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HIV-associated mycobacterium avium complex

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Related Terms
  • Acquired immune deficiency syndrome, acquired immunodeficiency syndrome, AIDS, antimicrobial, antiretroviral therapy, bacteria, bacterial infection, blood culture, bone marrow culture, CD4 cell, disseminated mycobacterium avium complex, fusion inhibitors, HAART, highly active antiretroviral therapy, HIV, human immunodeficiency virus, immune, immune defense system, immune system, immunocompromised, immunodeficiency, infection, MAI, mycobacterium, Mycobacterium avium, mycobacterium avium intracellulare, Mycobacterium intracellulare, OI, opportunistic infection, PIs, protease inhibitors, reverse transcriptase inhibitors, RTs, sputum sample analysis, weakened immune system, viral, viral infection, virus.

Background
  • Mycobacterium avium complex (MAC), or mycobacterium avium intracellulare (MAI), is a bacterial infection that is caused by either Mycobacterium avium or Mycobacterium intracellulare. These bacteria are very common. They are present in water, soil, dust and food. In fact, these bacteria are present in almost every human. However, a healthy immune system will prevent the bacteria from causing an infection. Therefore, individuals with a weakened immune system, especially HIV/AIDS patients, are at risk of developing MAC.
  • It is estimated that up to 50% of individuals with HIV/AIDS may develop MAC, especially if their CD4 count (helper T-cells that HIV infects and destroys) is lower than 50 cells per microliter of blood. The CD4 cells play a vital role in the immune system. When HIV destroys these cells, the body is vulnerable to infection and disease. MAC almost never causes infections in people who have a CD4 cell counts higher than 100 cells per microliter of blood.
  • MAC infection can be localized (limited to one part of the body) or disseminated (spread throughout the entire body, sometimes called DMAC). MAC infection often occurs in the lungs, intestines, bone marrow, liver and spleen.
  • Common symptoms of MAC include weight loss, fever, chills, night sweats, swollen glands, abdominal pain, diarrhea, inflammation and overall weakness. MAC usually affects the intestines and inner organs first.
  • The most common complication of DMAC is anemia, which may require a blood transfusion. If the infection involves many organs, it can cause fatal respiratory failure. Patients who have a localized infection have a low mortality rate.
  • In order to control, MAC, the immune system must be restored. Therefore, all patients who are not taking antiretroviral therapy (ART) should begin treatment. In general, MAC infection is treated with two or three antimicrobials for life in order to prevent the infection from recurring. HIV patients who have DMAC infections usually receive a combination of newer macrolide antibiotics (clarithromycin, azithromycin) with ethambutol and rifabutin.
  • Before macrolide antibiotics were developed, patients who had both AIDS and DMAC typically lived four months after diagnosis. According to a 1999 study, patients who received treatment with rifabutin, ethambutol and clarithromycin lived an average of nine months after diagnosis. Now that highly active antiretroviral therapy (HAART) is available to help reconstitute (restore) the immune system of HIV/AIDS patients, the prognosis has improved. According to a recent study, about 50% of HIV/AIDS patients were alive five years after being diagnosed with MAC.

Author information
  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
  1. AIDS Education & Training Centers National Resource Center. Mycobacterium Avium Complex. July 2006. . Accessed May 3, 2009.
  2. Centers for Disease Control and Prevention (CDC). . Accessed May 3, 2009.
  3. HIV InSite Knowledge Base. . Accessed May 3, 2009.
  4. Natural Standard: The Authority on Integrative Medicine. . Copyright © 2009. Accessed May 3, 2009.
  5. The Complete HIV/AIDS Resource. . Accessed May 3, 2009.

Causes
  • M. avium and M. intracellulare bacteria cause MAC infections. More than 95% of MAC infections in patients with HIV/AIDS are caused by M. avium. MAC is the most common cause of infection by nontuberculous mycobacteria (NTM) in patients with AIDS.
  • These bacteria are very common. They are present in water, soil, dust and food. In fact, these bacteria are present in almost every human. However, a healthy immune system will prevent the bacteria from causing an infection. Therefore, individuals with a weakened immune system, especially HIV/AIDS patients, are at risk of developing MAC.
  • MAC infection in AIDS patients is associated with a CD4cell count of less than 50 cells per microliter of blood.

Symptoms
  • MAC can be mild and localized or severe, affecting the entire body. Common symptoms include enlarged lymph nodes and fever. Other symptoms may include drenching sweats, diarrhea, weight loss, abdominal pain, fatigue, weakness, shortness of breath, mastitis (inflamed mammary glands), pyomyositis (inflamed muscle tissue), cutaneous (skin) abscess, brain abscess, anemia (low levels of red blood cells), neutropenia (low levels of white blood cells), thrombocytopenia (low levels of platelets), blood infections, viral hepatitis (viral infection of the liver), skin lesions and elevated liver function tests. The liver or spleen may also be enlarged.
  • There have also been reports of immune reconstitution syndrome (IRIS) associated with MAC. Once the immunocompromised patient receives treatment that restores immune system function, the body is capable of recognizing infectious organisms, such as MAC. If an infectious organism is present, it will trigger an overproduction of inflammatory mediators. This condition is called IRIS. This condition typically occurs shortly after highly active antiretroviral therapy (HAART) is initiated. Most cases of IRIS resolve in a few weeks with continued HIV treatment.

Diagnosis
  • General: Blood and bone marrow cultures are the most sensitive diagnostic tests for MAC. Since bone marrow cultures are more invasive a blood culture is the standard diagnostic procedure.
  • Blood culture: A sample of blood is placed in a special laboratory preparation, and then it is incubated in a controlled environment for one to two weeks. A positive culture will identify the disease-causing bacteria.
  • Bone marrow culture: A bone marrow culture is an invasive procedure. Therefore, it is only used when all other tests are negative, but the doctor suspects MAC. First a bone marrow biopsy is performed to obtain a tissue sample. During the procedure a needle is inserted into the marrow and a small sample is removed. It is then placed in a special laboratory preparation and incubated in a controlled environment for one to two weeks. A positive culture will identify the disease-causing bacteria.
  • Sputum-induction for histopathologic testing: A sputum sample analysis can be conducted to determine whether a patient has MAC. The patient will cough deeply, expelling material that comes up from the lungs into a sterile cup. The sample is then taken to a laboratory and placed in a medium under conditions that allow the bacteria to grow. Mycobacterial cultures grow MAC in about one to two weeks. However, interpreting the results may be difficult because MAC can colonize the respiratory tract without causing clinical infection. A positive culture will identify the disease-causing bacteria. Sensitivity of a sputum analysis varies widely (50-90%), and depends on proficiency in using the technique and the experience of the laboratory.
  • Imaging studies: High resolution computed tomography (HRCT) scanning has been shown to be more sensitive than chest radiography (X-ray) for revealing pulmonary abnormalities associated with MAC infection. An HRCT scan of the abdomen may reveal retroperitoneal lymphadenopathy (enlarged lymph nodes near the tissues in the abdominal wall) periaortic lymphadenopathy (enlarged lymph nodes around the aorta) and hepatosplenomegaly (enlarged liver and spleen).

Treatment
  • General: In order to control, MAC, the immune system must be restored. Therefore, all patients who are not taking antiretroviral therapy (ART) should begin treatment. In general, MAC infection is treated with two or three antimicrobials for life in order to prevent the infection from recurring. HIV patients who have DMAC infections usually receive a combination of newer macrolide antibiotics (clarithromycin, azithromycin) with ethambutol and rifabutin.
  • Antimicrobials: The U.S. Centers for Disease Control and Prevention (CDC) recommends the following two drug regimens: 500mg of the macrolide antibiotic clarithromycin (Biaxin®) twice daily, plus 15mg/kg of ethambutol (Myambutol®) once daily, or 500-600mg of azithromycin (Zithromax®) once daily, plus 15mg/kg of ethambutol (Myambutol®) once daily. Several studies suggest that azithromycin can effectively treat 55-60% of MAC infections. Higher doses of clarithromycin (1000mg or more) are associated with higher mortality rates.
  • Other antimicrobials commonly prescribed include rifabutin (Mycobutin®), levofloxacin (Levaquin®) and amikacin (Amikin®).
  • Patients who have MAC will continue treatment for life in order to prevent the infection from recurring.
  • Highly active antiretroviral therapy (HAART): When HIV reproduces, different strains of the virus emerge, and some are resistant to antiretroviral drugs. Therefore, it is common for healthcare providers to recommend a combination of antiretroviral drugs known as HAART. This strategy, developed by NIAID-support researchers, usually combines drugs from at least two different classes of antiretroviral drugs, and it has been shown to suppress the virus. While these drugs cannot cure HIV infection or AIDS, they can suppress the virus.
  • The U.S. Food and Drug Administration (FDA) has approved several antiretroviral drugs to treat HIV infected individuals. These drugs fall into three major classes: reverse transcriptase (RT) inhibitors, fusion inhibitors and protease inhibitors. In July 2006, the FDA approved a multi-class combination called Atripla®.
  • Fusion inhibitors prevent the virus from fusing with the cellular membrane, thus blocking entry into the cell. The fusion inhibitor Fuzeon® is FDA-approved.
  • Protease inhibitors interfere with the protease enzyme that HIV uses to produce infectious viral particles. They are a class of medication used to treat or prevent infection by viruses, including HIV and Hepatitis C. PIs prevent viral replication by inhibiting the activity of protease, an enzyme used by the viruses to cleave nascent proteins for final assembly of new virons. FDA-approved protease inhibitors include Agenerase®, Aptivus®, Crixivan®, Invirase®, Kaletra®, Lexiva®, Norvir®, Prezista®, Reyataz® and Viracept®.
  • Reverse transcriptase (RT) inhibitors disrupt the reverse transcription stage in the HIV lifecycle. During this stage, an HIV enzyme, known as reverse transcriptase, converts HIV RNA to HIV DNA. There are two main types of RT inhibitors. Non-nucleosideRT inhibitors bind to reverse transcriptase, preventing HIV from converting the HIV RNA into HIV DNA. Approved non-nucleoside RT inhibitors include Rescriptor®, Sustiva® and Viramune®.
  • Nucleoside/nucleotide reverse transcriptase inhibitors serve as faulty DNA building blocks, and once they are incorporated into the HIV DNA, the DNA chain cannot be completed. Therefore, the drugs prevent HIV from replicating inside a cell. Approved antiretrovirals include Combivir®, Emtriva®, Epivir®, Epzicom®, Hivid®, Retrovir®, Trizivir®, Truvada®, Videx EC®, Videx®, Viread®, Zerit® and Ziagen®.

Integrative therapies
  • Strong scientific evidence:
  • Probiotics: Probiotics are beneficial bacteria and are sometimes called friendly germs. They help maintain a healthy intestine by keeping harmful bacteria and yeasts in the gut under control. Most probiotics come from food sources, especially cultured milk products. Probiotics can be taken as capsules, tablets, beverages, powders, yogurts, and other foods. An increasing number of studies support the use of probiotics as a supplement to antibiotic therapy. Probiotic supplementation during a course of antibiotics has been studied for reducing adverse effects of antibiotics in the intestinal environment. This includes reducing growth of Clostridium difficile bacteria, which can lead to colitis, a common complication of antibiotics, especially in the elderly. Some probiotics may also help prevent the development of antibiotic resistance. In acutely ill children, synbiotics have been linked to greater weight gain and fewer bacterial illnesses after antibiotics are ended. The evidence consistently supports supplementation of antibiotics with probiotics.
  • Probiotics are generally considered to be safe and well-tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant. Caution is advised when using probiotics in neonates born prematurely or with immune deficiency.
  • Good scientific evidence:
  • Probiotics: Limited evidence with day care children suggests supplementation with Lactobacillus GG may reduce number of sick days, frequency of respiratory tract infections, and frequency of related antibiotic treatments. Fermented milk (with yogurt cultures and L. casei DN-114001) may reduce the duration of gastrointestinal and respiratory infections in elderly people. More research is needed to make a firm conclusion.
  • Probiotics are generally considered to be safe and well-tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant. Caution is advised when using probiotics in neonates born prematurely or with immune deficiency.
  • Unclear or conflicting scientific evidence:
  • Beta-glucan: Beta-glucan is a soluble fiber derived from the cell walls of algae, bacteria, fungi, yeast, and plants. PGG-glucan, an immunomodulator, has been studied in patients undergoing surgery, particularly abdominal surgery. Currently, PGG-glucan appears to have positive results in decreasing postoperative infections. More study is warranted to make a firm conclusion.
  • Avoid if allergic or hypersensitive to beta-glucan. When taken by mouth, beta-glucan is generally considered to be safe. Use cautiously with AIDS or AIDS-related complex (ARC). Avoid using particulate beta-glucan. Avoid if pregnant or breastfeeding.
  • Blessed thistle: Human research of blessed thistle as a treatment for bacterial infections is currently lacking. Laboratory studies report that blessed thistle (and chemicals contained in blessed thistle, such as cnicin and polyacetylene) may have activity against several types of bacterial infections and no effects on some types. Early studies report no activity of blessed thistle against herpes viruses, influenza, or poliovirus. Further evidence is necessary in this area before a firm conclusion can be drawn.
  • Blessed thistle is generally considered to be safe when taken by mouth in recommended doses for short periods of time, with few reported side effects such as birth defects, bleeding, breathing problems, bruising, cancer of the nose or throat, increased production of stomach acid, itching, kidney disease, liver toxicity, skin rash, stomach discomfort, stomach ulcers, and vomiting. Allergic reactions to blessed thistle including rash may occur, as well as cross-sensitivity to mugwort and Echinacea. Cross-reactivity may also occur with bitter weed, blanket flower, Chrysanthemum, coltsfoot, daisy, dandelion, dwarf sunflower, goldenrod, marigold, prairie sage, ragweed or other plants in the Asteraceae/Compositae family. Avoid if pregnant or breastfeeding.
  • Cranberry: Limited laboratory research has examined the antibacterial activity of cranberry. Further research is warranted in this area.
  • Avoid if allergic to cranberries, blueberries, or other plants of the Vaccinium species. Sweetened cranberry juice may affect blood sugar levels. Use cautiously with a history of kidney stones. Pregnant and breastfeeding women should avoid cranberry in higher amounts than what is typically found in foods.
  • Lavender: Early laboratory studies suggest that lavender oils may have topical antibiotic activity. However, this has not been well tested in human studies.
  • Avoid if allergic or hypersensitive to lavender. Avoid with a history of seizures, bleeding disorders, eating disorders (such as anorexia or bulimia), or anemia (low levels of iron). Avoid if pregnant or breastfeeding.
  • Prayer/distant healing: Prayer can be defined as a "reverent petition," the act of asking for something while aiming to connect with God or another object of worship. Prayer may help reduce the length of hospital stay as well as the duration of fever in patients with infections. However, early study is controversial and additional study is needed before a conclusion can be drawn.
  • Prayer is not recommended as the sole treatment approach for potentially serious medical conditions, and it should not delay the time it takes to consult with a healthcare professional or receive established therapies. Sometimes religious beliefs come into conflict with standard medical approaches and require an open dialog between patients and caregivers.
  • Probiotics: There is limited evidence that probiotic supplementation may reduce the presence of bacterial infections in the upper respiratory tract. Results are mixed regarding the ability of probiotics to reduce infective complications of medical treatment. More studies are needed to determine the effectiveness of probiotics for these indications.
  • Probiotics are generally considered to be safe and well-tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant. Caution is advised when using probiotics in neonates born prematurely or with immune deficiency.
  • Propolis: Propolis is a natural resin created by bees to make their hives. Propolis is made from the buds of conifer and poplar trees and combined with beeswax and other bee secretions. Animal and laboratory studies suggest that propolis may be a beneficial treatment for various types of bacterial infections. Additional research is needed to confirm these findings.
  • Avoid if allergic or hypersensitive to propolis, black poplar (Populas nigra), poplar bud, bee stings, bee products, honey, or Balsam of Peru. Severe allergic reactions have been reported. There has been one report of kidney failure with the ingestion of propolis that improved upon discontinuing therapy and deteriorated with re-exposure. Avoid if pregnant or breastfeeding because of the high alcohol content in some products.
  • Seaweed, kelp, bladderwrack: Bladderwrack (Fucus vesiculosus) is a brown seaweed found along the northern coasts of the Atlantic and Pacific oceans and North and Baltic seas. Another seaweed that grows alongside bladderwrack is Ascophyllum nodosum, andit is often combined with bladderwrack in kelp preparations. Laboratory research suggests that bladderwrack may have antibacterial activity. However, reliable human studies to support this use are currently lacking in the available literature.
  • Avoid if allergic or hypersensitive to Fucus vesiculosus or iodine. Avoid with a history of thyroid disease, bleeding, acne, kidney disease, blood clots, nerve disorders, high blood pressure, stroke, or diabetes. Avoid if pregnant or breastfeeding.
  • Selenium: Selenium is a mineral found in soil, water, and some foods. Preliminary research reports that selenium may be beneficial in the prevention of several types of infection, including recurrence of erysipelas (bacterial skin infection associated with lymphedema) or Mycoplasma pneumonia. Further research is needed to confirm the effects of selenium for infection prevention.
  • Avoid if allergic or hypersensitive to products containing selenium. Avoid with a history of non-melanoma skin cancer. Selenium is generally regarded as safe for pregnant or breastfeeding women. However, animal research reports that large doses of selenium may lead to birth defects.
  • Sorrel: There is currently not enough evidence on the proposed antibacterial effects of sorrel. More research is needed.
  • Avoid large doses of sorrel because there have been reports of toxicity and death. This may be because of the oxalate found in sorrel. Many sorrel tinctures contain high levels of alcohol and should be avoided when driving or operating heavy machinery. These sorrel formulations may cause nausea or vomiting when taken with the prescription drugs metronidazole (Flagyl®) or disulfiram (Antabuse®). Avoid if pregnant or breastfeeding.
  • Fair negative scientific evidence:
  • Macrobiotic diet: A macrobiotic diet has been advocated to preserve intestinal health. However, it apparently does not reduce the incidence of antibiotic resistant bacteria, nor infections caused by resistant strains in the gastrointestinal tract, compared to a diet with animal products.
  • Use cautiously with cancer or other medical conditions without expert planning or supplementation. Avoid in children or adolescents without professional guidance or appropriate supplementation. Avoid in pregnant or lactating women due to potential deficiencies, unless properly supplemented.
  • Probiotics: Bacterial infection translocation, the passage of bacteria from the gut to other areas of the body where they can cause disease, is of special concern in surgery. Limited evidence suggests that supplementation with probiotics may not reduce this problem.
  • Probiotics are generally considered to be safe and well-tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant. Caution is advised when using probiotics in neonates born prematurely or with immune deficiency.

Prevention
  • General: Preventative therapy is usually recommended for AIDS patients who have a CD4 cell count lower than 50 cells per microliter of blood. Based on the most recent research, clarithromycin appears to be the most effective drug for the prevention of MAC.
  • Clarithromycin (Biaxin®): Clarithromycin (Biaxin®) is FDA-approved for the prevention of MAC. Studies have shown that the drug reduces the number of MAC infections by 69%.
  • Clarithromycin is considered to be the most effective drug for the prevention of MAC. However, some researchers are concerned that if a person develops MAC while taking clarithromycin, the infection will be resistant to treatment. According to several studies, about 50% of patients who developed MAC while taking clarithromycin developed MAC infections that were resistant to the drug.
  • Rifabutin (Mycobutin®): According to a multi-center trial, rifabutin (Mycobutin®) can reduce the rate of MAC by almost 50% in AIDS patients. Several other studies show that the drug may help people live longer lives. Researchers have shown that taking rifabutin as a preventative treatment reduces the risk of fatality by 14%. The most serious side effects of rifabutin are low white blood cells counts and elevated liver enzymes.
  • Azithromycin (Zithromax®): Azithromycin (Zithromax®) has been FDA-approved for the prevention of MAC. This drug can be taken once a week due to its long half-life. One study found that azithromycin was more effective than rifabutin. The efficacy of azithromycin has not been compared to clarithromycin in studies.

Copyright © 2011 Natural Standard (www.naturalstandard.com)


The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

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