Pharmacotherapy Approaches in Nontuberculous Mycobacteria Infections.

Nontuberculous mycobacteria (NTM) comprise a heterogeneous group of organisms, with only a small subset known to cause disease in humans. Although NTM infection is not a reportable disease, both the increasing clinical recognition and recent advancements in laboratory diagnostic capabilities of NTM infections in immunocompromised and immunocompetent patients are rapidly evolving. We reviewed antimicrobial agents used to treat the most frequently encountered NTM infections and examined optimized drug dosing strategies, toxicity profiles, drug-drug interactions, and the role of therapeutic drug monitoring. Antimicrobial susceptibility testing and patient monitoring on therapy were also examined. We used PubMed to review the published literature on the management of select NTM pathogens, the common syndromes encountered since 2000, and select pharmacokinetic principles of select antimicrobial agents used since 1990. We included select clinical trials, systematic reviews, published guidelines, and observational studies when applicable. The prolonged duration and the necessity for combination therapy for most forms of NTM disease can be problematic for many patients. A multidisciplinary care team that includes pharmacy engagement may help increase rates of optimal patient tolerability and successful treatment completion.

Tuberculosis in an autosomal recessive case of chronic granulomatous disease due to mutation of the NCF1 gene

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[A cutaneous infection by Mycobacterium chelonae in a patient with rheumatoid arthritis]. / Infecção cutânea por Mycobacterium chelonae numa doente com artrite reumatóide.

There are no pathognomonic findings for cutaneous infection caused by Mycobacterium chelonae. The type and duration of therapy varies considerably among reports and no single antibiotic is considered the treatment of choice. A 61-year-old patient, suffering from rheumatoid arthritis (treated with metotrexate and salazopyrine), presented with violaceous nodules of the right leg that had been evolving for 6 months. She was underwent several skin biopsies. Tissue culture of the last showed an atypical mycobacteria, identified as M. chelonae. Despite improvement after a two-week course of treatment with clarithromycin, a switch to ciprofloxacin was made because of gastrointestinal intolerance. After 3 months, only slight improvement of the lesions was achieved and clarithromycin was reintroduced; significant clinical improvement occurred by the third month. Clarithromycin was continued a further two months until the patient quit on her own and. no recurrence was observed. Infections caused by M. chelonae frequently occur in the setting of immunological impairment. Contaminated water is the natural reservoir, but we were unable to establish the source of contamination. As was previously described, there was a significant delay between clinical presentation and diagnosis. Thus, a high index of suspicion and multiple biopsies with culture are of paramount importance to confirming the diagnosis.

Childhood atopy and allergic disease and skin test responses to environmental mycobacteria in rural Crete: a cross-sectional survey.

BACKGROUND: Through its powerful immunoregulatory effects, infection with atypical mycobacteria may exert a protective effect on the development of childhood allergic disease. OBJECTIVE: To examine the relationship between childhood atopy or allergic disease and previous infection with four species of atypical mycobacteria. METHODS: Eight hundred and six children aged 8-18 years and living in rural Crete--most of whom had had previous BCG immunization--underwent skin prick testing with 10 aeroallergens; their parents completed a standardized questionnaire relating to allergic disease. No less than 8 weeks later each child underwent intradermal skin tests with 0.1 mL solutions of four selected mycobacterial reagents (Aviumin C, Gordonin, Chelonin and Ranin I). RESULTS: Twenty-three percent of children were atopic on skin prick testing; far fewer had symptoms of asthma (5%) or hayfever in conjunction with a positive prick test to pollens (2%). Eighty percent of children had positive skin responses to one or more mycobacterial species. Among all children--and those with a BCG scar--there was no association between atopy or allergic symptoms and mycobacterial skin responses; among the few children without a BCG scar however those with positive mycobacterial responses were less likely to be atopic or to report allergic symptoms; these differences were not statistically significant. CONCLUSIONS: Our findings, in a population of BCG-immunized children, do not lend support to the suggestion that infection with atypical mycobacteria is protective against childhood allergic disease.

Role of Mycobacterium xenopi disease in patients with HIV infection at the time of highly active antiretroviral therapy (HAART). Comparison with the pre-Haart period.

BACKGROUND AND SETTING: A reliable and timely clinical, radiological, and bacteriological diagnosis, and an optimal treatment of non-tubercular mycobacteriosis (including Mycobacterium xenopi disease), remain an unanswered challenge for clinicians facing immunocompromised patients, including those with HIV infection. OBJECTIVE: The aim of our survey is to report the frequency, and the epidemiological, immunological, microbiological, clinical, and therapeutic features of all confirmed HIV-associated M. xenopi disease observed from 1993-2002, with special attention paid to eventual differences that emerged after the introduction of potent antiretroviral therapy (highly active antiretroviral therapy, HAART), on the basis of an international literature update. DESIGN AND RESULTS: Our series of 17 consecutive confirmed M. xenopi infections retrieved in 14 out of 3000 patients followed for HIV disease complications raises a broad series of clinical, diagnostic, therapeutic, and prophylactic concerns. The great majority of M. xenopi disease involved the lower respiratory tract, but atypical features including cavitation and prominent exudative features became apparent in patients successfully treated with HAART, pointing out the possible role of the so-called immune reconstitution syndrome in these episodes. CONCLUSIONS: Diagnostic problems represented by late or missed identification due to slow culture and frequently concomitant opportunistic disorders, join therapeutic difficulties due to the unpredictable in vitro antimicrobial susceptibility profile of these organisms, selection of treatment and chemoprophylaxis according with clinical-radiological and microbiological suspicion, and concomitantly administered medications.

Clinical trial of clarithromycin for cutaneous (disseminated) infection due to Mycobacterium chelonae.

OBJECTIVE: To determine if clarithromycin monotherapy is safe and effective in treating cutaneous disease (especially disseminated disease) due to Mycobacterium chelonae (formerly M. chelonae subspecies chelonae). DESIGN: An open, noncomparative trial of clarithromycin as single-drug therapy. SETTING: Nationwide referrals. PATIENTS: Culture-positive patients whose M. chelonae came from a cutaneous source and whose isolate was submitted to a single referral laboratory for susceptibility testing. INTERVENTION: Clarithromycin, 500 mg twice a day by mouth for 6 months. No attempt was made to alter use of immunosuppressive drugs. MAIN OUTCOME MEASURES: Acid-fast bacilli smears and cultures of skin lesions during and after treatment, with monitoring of clinical response, side effects, and development of new lesions. RESULTS: Fourteen patients (10 with disseminated disease) were enrolled in the study and completed at least 3 months of therapy. Underlying diseases included rheumatoid arthritis, other autoimmune disorders, and organ transplantation. All were taking corticosteroids (93%) or cyclophosphamide (7%). All patients had an excellent response to therapy, with only mild side effects from the drug. Two patients died of other diseases after improving clinically but while still taking medication. One noncompliant patient who prematurely discontinued therapy after 3.5 months relapsed 1 month later with an isolate resistant to clarithromycin. The remaining 11 patients have all completed therapy given for a mean of 6.8 months (range, 4.5 to 9 months). Therapy has been discontinued for 9 of the 11 patients for at least 6 months (mean, 7.1 months; range, 6 to 12 months), with no evidence of relapse. No remaining patient had positive acid-fast bacilli smears or cultures of skin lesions after 1 month of therapy. CONCLUSIONS: Clarithromycin may be the drug of choice for cutaneous (disseminated) disease due to M. chelonae, although more patients with long-term clinical follow-up need to be studied.

[The importance of the infective dose, nutritional value of the feed and vitamin content for the susceptibility in pigs to Mycobacterium intracellulare]. / Význam infekcní dávky, nutricní hodnoty krmiva a obsahu vitamínu pro vnímavost prasat k mycobacterium intracellulare.

The influence of infectious dose and nutrition on the pig susceptibility to Mycobacterium intracellulare, serotype 4, 8, was studied with 48 pigs--crossbreds LW X X L--divided into four equal groups. All groups of pigs were fed ad libitum by the mixture consisting of maize, wheat, barley, soybean meal, salt lick and MKP 1 mineral feed supplement. Individual groups were given different levels of meals of animal origin and biofactor supplements containing vitamins A, D2, B2, B12 and niacin. Single per os administration of the infectious dose of Mycobacterium intracellulare amounted to 0.01 or 0.1 mg of mycobacterial culture per one kg of live weight. The extent of patho-anatomical findings depended on the infection intensity. The infectious dose of 0.01 mg of the culture resulted in the changes in the form of exudative lymphadenitis with characteristic caseous degeneration in lymphatic glands only in three out of 24 pigs, i. e. in 12.5%. A tenfold dose of mycobacteria caused caseous lesions in the mandibular and intestinal glands in 50% out of 22 infected animals. The result of complex examination of the lymph glands proves the favourable effect of biofactor supplement on the resistance in pigs, particularly those infected with lower mycobacterial doses. Mycobacteriosis was proved in all experimental pigs fed the mixture containing no biofactor supplement. In the group of animals fed the mixture with biofactor supplement the result was positive in 66.6% of infected animals. It was observed that the biofactor supplement also had a positive influence on active excretion of M. intracellulare by faeces. In pigs infected with high dose of mycobacteria this excretion was proved in 27.2% of animals. In the pigs fed the mixture containing biofactor supplement, regardless of the infectious dose and amount of animal proteins, no elimination of mycobacteria by faeces was observed. Out of 14 pigs with the microscopic finding of tuberculosis in the lymph glands, the reaction with an induration diameter larger than 10 mm was found in eight animals, i. e. 57.2%, after intradermal tuberculinization with purified avian tuberculin after 74 days from infection.