that remain to be solved.

The Effect of Combined Therapy According to the Guidelines for the Treatment of Mycobacterium avium Complex Pulmonary Disease

“…However, there were no significant differences among the three groups of 400 mg/day, 600 mg/day and 800 mg/day CAMregarding the appearance rate of adverse reactions. Because the overall appearance rate of adverse reactions (24%) was almost the same as that of other reports (14,19), there were no problems concerning the safety of the CAM-containing four-drug regimen according to both guidelines.…”

“…In previous reports (14), the conversion rate was significantly higher in smear-negative, newly diagnosed and restricted lesion cases. In the long prospect, however, there is no guarantee that relapse will never occur after completion of the initial treatment, due to underlying diseases, including preexisting lung disorders and unknownfactors common to elderly patients (17).…”

“…Subsequently, the sputum conversion rate was significantly higher than that in our study (92% compared with 58%). Secondly, Tanaka et al (14) reported the efficacy of a four-drug regimen including CAM, RFP, EB, and initial aminoglycoside (KM) in Japan. They used 10 mg/kg/day of CAMand the dose of CAMin their study was similar to our protocol.…”

“…In our study, the sputum relapse rate was high (39%) even if the therapy according to both guidelines was performed. Considering the results in the study by Tanaka et al (14) in which the CAM-containing four-drug regimen was continued for at least two years for MACpulmonary disease, it is still not definite when to start and stop therapy. Because the method of assessment was restricted to the sputum conversion rate of MAC strains before and after the treatment in the previous reports, we think it is difficult to evaluate the whole clinical effect of patients treated by the assessment.…”

Molecular characterization and drug susceptibility profile of a Mycobacterium avium subspecies avium isolate from a dog with disseminated infection

“…Currently, however, due to a discrepancy between in vitro and in vivo MAC susceptibility to most antimicrobials, the Clinical and Laboratory Standards Institute (CLSI) recommends antibiotic sensitivity testing of human MAC isolates only for macrolides (CLSI, 2011). Indeed, macrolide monotherapy is the only treatment for which a correlation between in vitro MAC susceptibility and human clinical response has been demonstrated in controlled trials (Chaisson et al, 1994;Tanaka et al, 1999;Wallace et al, 1996). To the best of our knowledge, antimicrobial susceptibility testing of slow-growing NTM isolates from dogs has not been previously described in the literature.…”