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PubMed2004

Wasting syndrome and disruption of the somatotropic axis in simian immunodeficiency virus-infected macaques with Mycobacterium avium complex infection.

Mycobacterium avium is a common opportunistic infection of patients with acquired immunodeficiency syndrome (AIDS). We used the simian immunodeficiency virus (SIV)-infected rhesus macaque (Macaca mulatta) model to examine whether disseminated M. avium is associated with disruption of the somatotropic axis in AIDS. Macaques were followed prospectively, and body composition was determined by dual-energy x-ray absorption. Serum levels of insulin-like growth factor (IGF)-1, IGF binding protein-3, growth hormone (GH), and somatostatin were measured. SIV-infected macaques inoculated with mycobacteria had significant changes in body composition, perturbations of the somatotropic axis (characterized by increased GH/IGF-1 ratios) (day 0 [2.21] vs. day of death [DOD] [28.06]; P=.015, Mann-Whitney rank sum test), and increased serum somatostatin levels (day 0 [2.00 ng/mL] vs. DOD [8.58 ng/mL]; P=.026, Mann-Whitney rank sum test). These data document alterations in the somatotropic axis secondary to experimental disseminated M. avium infection and suggest that similar changes may contribute to alterations in body composition during AIDS.

Animals↗
PubMed1989

Different correlations of drug susceptibilities to colonial morphology in Mycobacterium avium complex strains.

In Mycobacterium avium and Mycobacterium intracellulare complex strains isolated from patients who were not treated previously by any antituberculosis drugs or from fowls, the colonial morphology, smooth, domed, opaque (SmD) or smooth, flat, transparent (SmT) colonial forms, significantly correlated with susceptibilities to rifampicin, minocycline, streptomycin, kanamycin, enviomycin, ethambutol, and sulfadimethoxine, whereas it did not correlate with susceptibilities to isoniazid, cycloserine, and ethionamide. Strains with the SmT colonial morphology were more resistant to the former seven drugs than strains with the SmD colonial morphology. Since the susceptibilities to antituberculosis drugs with large molecules correlated with the colonial morphology, it has been suggested that a permeability barrier that allows passage of small molecules but prevents passage of large molecules exists in the strains with the SmT colonial morphology.

Anti-Bacterial Agents↗
PubMed1991

Diagnosis of disease caused by Mycobacterium avium complex.

Isolation of Mycobacterium avium complex from sputum specimens in association with the appearance of a new cavitary (or infiltrative) lesion was studied in 299 patients from whom the organism was isolated one or more times. Of the patients studied, 114 showed only single isolation. Of these 114, only two patients (2 percent) had association with appearance of a cavitary lesion. Of 29 patients who showed two isolations, 26 (90 percent) had the association. Of 40 patients who showed three isolations, 39 (98 percent) had the association. All 116 patients who showed four or more isolations had the association with appearance of a cavitary lesion. Accordingly, of a total of 185 patients who showed two or more isolations, 181 (98 percent) had the association. Of these 181, 176 (97 percent) showed two or more isolations in the sputum examinations made in the initial three days. Therefore, the sputum examination in the first three days after onset of disease is most important for the diagnosis of disease caused by Mycobacterium avium complex. Since the probability that casual isolation of the organism occurs twice is extremely low, we can make the diagnosis of pulmonary infection caused by this organism by evidence of two or more isolations of the organism in the first few days after the onset of disease, which is associated with appearance of a new cavitary (or infiltrative) lesion. Moreover, theoretical consideration made in this study has led us to conclude that patients who have had a single isolation of the organism together with a new cavitary lesion should be regarded as having an infection.

Adult↗
PubMed2000

Distinct differences in repertoires of low-molecular-mass secreted antigens of Mycobacterium avium complex and Mycobacterium tuberculosis.

Antigens in a 4-week-old culture filtrate (CF) of Mycobacterium avium subsp. avium were separated in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and identified by Western blotting. The culture had minimal lysis of bacilli, giving a CF preparation consisting mainly of secreted proteins. Comparison with a similar CF of Mycobacterium tuberculosis with almost no contamination with intracellular proteins showed the presence of cross-reactive antigens homologous to the four components of the antigen 85 complex, as well as MPT32. These were major constituents of the M. avium subsp. avium CF. In addition, there were several low-molecular-mass bands (<15 kDa) in both species that did not cross-react with polyclonal and polyvalent rabbit antibodies in Western blotting. Furthermore, these bands were not detected in corresponding sonicate preparations, indicating high localization indexes, which is typical of soluble secreted proteins. A 14-kDa protein was selected for purification and more detailed characterization. The N-terminal amino acid sequence was determined, and a matching gene was found within the genomic sequence of M. avium subsp. avium which was highly homologous to Rv0455c of M. tuberculosis. The gene encoded a signal peptide typical of secreted mycobacterial proteins. A rabbit antiserum was raised against the purified protein, and the antigen was demonstrated by Western blotting in CFs of M. avium subsp. avium, Mycobacterium avium subsp. paratuberculosis, Mycobacterium intracellulare, and Mycobacterium scrofulaceum but was not detected in M. tuberculosis. This is a new example of a highly homologous gene being differentially expressed by different mycobacterial species.

Amino Acid Sequence↗
PubMed1990

[Cross-resistance relationship between streptomycin and kanamycin resistances in Mycobacterium smegmatis (strain Jucho)--comparison of the development patterns of resistances to streptomycin and kanamycin among Mycobacterium tuberculosis, Mycobacterium avium complex, and Mycobacterium smegmatis].

The resistance development pattern of Mycobacterium smegmatis strain 17023 (Jucho) to streptomycin and kanamycin was studied. The medium used was Ogawa egg medium, and the level of resistance was determined for each clone derived from single colony by the 'actual count' method. Hence, the resistance level was estimated as the highest concentration of drugs, in which small inocula consisting of 20 to 100 colony-forming units could grow after seven days incubation. Only one type of resistance mutants resistant to more than 1,000 micrograms/ml streptomycin was isolated and these mutants were also resistant to 8 micrograms/ml kanamycin. On the other hand, only one type of kanamycin-resistant mutants resistant to 8 micrograms/ml kanamycin was isolated and these mutants were also resistant to more than 1,000 micrograms/ml streptomycin. Accordingly, there was a complete cross-resistance relationship between streptomycin and kanamycin resistances. Therefore, there existed only one phenotype, which is simultaneously resistant to streptomycin and kanamycin. The mutants occurred at a rate of about 2 x 10(-8) per viable bacterial population of the parent strain. Streptomycin-dependent mutants occurred at a rate of about 2 x 10(-9). The number of resistant phenotypes to streptomycin and kanamycin was only one in M. smegmatis, while it was five in M. tuberculosis and 2 or 3 in M. avium complex (Tsukamura, M. and Mizuno, S.: J. Gen. Microbiol. 88: 269-274, 1975; Tsukamura, M.: Kekkaku 62: 445-458, 1987). The simplicity of the resistance system of M. smegmatis suggests that this organism is evolutionally primitive in the world of mycobacteria.

Drug Resistance, Microbial↗
PubMed1986

Ethambutol MICs and MBCs for Mycobacterium avium complex and Mycobacterium tuberculosis.

We determined the MICs of ethambutol for both Mycobacterium avium and Mycobacterium tuberculosis strains by using broth dilution (7H12 broth, radiometric method) and agar dilution (7H11 agar) methods. We found the MICs to be much lower in liquid than in solid medium. The broth-determined MICs for susceptible M. tuberculosis and most of the M. avium strains were comparable to the levels in blood of patients, being lower than the peak levels. We propose that the MICs, determined radiometrically in in 7H12 broth, be considered as tentative criteria for susceptibility testing of M. avium isolates in future clinical trials. The use of these values instead of critical concentrations should also be considered as an alternative to the conventional susceptibility testing method in chemotherapy of tuberculosis. Ethambutol produced bactericidal effects against both M. tuberculosis and M. avium, and the MIC/MBC ratios were in the same range for both species when MICs and MBCs were tested in 7H12 broth by conventional sampling and plating.

Culture Media↗
PubMed1997

Yield of computed tomography and bronchoscopy for the diagnosis of Mycobacterium avium complex pulmonary disease.

Mycobacterium avium complex (MAC) pulmonary disease with nodules and bronchiectasis is increasing. But the usefulness of computed tomography (CT) and bronchoscopy for diagnosis and the significance of MAC isolation from respiratory secretions are still unclear. For a 4-yr period, we prospectively examined the role of bronchoscopy with bronchial washing and transbronchial lung biopsy in 26 patients who had clusters of small nodules in the periphery of the lung associated with ectatic changes of the draining bronchi on the CT scan. None of them was infected with human immunodeficiency virus. Thirteen of the 26 patients (50%) had cultures positive for MAC, six in the sputum and 13 in the bronchial washing. Epithelioid granuloma was demonstrated in eight of 13 patients with culture-positive MAC and in two of 13 patients in whom MAC was culture-negative. Rapidly growing mycobacteria were cultured in the two patients. Seven of the eight biopsy-positive patients received treatment and responded by sputum conversion and/or radiographic improvement. We found that the CT finding was a useful clue to suspect MAC pulmonary disease and that the bronchial washing was more sensitive than the routine expectorated sputum for MAC isolation. Demonstration of granuloma in more than half of the MAC-positive patients would suggest that MAC may have invaded the lung tissue rather than colonized in the airways.

Adult↗
PubMed2006

Environmental risk factors for infection with Mycobacterium avium complex.

Infection with Mycobacterium avium complex is acquired from the environment, but risk factors for M. avium complex infection and disease are poorly understood. To identify risk factors for infection, the authors performed a 1998-2000 cross-sectional study in western Palm Beach County, Florida, using a population-based random household survey. M. avium complex infection was identified by use of the M. avium sensitin skin test. Of 447 participants, 147 (32.9%) had a positive test reaction, 186 (41.6%) had a negative test reaction, and, for 114 (25.5%), test results were indeterminate. Among the 333 participants with positive or negative M. avium sensitin skin tests, age-adjusted independent predictors of M. avium complex infection in a multivariate model included Black race (odds ratio = 3.8, 95% confidence interval: 2.2, 6.6), birth outside the United States (odds ratio = 2.1, 95% confidence interval: 1.1, 3.9), and more than 6 years' cumulative occupational exposure to soil (odds ratio = 2.7, 95% confidence interval: 1.3, 6.0). Exposure to water, food, or pets was not associated with infection. Results indicate that soil is a reservoir for M. avium complex associated with human infection and that persons whose occupations involve prolonged soil exposure are at increased risk of M. avium complex infection.

AIDS-Related Opportunistic Infections↗
PubMed2003

Isolated intracranial infection with Mycobacterium avium complex.

UNLABELLED: Mycobacterium avium-M. complex (MAC) has been linked to devastating respiratory and systemic illnesses in patients, especially in those who are immunosuppressed. The purpose of this study is to describe a case of isolated central nervous system (CNS) infection with MAC. This is a single case report of a patient with isolated intracranial mycobacterial infection. SETTING: the patient was treated and the immunohistochemical investigations were undertaken at the National Institutes of Health in Bethesda, Maryland, USA. INTERVENTION: the patient initially was treated with a cocktail of antimycobacterial medications. However, because his disease was refractory, he underwent a suboccipital craniotomy and evacuation of his cerebellar mass. The patient was determined to have a low production of interferon-gamma (INF-gamma) and tumor necrosis factor-alpha (TNF-alpha) when compared to normal values. Despite extensive radiographic imaging studies and biopsies, there was no evidence of another focus of MAC infection in this patient. We conclude that intracranial infectious lesions in patients such as ours should be treated with conventional systemic antibiotic regimens as the first-line of therapy. We suggest neurosurgical intervention in medically refractory cases of intracranial infections.

Adult↗
PubMedDate not supplied

Evaluation of Syngene DNA-DNA probe assays for the identification of the Mycobacterium tuberculosis complex and the Mycobacterium avium complex.

Two hundred mycobacterial cultures were used to evaluate two alkaline-phosphatase-labeled DNA probe (SNAP) kits developed by Syngene (San Diego, CA) for identification of Mycobacterium tuberculosis complex and M. avium complex. The M. tuberculosis complex SNAP probe, when compared with standard biochemical identification tests, gave results that were in agreement at 100% sensitivity and 98.7% specificity. Ninety-nine M. avium complex strains that were previously tested by the Gen-Probe M. avium complex probe assays and mycolic acid analysis were included to evaluate the M. avium complex SNAP assay which contained three probes, A (avium), I (intracellulare), and X. Eight strains identified as members of the M. avium complex by biochemical tests did not react with the three SNAP probes. These strains were also negative by the Gen-Probe assays. However, 23 strains identified as M. avium complex by biochemical tests and mycolic acid analysis and negative with the Gen-Probe assays gave positive results with the X probe and negative results with the A and I probes of the SNAP assay.

Alkaline Phosphatase↗
PubMed1991

[Reactivities of various mycobacteria species against DNA probes (Gen-Probe Rapid Diagnostic System) specific to Mycobacterium tuberculosis complex, Mycobacterium avium and Mycobacterium intracellulare].

Various mycobacterial species (22 species, 178 strains) were studied for their reactivity to DNA probe specific for Mycobacterium tuberculosis complex (MTC), M. avium or M. intracellulare, using Gen-Probe Rapid Diagnostic System (Gen-Probe Inc., San Diego, Calif., U.S.A.). All the MTC strains, including M. tuberculosis, M. africanum, M. bovis and M. microti reacted with MTC-DNA probe at the % hybridization value of 42.8-51.9% (values higher than 10% are regarded as positive), but their reactivity to MAC-DNA probes (0.8-2.5%) was under the cut off value (10%). The test strains (28 strains) of M. avium complex (MAC) segregated into two groups on the basis of reactivity to DNA probes specific for M. avium and M. intracellulare, that is, one group (16 strains) positively reacted with M. avium-probe but not with M. intracellulare-probe, and the other group (12 strains) showed the converse reactivity. The two groups did not show a reactivity with MTC-probe higher than the cut off value. Nontuberculous mycobacteria other than MAC, including M. kansasii, M. marinum, M. simiae, M. asiaticum, M. scrofulaceum, M. gordonae, M. szulgai, M. malmoense, M. xenopi, M. gastri, M. nonchromogenicum, M. terrae, M. triviale, M. fortuitum, and M. chelonae (subsp. abscessus and chelonae) reacted with neither MTC- nor MAC-probe and values for % hybridization (0.6-3.6%) were lower than the cut off value. These findings indicate extremely superior specificity of the DNA probes (Gen-Probe) for MTC, M. avium and M. intracellulare, thereby indicating the usefulness of Gen-Probe Rapid Diagnostic System for the MTC and MAC in clinical use.

Animals↗
PubMed1985

Improved detection times for Mycobacterium avium complex and Mycobacterium tuberculosis with the BACTEC radiometric system.

A total of 2,559 routine clinical specimens were cultured for mycobacteria by using BACTEC Middlebrook 7H12 medium (BACTEC), Lowenstein-Jensen slants (LJ), and Mycobactosel selective Middlebrook 7H11 slants (M7H11). Thirty-three isolates (1.3%) of M. avium complex and 82 isolates (3.2%) of M. tuberculosis were recovered. The BACTEC mean detection time of M. avium complex from 27 smear-negative specimens was earlier than that of conventional media for both decontaminated respiratory specimens (BACTEC, 12 days; LJ, 32 days; and M7H11, 38 days) and untreated tissue and fluid specimens (BACTEC, 8 days; LJ, 30 days; and M7H11, 31 days). The sensitivity for smear-negative M. avium complex with BACTEC (74%) was comparable to that with LJ (74%) and M7H11 (63%). The mean detection times of M. tuberculosis from 56 smear-positive respiratory specimens were 8 days for BACTEC, 16 days for LJ, and 17 days for M7H11, and sensitivities for the detection of positive cultures were 98% for BACTEC, 76% for LJ, and 79% for M7H11. The BACTEC mean detection time of M. tuberculosis in smear-negative specimens was better for tissues and fluids (14 days) than for respiratory specimens (24 days). BACTEC yielded substantially earlier detection of M. avium complex from all specimen types and of M. tuberculosis from smear-positive respiratory specimens. The rapid identification and susceptibility testing of M. tuberculosis in BACTEC agreed completely with conventional tests and provided a 3-week reduction in median time to final reports.

Culture Media↗
PubMed1989

Correlations among naturally occurring resistances to antituberculosis drugs in Mycobacterium avium complex strains.

In Mycobacterium avium complex strains, which were not exposed previously to any antituberculosis drugs, resistances to rifampin, minocycline, and kitasamycin, and resistances to streptomycin and kanamycin appeared frequently in the same strains. These data indicate that patterns of drug resistance in these organisms are not random but occur through linked mechanisms.

Animals↗
PubMed1998

Identification of mycobacteria by mycolic acid pattern.

BACKGROUND: Tuberculosis caused by Mycobacterium tuberculosis is a public health problem which has increased in importance during the last 12 years, due in part to the increasing number of cases caused by the association of acquired immunodeficiency syndrome (AIDS) and the appearance of multiple drug-resistant strains. Other mycobacteria which are often indistinguishable from tuberculosis have also increased. METHODS: Mycolic acid patterns were obtained from 53 clinical isolates of sputum, cerebrospinal fluid, bronchial washing, corneal ulcer, and bone marrow, as well as from 11 acid-fast stain smear-positive clinical specimens. Standardized mycolic acid extraction method was used to ensure the maximal extraction of mycolic acid derivatives to enhance the sensitivity of the method. A chromatographic column different from what others have employed and a different gradient elution from those reported in the literature were used, making a correlation between retention times for the chromatographic peaks obtained in this study and those previously reported for mycolic acid patterns from a strain of Mycobacterium avium necessary. Then, a comparison of retention times of mycolic acid pattern obtained in this study and those previously reported in the literature was carried out. Strains were identified as Mycobacterium tuberculosis complex, Mycobacterium avium complex, Mycobacterium fortuitum, Mycobacterium chelonae and Mycobacterium kansasii in less than 24 hours. RESULTS: In direct analysis of acid-fast stain smearpositive from 1+ to 4+ specimens, mycolic acid patterns were identified as Mycobacterium tuberculosis complex, Mycobacterium avium complex, Mycobacterium chelonae, and Mycobacterium kansasii, with a strong signal even in light 1+ positive samples. CONCLUSIONS: The results showed that identification of mycobacteria through mycolic acid pattern is a rapid, sensitive, and very useful method for identification of mycobacteria in the early diagnosis of the mycobacteriosis.

Chromatography, High Pressure Liquid↗
PubMed1995

Identification of Mycobacterium tuberculosis complex, Mycobacterium avium and Mycobacterium intracellulare by selective nested polymerase chain reaction.

A nested polymerase chain reaction (PCR) procedure was devised for identification of mycobacteria. The outer reaction exploiting genus-specific sequences on the 16S rRNA gene was able to amplify specifically strains of the genus Mycobacterium. The identification of Mycobacterium tuberculosis complex, Mycobacterium avium and Mycobacterium intracellulare was accomplished by selective reamplification of the outer PCR product in three distinct inner amplifications exploiting species-specific primers mapping to a hypervariable region of mycobacterial 16S rRNA. Detection of mycobacteria, other than those for which species-specific primers were used, was accomplished by adding a supplementary genus-specific upper primer to one of the inner reactions. Specificity of amplification was confirmed for clinical isolates and reference strains of different mycobacterial species with the exception of a M. intracellulare type 7 strain which was recognized as M. avium. The amplification protocol presented thus provides a reliable and cost-effective way for identification of clinically relevant mycobacteria.

Base Sequence↗
PubMed1991

Gen-Probe Rapid Diagnostic System for the Mycobacterium avium complex does not distinguish between Mycobacterium avium and Mycobacterium paratuberculosis.

Three reference and 16 field strains of Mycobacterium paratuberculosis were tested with the Gen-Probe Mycobacterium avium complex DNA probe (Gen-Probe Inc., San Diego, Calif.). All reference strains and 12 of 16 field strains gave positive hybridization results with the probe. This study shows that the M. avium complex probe does not distinguish between M. avium and M. paratuberculosis and indicates heterogeneity in the 16S rRNA gene of M. paratuberculosis.

Animals↗