Disseminated Mycobacterium Avium Complex Disease Research Articles

A Case of Disseminated Mycobacterium Avium Complex Disease Associated with Immunodeficiency Suspected of Bilateral Adrenal Tumors

A Case of Disseminated Mycobacterium Avium Complex Disease Associated with Immunodeficiency Suspected of Bilateral Adrenal Tumors

Disseminated Nontuberculous Mycobacteria in HIV-Infected Patients

Nontuberculous mycobacteria are ubiquitous in the environment and are increasingly implicated in human diseases worldwide. Currently, there are more than 150 species of Mycobacterium and it is likely that more will be discovered. The rapid increase in identified species in recent years is due to improved culturing techniques and more precise differentiations of species. The application of highly active antiretroviral therapy for the treatment of HIV disease dramatically reduced rates of all opportunistic infections including nontuberculous mycobacteria. Despite this decline, nontuberculous mycobacterium remains one of the most commonly encountered opportunistic infections in AIDS patients. Disseminated nontuberculous mycobacteria infections are seen exclusively among immunocompromised hosts, including those with AID. Disseminated disease is most commonly seen in association with profound immunosuppression. In HIV infected patients, dissemination does not typically occur unless the CD-4+ T-lymphocyte count is below 50/uL. Structural lung disease, such as chronic obstructive pulmonary disease, silicosis, pneumoconiosis or prior TB infection, predisposes to pulmonary infection. Nodular bronchiectasis is very strongly associated with nontuberculous mycobacteria infections. Disseminated Mycobacterium avium complex disease was one of the first opportunistic infections recognized as part of the syndrome of AIDS .Interest in disseminated Mycobacterium avium and nontuberculous mycobacteria infections increased as a result of the HIV epidemic, and therapeutic strategies to treat and prevent these diseases must be focused. Prevention and treatment regimens were lifelong because cure of nontuberculous mycobacteria was not achievable in AIDS patients with profound immune suppression.

Disseminated Mycobacterium Avium Complex infection in Acquired Immunedeficiency Syndrome patient

In the United States, the most common non-tuberculous species causing human diseases are slowly growing species; Mycobacterium avium complex (MAC) and Mycobacterium kansasii and rapidly growing species; Mycobacterium abscessus. With the advent of highly active antiretroviral therapy and MAC prophylaxis, disseminated MAC disease is seen infrequently. We report a case of 33-Year-old HIV (Human Immunodeficiency Virus), non-compliant patient presented with disseminated MAC disease. Sputum AFB smear, culture, and Bone marrow biopsy revealed Mycobacterium Avium Intracellulare by DNA (Deoxyribonucleic acid) probe. Following confirmation, he was initiated on Clarithromycin, Ethambutol and Rifabutin for one year of duration with follow up as outpatient.

Pigs as an experimental model for systemic Mycobacterium avium infectious disease

Mycobacterium avium complex (MAC) is an opportunistic pathogen in AIDS patients and pigs, and causes dissemination through primary intestinal lesions. However, its pathogenesis is not well understood. In this article, we hypothesize that pigs can provide a suitable experimental model of disseminated MAC disease. We compared the initial route of infection, the characteristics of the pathogenic strains, the immunological status of the hosts, and the histological characteristics. The route of infection and infective strains are similar in AIDS patients and pigs. Pigs can respond to infection by the formation of systemic epithelioid granuloma with sufficient cell-mediated immunity. However, there are differences in immunological status and histological features between AIDS patients and pigs. Therefore, pigs might be used as an appropriate animal model because of their good cell mediated immunity triggered by systemic mycobacterial infection. In conclusion, MAC infections in AIDS patients and pigs show similarities in terms of the initial route of infection and the genetic characteristics of the pathogenic strains.

The pathogenesis and the development mechanism of Mycobacterium avium complex infection

Mycobacterium avium complex (MAC) causes respiratory tract infections and develops granulomatous lesions in the alveolar areas and bronchioles in humans. In contrast with the above, the intestinal tract is the primary infection site of immunocompromised hosts, such as patients with acquired immune deficiency syndrome (AIDS), or animals, such as pigs. Recent studies have revealed that hosts with hereditary dysfunction of mediators in the Th-1 cascade as well as hosts with a high titer of auto-antibodies against interferon-gamma are susceptible to MAC, and such hosts facilitate dissemination of MAC. However, their disseminated lesions are formed mainly in the lung or in soft tissues, and the mechanism of development of MAC in such host may be different from that of AIDS-related MAC infection. In this review, we specifically discuss the development mechanism of disseminated MAC disease in recently-identified several pathological conditions.

Two cases of disseminated Mycobacterium avium infection associated with a new immunodeficiency syndrome related to CXCR4 dysfunctions

Disseminated Mycobacterium avium complex (MAC) infection is a rare but severe disease mostly seen in patients with AIDS. It has been previously described in patients suffering from other kinds of immunodeficiency (e.g. primary immunodeficiency diseases in children or hairy cell leukaemia). We report two cases of disseminated MAC disease in young women with extended granulomatosis that revealed a new form of severe immunodeficiency syndrome. Both clinical observations initially appeared to be very similar to WHIM syndrome (Warts, Hypogammaglobulinemia, Infection, Myelokathexis), a rare immunodeficiency disease correlated with CXC chemokine receptor 4 (CXCR4) mutation leading to an impaired internalization of the receptor upon its ligand CXCL12. We investigated the CXCR4 status of the lymphocytes in both patients and found a severe defect in CXCL12-promoted internalization but no mutation of its gene. Moreover, myelokathexis was not noted in bone marrow biopsies and therefore a diagnosis of WHIM syndrome could not be assessed. This immunodeficiency syndrome associated with CXCR4 dysfunction was responsible for severe MAC infection in our patients, with a fatal outcome in one case. It may be possible that these patients would have benefited from early antimycobacterial infection or azythromycin prophylaxis.

Mycobacterium avium complex infection in HIV/AIDS patients

Disseminated Mycobacterium avium complex (MAC) infection is a severe complication of advanced HIV/AIDS disease. Disseminated infection due to MAC appeared later in the natural history of HIV disease and was an independent predictor of mortality in patients before the extended use of highly active antiretroviral therapy (HAART). The use of combination schemes, including three or four antimicrobial agents followed by secondary prophylaxis and HAARTs, improved the survival and reduced mortality rates. However, subjects who ignore their serological status for HIV, or who are not receiving or do not tolerate HAART, are at high risk of developing disseminated MAC disease. In addition, patients who show a good immunological and virological response to HAART can develop episodes of immune reconstitution inflammatory syndrome associated with MAC, including supurative lymphadenitis and subcutaneous or soft-tissue abscesses. In this article, we describe the epidemiological, clinical, immunological, therapeutic and preventive aspects of MAC infection in HIV-seropositive patients in the pre- and post-HAART era.

肺<I>Mycobacterium avium</I> complex (MAC) 症の3姉妹例

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.

Disseminated Mycobacterium avium complex disease among patients infected with human immunodeficiency virus, 1985-2000.

Disseminated Mycobacterium avium complex disease remains a substantial cause of morbidity and mortality among patients with acquired immunodeficiency syndrome. From 1985 through 2000, we studied 1458 consecutive patients at Grady Memorial Hospital, Atlanta, with disseminated M. avium complex disease. There was a peak of 198 patients in the 1995, which decreased to 66 patients in 2000. In 1997, significantly more patients than in 1991 or 1994 were female (P<.001) or black (P<.001) and significantly fewer had acquired human immunodeficiency virus through homosexual contact (P<.001). In 1997, 50 (51%) of 99 of patients acquired M. avium complex disease despite receiving antimicrobial prophylaxis, but 32 (89%) of 36 patients did not adhere to the prophylaxis regimen. The median duration of survival of patients in 1991 was 110 days, whereas in 1994 it was 185 days, and in 1997 it was 339 days (P<.001). Prolonged survival was associated with receiving therapy that included clarithromycin and receiving combination antiretroviral therapy that included a protease inhibitor.

Significance of respiratory isolates of Mycobacterium avium complex in HIV positive and HIV negative patients

Objective: Mycobacterium avium complex (MAC) is isolated with increasing frequency from respiratory specimens. This study was an attempt to determine the significance of this in human immunodeficiency virus (HIV)-positive and HIV-negative patients. Methods: A retrospective cohort study was conducted at Bellevue Hospital, a large municipal hospital in New York City, including all patients with two or more respiratory tract specimens positive for MAC during the period January 1996 to October 1996. Results: Eighty patients met inclusion criteria. Forty-six were HIV-positive, and 34 were HIV-negative. Age, gender distribution, and race were comparable. Cough was a common complaint in all patients, whereas HIV-positive patients were significantly more likely to have fever (19 vs. 2, P < 0.0001). Abnormal chest radiographs were common in both groups (P > 0.8), although HIV-positive patients were more likely to have diffuse abnormalities (P < 0.0001). Focal radiographic findings were similar for both groups; however, there was a trend toward more lymphadenopathy in the HIV-positive group, though this did not reach statistical significance (P = 0.17). Notably, patients in both groups frequently had an established concurrent pulmonary diagnosis or evidence of disseminated MAC infection. Patients who were HIV-positive had Pneumocystis carinii pneumonia (n = 10), pneumonia (n = 10), and disseminated MAC disease (n = 12); whereas the concurrent disease in HIV-negative patients predominantly was active tuberculosis (n = 13). According to the recent American Thoracic Society-recommended criteria for the diagnosis of pulmonary disease caused by nontuberculous mycobacteria only 7 of 46 HIV-positive patients and 1 of 34 HIV-negative patients met clinical, bacteriologic, and radiographic criteria for pulmonary disease caused by MAC (P = 0.052). Conclusion: Mycobacterium avium complex often is cultured from patients with other lung diseases, and its presence in sputum infrequently signifies true disease, though it is more likely to do so in HIV-positive patients.

Antimicrobial susceptibility of coagulase-negative staphylococci isolated between 1991 and 1996 from a German university hospital

10. Havlir DV, Dube MP, Sattler FR, et al. Prophylaxis against disseminated Mycobacterium avium complex with weekly azithromycin, daily rifabutin or both. N Engl J Med 1996; 335: 392-8. 11. Horsburgh C R , Metchock B, Gordon SM, Havlik JA, McGowan JE, Thompson SE. Predictors of survival in patients with AIDS and disseminated Mycobacterium avium complex disease. J Infect Dis 1994; 170: 573-7. 12. Sathe SS, Gascone F' , Lo W, Pinto R , Reichman LB. Severe anemia is an important negative predictor for survival with disseminated Mycobacterilrm avilrm in acquired immunodeficiency syndrome. Am Rev Respir Dis 1990; 142: 1306-12. 13. Singer J, Thorne A, Phlipps P, et al. Predictors of survival and eradication of Mycobacterium avium complex bacteremia (MAC) in AIDS patients in the Canadian randomized treatment trial. Canadian HIV Trials: Network Protocol 020 Study Group. AIDS

Risk-benefit assessment of therapies for Mycobacterium avium complex infections.

Mycobacterium avium complex (MAC) is an important pathogen that can cause chronic lung disease in immunocompetent patients and disseminated disease in patients with the acquired immunodeficiency syndrome (AIDS). Treatment of MAC with antituberculosis drugs was unsatisfactory, but the introduction of the newer macrolides, clarithromycin and azithromycin, and of rifabutin has greatly improved the outcome of treatment regimens for MAC. However, these agents are also associated with many new treatment-related adverse effects and potential drug-drug interactions. Rifamycins [rifampicin (rifampin) more than rifabutin] induce cytochrome P450 enzymes and accelerate the metabolism of clarithromycin and HIV protease inhibitors. Conversely, clarithromycin inhibits these enzymes, resulting in increased rifabutin toxicity. The net results are treatment regimens that may be extremely difficult to tolerate, especially for elderly or debilitated patients. Clarithromycin and azithromycin must be administered in combination with other agents such as ethambutol to prevent the emergence of macrolide resistance. Unfortunately, not all patients respond to the combination of a macrolide, rifabutin and ethambutol, and many have significant adverse effects (mostly gastrointestinal) with this regimen. For some patients the treatment is worse than the disease. The same 3-drug regimen is also effective therapy for disseminated MAC in AIDS patients, in whom the additional problem of a rifamycin/protease inhibitor interaction may be present. Fortunately, as opposed to pulmonary MAC disease in immunocompetent patients, disseminated MAC disease is a diminishing problem because of effective prophylactic regimens for MAC and improved antiretroviral therapy for HIV. Significant progress has been made in the treatment of MAC disease with the introduction of the newer macrolides. It is to be hoped that even better drugs that are more active against MAC and are associated with less toxicity and drug-drug interactions will be introduced in the future.

Clarithromycin, Rifabutin and Clofazimine for Treatment of Disseminated Mycobacterium avium Complex Disease in AIDS Patients

Objective: To evaluate the efficacy and tolerability of clarithromycin plus rifabutin plus clofazimine for the treatment of disseminated Mycobacterium avium complex (MAC) disease in patients with AIDS.

Case Report: Mycobacterium avium Complex Infection as a Cause of Fever of Unknown Origin in HIV Disease

Fever of unknown origin (FUO) is a common presenting complaint in patients with HIV disease. This article presents a case where Mycobacterium avium Complex (MAC) infection is identified as the cause of FUO in a patient with late stage HIV disease, and reviews the diagnostic and therapeutic strategy for effective management of this condition. MAC is an atypical mycobacterium which causes disseminated disease in up to 50% of HIV patients at some point during their illness. Studies have found it to be responsible for FUO in up to 21% of cases where a cause of fever could be identified. Blood cultures are a sensitive method of detecting MAC infection, and a single positive blood culture is diagnostic for disseminated MAC disease. Current laboratory techniques allow identification of MAC in the blood within 7 to 14 days of collection. The most effective treatment protocol for dissemi-nated MAC disease involves a three drug regimen of rifabutin, ethambutol and clarithromycin, that leads to rapid clearance of the organism from the blood and significant reduction in the severity of symptoms. Primary prophylaxis with clarithromycin has also been shown to reduce the incidence of MAC infection in HIV patients. Given that MAC has been found to have a significant impact on the mortality of HIV patients, it is important to maintain high diagnostic suspicion when evaluating patients with FUO so that treatment may begin promptly to improve patients’ quality of life and prolong survival.

Management of Asymptomatic HIV Infection

Patients are asymptomatic during the majority of HIV infection. The virus, however, is actively replicating, producing over 1 billion particles per day during this steady-state of the disease. Management of asymptomatic HIV infection involves initial recognition of infection and counselling to prevent its further spread. When HIV infection has been confirmed, assessment consists of a careful history, physical examination and laboratory studies. The latter include serological tests for past exposure to infectious agents such as syphilis, hepatitis viruses, cytomegalovirus and toxoplasmosis. A purified protein derivative (PPD) skin test should also be performed. The immunological and virological status of the patient is assessed by quantifying CD4+ count and plasma HIV RNA levels. With the aid of these data, a decision can be made on the use of antiretroviral therapy. Didanosine (ddI) is the only currently acceptable monotherapy. Combinations of antiretroviral drugs which have undergone evaluation include zidovudine (AZT) plus didanosine, zidovudine plus zalcitabine (ddC), zidovudine plus lamivudine (3TC), didanosine plus lamivudine, zidovudine plus didanosine plus nevirapine, zidovudine plus saquinavir, zidovudine plus zalcitabine plus saquinavir (D4T), zidovudine plus ritonavir, zidovudine plus lamivudine plus indinavir, and ritonavir plus saquinavir. The optimum combination treatment has not been defined, but many appear promising. In addition, treatment for subclinical infections and prophylaxis should be administered. These include treatment of all PPD-positive patients with isoniazid 300 mg/day orally for 1 year; prophylaxis against Pneumocystis carinii pneumonia for all patients with CD4+ counts <200/mm3 with cotrimoxazole (trimethoprim plus sulfamethoxazole) one double-strength tablet daily, dapsone or dapsone plus trimethoprim; prophylaxis against toxoplasmosis in patients with CD4+ counts <100/mm3 with cotrimoxazole or with dapsone plus pyrimethamine; prophylaxis against disseminated Mycobacterium avium complex disease in patients with CD4+ counts <75/mm3 with azithromycin 1200mg orally once weekly, clarithromycin 500mg orally twice daily, or rifabutin 300 mg/day orally; and prophylaxis against Streptococcus pneumoniae pneumonia and bacteraemia by administration of the 23-valent pneumococcal vaccine. Although cytomegalovirus disease occurs in most patients with advanced HIV disease (CD4+ <50/mm3), primary prophylaxis is not recommended because of conflicting data concerning the efficacy of oral ganciclovir. Primary prophylaxis against cryptococcosis is not recommended because of the low incidence of this infection.

MYCOBACTERIAL COMPLICATIONS OF HIV INFECTION

Tuberculosis is the most common opportunistic infection worldwide and is caused by the only readily transmissible pathogen among persons with HIV infection. If treatment is initiated promptly and is supervised appropriately, cure, fortunately, is highly likely. Isoniazid preventive therapy substantially reduces the risk of tuberculosis in persons with HIV infection. Of the nontuberculous mycobacteria, Mycobacterium avium complex (MAC) is the most frequent cause of disease; however, disseminated MAC disease usually is not seen until the CD4+ cell count is less than 50 cells/L. Newer agents, such as the macrolides and rifabutin, form the nucleus of treatment regimens and also are effective in preventing the disease.

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.

Therapeutic options for the management and prevention of Mycobacterium avium complex infection in patients with the acquired immunodeficiency syndrome.

Atypical mycobacteria that cause disseminated disease result in significant morbidity and mortality among patients with advanced human immunodeficiency viral infection. Although significant progress has been made with respect to our understanding of the epidemiology, microbiology, and pathogenesis of Mycobacterium avium complex (MAC) infections in patients with the acquired immunodeficiency syndrome (AIDS), treatment and prevention strategies are still emerging. A series of case-controlled studies and clinical trials evaluated various combinations of traditional and investigational antimycobacterial agents, and demonstrated modest clinical and microbiologic success in the treatment of disseminated MAC infection. Prevention studies proved rifabutin and clarithromycin to be rational prophylaxis agents. Continued identification of optimum combination regimens remains essential to curtail the increasing frequency of disseminated MAC disease in patients with AIDS.

Treatment of disseminated Mycobacterium avium complex disease: a clinician's perspective

We studied the activities of clarithromycin and fluoroquinolones (gatifloxacin, sitafloxacin, levofloxacin) in combination with other antimycobacterial drugs against extracellular and intramacrophage Mycobacterium avium complex (MAC). Clarithromycin potentiated the activities of rifampicin and rifalazil against both extracellular and intramacrophage MAC. In contrast, all the test quinolones exhibited antagonistic effects against extracellular MAC when combined with either clarithromycin or rifamycins. Such an antagonism was not observed for the activity of these combinations against intramacrophage MAC. Combined effects were observed with combinations of these fluoroquinolones with either ethambutol or streptomycin. Similar profiles were seen for the activities of two-drug combinations of clarithromycin or fluoroquinolones with other drugs against intramacrophage MAC isolated from pulmonary and disseminated MAC infections.

Rifabutin for the Prevention of Mycobacterium avium Complex Bacteraemia in AIDS and HIV-Positive Patients with CD4 Counts ≤ 200 Cells/μl

In an open-label, nonrandomised, noncomparative treatment investigational new drug (IND) study, 536 patients with either the acquired immunodeficiency syndrome (AIDS) or positive human immunodeficiency virus (HIV) serology and low CD4 counts were administered rifabutin 300 mg/day prophylactically in an attempt to prevent or delay the development of Mycobacterium avium complex (MAC) bacteraemia. The purpose of the study was to allow HIV-positive and AIDS patients wider access to rifabutin for MAC prophylaxis while the application for marketing approval was under review. Patients included in the study had either a diagnosis of AIDS and a CD4 count of ≤ 200 cells/µl or were HIV-positive with a CD4 count of ≤ 100 cells/µl (but without an AIDS-defining event). Patients eligible for inclusion were to have no evidence of disseminated MAC disease as evaluated by a blood culture taken within 21 days before treatment. 19 of 533 evaluable patients (3.6%) with negative baseline cultures developed MAC bacteraemia. In addition, MAC was isolated from the sputum of 1 other patient. Fever, night sweats, diarrhoea and abdominal pain remained absent in 57 to 71% of patients. CD4 counts and Karnofsky scores generally remained stable or improved in more than 80% of patients. The most common adverse events (those with a frequency > 1%) attributable to rifabutin were leucopenia (7.1%), rash (5.2%), nausea and diarrhoea (4.1% each), headache (3.0%) and abdominal pain (2.2%). The results of this study, within the limitations of the study design, are consistent with the findings of phase III placebo-controlled clinical trials showing that rifabutin prevents or delays MAC bacteraemia in HIV-positive or AIDS patients with low CD4 counts. Rifabutin appears to be well tolerated with a relatively low incidence of (mostly minor) adverse events.