minocycline and Mycobacterium-avium-intracellulare-Infection

We report a case of cutaneous atypical mycobacteriosis in a 12-year-old healthy girl due to Mycobacterium avium. The cutaneous symptoms were three well-defined subcutaneous nodules on both buttocks and on the posterior surface of the left thigh. One had a fistulous opening on the skin surface. Histopathological examination revealed epithelioid cell granulomas surrounded by dense lymphocytic infiltration and acid-fast bacteria were seen with modified periodic acid-carbol fuchsin staining. Using Ogawa's medium at 37 degrees C, acid-fast bacteria were isolated from the biopsied specimen and identified by the DNA-DNA hybridization method as Mycobacterium avium. In drug susceptibility test, these were resistant to all antituberculous drugs. Oral administration of minocycline 100 mg/day for two months had little effect on the two remaining lesions, which were therefore excised. Based upon reported cases of Mycobacterium avium complex, we considered that our pediatric patient with multiple intradermal or subcutaneous nodules on the buttocks and the thigh exhibited the characteristic symptoms of M. avium infection.

Topics: Administration, Oral; Anti-Bacterial Agents; Antitubercular Agents; Buttocks; Child; Coloring Agents; Cutaneous Fistula; DNA, Bacterial; Drug Resistance, Microbial; Female; Granuloma; Humans; Lymphocytes; Minocycline; Mycobacterium avium; Mycobacterium avium-intracellulare Infection; Periodic Acid; Phenols; Rosaniline Dyes; Skin Diseases, Bacterial; Tetracycline Resistance; Thigh

An open clinical trial for the treatment of Mycobacterium avium intracellulare complex (MAIC) lung disease in human immunodeficiency virus (HIV)-seronegative patients.. To assess the efficacy and tolerance of clarithromycin (0.75-2 g/day) combined with minocycline (200 mg/day) and clofazimine (100 mg/day) for 15 months.. The study was carried out from August 1992 to June 1994 by pulmonologists of various French medical centres. The patients to be enrolled were of either sex, over 18 years of age, HIV-seronegative and suffering from MAIC lung disease, with a confirmed bacteriological and radiological diagnosis. Examinations were to be performed after 1, 2, 3, 6, 9, 12 and 15 months of treatment.. Thirty patients were included, 16 males and 14 females. Eight did not complete the study due to deviations from protocol or adverse effects. The remainder completed the study with a post-treatment follow-up of 27 +/- 7 months. Among the 22 evaluable patients, 18 had a history of lung disease. Tolerance to the drugs was generally good, apart from three cases of hepatic disturbances and three cases of ototoxicity, which required a decrease in clarithromycin dosage after a short interruption of treatment. There were 14 treatment successes, seven treatment failures, defined by absence of bacteriologic conversion, and in one patient the disease evolution remains uncertain.. The combination of clarithromycin with minocycline and clofazimine proved effective with persistently negative cultures in 64% of the patients, and an overall good drug tolerance.

Topics: Adult; Aged; Anti-Bacterial Agents; Clarithromycin; Clofazimine; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV Seronegativity; Humans; Male; Middle Aged; Minocycline; Mycobacterium avium-intracellulare Infection; Treatment Outcome; Tuberculosis, Pulmonary

No treatment was established for disseminated M. avium intracellulare (MAC) infection, a common disease of end stage of AIDS. An open study was conducted to assess in 173 AIDS patients, the activity of clarithromycin. Initial bacteriologic eradication from blood was observed in 136/147 evaluable patients (93%). Acquired resistance to clarithromycin associated with relapse appeared to develop after 2 to 7 months of drug treatment in 31/136 patients with initial success. Early bacteriological relapse was associated with clinical deterioration. Side effects of drug treatment were elevated liver enzymes (26%) and impaired hearing (4%). Side effects conducted to stop treatment in 14 cases (8%) to modified treatment in 8 cases (5%). Our study gave new argues for activity of clarithromycin in disseminated MAC infection.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antitubercular Agents; Child; Clarithromycin; Clofazimine; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Fluoroquinolones; Hearing Disorders; Humans; Liver Function Tests; Male; Middle Aged; Minocycline; Mycobacterium avium-intracellulare Infection; Recurrence; Treatment Outcome

Our aim was to identify the pharmacokinetic/pharmacodynamic parameters of minocycline in the hollow-fibre system (HFS) model of pulmonary Mycobacterium avium complex (MAC) and to identify the optimal clinical dose.. Minocycline MICs for 55 MAC clinical isolates from the Netherlands were determined. We also co-incubated primary isolated macrophages infected with MAC with minocycline. Next, we performed a 28 day HFS-MAC model dose-response study in which we mimicked pulmonary concentration-time profiles achieved in patients. The HFS-MAC model was sampled at intervals to determine the minocycline pharmacokinetics and MAC burden. We identified the AUC0-24/MIC ratios associated with 1.0 log10 cfu/mL kill below day 0 (stasis), defined as a bactericidal effect. We then performed 10000 Monte Carlo experiments to identify the optimal dose for a bactericidal effect in patients.. The MIC for 50% and 90% of cumulative clinical isolates was 8 and 64 mg/L, respectively. Minocycline decreased MAC bacterial burden below stasis in primary isolated macrophages. In the HFS-MAC model, minocycline achieved a microbial kill of 3.6 log10 cfu/mL below stasis. The AUC0-24/MIC exposure associated with a bactericidal effect was 59. Monte Carlo experiments identified a minocycline susceptibility MIC breakpoint of 16 mg/L. At this proposed breakpoint, the clinical dose of 200 mg/day achieved the bactericidal effect exposure target in ∼50% of patients, while 400 mg/day achieved this in 73.6% of patients, in Monte Carlo experiments.. Minocycline at a dose of 400 mg/day is expected to be bactericidal. We propose a clinical trial for validation.

Topics: Algorithms; Anti-Bacterial Agents; Bayes Theorem; Cell Line; Humans; Macrophages; Microbial Sensitivity Tests; Minocycline; Models, Biological; Monte Carlo Method; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Pneumonia, Bacterial