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PubMed1999

Efficacy and safety of an intravenous induction therapy for treatment of disseminated Mycobacterium avium complex infection in AIDS patients: a pilot study.

Monotherapy with macrolides for the treatment of disseminated Mycobacterium avium complex (MAC) bacteraemia leads to drug resistance and relapse of bacteraemia. Gastrointestinal intolerance is a common reason for treatment withdrawal of multidrug regimens. We have assessed the efficacy and safety of initial parenteral therapy together with a macrolide, for disseminated MAC infection, defined as two positive blood cultures, in AIDS patients. Patients received a daily infusion of amikacin 15 mg/kg + ethambutol 20 mg/kg + ciprofloxacin 400 mg/day, for 1 month, together with a macrolide by oral route. Fifteen patients were included and 13 (86%) achieved negative culture before the end of parenteral therapy.

AIDS-Related Opportunistic Infections↗

PubMed1993

[Activity of defensins from human neutrophils against Mycobacterium avium complex].

We examined the activity of defensins from human neutrophils against Mycobacterium avium complex (MAC). MAC were cultured in the presence of defensins at 37 degrees C for 4-48 hours. After incubation, colony counts were enumerated by colony-forming units (CFU). Human neutrophil peptide-1 (HNP-1) at 5 micrograms/ml had the ability to kill MAC. We tested 8 strains of MAC. HNP-1 was successful in killing every strain, although the degree of killing varied from strain to strain. We also found that HNP-2 and HNP-3 were as effective in killing MAC as HNP-1. We suggest that defensins play an important role in the host defenses against MAC.

Blood Bactericidal Activity↗

PubMed1992

In vitro, in vivo, and intracellular chemotherapeutic activity of B746, a clofazimine analogue against Mycobacterium avium complex.

B746, an analogue of clofazimine, was compared with the parent compound for its activity against Mycobacterium avium complex (MAC), using several methods. All the studies using simulated in vivo conditions, and those with macrophages from healthy mice or from those treated with these drugs, revealed B746 to be similar to clofazimine. When used alone against experimental MAC infections in beige mice, B746 required an optimal dose of 20 mg/kg. At that dose it proved to be inferior to clofazimine, given at the same dose, but was slightly superior to streptomycin given intramuscularly at 150 mg/kg. On the other hand, in combination with other drugs, it proved to be inferior when given along with either clofazimine or streptomycin. Addition of B746 did not improve the chemotherapeutic efficacy of streptomycin-clofazimine combination in the treatment of established MAC infections of beige mice.

Animals↗

PubMed1989

Studies on the mechanisms of the synergistic effects of ethambutol and other antibacterial drugs on Mycobacterium avium complex.

Synergistic effects of combinations of anti-mycobacterial drugs on Mycobacterium avium complex (MAC) in vitro was studied by radiometric respirometry. Pronounced synergy was seen for several drug combinations where ethambutol was found to be the key drug in the synergistic potentiation. Microcalorimetric studies show that a very rapid physico-chemical interaction occurs between the cell-surface of MAC and ethambutol. When MAC cells were pretreated with ethambutol and then subjected to streptomycin the thermal response significantly differed from that seen with MAC cells which had not been pretreated. The typical thermal effects of the interaction of ethambutol with live and UV-killed MAC cells was not seen with heat-killed MAC cells. It is proposed that specific cell-surface protein(s) act as receptors in the initial interaction with ethambutol.

Anti-Bacterial Agents↗

PubMed1996

Effect of ethambutol on emergence of clarithromycin-resistant Mycobacterium avium complex in the beige mouse model.

An animal model was developed for studying macrolide-resistant Mycobacterium avium complex (MAC) and to measure the effect of ethambutol on resistance. MAC-infected beige mice were given clarithromycin daily; the frequency of clarithromycin-resistant MAC after 8 and 12 weeks was 10(-3) and 10(-2), respectively. Combined ethambutol plus clarithromycin did not increase anti-MAC activity, but clarithromycin-resistant MAC was less frequent (P < .05). The frequency of clarithromycin-resistant MAC in mice receiving the combination was significantly higher than that in untreated mice. These results are consistent with two human trials, which showed that adding ethambutol reduced the frequency of clarithromycin-resistant MAC. Results of the present study suggest that with an initially high level of MAC infection, the addition of ethambutol may only delay resistance. This mouse test system will be useful for investigating the influence of the level of MAC infection and the effect of other drugs on the frequency of resistant MAC.

Animals↗

PubMed1991

Ethanol augments intracellular survival of Mycobacterium avium complex and impairs macrophage responses to cytokines.

Chronic ethanol ingestion predisposes to tuberculosis and bacterial pneumonia. Mycobacterium avium complex (MAC) organisms cause bacteremia in patients with AIDS. Cultured human monocyte-derived macrophages and murine Kupffer cells were exposed to 10-100 micrograms/dl ethanol; significantly greater intracellular growth of MAC strains 100 (serovar 8) and 101 (serovar 1) occurred in ethanol-treated cells than in controls (range, 58% +/- 7%-70% +/- 5%; P less than .05 for 50 and 100 micrograms/dl ethanol vs. control). Both cell types, when treated with 10(3) units/ml recombinant tumor necrosis factor (TNF) or 10(2) units/ml granulocyte-macrophage colony-stimulating factor (GM-CSF) in the presence of 10-100 micrograms/dl ethanol, killed significantly fewer MAC than controls (49% +/- 12% decrease for GM-CSF and 57% +/- 16% for TNF; P less than .05 for all comparisons). C57BL black mice infected intravenously with MAC strain 101 were given ethanol as 4% of total calories daily; after 21 days they had greater numbers of MAC in blood, liver, and spleen than controls. Ethanol's effects on the interaction between the host and MAC favor progressive infection.

Alcoholism↗

PubMed1997

The role of advanced generation macrolides in the prophylaxis and treatment of Mycobacterium avium complex (MAC) infections.

Since the start of the acquired immunodeficiency syndrome (AIDS) epidemic, the role of Mycobacterium avium complex (MAC) as an opportunistic pathogen in advanced AIDS patients has become more and more clear. Once identified in an advanced AIDS patient it is possible to find evidence that the MAC organism and infection is not only present in the pulmonary tree, but has also disseminated to a wide variety of body organs. Treatment of MAC or disseminated MAC (DMAC) infections has historically been very difficult due to the inherent resistance of the MAC pathogen to most standard antimycobacterial agents. This has resulted in the development of new agents for the prevention of DMAC infection as well as combinations of both new and standard agents for its treatment. Three drugs are currently approved for single-agent DMAC prophylaxis, including rifabutin, azithromycin and clarithromycin. Combinations of agents for DMAC treatment are highly variable in content but most experts agree that all combinations should contain one of the advanced generation macrolides (azithromycin or clarithromycin). Both of these agents have favourable intracellular pharmacokinetics and pharmacodynamics which maximise their effects against this mostly intracellular pathogen. Due to the paucity of comparative data, no one macrolide can be recommended over the other. However, the expected increase in compliance, lower weekly and annual costs, and lack of any drug interactions may make azithromycin a preferable choice, but this should be decided on a case-by-case basis.

Anti-Bacterial Agents↗

PubMed1993

Superoxide dismutase activity of Mycobacterium avium complex (MAC) strains isolated from AIDS patients.

OBJECTIVE: To explore whether Mycobacterium avium complex (MAC) strains isolated from AIDS patients produce and secrete superoxide dismutase (SOD). DESIGN: SOD was assayed in the crude extracts and in cell-free medium of 18 MAC strains (MAC 101, LR and SK strains) isolated from AIDS patients to determine intracellular and extracellular activity. The SODs were characterized by PAGE and by their sensitivity to azide, cyanide and hydrogen peroxide. RESULTS: SOD activity was detected in cell extracts as well as in extracellular medium of all AIDS-MAC strains. PAGE demonstrated a single activity band for each strain, though there were differences in mobility. All LR strains demonstrated an activity band with Rf = 0.30, while SOD band for MAC 101 and for SK strains migrated further (Rf = 0.87). The differences in mobility correlated with differences in sensitivity to NaN3 and H2O2. The SOD activity of LR strains was irreversibly inhibited 100% by 5 mM H2O2, and exhibited greater sensitivity to NaN3, suggesting the presence of iron in the enzyme. The SOD activity of SK strains and MAC 101, however, was not inhibited by 5 mM H2O2 but was inhibited to a lesser extent by NaN3, which is characteristic of a manganese-containing SOD. CONCLUSION: Our data indicate that MAC strains are rich in manganese- or iron-containing SOD, which could contribute to the organism's resistance to the oxidative burst of activated macrophages. The secretion of SOD may play an important role in the pathogenesis of MAC strains.

Acquired Immunodeficiency Syndrome↗

PubMed1990

Infection with Mycobacterium avium complex in Australian patients with AIDS.

Data supplied by tuberculosis reference laboratories in Australia indicate that from mid-1985 to the end of 1988, 202 patients with the acquired immunodeficiency syndrome (AIDS) were diagnosed as having concomitant infection caused by organisms of the Mycobacterium avium complex. This figure represents 17.3% of all AIDS cases diagnosed. Serotyping showed that the majority of isolates were serovars of M. avium, namely serovars 1, 4 and 8. There is evidence of geographic differences in the dominant serovar. Of 45 patients with isolates from more than one site of the body, 17 (38%) were infected with at least two different serovars. The findings show the importance of disseminated atypical mycobacteriosis in patients with AIDS, and they provide data for use in defining the epidemiology and natural history of such infections.

Acquired Immunodeficiency Syndrome↗

PubMed1997

[2 cases of lung disease caused by Mycobacterium avium complex occurred in middle-aged women without underlying disorders, which we observed for more than 30 years].

We reported 2 cases of Mycobacterium avium complex lung disease occurred in middle-aged women without underlying disorders, which we could observe for more than 30 years. One case was a 42-year-old woman started with bloody sputum, and the other was a 43-year-old woman with cough and sputum. In both cases, chest X ray films were normal on their first visit. More than 15 years after their first visit, Mycobacterium avium complex was isolated from their sputum or bronchial washing. During the observation, a cluster of small nodules in the periphery of the lung and bronchiectasis appeared and deteriorated, and excretion of the bacilli increased gradually. Their past history and family history were normal. Since lung disease caused by Mycobacterium avium complex progresses very slowly, long-time observation would be necessary to consider its pathogenesis.

Adult↗

PubMed1990

Serovars of Mycobacterium avium complex isolated from patients in Sweden.

The serovars of clinical isolates of Mycobacterium avium complex from 24 acquired immunodeficiency syndrome (AIDS) and 140 non-AIDS patients in Sweden were studied by using type-specific antisera. A wide distribution of serovars was seen. Serovar 6 was predominant in both groups of patients, isolated from 33 and 16% of the AIDS and non-AIDS patients, respectively. The results indicate geographical as well as disease-related differences in the distribution of M. avium complex serovars of clinical importance.

Acquired Immunodeficiency Syndrome↗

PubMed1990

Activities of clarithromycin, sulfisoxazole, and rifabutin against Mycobacterium avium complex multiplication within human macrophages.

The activities of clarithromycin, sulfisoxazole, and rifabutin against three virulent strains of Mycobacterium avium complex isolated from patients with acquired immunodeficiency syndrome were evaluated in a model of intracellular infection. Human monocyte-derived macrophages were infected at day 6 of culture with M. avium complex. Intracellular bacteria were counted 60 min after inoculation. Extra- and intracellular bacteria were counted at days 4 and 7 after inoculation. The concentrations used were 4 micrograms of clarithromycin per ml (MICs for the three strains, 4, 4, and 4 micrograms/ml), 50 micrograms of sulfisoxazole per ml (MICs, 50, 25, and 25 micrograms/ml), and 0.5 micrograms of rifabutin per ml (MICs, 2, 0.5, and 0.5 micrograms/ml). Compared with controls, clarithromycin and rifabutin slowed the intracellular replication of the three strains (at day 7 after inoculation, P was less than 0.01 for the first strain and less than 0.001 for the two others). Sulfisoxazole was ineffective against the three strains. Clarithromycin was as effective as rifabutin. Clarithromycin plus rifabutin was as effective as each single agent. Clarithromycin plus sulfisoxazole was as effective as clarithromycin alone.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Treatment and prophylaxis of disseminated Mycobacterium avium complex in HIV-infected individuals.

OBJECTIVE: To review the pathophysiology, epidemiology, treatment, and prophylaxis of disseminated Mycobacterium avium complex (MAC) infection in HIV-infected individuals. DATA SOURCES: A MEDLINE (January 1966-July 1997) and AIDSLINE (January 1980-July 1997) search of basic science articles pertinent to the MAC infection in HIV-infected patients. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in the review. Pertinent information, as judged by the authors, was selected for discussion. DATA SYNTHESIS: The organism, epidemiology, and pathophysiology of disseminated MAC are discussed for background. A review of clinical trials for the treatment and prophylaxis of disseminated MAC are presented, along with unresolved issues concerning these topics. CONCLUSIONS: The incidence of disseminated MAC has increased dramatically with the AIDS epidemic. The infection can lead to increased morbidity and mortality in HIV-infected patients. Treatment regimens for patients with a positive culture for MAC from a sterile site should include two or more drugs, including clarithromycin. Prophylaxis against disseminated MAC should be considered for patients with a CD4 cell count of less than 50/mm3.

4-Quinolones↗

PubMed1989

The hamster model of chronic Mycobacterium avium complex infection.

Male golden Syrian hamsters were evaluated as a model for the pathogenesis of human infection with Mycobacterium avium complex. Intratracheal inoculation produced a chronic, nonfatal, pulmonary and disseminated infection (overall rate, 86%). The frequency of infection in hamsters that received 5 x 10(8) versus 1 x 10(8) colony forming units (cfu) was not significantly different (87% and 92%, respectively), but 1 x 10(7) cfu produced infection in only 78% of inoculated animals (P = .034). The percentage of animals developing pulmonary infection with M. avium complex did not differ between inoculum groups (77%-80%). Disseminated infection occurred significantly less frequently in the 1 x 10(7) group (46%) compared with the 5 x 10(8) (79%) and 1 x 10(8) (68%) groups (P = .001 and .056, respectively). After seven weeks, partial clearance of M. avium complex from the lungs coincided with an increased number of animals with splenic involvement. The hamster may be a useful model for human infection with M. avium complex.

Animals↗

PubMed2001

Underuse of primary Mycobacterium avium complex and Pneumocystis carinii prophylaxis in the United States.

BACKGROUND: Little is known about the rates of Mycobacterium avium complex (MAC) and Pneumocystis carinii (PCP) prophylaxis adherence to guidelines and how they have changed after introduction of effective antiretroviral therapy. OBJECTIVE: To determine rates of primary prophylaxis for MAC and PCP and to evaluate the influence of sociodemographic characteristics, region, and provider experience. DESIGN: National probability sample cohort of HIV patients in care. SETTING: One hundred sixty HIV health care providers. PATIENTS: A total of 2864 patients interviewed in 1996 to 1997 (68% response) and 2267 follow-up interviews, representing 65% of surviving sampled patients (median follow-up, 15.1 months). MEASUREMENTS: Use of prophylactic drugs, most recent CD4 count, sociodemographics, and regional and total HIV patients/providers. RESULTS: Of patients eligible for primary MAC prophylaxis (most recent CD4 count <50/mm(3) ), 41% at baseline and 40% at follow-up patients were treated. Of patients eligible for primary PCP prophylaxis (i.e., those with CD4 counts <200/mm(3) ), 64% and 72% were treated, respectively. MAC prophylaxis at baseline was less likely in African American (adjusted odds ratio [OR], 35; 95% confidence interval [CI], 0.20-0.59), Hispanic (OR, 27; 95% CI, 0.08-0.94) and less-educated (OR, 0.61; 95% CI, 0.36-1.0) patients and more likely in U. S. geographic regions in the Pacific West (OR, 4.9; 95% CI, 1.0-23) and Midwest (OR, 6.4; 95% CI, 1.2-33) and in practices with more HIV patients. CONCLUSIONS: Most eligible patients did not receive MAC prophylaxis; PCP prophylaxis rates were better but still suboptimal. Our results support outreach efforts to African Americans, Hispanics, the less educated, and those in the northeastern United States and in practices with fewer HIV patients.

AIDS-Related Opportunistic Infections↗

PubMed1998

Preventing Mycobacterium avium complex in patients who are using protease inhibitors: a cost-effectiveness analysis.

BACKGROUND: Practice guidelines recommending Mycobacterium avium complex (MAC) prophylaxis for patients with HIV disease were based on clinical trials in which individuals did not receive protease inhibitors. OBJECTIVE: To estimate the cost-effectiveness of strategies for MAC prophylaxis in patients whose treatment regimen includes protease inhibitors. DESIGN: Decision analysis with Markov modelling of the natural history of advanced HIV disease. Five strategies were evaluated: no prophylaxis, azithromycin, rifabutin, clarithromycin and a combination of azithromycin plus rifabutin. MAIN OUTCOME MEASURES: Survival, quality of life, quality-adjusted survival, health care costs and marginal cost-effectiveness ratios. RESULTS: Compared with no prophylaxis, rifabutin increased life expectancy from 78 to 80 months, increased quality-adjusted life expectancy from 50 to 52 quality-adjusted months and increased health care costs from $233000 to $239800. Ignoring time discounting and quality of life, the cost-effectiveness of rifabutin relative to no prophylaxis was $44300 per life year. Adjusting for time discounting and quality of life, the cost-effectiveness of rifabutin relative to no prophylaxis was $41500 per quality-adjusted life year (QALY). In comparison with rifabutin, azithromycin was associated with increased survival, increased costs and an incremental cost-effectiveness ratio of $54300 per QALY. In sensitivity analyses, prophylaxis remained economically attractive unless the lifetime chance of being diagnosed with MAC was less than 20%, the rate of CD4 count decline was less than 10 x 10(6) cells/l per year, or the CD4 count was greater than 50 x 10(6) cells/l. CONCLUSION: MAC prophylaxis increases quality-adjusted survival at a reasonable cost, even in patients using protease inhibitors. When not contraindicated, starting azithromycin or rifabutin when the patient's CD4 count is between 50 and 75 x 10(6) cells/l is the most cost-effective strategy. The main determinants of cost-effectiveness are CD4 count, viral load, place of residence and patient preference.

AIDS-Related Opportunistic Infections↗

PubMed1990

Mycobacterium avium complex tenosynovitis of the index finger.

A rare case of tenosynovitis of the right index finger caused by Mycobacterium avium complex is reported. A high index of suspicion resulted in early culture-based diagnosis. Surgical synovectomy combined with a prolonged course of antituberculous medications resulted in normal hand function.

Female↗

PubMed2000

Lady Windermere syndrome: middle lobe bronchiectasis and Mycobacterium avium complex infection due to voluntary cough suppression.

An 81-year-old woman who presented with middle lobe bronchiectasis and Mycobacterium avium complex infection is described. She had a history of habitual suppression of cough, as in Lady Windermere syndrome. She was thin and had mild kyphoscoliosis but had no history of smoking or connective tissue disease. The middle lobe and lingula are predisposed to chronic inflammation because of their particular anatomic structures. Inability to clear the secretions from the airway due to voluntary cough suppression may predispose to bronchiectasis and M. avium complex infection.

Aged↗