Disseminated coinfection with Mycobacterium avium complex and Mycobacterium kansasii in a patient with AIDS and liver abscess.
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Acquired Immunodeficiency Syndrome↗
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Identification of various serovar strains of Mycobacterium avium complex by using DNA probes specific for Mycobacterium avium and Mycobacterium intracellulare.
Reference strains of the Mycobacterium avium complex (MAC) belonging to serovars 1 to 28 were examined with DNA probes (Gen Probe Rapid Diagnostic System for the MAC; Gen Probe Inc., San Diego, Calif.) specific for either M. avium or Mycobacterium intracellulare. This study revealed that the earlier designations of the MAC serovars, in which serovars 1 to 3 and 4 to 28 were regarded as M. avium and M. intracellular, respectively, should be revised as follows. First M. avium includes serovars, 1 to 6, 8 to 11, and 21. Second, M. intracellulare includes serovars 7, 12 to 20, and 25. However, other serovars, such as serovars 22 to 24 and 26 to 28, involve M. intracellulare, Mycobacterium scrofulaceum, and MAC that are lacking in the reactivity with either DNA probe and that are too disordered to enable a conclusive description here, particularly concerning their taxonomic positions in the MAC.
Antigens, Bacterial↗
Hemolysin as a virulence factor for systemic infection with isolates of Mycobacterium avium complex.
Isolates of the Mycobacterium avium complex were examined for hemolysin expression. Only invasive isolates of M. avium were observed to be hemolytic (P < 0.001), with activity the greatest for isolates of serovars 4 and 8. Thus, M. avium hemolysin appears to represent a virulence factor necessary for invasive disease.
AIDS-Related Opportunistic Infections↗
A retrospective study of the addition of ciprofloxacin to clarithromycin and ethambutol in the treatment of disseminated Mycobacterium avium complex infection.
Disseminated Mycobacterium avium complex (DMAC) infection is associated with increased morbidity and mortality in HIV-infected individuals. The combination antibiotic regimens containing clarithromycin can decrease symptoms and improve survival in patients with DMAC, however, optimal therapy remains to be defined. Quinolones have been widely used in the treatment of DMAC but their utility has not been established. A retrospective cohort study of DMAC infection was established in a metropolitan hospital providing comprehensive care to over 3000 HIV-infected individuals. Medical records of patients with DMAC diagnosed at the Parkland Memorial Hospital from 1991 to 1994 were reviewed for therapeutic regimens for DMAC, concomitant therapy for HIV and Pneumocystis carinii prophylaxis and date of death. Subjects were included if they were treated with clarithromycin and ethambutol. Cases were defined as those patients who received more than 30 days of ciprofloxacin as therapy for DMAC in addition to the other drugs that they received. The primary endpoint was the time to death from the data of DMAC diagnosis. Covariates effecting survival were analysed through the Cox proportional hazards model. Eighty-nine subjects with DMAC who were treated with clarithromycin and ethambutol were identified. Fifty-eight received ciprofloxacin in addition to clarithromycin and ethambutol. The time to death was significantly better in those subjects who were treated with ciprofloxacin than those who were not (489 days vs 281 days, P=0.01). The sole significant predictor of improved survival on Cox proportional hazards model was ciprofloxacin therapy. Subjects treated with combination of clarithromycin, ethambutol and ciprofloxacin had improved survival over those treated with clarithromycin and ethambutol alone.
Anti-Bacterial Agents↗
Altered expression profile of the surface glycopeptidolipids in drug-resistant clinical isolates of Mycobacterium avium complex.
Members of the Mycobacterium avium complex are the most frequently encountered opportunistic bacterial pathogens among patients in the advanced stage of AIDS. Two clinical isolates of the same strain, numbers 397 and 417, were obtained from an AIDS patient with disseminated M. avium complex infection before and after treatment with a regimen of clarithromycin and ethambutol. To identify the biochemical consequence of drug treatment, the expression and chemical composition of their major cell wall constituents, the arabinogalactan, lipoarabinomannan, and the surface glycopeptidolipids (GPL), were critically examined. Through thin layer chromatography, mass spectrometry, and chemical analysis, it was found that the GPL expression profiles differ significantly in that several apolar GPLs were overexpressed in the clinically resistant 417 isolate at the expense of the serotype 1 polar GPL, which was the single predominant band in the ethambutol-susceptible 397 isolate. Thus, instead of additional rhamnosylation on the 6-deoxytalose (6-dTal) appendage to give the serotype 1-specific disaccharide hapten, the accumulation of this nonextended apolar GPL probably provided more precursor substrate available for further nonsaccharide substitutions including a higher degree of O-methylation to give 3-O-Me-6-dTal and the unusual 4-O-sulfation on 6-dTal. Further data showed that this alteration effectively neutralized ethambutol, which is known to inhibit arabinan synthesis. Thus, in contrast with derived Emb-resistant mutants of Mycobacterium smegmatis or Mycobacterium tuberculosis, which are devoid of a surface GPL layer, the lipoarabinomannan from resistant 417 isolate grown in the presence of this drug was not apparently truncated.
AIDS-Related Opportunistic Infections↗
Use of four DNA insertion sequences to characterize strains of the Mycobacterium avium complex isolated from animals.
The Mycobacterium avium complex (MAC) includes the closely related species M. avium, M. intracellulare and M. paratuberculosis. The insertion elements IS900, IS901, IS1245 and IS1311 were used as DNA probes to characterize by restriction fragment polymorphisms (RFLPs) eight reference strains, three animal isolates of M. paratuberculosis from outside New Zealand and 61 selected New Zealand MAC isolates from cattle, deer, pigs, sheep and humans. IS900 was found only in strains of M. paratuberculosis. All MAC strains contained IS1311 and the RFLPs associated with this insertion element divided M. paratuberculosis strains into the same groups as IS900 RFLPs. Except for M. paratuberculosis, all MAC strains contained IS1245 and the majority of those from lesions in cattle, deer and pigs also contained IS901. All animal strains containing IS901 had the same RFLPs with IS901, IS1245 and IS1311. In three cases, these apparently identical strains could be differentiated by restriction fragment analysis with BstEII. IS901 was not present in four human isolates or in isolates from deer without lesions. These results indicate that a very closely related group of strains causes the majority of non-paratuberculosis MAC lesions in animals in New Zealand.
Animals↗
Production, characterization, and species specificity of monoclonal antibodies to Mycobacterium avium complex protein antigens.
The incidence of Mycobacterium avium-Mycobacterium intracellulare complex infections has increased in recent years primarily because a significant proportion of acquired immunodeficiency syndrome patients develop disseminated M. avium complex disease. In an effort to develop new tools to study these infections, we have produced eight monoclonal antibodies directed against M. avium. Western blot (immunoblot) specificity analysis and protease sensitivity assays indicate that four of these antibodies recognize M. avium-specific protein epitopes and two react with M. avium complex-specific peptide determinants. These monoclonal antibodies may be useful clinically in the diagnosis of M. avium complex disease and in the laboratory for isolation and characterization of native and recombinant M. avium complex antigens.
Acquired Immunodeficiency Syndrome↗
[AIDS and Mycobacterium avium complex infection].
Infections with Mycobacterium avium complex (MAC) are the next most common complication in AIDS patients, and disseminated MAC infection is considered as an indicator disease of AIDS. Bacteriological and clinical features of MAC infection complicated with AIDS were reviewed. The number of AIDS patients in Japan has been increasing in a similar rate as in USA and Africa, so the members of Japanese Society for Tuberculosis should be ready for medical care of AIDS patients complicated with mycobacterial infections.
Acquired Immunodeficiency Syndrome↗
Factors related to response to intermittent treatment of Mycobacterium avium complex lung disease.
RATIONALE: Mycobacterium avium complex pulmonary disease (MAC-PD) is associated with substantial morbidity, and standard daily multidrug therapy is difficult to tolerate. OBJECTIVES: To characterize response to a three-times-weekly (TIW) regimen of clarithromycin, ethambutol, and rifampin. METHODS: A 1-yr prospective noncomparative trial of TIW treatment was conducted during 2000-2003 in 17 U.S. cities. Participants were 91 HIV-negative adults, diagnosed with moderate to severe MAC-PD, who originally participated in a trial of an inhaled IFN-gamma treatment. Improvement in sputum culture, high-resolution computed tomography (HRCT), and symptoms were assessed. RESULTS: Treatment response rates (and median response times) were 44% (2 mo or longer) for culture, 60% (5.5-11.5 mo) for HRCT, and 53% (8.5 mo) for symptoms. Having noncavitary, compared with cavitary, disease increased culture response by 4.0 times (95% confidence interval [CI], 1.7-9.2) and HRCT response by 4.9 times (95% CI, 1.9-13.0). Culture response was 1.5 times (95% CI, 1.1-2.2) higher for older subjects and 2.2 times (95% CI, 1.0-4.7) higher for previously untreated subjects. Being smear-negative increased culture response by 2.3 times (95% CI, 1.1-5.2) but decreased HRCT response by 4.4 times (95% CI, 1.7-11.5). Increasing ethambutol use by 5 mo increased culture response by 1.5 times (95% CI, 1.0-2.1) but decreased symptom response. Not having chronic obstructive pulmonary disease, bronchiectasis, or poor lung function increased symptom response by 1.9 to 3.9 times. CONCLUSIONS: TIW therapy was less effective for MAC-PD patients with cavitary disease and a history of chronic obstructive pulmonary disease, bronchiectasis, or previous treatment for MAC-PD. Further research is needed to study the long-term outcomes of TIW treatment.
Aged↗
Proposal to elevate the genetic variant MAC-A, included in the Mycobacterium avium complex, to species rank as Mycobacterium chimaera sp. nov.
The possibility that the strains included within the Mycobacterium avium complex (MAC), but not belonging either to M. avium or to Mycobacterium intracellulare, may be members of undescribed taxa, has already been questioned by several taxonomists. A very homogeneous cluster of 12 strains characterized by identical nucleotide sequences both in the 16S rDNA and in the 16S-23S internal transcribed spacer was investigated. Similar strains, previously reported in the literature, had been assigned either to the species M. intracellulare on the basis of the 16S rDNA similarity or to the group of MAC intermediates. However, several phenotypical and epidemiological characteristics seem to distinguish these strains from all other MAC organisms. The unique mycolic acid pattern obtained by HPLC is striking as it is characterized by two clusters of peaks, instead of the three presented by all other MAC organisms. All of the strains have been isolated from humans and all but one came from the respiratory tract of elderly people. The clinical significance of these strains, ascertained for seven patients, seems to suggest an unusually high virulence. The characteristics of all the strains reported in the literature, genotypically identical to the ones described here, seem to confirm our data, without reports of isolations from animals or the environment or, among humans, from AIDS patients. Therefore, an elevation of the MAC variant was proposed and characterized here, with the name Mycobacterium chimaera sp. nov.; this increases the number of species included in the M. avium complex. The type strain is FI-01069T (=CIP 107892T=DSM 44623T).
Aged↗
Enzyme immunoassay for identification of heat-killed mycobacteria belonging to the Mycobacterium tuberculosis and Mycobacterium avium complexes and derived from early cultures.
A simple enzyme-linked immunosorbent assay was developed for the identification of cultured mycobacteria belonging to the Mycobacterium tuberculosis complex, the Mycobacterium avium complex, and Mycobacterium kansasii. Six monoclonal antibodies were used: two (F23-49 and F24-2) were specific for the M. tuberculosis complex, two (F85-2 and F85-10) were specific for the identification of the M. avium complex, one (F126-22) was specific for M. kansasii, and one (F141-3) was broadly reactive and distinguished mycobacteria from other bacteria. In the enzyme-linked immunosorbent assay only 10(6) to 10(7) bacteria derived from early cultures (2 to 3 weeks) were needed for each monoclonal antibody. For the M. tuberculosis complex the sensitivity and specificity were both 100%. For the M. avium complex the specificity was 100% and the sensitivity was 70%. The three M. kansasii strains tested could all be identified as M. kansasii.
Antibodies, Monoclonal↗
Factors affecting invasion of HT-29 and HEp-2 epithelial cells by organisms of the Mycobacterium avium complex.
Organisms of the Mycobacterium avium complex cause disseminated blood-borne infection in patients with AIDS, who acquire the infection mainly through the gastrointestinal tract. Prior to causing infection, M. avium must colonize and invade the intestinal mucosa. This study examined the ability of several serovars of the M. avium complex to bind to and invade the HT-29 intestinal mucosal cell line and the HEp-2 laryngeal cell line. Logarithmic-phase M. avium was more efficient in binding and invasion than organisms in the stationary phase of growth. Bacteria incubated at 37 and 40 degrees C adhered to and invaded HT-29 cells more efficiently than bacteria cultured at 30 degrees C. The ability of M. avium to invade HT-29 and HEp-2 cells was inhibited when the cells were incubated with cytochalasin B prior to exposure to the bacterium, suggesting active participation of the mammalian cell in the process of internalization. Two protein kinase inhibitors, staurosporine and H7, blocked invasion of M. avium, and a specific tyrosine protein kinase inhibitor, genistein, also blocked the internalization but not the binding of bacteria. The findings suggest that M. avium binds to a specific receptor(s) on the epithelial cells and uses the cytoskeleton of the mammalian cell to become internalized.
Alkaloids↗
Recommendations on prophylaxis and therapy for disseminated Mycobacterium avium complex disease in patients infected with the human immunodeficiency virus. Public Health Service Task Force on Prophylaxis and Therapy for Mycobacterium avium Complex.
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AIDS-Related Opportunistic Infections↗
DNA probe reactivity of Mycobacterium avium complex isolates from patients without AIDS.
Mycobacterium avium complex isolates from 27 patients without AIDS and from 76 patients with AIDS were analyzed with the Gen-Probe Rapid Diagnostic System for Mycobacterium avium complex, and a retrospective chart review was performed to determine clinical significance of the isolates. While 87% of isolates from AIDS patients reacted only with the M. avium probe, only 37% from non-AIDS patients were M. avium probe positive (p less than 0.001). This pattern among non-AIDS patients was also observed among the 13 patients from whom isolates were considered to be clinically significant. Reactivity to both probes occurred with three isolates, two from non-AIDS patients that were not clinically significant and one from an AIDS patient. Results of further testing suggested that these represented dual infection with two coexisting strains. Awareness of the differences in DNA probe reactivity between isolates from AIDS and non-AIDS patients may influence testing strategies in the clinical laboratory.
Acquired Immunodeficiency Syndrome↗
The pathophysiology of disseminated Mycobacterium avium complex disease in AIDS.
Mycobacterium avium complex (MAC) organisms cause disseminated disease in patients with AIDS. The organisms penetrate the gastrointestinal mucosa by unknown mechanisms and are phagocytosed by macrophages in the lamina propria. These cells cannot kill the organisms, and MAC spreads through the submucosal tissue. Lymphatic drainage transports mycobacteria to abdominal lymph nodes, from which the organisms enter the bloodstream. Hematogenous spread can occur to many sites, but spleen, bone marrow, and liver are the most common. Tissue destruction is rare, and most signs and symptoms of MAC disease are due to elaboration of cytokines. MAC is rarely the direct cause of death but increases the risk for superinfection; death may result from malnutrition or other infections.
AIDS-Related Opportunistic Infections↗
Immune response & modulation of immune response induced in the guinea-pigs by Mycobacterium avium complex (MAC) & M. fortuitum complex isolates from different sources in the south Indian BCG trial area.
A total of 139 guineapigs were used to study the immune response and its modulation induced by Mycobacterium avium complex (MAC) and M. fortuitum complex strains obtained from different sources in the south Indian BCG trial area. The guineapigs were divided into groups and some were directly sensitised/immunised with different MAC strains. M. fortuitum complex strain or BCG and others were sensitised with MAC or M. fortuitum complex and then immunised with BCG. The resulting delayed type hypersensitivity (DTH) response in the different groups of guineapigs was studied by skin tests using PPD-RT23 and PPD-B, and protective response was studied by challenging the guineapigs with a south Indian low virulent strain of M. tuberculosis and enumerating the bacilli in spleen at different points of time. The 3 strains of MAC induced similar low levels of DTH to PPD-RT23 but much higher and varying levels of DTH to PPD-B. MAC strains from soil and sputum induced different levels of immune modulation during subsequent immunisation with BCG on the DTH response to PPD-RT23 and PPD-B. At 2 wk after challenge, 23.8, 81 and 90.5 per cent protection was induced by the standard strain, soil isolate and sputum isolate of MAC, respectively, while 33.3 per cent protection was induced by the M. fortuitum complex strain compared to the protection induced by BCG alone. Prior exposure to MAC or M. fortuitum complex did not have any modulatory effect on the protective immunity due to BCG at this time point. However, at 6 wk after challenge, while the guineapigs immunised with BCG were protected, modulation of the protective response resulting from BCG was observed in the guineapigs sensitised with MAC and M. fortuitum from soil.
Animals↗
Sentinel-site surveillance of Mycobacterium avium complex pulmonary disease.
The incidence of Mycobacterium avium complex (MAC) pulmonary disease in HIV-negative patients was studied prospectively from January 1, 2000 to December 31, 2002 through 32 sentinel sites distributed all over France. Among the 275 patients who yielded MAC isolates from respiratory clinical specimens, 101 (36.7%) met the bacteriological, radiographical and clinical criteria established by the American Thoracic Society for nontuberculous mycobacterial respiratory disease. Of these 101 patients, 81 had underlying lung disease, mainly previous tuberculosis, bronchectasis or chronic obstructive pulmonary disease. Among the 20 patients with no underlying lung disease, 12 had a predisposing factor such as leukaemia or immunosuppressive treatment and eight had no predisposing factor. All patients with MAC respiratory disease had clinical symptoms, commonly cough and fatigue, and 52 (51.5%) were sputum smear positive for acid-fast bacillus. The ratio of patients with Mycobacterium avium complex pulmonary disease to patients with pulmonary tuberculosis in France was estimated to be 3% and the incidence of Mycobacterium avium complex pulmonary disease in France was 0.2 per 100,000 inhabitants.
Adolescent↗
Case report. Diagnosis of disseminated Mycobacterium avium complex infection by liver biopsy.
Mycobacterium avium complex (MAC) infection is a common complication of HIV/AIDS. Signs and symptoms of this infection are nonspecific and include fever, weight loss, diarrhea, and abnormal levels of liver enzymes, especially elevated alkaline phosphatase levels. Diagnosis can be achieved through several methods, but liver biopsy may be the most rapid and efficient. We present a case that illustrates the potential value of liver biopsy in diagnosing disseminated MAC infection.
AIDS-Related Opportunistic Infections↗