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PubMed2000

Clinical prediction model for differentiation of disseminated Histoplasma capsulatum and Mycobacterium avium complex infections in febrile patients with AIDS.

BACKGROUND: Disseminated infection with Histoplasma capsulatum and Mycobacterium avium complex (MAC) in patients with AIDS are frequently difficult to distinguish clinically. METHODS: We retrospectively compared demographic information, other opportunistic infections, medications, symptoms, physical examination findings and laboratory parameters at the time of hospital presentation for 32 patients with culture documented disseminated histoplasmosis and 58 patients with disseminated MAC infection. RESULTS: Positive predictors of histoplasma infection by univariate analysis included lactate dehydrogenase level, white blood cell (WBC) count, platelet count, alkaline phosphatase level, and CD4 cell count. By multivariate logistic regression analysis, those characteristics that remained significant included a lactate dehydrogenase value > or =500 U/L (risk ratio [RR], 42; 95% confidence interval [CI], 18.53-97.5; p < .001), alkaline phosphatase < or =300 U/L (RR, 9.35; 95% CI, 2.61-33.48; p = .008), WBC < or =4.5 x 10(6)/L (RR, 21.29; 95% CI, 6.79-66.75; p = .008), and CD4 cell count (RR, 0.958; 95% CI, 0.946-0.971; p = .001). CONCLUSIONS: A predictive model for distinguishing disseminated histoplasmosis from MAC infection was developed using lactate dehydrogenase and alkaline phosphatase levels as well as WBC count. This model had a sensitivity of 83%, a specificity of 91%, and a misclassification rate of 13%.

AIDS-Related Opportunistic Infections↗

PubMed1993

Isolation of Mycobacterium avium complex from water in the United States, Finland, Zaire, and Kenya.

Disseminated infection with organisms of the Mycobacterium avium complex (MAC) is a common complication of AIDS in the United States and other developing countries, but it is rare or absent in sub-Saharan Africa. To assess the comparative likelihood of exposure to MAC in these geographic areas, we used a standard protocol to culture 91 water samples from environmental sites and piped water supply systems in the United States, Finland, Zaire, and Kenya. MAC was isolated from all geographic areas and from 22 of 91 (24%) samples. Isolation rates were 13 of 47 (28%) for environmental samples and 9 of 44 (20%) for water supply samples. Overall isolation rates were 18 of 52 (35%) samples in the United States and Finland, whereas they were 4 of 39 (10%) samples in Zaire and Kenya (P = 0.015). MAC isolation rates from water supply systems were 8 of 25 (32%) samples in the United States and Finland and 1 of 19 (5%) samples in Zaire and Kenya (P = 0.056). MAC was isolated from hospital water in the United States and Finland but not in hospital water in Zaire and Kenya. Serovar determinations showed that six of eight isolates from the United States were serovar 4 or 8. One MAC isolate from Zaire was identified as an "X" mycobacterium. These data suggest that exposure to MAC in water is likely in diverse areas of the world, but that the likelihood of human exposure to the organism in water may be slightly less in sub-Saharan Africa than in developed countries in the Northern Hemisphere.

AIDS-Related Opportunistic Infections↗

PubMed1996

New trends in the drug therapy of localized and disseminated Mycobacterium avium complex infection.

Recent advances in the drug therapy of localized and disseminated infection with Mycobacterium avium complex (MAC) are reviewed. MAC infection is the most commonly reported bacterial infection in patients with AIDS, and the frequency of this infection in patients negative for the human immunodeficiency virus (HIV) is increasing. The main portals of entry for MAC are the gastrointestinal and respiratory tracts. Localized MAC infection is more common in HIV-negative than HIV-infected patients. The symptoms of disseminated MAC disease are those typical of advanced HIV disease. The most reliable diagnosis is provided by blood cultures; radiometric culturing techniques are favored. The overall treatment of MAC infection has improved greatly with the introduction of new agents during the past 15 years; survival time has been extended. Clarithromycin and azithromycin have proven effective against both localized and disseminated MAC infection. Clarithromycin is the cornerstone of therapy for disseminated infection. Ciprofloxacin has been successfully used to treat disseminated infection as part of a four-drug regimen including rifampin, ethambutol, and clofazimine. Rifabutin has substantial efficacy when combined with other agents. Liposomal aminoglycosides, such as amikacin, and interferon gamma have shown some initial promise. Rifabutin is currently recommended for the prevention of MAC disease in HIV-infected patients. Clarithromycin and azithromycin have also shown efficacy for prophylaxis, and fluoroquinolones may play a preventive role as well. New drug therapies are improving the outlook for persons infected with MAC.

AIDS-Related Opportunistic Infections↗

PubMed1990

[In-vitro combined effect of antituberculosis drugs on Mycobacterium avium complex].

In-vitro combined activity of antituberculosis drugs on Mycobacterium avium complex strain 13034 (serotype 18) was observed. A twofold dilution series of each drug was combined with 17 additional drugs and the control without drug. Each medium was inoculated by a 0.02 ml-sample of four different bacterial suspensions, original suspension (10 mg wet weight per ml) and its 10(-5), 10(-6) and 10(-7) suspensions, and incubated at 37 degrees C for 28 days. The inoculation was made by a spiral loop that can deliver a 0.02 ml-sample by one inoculation. Since a total of media reached 6480 (1620 combinations x 4 different suspensions), only one strain was investigated in this study. Inoculation size used for determining minimal inhibitory concentrations was adjusted to 20 to 80 colony-forming units per medium. This was obtained by inoculating 10(-6) suspensions. The diameter of colonies was measured on media that were inoculated with 10(-7) suspensions. Since 96% confidence limits of determining minimal inhibitory concentrations are between 1/4 to fourfold, decrease or increase of the minimal inhibitory concentration equal to or above this level was regarded as significant. Such significant change of the minimal inhibitory concentrations occurred in combinations of drugs is shown in Table 2. As shown in tables, no antagonism was observed. The combinations, in which significant decrease was seen, contained ethambutol, sulfadimethoxine and ethionamide. It was shown that these concentrations of the drugs cause marked delay of growth. In control medium, the diameter of colonies was 5-6 mm, whereas in media containing one of these drugs, it was 1 mm.(ABSTRACT TRUNCATED AT 250 WORDS)

Antitubercular Agents↗

PubMedDate not supplied

Controversies in the management of Mycobacterium avium complex infection in AIDS patients.

OBJECTIVE: To update readers on the clinical management of infections secondary to Mycobacterium avium complex (MAC) in patients with AIDS. A general description of the organism, culture and susceptibility testing, and clinical manifestations of the disease is provided. Several aspects of the treatment of the disease, including an historical perspective, current approaches, and future research opportunities, are described. DATA SOURCES: Current medical literature, including abstracts presented at international meetings, is reviewed. References were identified through MEDLINE, Current Contents, and published meeting abstracts. STUDY SELECTION: Data regarding the epidemiology, clinical manifestations, culture and susceptibility testing, and treatment of MAC are cited. Specific attention is given to the management of patients with MAC infection. DATA EXTRACTION: Information contributing to the discussion of the topics selected by the author is reviewed. Data supporting and disputing specific conclusions are presented. DATA SYNTHESIS: Disseminated MAC infection is diagnosed antemortem in approximately 30 percent of patients with AIDS; postmortem rates of isolation exceed 50 percent. The incidence of MAC may increase as attempts at isolating the organism become more aggressive. The traditional approach to the isolation, susceptibility testing, and treatment of MAC has been derived from the management of Mycobacterium tuberculosis, with disappointing results. Newer radiometric in vitro methods of susceptibility testing appear to show more promise. Current mouse models of MAC are not true AIDS models; new CD4-deficient mouse models are being developed. Clinical mycobacteriologic and pharmacokinetic laboratory support have been underused, with treatment generally proceeding empirically. New agents that may contribute to the management of disseminated MAC infection include the macrolide derivatives clarithromycin and azithromycin. Research also continues with new rifamycins (including rifabutin) and fluoroquinolones (ciprofloxacin, sparfloxacin). Preliminary results suggest a central role for macrolides in the treatment of disseminated MAC; effective companion drugs are needed to prevent the rapid emergence of macrolide-resistant MAC. CONCLUSIONS: Treatment results for disseminated MAC infection remain poor. Therapy may be improved by selecting drugs on the basis of susceptibility data for each isolate, rather than by using empiric regimens based on susceptibility trends. Significant antimycobacterial drug malabsorption has been documented, and may contribute to poor outcomes. More-potent agents are needed to improve the clinical outcome in AIDS patients with MAC.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Oral Mycobacterium avium complex infection in a patient with HIV-related disease. A case report.

Mycobacterium avium complex infection is a common complication of the later stages of AIDS. Although a recognized cause of oral lesions, atypical mycobacteria are rarely detected in AIDS-related oral ulceration. Here we report a case of oral ulceration in a patient in the later stages of AIDS in which atypical mycobacteria were detected both histologically and microbiologically. The features of this case are similar to the one other case previously reported permitting some characterization and comparison of the clinical features of mycobacterium avium complex infection in AIDS.

AIDS-Related Opportunistic Infections↗

PubMed2000

Mycobacterium avium complex pleuritis accompanied by diabetes mellitus.

A 72-year-old woman with diabetic nephropathy was hospitalized with peripheral edema in the extremities and weight increase. After diuretics and human serum albumin administration, her condition improved. From the 15th day she had run a subfever and her breathing was diminished in the left lower lung field. A plain chest X-ray film showed pleural effusion over the left lung field. The fluid was exudative. Fluid cultures were negative. A tuberculin reaction was negative. Polymerase chain reaction method disclosed mycobacterium avium complex, indicating rare pleuritis due to mycobacterium avium complex. Eighteen days after chemotherapy, pleural effusion disappeared. Although her hemoglobin A1c (HbA1c) levels were maintained from 6.0 to 6.5% over 4 years, urinary albumin excretion levels and serum creatinine levels increased, indicating deteriorating diabetic nephropathy. Serum albumin levels remained low (3.3-3.6 g/dl). Malnutrition, impaired cellular immunity and apparently abnormal microvascular circulation due to diabetes mellitus may consequently have induced pleuritis due to mycobacterium avium complex.

Aged↗

PubMed2000

[A case of pneumonia caused by Mycobacterium avium complex successfully treated with clarithromycin].

We reported on a 79-year-old woman with pneumonia caused by Mycobacterium avium complex (MAC). She was admitted with fever, general fatigue, and cough. A chest X-ray film showed infiltrative shadows in the right lung field. In spite of administration of conventional antibiotics, the infiltrative shadows enlarged. A chest CT scan revealed areas of consolidation and ground glass opacities. Bronchoalveolar lavage (BAL) examination revealed an increased number of lymphocytes. Transbronchial lung biopsy revealed many granulomatous regions with giant cells. Mycobacterium intracellulare was found in the culture of BAL fluid and identified by PCR. Treatment was started with rifampicin, ethambutol, and clarithromycin. However, rifampicin and ethambutol were soon discontinued because of severe anorexia. Her symptoms and the radiographic appearance markedly improved following treatment of clarithromycin alone. Subsequently small doses of rifampicin and ethambutol were restarted because her general condition was much improved. These findings suggest that clarithromycin is an effective and tolerable agent for elderly patients with MAC.

Aged↗

PubMed1987

Rapid identification of Mycobacterium avium complex in culture using DNA probes.

A commercial DNA probe procedure for identification of Mycobacterium avium complex isolates was evaluated for accuracy and applicability for use in the clinical laboratory. The test (Gen-Probe Rapid Diagnostic System for Mycobacterium Avium Complex; Gen-Probe Corp., San Diego, Calif.) uses hybridization in solution of two 125I-labeled cDNA probes. One probe is complementary to rRNA from M. avium, and the other is complementary to rRNA from M. intracellulare. Results are expressed as absolute percent hybridization, with values greater than or equal to 10% considered positive. The procedure accurately identified all 134 M. avium complex isolates and concomitantly identified them to species level. There were no false-positives with 66 other mycobacteria, including 22 M. tuberculosis and 18 M. kansasii isolates, or with 8 Nocardia isolates. The mean percent hybridization (+/- the standard deviation) of M. avium probe-positive isolates (94 isolates) was 48.0 +/- 9.9 (range, 11.5 to 72.7); for M. intracellulare (40 isolates), it was 45.7 +/- 8.8 (range, 22.7 to 60.7). Among the 74 non-M. avium complex isolates, the percent hybridization range was 1.0 to 4.2, except for a single value of 9.7 which was less than 5 when the test was repeated. Four M. avium complex isolates reacted positively with both probes on initial testing, and three were confirmed. On repeat testing of subcultures, each reacted with only one probe, suggesting the presence of a mixed culture. The procedure can be completed in as little as 2 h and could easily be performed in most clinical laboratories.

Culture Media↗

PubMed1996

[Molluscum contagiosum-like papules within the scope of disseminated infection with Mycobacterium avium complex in an AIDS patient].

A 38-year-old HIV-positive man had several attacks of high fever associated with extensive perspiration over a 10-week period. Simultaneously, he developed molluscum contagiosum-like papules and an erythematous plaque on the face, ulcerated papules on both shoulders and buttocks and subcutaneous nodules on the arms. Histological examination of biopsy specimens revealed a diffuse, histiocytic infiltrate with abundant rod-shaped bacteria. Mycobacterium avium complex was cultured from the tissue and Mycobacterium avium complex DNA was detected by the polymerase chain reaction. The diagnosis of disseminated disease was additionally confirmed by culturing Mycobacterium avium complex from blood, sputum and stool. The skin lesions healed completely within 10 weeks by a multiagent as the patient was treated with a drug therapy. We describe the differential diagnosis, diagnostic procedures and therapy of disseminated infection with Mycobacterium avium complex.

AIDS-Related Opportunistic Infections↗

PubMed2002

Serodiagnosis of pulmonary disease due to Mycobacterium avium complex with an enzyme immunoassay that uses a mixture of glycopeptidolipid antigens.

It is difficult to distinguish pulmonary disease due to Mycobacterium avium complex (MAC) from that due to other mycobacteria, such as Mycobacterium tuberculosis and Mycobacterium kansasii. We developed an enzyme immunoassay (EIA) for diagnosis of MAC pulmonary diseases that uses glycopeptidolipid (GPL) antigens specific for MAC, and we used it for diagnosis in immunocompetent patients. The mean optical densities (+/- standard deviation) of serum immunoglobulin G antibodies to GPLs in patients with MAC disease, MAC colonization, M. kansasii disease, and tuberculosis and in healthy subjects were 0.778+/-0.784, 0.042+/-0.035, 0.059+/-0.035, 0.071+/-0.035, and 0.030+/-0.027, respectively. A significant increase in the level of anti-GPL antibodies was detected in patients with MAC disease. The level of anti-GPL antibodies reflected disease activity, because the level was decreased in culture-negative patients who had conversion of culture results. When a cutoff level of seropositivity (0.119) was defined, the sensitivity of EIA for diagnosis of MAC disease was 92.3%, and the specificity was 96.7%. Measurement of serum anti-GPL antibodies is useful for both the diagnosis of and assessment of activity in MAC disease.

Adolescent↗

PubMed2003

The effect of combined therapy according to the guidelines for the treatment of Mycobacterium avium complex pulmonary disease.

OBJECTIVE: To investigate whether the combined therapy according to the guideline proposed by American Thoracic Society (ATS) and Japanese Society for Tuberculosis (JST) is clinically appropriate for Mycobacterium avium complex (MAC) pulmonary disease. PATIENTS: Seventy-one patients in whom MAC pulmonary disease was diagnosed at Kawasaki Medical School and our associated ten hospitals were prospectively studied. RESULTS: Seventy-one patients with Mycobacterium avium complex (MAC) pulmonary disease were 27 males and 44 females with a mean age of 64.4 +/- 10.2 years old. Patients received 400 mg/day or 600 mg/day of clarithromycin plus ethambutol, rifampicin, and initial streptomycin for 12 months. Among 71 patients who received more than 12 months of therapy, 41 patients (57.7%) converted their sputum to negative within six months after the initiation of this regimen, 16 of 41 patients (39.0%) relapsed, and 23 of 71 patients (32.4%) obtained clinical improvement on chest X-ray and/or clinical symptoms. The mortality rate had a comparatively good prognosis with a low incidence of 2.8%. Although the species of pathogen (M. avium or M. intracellulare) did not significantly affect the conversion rate or clinical improvement, the infectious form with or without respiratory underlying disease, the characteristics and extent of lesion on chest X-ray, and the dose of clarithromycin significantly influenced the conversion rate or clinical improvement. There were no problems concerning adverse reactions for this regimen. CONCLUSION: This combined therapy, according to the guideline proposed by ATS and JST, was one of the effective treatments compared to the clinical effect of only antituberculous drugs through this study. However, this combined therapy was unsatisfactory compared to the clinical effect for pulmonary tuberculosis. The development of new companion drugs for MAC pulmonary diseases is needed.

Adult↗

PubMed2003

Mastitis due to Mycobacterium avium complex in an HIV-infected woman taking highly active antiretroviral therapy.

Although infection with Mycobacterium avium complex (MAC) is common in HIV-infected patients with CD4+ T cell counts less than 100/mm3, localized infection of the breast is uncommon. A brief literature review of mastitis from atypical mycobacteria is presented, along with the first reported case of localized MAC infection of the nonaugmented breast in an HIV-infected woman taking highly active antiretroviral therapy.

AIDS-Related Opportunistic Infections↗

PubMed2002

Profiles of the mRNA expression by macrophages infected with Mycobacterium leprae and Mycobacterium avium complex.

In the present study, we examined profiles of the interaction of Mycobacterium leprae and Mycobacterium avium complex (MAC) with murine peritoneal macrophages (M phi s) in terms of up-regulation of M phi expression of proinflammatory and immunosuppressing cytolines (CKs) after infection. First, the reverse transcription polymerase chain reaction (RT-PCR) assay revealed that both MAC and M. leprae infections up-regulated M phi mRNA expression IL-12, TNF-alpha, IL-10, and transformating growth factor-beta (TGF-beta), except that M. leprae-infected M phi s showed no increase in the IL-12 mRNA expression. Second, the RT-PCR assay also showed some differences between M. leprae- and MAC-infected M phi s with respect to the modes of IL-10 and inducible nitric oxide synthase (iNOS) mRNA expression. That is MAC, but not M. leprae, infection caused a prolonged increase in the expression of IL-10 and iNOS mRNAs. Third, a ribonuclease protection assay revealed that M phi s co-infected with MAC and M. leprae showed the Il-12, TNF-alpha and IL-10 mRNA expression in an intermediate mode of those of M phi s infected with either M. leprae or MAC alone. This implies that the CK expression of M. leprae-infected M phi s may be modified by co-infection with MAC. These findings may suggest differential interactions of M. leprae and MAC organisms with murine peritoneal M phi s in terms of the activation of signal transduction pathways for expression of some kinds of immunoregulatory cytokines and immunoprotective enzymes.

Animals↗

PubMed2003

High-resolution computed tomography appearance of pulmonary Mycobacterium avium complex infection after exposure to hot tub: case of hot-tub lung.

Reports detailing Mycobacterium avium complex (MAC) infection in an immunocompetent host after exposure to hot tub (hot-tub lung) are few and have not focused on the radiographic presentation. On high-resolution computed tomography (HRCT), hot-tub lung caused by MAC infection closely resembles subacute hypersensitivity pneumonitis and is difficult to distinguish based on imaging parameters alone. Centrilobular nodules of ground-glass attenuation with beading of the interlobular septae are prominent features on HRCT. Correlation of clinical history with radiographic, pathologic, and microbiologic findings are necessary to establish a diagnosis of hot-tub lung.

Adrenal Cortex Hormones↗

PubMed1999

IL-12-Independent costimulation pathways for interferon-gamma production in familial disseminated Mycobacterium avium complex infection.

We have described previously a family with an apparent genetic susceptibility to disseminated Mycobacterium avium complex infection and an underlying defect in IL-12 regulation leading to abnormally low interferon-gamma production. Their T cells appear to act normally when in the presence of normal accessory cells. Cell-to-cell contact was necessary for normal monocytes to complement the familial patient monocyte defect, suggesting the familial defect in interferon-gamma costimulation involves pathways requiring cell surface molecule interactions. In an effort to better characterize the abnormality in these patients, we examined the role of known costimulatory molecules in residual costimulation by patient PBMC compared to normals. Whereas normals utilized CD40/CD40L interactions and IL-12 production for optimal interferon-gamma costimulation in PHA-stimulated cocultures, familial patient interferon-gamma production was low and unaffected by their blockade. CD86 blockade caused a greater than 50% reduction in both normal and familial patient interferon-gamma production, implying that a majority of residual familial patient costimulation required this pathway. Furthermore, selected myelomonocytic cell lines (K562 and THP1) acted as potent accessory cells for interferon-gamma production by familial patient and normal T cells, largely independent of IL-12 production. However, CD86 blockade of K562 cell/familial cell cocultures resulted in less than a 20% reduction in interferon-gamma production, indicating that familial patient cells respond to IL-12- and CD86-independent costimulatory signals for interferon-gamma as well. Thus, we demonstrate that the familial defect also involves interferon-gamma costimulation pathways requiring both CD40/CD40L interaction and IL-12 production, while residual pathways remain that allow low-level interferon-gamma production. Familial Mycobacterium avium patient monocytes and certain myelomonocytic cell lines can be exploited to investigate IL-12-independent costimulation for interferon-gamma production.

Antigens, CD↗

PubMed2000

The ESP culture system for drug susceptibilities of Mycobacterium avium complex.

OBJECTIVE: To validate the non-radiometric, broth-based ESP system for determining Mycobacterium avium complex (MAC) susceptibilities. METHODS: MAC isolates from sterile body sites of 20 adult HIV-infected patients who were failing their present MAC regimen were identified. Susceptibilities were determined and comparisons made between the agar proportion method and the ESP system for clarithromycin, ethambutol, sparfloxacin and cycloserine. RESULTS: Ninety-nine percent of the MICS generated by the ESP system user identical to or lower than the MICs determined by the agar proportion METHOD: In vitro resistance was documented by the ESP system for 86% of the drugs that patients were taking at the time of breakthrough, and no resistance was seen to cycloserine, a drug that no patient was taking. CONCLUSIONS: The ESP system, a fast and reliable method for determining MAC susceptibilities, could be used to optimize MAC regimens in a timely fashion, avoid the use of ineffective drugs, minimize emerging resistance and ultimately improve outcome.

AIDS-Related Opportunistic Infections↗

PubMed2004

Mycobacterium avium complex in patients with HIV infection in the era of highly active antiretroviral therapy.

Disseminated Mycobacterium avium complex (MAC) infection is a common complication of late-stage HIV-1 infection. Since the advent of highly active antiretroviral therapy (HAART), the rate of MAC infection has declined substantially, but patients with low CD4 cell counts remain at risk. Among patients in the Johns Hopkins cohort with advanced HIV disease, the proportion developing MAC has fallen from 16% before 1996 to 4% after 1996, with a current rate of less than 1% per year. Factors associated with developing MAC include younger age, no use of HAART, and enrollment before 1996. Prophylaxis with azithromycin or clarithromycin is recommended for all patients with CD4 counts less than 50 cells/mL. Optimum treatment for disseminated MAC includes clarithromycin and ethambutol, and another investigation suggests that the addition of rifabutin might reduce mortality. Both prophylaxis and treatment of disseminated MAC can be discontinued in patients who have responded to HAART, and specific guidelines for withdrawing treatment have been published. Although HAART has altered the frequency and outcome of MAC infection, it remains an important complication of AIDS.

AIDS-Related Opportunistic Infections↗