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PubMed1992

An animal model of Mycobacterium avium complex disseminated infection after colonization of the intestinal tract.

Mycobacterium avium complex infections occur in 30%-80% of patients with AIDS. Recent evidence supports the gastrointestinal tract as the source of M. avium. Although a reproducible animal model exists, a model more closely resembling the infection in AIDS patients is needed to answer pertinent questions regarding response to therapy and prophylaxis. Beige mice were infected orally (1 x 10(8) or 1 x 10(4) cfu, five doses), and consistent, reproducible disseminated infections after 4 and 8 weeks, respectively, were obtained. Bacteremia was observed in none to 70% of the animals depending on the strain used, and mortality ranged from none to 33%, also depending on the strain used. Concomitant ingestion of ethanol (4% of daily dietary calories) was associated with a significant increase in the number of viable bacteria recovered from liver, spleen, and appendix compared with animals not receiving ethanol. The orally infected animal model closely resembles M. avium infection in humans and may be important in investigating prophylaxis and therapy of this infection.

Acquired Immunodeficiency Syndrome↗

PubMed1989

Comparative in-vitro activity of twenty antimicrobial agents against clinical isolates of Mycobacterium avium complex.

The in-vitro susceptibility of Mycobacterium avium complex isolates, obtained from immunosuppressed patients with and without the Acquired Immunodeficiency Syndrome (AIDS), to various antimicrobial agents was determined. Amikacin, the 4-quinolone compounds--ciprofloxacin, temafloxacin and PD 117558--and the penem SCH 34343 were active against most of the isolates. In-vitro synergism using selected antimicrobial combinations could not be demonstrated. No differences in the susceptibility, depending upon the source of the isolates (AIDS or non-AIDS), were noted.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

Current strategies for the prevention and treatment of disseminated Mycobacterium avium complex infection in patients with AIDS.

Disseminated Mycobacterium avium complex (MAC) infection is a common opportunistic disease in patients with acquired immunodeficiency syndrome and is associated with significant morbidity and mortality. Macrolides effectively prevented and treated the disease in clinical trials. In general, prophylaxis with clarithromycin or azithromycin is indicated for patients with CD4 cell counts below 50 cells/mm3. Treatment of disseminated MAC infection is lifelong and must include two agents with antimycobacterial activity. Clarithromycin plus ethambutol is considered the standard regimen. Potential alternatives are azithromycin, rifabutin, ciprofloxacin, clofazamine, and amikacin. Several factors influence drug selection, such as the patient's immune status, evidence of treatment safety and efficacy, drug interactions, and potential for resistance.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

[Mycobacterium avium complex infections: the point on the treatments].

Mycobacterium avium complex (MAC) infections are the most frequent opportunistic infections in AIDS. Since progress in antiretroviral drugs enables AIDS patients to survive longer, these infections involve an increasing number of sick people. Few controlled assays have evaluated the efficiency of several antibiotics. When used in monotherapy, clarithromycin (one gram twice a day) appeared as the most efficient drug while the effectiveness of azithromycin, clofazimine, rifampin and liposomal encapsulated gentamicin have not been truly proved. Due to its bacteriologic and clinical effects, the most interesting polytherapeutic scheme is the association of clarithromycin (1 g twice a day), ethambutol (15 mg per kg and per day) and rifabutin (600 mg per day).

AIDS-Related Opportunistic Infections↗

PubMed1994

Autopsy findings in AIDS patients with Mycobacterium avium complex bacteremia.

To study the pathogenesis of Mycobacterium avium complex (MAC) bacteremia, the extent of organ involvement was determined in a retrospective cohort of 44 AIDS patients with MAC bacteremia and complete autopsies between 1988 and 1992. Clinical and microbiologic histories were reviewed and lymph nodes, spleen, liver, bone marrow, small intestine, and colon from each autopsy were systematically evaluated for the presence of mycobacteria or foamy histiocytes. Of the patients, 30% had no histologic evidence of MAC. In the remaining 70%, reticuloendothelial and gastrointestinal involvement was most common, but the number and distribution of involved sites was highly variable. The risk of developing detectable histologic involvement was related to the duration of bacteremia. In contrast to the prevailing concept, our data suggest that MAC bacteremia may precede widespread tissue disease.

AIDS-Related Opportunistic Infections↗

PubMed1992

Use of DNA probes to detect Mycobacterium intracellulare and "X" mycobacteria among clinical isolates of Mycobacterium avium complex.

A mycobacterial DNA probe (designated X) was recently developed to help identify Mycobacterium avium complex (MAC) isolates that are nonreactive with probes specific for M. avium or Mycobacterium intracellulare. The prevalence of X probe-positive mycobacteria in clinical specimens and their role in causing disease is unknown. Using a DNA probe kit that includes the X probe, we characterized 100 consecutive clinical MAC isolates as M. avium, M. intracellulare, or X. Lysates from 81 of the isolates reacted with the M. avium probe, 13 with the M. intracellulare probe, 3 with the X probe, and 3 failed to hybridize with any of the probes. All three X-positive isolates were recovered from sputa of patients who were recent immigrants to the United States and who presented with hemoptysis. One isolate was from a Hispanic man infected with human immunodeficiency virus type 1 (HIV-1) and the other 2 were from Filipino patients with no HIV-1 risk factors. This study also showed a higher than expected number of M. intracellulare isolates from blood and cerebrospinal fluid of HIV-1-infected patients.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Clinical and epidemiological correlates of genotypes within the Mycobacterium avium complex defined by restriction and sequence analysis of hsp65.

Species identification of isolates of the Mycobacterium avium complex (MAC) remains a difficult task. Although M. avium and Mycobacterium intracellulare can be identified with expensive, commercially available probes, many MAC isolates remain unresolved, including those representing Mycobacterium lentiflavum as well as other potentially undefined species. PCR restriction analysis (PRA) of the hsp65 gene has been proposed as a rapid and inexpensive approach. We applied PRA to 278 MAC isolates, including 126 from blood of human immunodeficiency virus (HIV)-infected patients, 59 from sputum of HIV-negative patients with chronic obstructive pulmonary disease, 88 from environmental sources, and 5 pulmonary isolates from a different study. A total of 15 different PRA patterns were observed. For 27 representative isolates, a 441-bp fragment of the hsp65 gene was sequenced; based on 54 polymorphic sites, 18 different alleles were defined, including 12 alleles not previously reported. Species and phylogenetic relationships were more accurately defined by sequencing than by PRA or commercial probe. The distribution of PRA types and, by implication, phylogenetic lineages among blood isolates was significantly different from that for pulmonary and environmental isolates, suggesting that particular lineages have appreciably greater virulence and invasive potential.

Bacterial Proteins↗

PubMed2004

[Distribution of PRA patterns of clinical isolates of the Mycobacterium avium complex from Spain and South America].

Mycobacterium avium complex (MAC) infections are the most frequent systemic infections associated with advanced AIDS. DNA probes for accurate identification of mycobacteria are available but are very expensive in many Latin American settings. Consequently, most Latin American diagnostic laboratories employ inaccurate and outdated tests for mycobacteria identification. Therefore, PCR restriction analysis (PRA) of the hsp65 gene was evaluated for the identification of 163 MAC human isolates originated from Spain and South America. The predominant PRA type in each country was: M. avium type I in Argentina (23/42, 55%) and Brazil (48/72, 67%), M. avium type II in Spain (18/26, 69%) and M. avium type III in Colombia (10/23, 43%). The Colombia frequency is noteworthy, since the PRA type III was quite infrequent in the other three countries. Furthermore, its presence has not been reported outside the Americas. The advantages and disadvantages of PRA in diagnostic mycobacteriology are discussed.

Humans↗

PubMed2026

Prospective outcomes of adults with speciated Mycobacterium avium complex lung disease, 2021-2026.

RATIONALE: Mycobacterium avium complex lung disease (MAC-LD) is clinically heterogeneous and carries diverse outcomes. OBJECTIVES: To describe predictors of clinical progression of MAC-LD in a state-wide cohort. METHODS: We enrolled adults with MAC-LD from across Virginia, USA starting in 2021. Every 6 months we performed respiratory quality of life questionnaire, scored CT scans, and recorded respiratory mycobacterial cultures including MAC speciation. Outcomes were classified using NTM-NET consensus definitions, factors predicting clinical progression analyzed by Poisson regression, and hierarchical clustering on principal components derived from Factorial Analysis of Mixed Data. MEASUREMENTS AND MAIN RESULTS: Of 105 participants the median follow-up was 917 days. Mean age was 69.8 years, 79 (75%) were women, and 70 (67%) had nodular bronchiectasis. M. intracellulare was the most common species, present in 48 (46%) participants at enrollment, followed by M. avium (29, 28%), and M. intracellulare subspecies chimaera (11, 10%). Only 2 (9%) of 22 evaluable participants met the NTM-NET definition of cure. In all participants after multivariable adjustment, older baseline age (incidence rate ratio 1.03 [1, 1.06], p = 0.04) and fibrocavitary CT scan pattern (2.57 [1.33, 4.96], p = 0.005), were associated with unfavorable 12-month clinical progression. Species type and species persistence contributed to characteristics of three distinct phenotypes of MAC-LD of varying severity and clinical progression. CONCLUSIONS: The majority of participants were not assessable for MAC-LD treatment outcomes using strict NTM-NET definitions. Species informed phenotypes of MAC lung disease are prognostically useful and can inform routine management and trial design.

M. intracellulare↗

PubMed1993

Exposure to ethanol up-regulates the expression of Mycobacterium avium complex proteins associated with bacterial virulence.

Mycobacterium avium complex (MAC) organisms are the most common bacterial cause of disseminated infection in patients with AIDS. MAC, facultative intracellular bacteria, invade and multiply within macrophages. Treatment of MAC-infected macrophages with ethanol (10-100 micrograms/dL) is associated with increased intracellular multiplication of MAC. To investigate whether this enhanced growth is due to a stress-related response induced by nonlethal concentrations of ethanol, strain 101 (serovar 1) was exposed to ethanol, and the regulation of the expression of proteins was examined. Exposure of MAC to ethanol (range, 10-100 micrograms/dL) was associated with up-regulation of the expression of a number of bacterial proteins, some of which (65 and 33 kDa) interfered with macrophage functions, such as production of superoxide anion and killing of Staphylococcus aureus. Thus, exposure of MAC to small concentrations of ethanol may induce a stress-related response with consequent increase in the synthesis of proteins possibly associated with its ability to survive within macrophages.

Bacterial Proteins↗

PubMed1989

[Cross-resistance relationships of antituberculosis drugs in Mycobacterium avium complex].

At present, infection caused by Mycobacterium avium complex is usually treated by chemotherapy of antituberculosis drugs. However, cross-resistance relationships of antituberculosis drugs in the M. avium complex have not yet been studied. In the present study, we studied on this subject using three strains which were isolated from sputum specimens of patients who were not treated by any antituberculosis drugs: strain 13008 (serotype 20), strain 13016 (serotype 4) and strain 13034 (serotype 18). The methods used for isolating mutants resistant to rifampicin, isoniazid, ethambutol, streptomycin, kanamycin and/or enviomycin were described previously (Tsukamura, M: Kekkaku 62: 445-458, 1987). Mutants resistant to ethionamide were isolated from strains 13008 and 13016 at a rate of 10(-6) and mutants resistant to kitasamycin at a rate of 10(-5) to 10(-6) (these were not isolated from strain 13034). In contrast, mutants resistant to minocycline were isolated from strain 13034 only at a rate of 10(-4). Susceptibility testings to antituberculosis drugs were carried out as follows. Bacterial suspensions, 10 mg wet weight/ml, were prepared from ten day-old cultures of the strains growing on Ogawa egg medium slants. Each 0.02 ml-sample of the suspensions was inoculated onto Ogawa egg medium with or without a drug by a spiral loop. The media inoculated were incubated at 37 degrees C for 14 days. Minimal inhibitory concentration was determined as a concentration, on which no membraneous growth could occur. The results are shown in Tables 1 to 3. Cross-resistance relationships were observed only between ethionamide and isoniazid. Ethionamide-resistant mutant strains were resistant to isoniazid.(ABSTRACT TRUNCATED AT 250 WORDS)

Antitubercular Agents↗

PubMed1992

[Evaluation of the alkaline-phosphatase labeled DNA probes for Mycobacterium tuberculosis and Mycobacterium avium complex].

Non-radioisotopic, alkaline phosphatase-labeled DNA (AP-DNA) probe tests for the identification of Mycobacterium tuberculosis complex (Mtb) and Mycobacterium avium complex (MAC) were evaluated. The overall agreement, sensitivity and specificity of the AP-DNA probes for Mtb and MAC were 100% respectively compared with the conventional biochemical method. Because the procedure is rapid (it can be completed approximately 120 min), safe (it does not use radioisotopes) and convenient (it does not need the special equipment to be performed), it can be easily performed in any clinical laboratory.

Alkaline Phosphatase↗

PubMed2000

Cytokine profiles in immunocompetent persons infected with Mycobacterium avium complex.

To evaluate the immunologic factors that contribute to protection against Mycobacterium avium complex (MAC), cytokine production by peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus-negative persons with pulmonary MAC (MAC patients) and healthy control subjects with a delayed hypersensitivity skin test response to M. avium sensitin (MAS-positive control subjects) was measured. In MAC patients, mycobacterium-stimulated PBMC produced higher concentrations of interleukin (IL)-10 but lower concentrations of interferon (IFN)-gamma, IL-12, and tumor necrosis factor (TNF)-alpha, compared with PBMC from MAS-positive control subjects. Immunolabeling for intracellular IL-10 revealed that this cytokine was produced by both monocytes and T cells. Alveolar macrophages produced TNF-alpha and IL-10 in response to MAC, which suggests that these cytokines are produced in the lungs of patients with pulmonary disease caused by this pathogen. Our findings suggest that IFN-gamma, TNF-alpha, and IL-12 contribute to protection against MAC, whereas IL-10 is immunosuppressive.

Adult↗

PubMed1990

Geographic distribution, frequency, and specimen source of Mycobacterium avium complex serotypes isolated from patients with acquired immunodeficiency syndrome.

Isolates of Mycobacterium avium complex from 727 patients with acquired immunodeficiency syndrome (AIDS) were submitted by medical centers across the United States to the Centers for Disease Control for serotyping. We were able to type 630 (87%) of these isolates by our seroagglutination procedure. Almost all typeable isolates were M. avium (serotypes 1 to 6 and 8 to 11). Blood was the major specimen source for both M. avium and the nontypeable isolates. M. intracellulare serotypes made up only 3% of all isolates from AIDS patients, with sputum being the major specimen source. More than 50% of the isolates originated from either New York or California, with serotype 4 being isolated most frequently in New York and serotype 8 appearing most frequently in California. AIDS patients in Los Angeles had a significantly higher isolation frequency for serotype 8 and a significantly lower one for serotype 4 in comparison with patients in either San Francisco or New York City.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Species identification of Mycobacterium avium complex isolates by a variety of molecular techniques.

Organisms in the Mycobacterium avium complex (MAC; M. avium, M. intracellulare, and "nonspecific or X" MAC) are emerging pathogens among individual organisms of which significant genetic variability is displayed. The objective of the present study was to evaluate various molecular methods for the rapid and definitive identification of MAC species. Isolates were obtained from both human immunodeficiency virus (HIV)-positive patients and HIV-negative patients with and without known predisposing conditions. The isolates were initially hybridized with nucleic acid probes complementary to the rRNA of the respective mycobacterial species (AccuProbe Culture Confirmation kits for M. avium, M. intracellulare, and MAC species; Gen-Probe). Isolates were also examined by PCR and in some cases by Southern blot hybridization for the insertion element IS1245. Two other techniques included a PCR assay that amplifies the mig gene, a putative virulence factor for MAC, and hsp65 gene amplification and sequencing. This study led to the following observations. Eighty-five percent of the isolates from HIV-positive patients were M. avium and 86% of the isolates from HIV-negative patients were M. intracellulare. Fifteen of the M. avium isolates did not contain IS1245 and 7% of the M. intracellulare isolates were found to carry IS1245. All of the M. avium strains were mig positive, and all of the M. intracellulare strains were mig negative.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

[Peritonitis with Mycobacterium avium complex in a patient with alcoholic cirrhosis].

Before highly active antiretroviral therapy were available, disseminated Mycobacterium avium complex infection was common in adults with HIV. Diagnosis was often made by blood culture in these immunocompromised patients. Although Mycobacterium avium complex disease can involve any organ of the body, infection of serosal surfaces is very rare. Mycobacterium avium complex peritonitis is rare and usually occurs in immunocompetent patients with chronic ambulatory peritoneal dialysis. We report a case of Mycobacterium avium complex peritonitis in a patient with alcoholic cirrhosis with no evidence of HIV infection. Diagnosis was made by culture of a lymphocytic ascites which showed Mycobacterium avium complex at 4 weeks. Interestingly, blood and hepatic cultures remained negative. At three months, marked improvement occurred with antimycobacterial treatment, so that orthotopic liver transplantation could be performed.

Anti-Bacterial Agents↗

PubMed1998

Early pulmonary resection for localized Mycobacterium avium complex disease.

BACKGROUND: Results of antituberculous chemotherapy for Mycobacterium avium complex disease remain disappointing. Pulmonary resection during an early stage of the disease, therefore, may be beneficial to patients whose disease is localized and who can tolerate a resectional operation. METHODS: Thirty-three patients with localized M avium complex disease underwent 33 pulmonary resections between 1979 and 1996. There were 17 males and 16 females, with a mean age of 50 years (range, 30 to 69 years). Lobectomy was performed in 26 patients, pleuropneumonectomy in 1, segmentectomy in 5, and wedge resection in 1. RESULTS: There was no operative mortality. After pulmonary resection, 31 (94%) patients attained sputum-negative status. Bronchopleural fistula occurred in one patient who underwent a right upper lobectomy. There were two late deaths. A patient with bronchopleural fistula died of respiratory failure two years postoperatively. Another patient died of an unknown cause 12 years postoperatively. Of the 31 patients with negative sputum status postoperatively, only 2 patients (6%) had relapse at 1 and 9 years after operation. CONCLUSIONS: We recommend that patients with this disease be considered for pulmonary resection as early as possible.

Adult↗

PubMedDate not supplied

Analysis of chest CT in patients with Mycobacterium avium complex pulmonary disease.

BACKGROUND: The radiographic changes of Mycobacterium avium complex (MAC) pulmonary disease during therapy have not been studied well. OBJECTIVE: To assess the efficacy of antituberculous drug therapy against MAC pulmonary disease using computed tomography (CT). METHOD: We analyzed chest CT scans before and after antituberculous therapy in 30 patients (21 women, 9 men) with MAC pulmonary disease. To evaluate radiographic changes during therapy, we defined a 'degree of improvement' (DI) that is calculated according to the CT appearance. RESULTS: DI was better (1.35 +/- 0.21) in patients who had converted sputum culture than in those who had not (0.44 +/- 0.25) (p < 0.05). In patients who were diagnosed by bronchial washing, DI was better (1.60 +/- 0.22) than in patients who were diagnosed by sputum (0.67 +/- 0.20) (p < 0.01). We categorized the CT appearance into 6 types: small nodules, cavities, bronchial wall thickening, infiltration, pleural thickening and atelectasis. Patients who showed pleural thickening had a significantly worse DI (0.12 +/- 0.40) than those who did not (1.23 +/- 0.18) (p < 0.01). Most of the lesions that disappeared after therapy were small nodules. CONCLUSION: These results indicate that chest CT might be a useful tool for the prediction or assessment of drug therapy for MAC pulmonary disease.

Anti-Bacterial Agents↗