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PubMed2005

Mycobacterium avium complex infection in kidney transplant patients.

Mycobacterium avium complex (MAC) infections have been reported rarely in renal transplant patients. Consequently the clinical course and optimal treatment of these patients are not well understood. We present 3 patients with MAC infections after receiving a renal transplant (2 with generalized and 1 with localized infection). All patients were treated with combination antibiotic therapy and reduction of immunosuppression. One patient experienced clinical control of disease but a mild cellular rejection that was successfully treated with high-dose corticosteroids. One patient died of disseminated MAC infection. The patient with localized infection died of unrelated causes. In summary, MAC infection, although rare in renal transplant patients, may respond to combination antimicrobial therapy and reduction of immunosuppression.

Adult↗

PubMed1999

A randomized, placebo-controlled study of rifabutin added to a regimen of clarithromycin and ethambutol for treatment of disseminated infection with Mycobacterium avium complex.

Current guidelines suggest that disseminated Mycobacterium avium complex (MAC) infection be treated with a macrolide plus ethambutol or rifabutin or both. From 1993 to 1996, 198 AIDS patients with MAC bacteremia participated in a prospective, placebo-controlled trial of clarithromycin (500 mg b.i.d.) plus ethambutol (1,200 mg/d), with or without rifabutin (300 mg/d). At 16 weeks, 63% of patients in the rifabutin group and 61% in the placebo group (P = .81) had responded bacteriologically. Changes in clinical symptoms and time to survival were similar in both groups. Development of clarithromycin resistance during therapy was similar in the two groups; of patients who had a bacteriologic response, however, only 1 of 44 (2%) receiving rifabutin developed clarithromycin resistance, vs. 6 of 42 (14%) in the placebo group (P = .055). Thus, rifabutin had no impact on bacteriologic response or survival but may protect against development of clarithromycin resistance in those who respond to therapy.

AIDS-Related Opportunistic Infections↗

PubMed1989

Amikacin, ciprofloxacin, and imipenem treatment for disseminated Mycobacterium avium complex infection of beige mice.

The Mycobacterium avium complex (MAC) is a common cause of disseminated infection in patients with acquired immunodeficiency syndrome and is increasingly seen as a cause of infection in other immunocompromised patients. Traditional antimycobacterial therapy often is ineffective, and there is a clear need for antibiotics with proven activity against the MAC. Three agents, amikacin, ciprofloxacin, and imipenem, were tested in vitro for activity against MAC strain 101. Amikacin was bacteriostatic, with an MIC of 4.8 micrograms/ml, which is significantly lower than the concentration in serum obtained with standard dosing. Imipenem and ciprofloxacin had little or no activity alone (MICs, greater than 16 and 4.7 micrograms/ml, respectively), but when they were combined with amikacin there was bactericidal activity. Each agent was tested individually and in combination by using the beige mouse model of disseminated MAC infection. There was no mortality in a group of animals infected with MAC 101 and treated with amikacin alone; also, there was a significant decrease in the infection of the blood, liver, and spleen. There was no apparent improvement in therapeutic effectiveness when amikacin was combined with the other agents. Neither ciprofloxacin nor imipenem was active as a single agent, which was consistent with the in vitro activities of these agents. Amikacin in combination with traditional antimycobacterial agents warrants further study as potential therapy for disseminated MAC infections.

Amikacin↗

PubMed2000

[A study on the effect of combined chemotherapy on Mycobacterium avium complex pulmonary disease].

Annual incidence of Mycobacterium avium complex (MAC) pulmonary disease has been gradually increasing in the last 10 years in Japan, however, the optimal therapeutic regimen for the disease has not yet established. We investigated the effect of our new regimen in twenty seven cases of pulmonary MAC infection without HIV infection, diagnosed according to the American Thoracic Society criteria during the period from January 1996 to October 1997 at our hospital. These patients were treated with rifampicin (RFP), ethambutol (EB) and clarithromycin (CAM) for more than 12 months, together with streptomycin (SM) initially (first 2-3 months), except one patient who was treated for 11 months only. Twenty-four months after the therapy, sputum cultures converted from positive to negative in 13 patients and the amount of bacilli in sputum reduced in two patients. The radiological findings improved in 10 patients, showed no significant changes in 11 patients, while worsened in the remaining 6 patients. As to adverse reactions 1 case of liver damage, 3 cases of skin disorders, 4 cases of gastrointestinal malfunctions, and 1 case of optic neuritis were observed. This regimen was safe and tolerable even in the elderly outpatients, but not so effective against MAC pulmonary disease compared with the results of recent reports from the U.S. and Europe. Size of pulmonary lesions was closely associated with the effectiveness in this study. However, five bacteriologically converted cases did not show radiological improvement, and the reasons behind this fact remain to be investigated.

Adult↗

PubMed1993

Comparison of four decontamination methods for recovery of Mycobacterium avium complex from stools.

The presence of Mycobacterium avium complex (MAC) in stool specimens may be a predictor of disseminated MAC infection, yet the methods for decontaminating stools have not been evaluated for their usefulness in recovering MAC organisms. In the present study, four decontamination methods commonly used to recover acid-fast bacteria from respiratory specimens were compared for their utility in recovering MAC from stool specimens. Ten strains of MAC were used at a level of 10(4) to 10(6) CFU to seed the stool specimens. Specimens were divided into four portions and were decontaminated by using the following treatments: (i) N-acetyl-L-cysteine-sodium hydroxide (NALC-NaOH), (ii) cetylpyridinium chloride-sodium chloride (CPC-NaCl), (iii) oxalic acid, or (iv) benzalkonium chloride-trisodium phosphate (BC-TSP). The specimens were then plated onto a total of five pieces of selective and nonselective egg- and agar-based media. The oxalic acid method yielded the greatest number of MAC CFU from seeded stool samples; this was followed by NALC-NaOH, BC-TSP, and CPC-NaCl. The difference between the oxalic acid method and each of the other methods was statistically significant (analysis of variance at the 95% significance level). Although more MAC CFU was recovered from seeded stool samples by using oxalic acid than NALC-NaOH, no difference in culture positivity rates was observed when the two methods were used to test 368 clinical stool specimens processed with either oxalic acid (164 specimens) or NALC-NaOH (204 specimens) (P = 0.07) or 67 specimens processed by both methods (P = 0.77). The oxalic acid and NALC-NaOH decontamination methods both appear to be useful for the recovery of MAC organisms from stool specimens.

AIDS-Related Opportunistic Infections↗

PubMed1996

Liposomal amikacin: improved treatment of Mycobacterium avium complex infection in the beige mouse model.

Disseminated Mycobacterium avium complex (MAC) infection has reached epidemic proportions and is a major cause of morbidity and mortality in AIDS patients. We have developed a liposomal preparation of amikacin, VS107, which incorporates the drug in 54-65 nm diameter unilameller phospholipid vesicles and is stable at 4 degrees C for more than 4 months. VS107 exhibits superior microbiological and pharmacological activity over the free amikacin and improves the survival of mice in the established model for MAC infection. The serum half-life of VS107 in mice was 9.1 h and a peak serum level of 730 mg/L was obtained after administering three doses of 160 mg/kg. For the therapeutic study, beige mice infected with 10(7) cfu M. avium complex strain 101 were randomised to be treated with placebo liposomes, buffer, free amikacin or VS107 The drugs were administered via the caudal vein thrice weekly for 1, 3, 5 or 7 weeks beginning 5 days after infection. After 51 days of treatment with VS107, the number of viable M. avium in the liver and spleen was a 100 fold lower than was achieved with conventional amikacin (P < 0.01), and more than six decimal logarithms lower than was found untreated controls (P < 0.001). VS107 was well tolerated and might be a suitable candidate for treating human MAC infections.

Amikacin↗

PubMed2005

[Three sisters of pulmonary Mycobacterium avium complex disease].

We reported three sisters of pulmonary Mycobacterium avium complex (MAC) disease. The oldest sister was complaining of bloody sputum, and cultures were positive for M. avium. By monotherapy with clarithromycin, symptom and imaging findings had shown no progression for six years. The second sister was complaining of productive cough, and cultures were positive for M. intracellulare. Her symptom and imaging findings had shown no progression for seven years without any treatment. The third sister had rheumatoid arthritis and diabetes mellitus, and cultures were positive for M. intracellulare. Although she received chemotherapy with rifampicin, clarithromycin, ethambutol, and kanamycin, symptom and imaging findings had progressed gradually. She died of respiratory failure four years later. Autopsy findings revealed no disseminated MAC disease. The results which three cases showed different isolate patterns and clinical courses suggest the importance of underlying anti-mycobacterial immunological impairment and defects of local host defense rather than virulence of infected strains as the pathogenesis of pulmonary MAC disease.

Aged↗

PubMed2005

Mycobacterium avium complex pulmonary disease in immunocompetent patients.

Mycobacterium avium complex is becoming increasingly recognized as one of the most common mycobacterial pathogens in humans. It is rapidly becoming a significant cause of pulmonary disease even in those with an intact immunity. In 1997, the American Thoracic Society published recommendations for the diagnosis and treatment of nontuberculous mycobacteria. On the basis of the authors' clinical experience of the myriad presentations of pulmonary Mycobacterium avium complex disease in an immunocompetent host, a clinical classification is proposed. The current data are summarized, and a practical approach to management of the various pulmonary forms of the disease is provided.

Alveolitis, Extrinsic Allergic↗

PubMed1996

Rapid detection of mutations associated with macrolide resistance in Mycobacterium avium complex.

Macrolide resistance in Mycobacterium avium can be detected with an adaption of a commercially available RNA/RNA duplex mismatch assay (Ambion, Austin, Tex.). The sensitivity and specificity values for the assay were 100% when evaluated against 41 macrolide-resistant and -susceptible strains of M. avium. Resistant subpopulations of approximately 20% could be readily detected. The assay is simple to perform and interpret, inexpensive, and rapid (< 24-h turnaround).

Anti-Bacterial Agents↗

PubMed1988

Tumor necrosis factor, alone or in combination with IL-2, but not IFN-gamma, is associated with macrophage killing of Mycobacterium avium complex.

Organisms belonging to the Mycobacterium avium complex (MAC) are the most common bacterial pathogens in patients with AIDS but factors associated with the activation of cellular defense mechanisms against this atypical mycobacterium have not been defined. Peritoneal macrophages harvested from a chronic MAC infection in C57 black mice are able to kill approximately 86% of intracellular MAC in contrast to 0 to 20% killing by unstimulated human and mouse macrophages in vitro. The availability of human rTNF-alpha, rIFN-gamma, and rIL-2 permitted evaluation of the role of each of these lymphokines/monokines, alone or in combination, in activating macrophages in vitro to kill MAC. Human monocyte-derived macrophages were cultured in vitro, stimulated with rIL-2, rIFN-gamma, or rTNF, and then infected with MAC (serovars 1 and 8). Mouse peritoneal macrophages were harvested, cultured in vitro, and stimulated with rIFN-gamma. rTNF (10(4) U/ml) was associated with a modest increase of intracellular killing of MAC (58 +/- 5%) even when utilized 24 or 48 h after macrophage infection or when administered for 5 consecutive days after infection (78.1 +/- 4%). Both human and murine IFN-gamma were associated with increased intracellular growth of MAC (32 +/- 4% for murine and 38 +/- 3% for human macrophages). However, intracellular killing (53 +/- 6% compared with control) was observed after 6 days of treatment with IFN-gamma. This latter effect was fully blocked by anti-TNF antibody, whereas rIL-2 alone did not augment the intracellular killing of MAC by human macrophages. rTNF plus either rIFN-gamma or rIL-2 triggered significant increases in superoxide anion production, but subsequent MAC killing was no greater than with rTNF alone. Treatment of macrophages with 10 U/ml of rTNF followed by rIL-2 (200 U/ml) was associated with 68% of intracellular killing. TNF seems to be an important monokine, promoting activation of mycobactericidal mechanisms in human macrophages.

Animals↗

PubMed2003

Mycobacterial interspersed repetitive units (MIRU) differentiate Mycobacterium avium subspecies paratuberculosis from other species of the Mycobacterium avium complex.

Mycobacterial interspersed repetitive units (MIRU) comprise short tandem repeat structures found at multiple loci throughout the Mycobacterium tuberculosis genome and have been used for typing these pathogens. We have identified MIRU at 18 conserved loci throughout the common portions of the Mycobacterium avium subspecies paratuberculosis (MAP) and M. avium subspecies avium (MAA) genomes. Six of these loci were found to differ between MAA and MAP in the number of tandem repeat motifs occurring at each MIRU locus. Locus specific PCR at 4 of these loci segregated MAP into two major groups, which could be differentiated from ovine-pigmented strains of MAP and the MAP vaccine strain 316F. The same PCR differentiated MAA into five MIRU profiles. PCR at either MIRU locus 1 or MIRU locus 4 distinguished between MAP and all other M. avium complex (MAC) tested. PCR at both loci 1 and 4 also distinguished MAP from Mycobacterium intracellulare. MIRU typing may provide an additional simple and rapid procedure for the differentiation between MAP and other MAC.

Amino Acid Sequence↗

PubMed1998

Polyclonal Mycobacterium avium complex infections in patients with nodular bronchiectasis.

Mycobacterium avium complex (MAC) isolates among patients with chronic lung disease were studied for their heterogeneity using genetic identification methods, pulsed field gel electrophoresis (PFGE) and seroagglutination. A mean of 7.3 cultures per patient were collected from 17 patients with nodular bronchiectasis who were elderly (mean age 66 yr), predominantly female (76%), had smoked a mean of only 5 pack-years, and had multifocal bronchiectasis. A mean of 7.7 cultures per patient were collected from nine patients with upper lobe cavitary disease who were younger (mean age 52 yr), predominantly male (78%), and heavy smokers (mean 56 pack-yr). A mean of 2.9 PFGE types (genotypes) per patient (range, 1 to 9) were identified in the nodular bronchiectasis group, with 15 of 17 patients (88%) having two or more genotypes and 9 of 17 (53%) having three or more genotypes. In contrast a mean of 1.2 genotypes were identified in the patients with cavitary disease, with only 1 of 9 (11%) having two or more genotypes. Mycobacterium intracellulare was the most frequently recovered genotype in both groups and most isolates were rough or nontypable by seroagglutination. Some genotypes from the same patient considered different by current PFGE criteria had the same serotype and shared 11 to 20 common PFGE bands, suggesting they were related. These data demonstrate that patients with nodular bronchiectasis have multiple and/or repeated infections due to MAC whereas patients with upper lobe cavitary disease are usually infected with only a single strain.

Adult↗

PubMed2001

Isolated intrathoracic presentation of Mycobacterium avium complex in an immunocompetent child.

Mycobacterium avium complex (MAC) is a rare cause of isolated intrathoracic disease in the immunocompetent child; delays in diagnosis and treatment are common. The current case is an 11-month-old girl with symptoms, signs, and radiographic findings of bronchial obstruction. Comparison of this case to the literature revealed that there is a characteristic presentation of intrathoracic MAC infection in immunocompetent children (children aged 3 years or less, without exposure to Mycobacterium tuberculosis, presenting with clinical and radiographic evidence of bronchial obstruction) that should increase our index of suspicion for this diagnosis. This is particularly important since M. tuberculosis can present in a similar pattern.

Bronchography↗

PubMed1994

Mycobacterium avium complex: advances in therapy.

Disseminated Mycobacterium avium complex (MAC) is one of the most common opportunistic infections in AIDS patients and is increasingly recognized as a significant pathogen in chronic pulmonary disease in nonimmunocompromised patients. Important progress in therapy has occurred over the last several years. In AIDS patients, multidrug therapy has been shown to be beneficial in terms of reducing circulating bacteremia and improving clinical symptoms. Clarithromycin and azithromycin, two broad-spectrum antimicrobials with minimal activity against Mycobacterium tuberculosis, have emerged as potent, well tolerated agents pivotal to treatment regimens. In AIDS patients, rifabutin prophylaxis reduced the frequency of MAC bacteremia by 50% in two placebo controlled trials. Despite these advances, there remains a need for determining the optimal combination regimens for therapy, and more effective drugs for prophylaxis which are beneficial both in terms of survival and functional capacity of patients.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

[Treatment and prevention of Mycobacterium avium complex infection in AIDS].

Since Mycobacterium avium complex (MAC) infects most, if not all, HIV-positive patients, effective regimens for its treatment and prophylaxis are a necessity. We review here the available literature in an attempt to establish clear-cut criteria for the administration of antibiotics and immunotherapy and for the prophylactic treatment of MAC infections. Several antibiotics, chiefly in combination regimens, are active against MAC. Recent data indicate rifabutin as a first-line antibiotic for the treatment of MAC infections. However, since this antibiotic accelerates hepatic metabolism of many drugs (zidovudine in particular), it has the potential to reduce their serum concentrations and hence limit their antiviral activity. Moreover, rifabutin is active against retroviruses only at extremely high concentrations which are not reached in vivo at normally-prescribed dosages. The recent demonstration that the cytokine interferon-gamma (IFN-gamma) in combination with conventional antibiotic therapy may be effective for disseminated MAC infections indicates that immunotherapy could play a pivotal role in the treatment of MAC infections. Lifetime prophylaxis with rifabutin (300 mg/die) is advised for all patients with HIV infection and fewer than 100 CD4 T lymphocytes/mm3 in the peripheral blood: this antibiotic regimen significantly reduces the frequency of disseminated MAC infections. Further studies are required to evaluate the effectiveness of other prophylactic regimens such as azithromycin and clarithromycin. We conclude that rifabutin and immunotherapy with IFN-gamma will play a key role in the treatment of MAC infections.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Cellular immune responses to ESAT-6 discriminate between patients with pulmonary disease due to Mycobacterium avium complex and those with pulmonary disease due to Mycobacterium tuberculosis.

ESAT-6 (for 6-kDa early secreted antigenic target) is a secreted antigen found almost exclusively in organisms of the Mycobacterium tuberculosis complex. We compared in vitro gamma interferon (IFN-gamma) responses by peripheral blood mononuclear cells to this antigen in patients with pulmonary disease due to either Mycobacterium avium complex (MAC) or Mycobacterium tuberculosis with those in healthy, skin test-negative, control subjects. Significant IFN-gamma responses to ESAT-6 were detected in 16 (59%) of 27 M. tuberculosis pulmonary disease patients, 0 (0%) of 8 MAC disease patients, and 0 (0%) of 8 controls. Significant IFN-gamma responses to M. tuberculosis purified protein derivative were detected in 23 (85%) of 27 M. tuberculosis disease patients, 2 (25%) of 8 MAC disease patients, and 5 (63%) of 8 healthy controls. M. avium sensitin was recognized in 24 (89%) of 27 M. tuberculosis disease patients, 4 (50%) of 8 MAC disease patients, and 1 (13%) of 8 controls. IFN-gamma responses to ESAT-6 are specific for disease due to M. tuberculosis and are not observed in patients with MAC disease or in healthy controls.

Adult↗

PubMed2006

Distribution of hsp65 PCR-restriction enzyme analysis patterns among Mycobacterium avium complex isolates in Thailand.

A total of 227 clinical Mycobacterium avium complex isolates from Thailand were differentiated into species and types by using PCR-restriction enzyme analysis of hsp65. The distribution of types showed the predominance of M. avium I (77%) in blood specimens, whereas M. intracellulare I was more commonly found in pulmonary specimens (44.2%). In addition, infections with M. avium were more likely to be found in younger adults (20 to 39 years old), while infections with M. intracellulare were more likely to be found in older adults (> or =60 years old). Our results provide the useful epidemiological information that some particular types have more invasive and virulent characters than others.

Adolescent↗

PubMed1993

Conventional identification characteristics, mycolate and fatty acid composition, and clinical significance of MAIX AccuProbe-positive isolates of Mycobacterium avium complex.

A total of 145 isolates belonging to the Mycobacterium avium complex (MAC) were tested with commercial acridinium ester-labeled DNA probes (AccuProbe, Gen-Probe). M. avium and M. intracellulare probes reacted with 102 and 36 isolates, respectively. The remaining seven isolates were clearly positive with the new probe, designated MAIX. Thus, the combined sensitivity of M. avium and M. intracellulare probes was 95.2%. The MAIX probe improved the sensitivity up to 100%. The MAIX probe also reacted with all M. avium (n = 20) and M. intracellulare (n = 20) isolates tested. Three of the seven MAIX-positive isolates were considered clinically significant. We conclude that the new MAIX probe should be used, in addition to M. avium and M. intracellulare probes, for the identification of MAC isolates. Our results also suggest that the probe may be used alone to cover the whole MAC when species differentiation is not required.

Bacterial Typing Techniques↗