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PubMed2003

The complexity of HLA class II (DRB1, DQB1, DM) associations with disseminated Mycobacterium avium complex infection among HIV-1-seropositive whites.

Earlier associations of polymorphism in classic HLA class II (DRB1 and DQB1) genes have been extended to include the accessory genes DMA and DMB as determinants of disseminated Mycobacterium avium complex (DMAC) infection among HIV-1-seropositive whites. From the Multicenter AIDS Cohort study, 176 DMAC cases were matched with 176 controls in a nested case-control study. PCR-based HLA genotyping techniques were used to resolve variants of DRB1 and DQB1 to their four-digit or five-digit alleles, and single-strand conformation polymorphism was used to resolve sequences in exon 3 at each DM locus. The DMA*0102 allele occurred less frequently among DMAC cases than among controls (OR = 0.46, p =.02). Combinations of DRB1 alleles with or without specific DMA and DMB variants showed significant differences in distributions between the cases and controls, but both of the previously associated class II alleles (DRB1*1501 and DRB1*0701) showed stronger positive associations with DMAC in the absence than in the presence of DMA*0102. Apparent joint effects of DRB1 and DM allelic combinations on occurrence and timing of DMAC suggest that class II disease relationships may be better predicted by biologically plausible interactive combinations than by polymorphisms in individual genes.

AIDS-Related Opportunistic Infections↗

PubMed1986

A four-drug regimen for initial treatment of cavitary disease caused by Mycobacterium avium complex.

Forty-six patients with positive sputum cultures for Mycobacterium avium complex and cavitary disease were placed on a 4-drug regimen consisting of isoniazid, rifampin, and ethambutol daily and streptomycin twice weekly. Forty-two (91.3%) converted their sputum to negative and 4 (8.7%) failed to convert. All of the 4 nonconverters had prior subtotal gastrectomy. Twenty-two patients were available for long-term follow-up: 12 patients completed 24 months of chemotherapy, all experienced sputum conversion, but 2 reactivated, 1 at 9 and the other at 27 months after termination of chemotherapy. These 2 patients had prior subtotal gastrectomy. Ten patients completed 18 months of chemotherapy with sputum conversion, 2 of these reactivated but had not had prior subtotal gastrectomy. In this group of patients, subtotal gastrectomy appeared to be an adverse risk factor for both initial treatment response and reactivation in pulmonary disease caused by Mycobacterium avium complex.

Antitubercular Agents↗

PubMed1998

Genetic diversity among Mycobacterium avium complex strains recovered from children with and without human immunodeficiency virus infection.

The genetic diversity and molecular epidemiology of Mycobacterium avium complex (MAC) infections in children with and without human immunodeficiency virus (HIV) infection were evaluated. Isolates recovered from 136 children were subtyped by sequence analysis of a 360-bp region of the gene (hsp65) encoding a 65-kDa heat-shock protein. Twenty-one distinct hsp65 alleles were identified. On the basis of hsp65 genotype, 6 isolates were not MAC organisms. Of the remaining 130 samples, 61% were M. avium, 37% were Mycobacterium intracellulare, and 2% were species nonspecific MAC. Eighty-eight percent of the isolates obtained from HIV-infected children were M. avium. In contrast, only 38% of the isolates obtained from children without HIV infection were M. avium (chi2 test, P < .001). M. avium isolates were further subtyped by Southern blot analysis with insertion element IS1245. Taken together, no evidence for a single clonal M. avium strain causing infection was detected.

AIDS-Related Opportunistic Infections↗

PubMed1994

Utility of paired blood cultures and smears in diagnosis of disseminated Mycobacterium avium complex infections in AIDS patients.

For 273 patients evaluated for disseminated Mycobacterium avium complex infection, a total of 1,047 mycobacterial blood cultures (MBCs) were submitted; the M. avium complex was recovered from 140 (13%) of the specimens. Results for the paired MBCs were highly concordant: in 392 of 462 (85%) culture sets, both MBCs were negative, in 53 of 462 (11%) sets, both MBCs were positive, and in only 17 of 462 (4%) sets was one culture positive and the other negative. Acid-fast smears were done on sediments from 671 specimens; smears were positive for 4 of 98 (4%) cultures that grew the M. avium complex. A single MBC should be obtained and then repeated if negative and disseminated M. avium complex infection is still clinically suspected. Use of direct acid-fast smears of sediments is not a reliable means of detecting mycobacteremia.

AIDS-Related Opportunistic Infections↗

PubMed1999

Effect of clarithromycin regimen for Mycobacterium avium complex pulmonary disease.

We have investigated the efficacy of a clarithromycin-containing four-drug regimen for Mycobacterium avium complex (MAC) pulmonary disease in 46 patients without acquired immunodeficiency syndrome (AIDS). The patients were 14 males and 32 females with a mean age of 60.9 +/- 11.5 yr. Patients received 10 mg/kg/d of clarithromycin plus ethambutol, rifampin, and initial kanamycin and subsequent quinolone for 24 mo. Seven patients (15.2%) were dropped in the first 6 mo. Among 39 patients who received more than 6 mo of therapy, 28 patients (71.8%) converted their sputa to negative: 26 of 31 patients (83.9%) infected with clarithromycin-susceptible strains and two of eight patients (25.0%) with resistant or intermediate strains. The timing of sputum conversion was 3.6 +/- 1.9 mo, with a range of 2 to 9 mo. The conversion rate was significantly lower in patients who were infected with clarithromycin-resistant or intermediate strains, who had had prior therapy (55.0% versus 89.5%), or who were acid-fast bacilli (AFB) smear-positive at entry (60.7% versus 100%). The age and sex of patients, the species of pathogen (M. avium or M. intracellulare), type and extent of the disease, and the use of kanamycin did not significantly affect the conversion rate. Although the regimen was efficacious for newly treated patients, frequent adverse reactions and a low conversion rate of sputum in retreated patients are problems that remain to be solved.

Adult↗

PubMed1989

In vitro activities of several new macrolide antibiotics against Mycobacterium avium complex.

The in vitro activities of 12 macrolide compounds against 28 Mycobacterium avium complex strains isolated from patients with acquired immunodeficiency syndrome were determined by the conventional proportion method and by the BACTEC method. Clarithromycin (A-56268; TE-031), a new macrolide compound, was the most active agent tested, inhibiting 90% of strains at an MIC of 4 micrograms/ml by the BACTEC method. Roxithromycin (RU 28965) and erythromycylamine inhibited 90% of strains at 16 micrograms/ml. The organisms showed high levels of resistance to most other macrolide compounds.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

A case of Mycobacterium avium complex infection showing solitary pulmonary mass.

We report a case of Mycobacterium avium complex (MAC) infection showing a solitary pulmonary mass. High-resolution computed tomography (CT) revealed a well-defined, lobulated mass (32x25 mm) without calcification, cavitation, or bronchiectasis on the right upper lobe. There were no abnormalities in other sites of the lung even on high-resolution CT. The diagnosis was established by open lung needle biopsy. The patient exhibited a large solitary pulmonary mass caused by MAC infection, suggesting that, although the incidence is rare, MAC infection can show a solitary mass that is radiographically indistinguishable from lung cancer.

Biopsy, Needle↗

PubMed1997

Surgical management of Mycobacterium avium complex disease.

Between July 1991 and October 1996, eight patients with Mycobacterium avium complex (MAC) underwent pulmonary resection in our department. There was equal distribution of men women. The length of the preoperative period averaged 8.1 months (range: 1 to 30 months). Surgical resection was complete, consisting of lobectomy in 4 patients, lobectomy with partial resection in 2, segmentectomy in 1, and segmentectomy with partial resection in 1. There were no major complications postoperatively. No patients had positive sputum culture with MAC just after operation; however, one patient had positive sputum culture 6 months after operation. Our results show the good outcome of resectional surgery for MAC in properly selected patients, who should be operated as early as possible.

Female↗

PubMed1994

Comparison of virulence of Mycobacterium avium complex (MAC) strains isolated from AIDS and non-AIDS patients.

Mycobacterium avium complex (MAC) strains from AIDS and non-AIDS patients and from the environment were studied for their colony morphology and virulence in beige mice. The majority of the MAC isolates from AIDS patients, in contrast to those from non-AIDS patients and the environment, showed increased virulence. Similarly, the majority of the MAC isolates from AIDS patients formed smooth transparent (ST) colonies, whereas most of the non-AIDS isolates formed smooth opaque (SO) or intermediate (IM) type of colonies. MAC isolates from the same AIDS patient obtained at different times were found to be heterogenic with respect to serotype, RFLP and glycolipid patterns, suggesting that these patients might be infected with more than one strain of MAC.

AIDS-Related Opportunistic Infections↗

PubMed2003

Hospital water as a source of Mycobacterium avium complex isolates in respiratory specimens.

The clinical significance of recovery of Mycobacterium avium complex (MAC) organisms from respiratory specimens is poorly understood. One hundred sixty-one respiratory MAC isolates from 131 patients at Grady Memorial Hospital (Atlanta) and 13 MAC isolates from the hospital's hot water system were examined. Of the 131 patients, 35 (27%) had MAC disease, and 96 (73%) did not; 94 (72%) were human immunodeficiency virus infected. Ten different clusters were identified by pulsed-field gel electrophoresis. Patients without MAC disease were significantly more likely to have clustered isolates than were patients with MAC disease. Of 110 MAC isolates recovered from patients without MAC disease, 72 (65%) were part of a single large cluster that contained isolates recovered from the hospital's hot water system; 13 (25%) of 51 isolates from patients with MAC disease were also in this cluster. We conclude that acquisition of MAC from institutional water systems leads to substantial MAC disease but that most patients with MAC recovered from respiratory specimens have only transient colonization by MAC.

Carrier State↗

PubMed1997

Mycobacterium avium complex infection. Pharmacokinetic and pharmacodynamic considerations that may improve clinical outcomes.

Mycobacterium avium complex (MAC) is an infrequent pulmonary pathogen in immunocompetent hosts. In patients with AIDS, MAC causes disseminated infection (DMAC) in up to 50% of those with CD4+ counts less than 100 cells/mm3. A significant portion of the total body burden of MAC is found inside macrophages, and the distribution of organisms has implications for drug therapy. Clarithromycin, azithromycin, and rifabutin all appear to enter these cells well; rifampicin (rifampin), ethambutol, ciprofloxacin, and other agents also appear to enter these cells. MAC susceptibility is probably best tested using the radiometric method (BACTEC). Susceptibility break-points have been proposed for the various anti-MAC agents; however, solid clinical correlations have been achieved only for clarithromycin. Further research is required to establish break-points for the other agents. Based on current data, azithromycin and clarithromycin appear to be key drugs in the treatment of MAC, while rifabutin has been used more often than rifampicin in studies involving patients with AIDS. Among the drugs traditionally used for M. tuberculosis (TB), ethambutol, rifampicin and streptomycin are perhaps the most useful for MAC. Amikacin and clofazimine may also be useful. The limited data available on AIDS patients with MAC, plus additional data from AIDS patients with TB, suggest that malabsorption of the oral antimycobacterial drugs is common. Some drugs (rifampicin and ethambutol) appear to be particularly affected. Because most of the studies of DMAC have not evaluated the pharmacokinetics of the drugs, questions of drug efficacy cannot be separated from questions of biovailability. This significant oversight in study design should be eliminated from future investigations. Patient-specific susceptibility data combined with therapeutic drug monitoring and dosage individualisation is one way to identify problems with drug therapy and to overcome them. Because many of the drugs used in patients with AIDS affect the metabolism of concurrently used drugs, therapeutic drug monitoring is a valuable asset for untangling multiple drug interactions. Since drug therapy is the only aspect of a mycobacterial infection within our control, the better we control the drug therapy, the better our patients should do.

AIDS-Related Opportunistic Infections↗

PubMed1992

Comprehensive approach to identification of serovars of Mycobacterium avium complex.

Serotyping of nontuberculous mycobacteria, especially those of the Mycobacterium avium complex, provides important epidemiological information, particularly in tracing origins of infections. Seroagglutination with whole cells and polyclonal rabbit antibodies was the original way of identifying serovars and is still commonly used. The discovery of the glycolipid nature of the typing antigens allows differentiation of serovars on the basis of thin-layer chromatography of whole antigens and gas chromatography-mass spectrometry of the characteristic sugars of the oligosaccharide haptens of these antigens. In particular, the generation of monoclonal antibodies to the glycolipid antigens allows facile differentiation of serovars through enzyme-linked immunosorbent assay. All of these protocols were applied in developing a comprehensive approach to the typing of members of the M. avium complex.

Antibodies, Monoclonal↗

PubMed1994

Serovars of Mycobacterium avium complex isolated from patients in Denmark.

Danish isolates of Mycobacterium avium complex were serotyped by the use of seroagglutination. The most prevalent serovars among patients with AIDS (n = 89) were 4 and 6, while among non-AIDS patients the most prevalent serovars were 1, 6, and 4, with no major differences between those in patients with pulmonary disease (n = 65) and those in patients with lymph node infection (n = 58). The results suggest a Scandinavian distribution of serovars with a predominance of serovar 6 and fail to demonstrate any selective protection against different serovars by Mycobacterium bovis BCG vaccination.

Acquired Immunodeficiency Syndrome↗

PubMed1997

Distribution of serotypes, IS901 and a 40 kDa protein in Mycobacterium avium complex strains isolated from man and animals in Denmark.

The aim of the present study was to characterize all strains of the Mycobacterium avium complex isolated in Denmark in 1993. A total of 141 M. avium complex strains (86 from man, 38 from animals, and 17 from peat) were analysed by serotyping, ELISA specific for a 40 kDa protein, and IS901-specific PCR. Serotype analysis showed that the most frequent serotypes among human strains were serotype 4 (27%) and serotype 6 (19%), which differs from an earlier survey where serotype 1 was most prevalent. The most frequent serotypes in animals were serotype 2 (53%) and serotype 6 (13%), whereas the most prevalent serotypes among strains isolated from peat were serotype 4 (29%) and serotype 9 (18%). There was a concurrent appearance of IS901 and p40 in all strains. Only M. avium complex strains isolated from animals, and belonging to serotype 1 or serotype 2, contained the IS901/p40 markers. The different distribution of serotypes of M. avium complex strains in animals and man, and the presence of IS901/p40 exclusively in animal strains, suggests that transmission of M. avium from animals to man is not of significance in Denmark.

Animals↗

PubMed2001

No beneficial effect of interferon-gamma treatment in 2 human immunodeficiency virus-infected patients with Mycobacterium avium complex infection.

Two human immunodeficiency virus-infected patients with refractory disseminated Mycobacterium avium complex infection were treated with recombinant interferon-gamma (IFN-gamma) given subcutaneously for 3 and 4 months, respectively. Although both patients demonstrated some clinical improvement initially, IFN-gamma therapy did not produce sustained benefit.

AIDS-Related Opportunistic Infections↗

PubMed1996

Clarithromycin against Mycobacterium avium complex infections.

The turning point in antimicrobial therapy of Mycobacterium avium infections came with the development of two new macrolides, clarithromycin and azithromycin. Controlled clinical trials, the first ever conducted with any agent among patients with M. avium infection, indicated the high efficiency of clarithromycin, in either acquired immune deficiency syndrome (AIDS) patients having a disseminated infection or non-AIDS patients with localized pulmonary disease. Monotherapy with clarithromycin resulted in elimination of bacteremia in almost all patients with disseminated infection, which is inevitably followed by a relapse of bacteremia in patients who survived long enough to reach this event. The strains susceptible to clarithromycin isolated before therapy contained 10(-8) or 10(-9) resistant mutants, and the relapses of bacteremia were caused by multiplication of these pre-existing mutants. Clarithromycin-resistance was associated with a mutation in the 23S rRNA gene. Cross-resistance between clarithromycin and azithromycin was confirmed with laboratory mutants and clinical isolates. At least two methods for determining the susceptibility of the M. avium isolates to clarithromycin are available: one is minimum inhibitory concentration (MIC) determination on Mueller-Hinton agar (pH 7.4) supplemented with 10% Oleic acid-albumin-dextrose catalase, the other is MIC determination in 7H12 broth, also at pH 7.4. The breakpoints for 'susceptible' for these methods are < or = 8.0 micrograms/ml and < or = 2.0 micrograms/ml, respectively. The breakpoints for 'resistant' are > 128 micrograms/ml for the agar method and > 32.0 micrograms/ml for the broth method. The predictability value of MIC determination was confirmed by comparing the test results with the patients' clinical and bacteriological response to therapy. The remaining major problem in the therapy of the M. avium infections is a selection of companion drugs to be used in combination with clarithromycin (or azithromycin) to prevent the emergence of the macrolide-resistance. A number of clinical trials are now in progress to find a solution to this problem.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

Mycobacterium avium complex (MAC): an unusual potential pathogen in cerebrospinal fluid of AIDS patients.

Mycobacterium avium complex (MAC) is frequently isolated from patients with late complications of Acquired Immunodeficiency Syndrome (AIDS), especially in North America and Europe. However, its isolation from the central nervous system (CNS) has been seldom reported in these countries. MAC infections in AIDS patients in African and Latin American countries are believed to be uncommon. We report the isolation of MAC from cerebrospinal fluid (CSF) of 11 AIDS patients out of 1723 (0.63%) seen at "Centro de Referência e Treinamento-AIDS", São Paulo and discuss the significance of its isolation.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Molecular epidemiology of Mycobacterium avium complex isolated from patients with and without AIDS in Brazil and England.

Mycobacterium avium complex (MAC) is ubiquitous throughout the world. It is an opportunistic pathogen in AIDS patients but the number of cases in HIV negative patients is also increasing. The aim of this study was to determine whether patients were being infected with different MAC strains or whether one strain was dominant. DNA obtained from isolates in Brazil and England were compared using pulsed field gel electrophoresis (PFGE). Strains from 22 Brazilian patients clustered into 7 groups but 68/90 patients had a unique strain. In all patients, Brazilian and English, the same strain was isolated repeatedly over time, some over several years. This study shows that it is most likely that Man is infected from the environment and that one strain can survive without change for many years both in the environment and in Man.

AIDS-Related Opportunistic Infections↗