Mycobacterium, with AIDS

The most common opportunistic diseases and their frequencies found before death in patients with AIDS between 1990 and 1994 were Pneumocystis carinii pneumonia (PCP), Mycobacterium avium complex, and cytomegalovirus disease. 

It was found that the HIV envelope glycoprotein in vitro increases the production of NO by human monocyte-derived macrophages [114]. NO production is increased in patients who have AIDS [115], and the increased concentrations of nitrite in AIDS patients with opportunistic infections is caused by T gondii, Pneumocystis carinii, Mycobacterium tuberculosis, and Mycobacterium avium, whereas nitrite concentrations are normal in symptom-free patients. It was also confirmed that there was increased production of NO in the sera of children with HIV-1 infection, and of circulating cytokines, such as interleukin lp, tumor necrosis factor a, and interferon y. It is postulated that rises in the concentrations of these cytokines may represent a substantial stimulation of NO production [116]. In contrast, it has been shown that there was no altered endogenous nitrate formation in eight patients with AIDS, most of whom had opportunistic infections [117]. It has also been noted that there were high... 

AIDS is a life-threatening disorder because of the susceptibility of the immunocompromised patient to severe infections and certain forms of cancer.65 73 76 101.113 [n particular, patients with AIDS often suffer from severe viral infections (CMV, various herpesvirus infections), bacterial infections (Mycobacterium tuberculosis), fungal infections (Pneumocystis jiroveri), and infections caused by various other microbes and parasites. Patients with AIDS also develop relatively unusual neoplastic diseases, such as Kaposi sarcoma. 

The infectious killer disease, tuberculosis (TB), is the leading cause of death worldwide from a single human pathogen, claiming more adult lives than diseases such as acquired immunodeficiency syndrome (AIDS), malaria, diarrhea, leprosy, and all other tropical diseases combined. The organism usually responsible, the tubercle bacillus, Mycobacterium tuberculosis (MT), was discovered by Robert Koch in 1882. However, M. bovis, which infects cattle, may also infect humans, and M. africanum is a cause of TB in West Africa. Furthermore, a number of normally nonpathogenic mycobacteria, especially M. avium, M. intracellulare, and M. scrofulaceum, cause opportunistic infectious disease in patients with AIDS. Pulmonary TB, the most common type of the disease, is usually acquired by inhalation of the bacillus from an infectious patient and causes irreversible lung destruction (Newton et al., 2000). 

Interest in the nontuberculous (atypical) mycobacteria, especially members of the Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium scro-fulaceum complex, has also been stimulated by AIDS. Infection with the M. avium complex is seen in up to 50% of patients with AIDS in some areas of the world.3 A review of U.S. cases found an overall 5.5% incidence of M. avium complex in AIDS patients.3 Leprosy, however, is clearly on the wane, although it remains a substantial problem.4 Its prevalence has been steadily diminished to a present-day worldwide figure of about 3 million registered cases and 5.5 million estimated cases, owing in part to a most effective multiple-drug regimen. The World Health Assembly has dedicated itself to the technical elimination of leprosy (that is, a prevalence of less than 1 per 10,000 population) by the turn of the century. 

Rifabutin (t 36 h) has similar activity and adverse reactions, and is used for prophylaxis of Mycobacterium avium infection in patients with AIDS, and for treatment of tuberculous and nontuberculous mycobacterial infection in combination with other drugs. 

A 35-year old Caucasian man with AIDS and multiple opportunistic infections, including Mycobacterium kansasii and Mycobacterium avium complex (MAC) disease developed moderate to severe primary sensorineural hearing loss after 4—5 months of therapy with oral azithromycin 500 mg/day. Other medications included ethambutol, isoniazid, rifabutin, ciprofloxacin, co-trimoxazole, fluconazole, zidovudine (later switched to stavudine), lamivudine, indinavir, methadone, mod-ified-release oral morphine, pseudoephedrine, diphenhydramine, megestrol acetate, trazodone, sorbitol, salbutamol by metered-dose inhaler and nebulizer, ipratropium, and oral morphine solution as needed. Significant improvement of the hearing impairment was documented 3 weeks after drug withdrawal. 

Gastrointestinal symptoms were the most common adverse effects reported in a trial of azithromycin in disseminated Mycobacterium avium complex in 62 patients with AIDS (30). Erythromycin is a motilin receptor agonist (31-33). This mechanism may be at least partly responsible for the gastrointestinal adverse effects of macrolides. Azithromycin may act on gastrointestinal motility in a similar way to erythromycin, as it produces a significant increase in postprandial antral motility (34). 

Oldfield EC 3rd, Fessel WJ, Dunne MW, Dickinson G, Wallace MR, Byrne W, Chung R, Wagner KF, Paparello SF, Craig DB, Melcher G, Zajdowicz M, Williams RF, Kelly JW, Zelasky M, Heifets LB, Berman JD. Once weekly azithromycin therapy for prevention of Mycobacterium avium complex infection in patients with AIDS a randomized, double-blind, placebo-controlled multicenter trial. Clin Infect Dis 1998 26(3) 611-19. 

Organisms of the Mycobacterium avium complex (MAC) commonly cause disseminated bacterial infection among patients with AIDS. There is evidence that immunoprophylaxis against MAC infection may be possible. A heat-killed Mycobacterium vaccae vaccine was given in a three-dose schedule to 12 HIV-infected adults with CD4 cell counts below 300 x 10 /1 (107). The vaccine was well tolerated and produced detectable immunological responses in 3 of 11 subjects who completed the trial. 

Baril I, Jouan M, Agher R, et al. Impact of highly active antiretroviral therapy on onset of mycobacterium avium complex infection and cytomegalovirus disease in patients with AIDS. AIDS 2000 14 2593. 

Chaisson, R. E., Benson, C. A., Dube, M. P., Heifets, L. B., Korvick, J. A., Elkin, S., Smith, T., Craft, J. C., and Sattler, F. R. (1994). Clarithromycin therapy for bacteremic Mycobacterium avium complex disease. A randomized, double-blind, dose-ranging study in patients with AIDS. AIDS Clinical Trials Group Protocol 157 Study Team. A/m. Intern. Med. 121, 905-911. 

Freedberg, K. A., Cohen, C. J., and Barber, T. W. (1997). Prophylaxis for disseminated Mycobacterium avium complex (MAC) infection in patients with AIDS A cost-effectiveness analysis. J. Acquir. Immune Defic. Syndr. Hum. Retroviral. 15, 275-282. 

Rifamycin P (14) was synthesized, and the biological activities of 14 and some derivatives of this compound were reported [66]. According to the report, the derivatives were more active than 14 against the Mycobacterium avium complex and other slowly and rapidly growing non-tuberculous mycobacteria. These organisms frequently cause systemic infections in patients with AIDS, and it was suggested that 2 -(diethylamino)rifamycin P appeared suitable for further investigation. 

Tuberculosis is caused by acid-fast bacillus Mycobacterium tuberculosis. It is a major health problem and kills more than any other infectious disease. One and one-half billion people have TB. There are 8 million new cases each year. The incidence had decreased in the United States but increased again in the 1980s. This has been attributed in part to the numbers of persons with AIDS which compromises the immune system. 

Clofazimine is also used to treat Mycobacterium avium infections which frequently occur in patients with AIDS (acquired immunodeficiency s)mdrome), (Masur et al., 1987 Woods and Washington, 1987 Gangadharam et al., 1988 Lindholm - Levy and Heifets, 1988 Young, 1988). 

Mycobacterium avium serovar-8 specific glycopeptidolipid allelic exchange mutant Mycobacterium avium are ubiquitous environmental organisms and a cause of disseminated infection in patients with end-stage AIDS)... 

Mycobacteria of the Mycobacterium avium complex are implicated in disseminated bacterial infections in AIDS patients. RFLP studies followed by hybridization with radiolabeled probe specific for an insertion sequence in M. avium (IS 1311) have been useful for typing M. avium stains (R2). A variety of molecular techniques are available for the diagnosis of Chlamydia trachomatis infection. In addition to PCR, a method based on the ligase chain reaction has also been found to be sensitive to the detection of C. trachomatis infection in urine specimens collected from male and female subjects (VI). The differentiation between low-risk genotypes of human papilloma virus (HPV 6 or 11) from genotypes of high... 

Mycobacterium is a genus of bacteria that has characteristic cell walls and unusual staining properties. AIDS patients are most commonly infected with an atypical form of tuberculosis bacterium called Mycobacterium avium inter-cellulare. This bacterium does not normally cause disease in healthy people, but in AIDS patients, it may cause tuberculosis-like disease in the lungs. The infection can also involve numerous other tissues, such as the bone marrow, and bacteria may be present in the blood at very high levels. Patients with this opportunistic infection will have fevers and low number of white blood cells. These infections are often resistant to drugs. 

Azithromycin, though less active against streptococci and staphylococci than erythromycin, is far more active against respiratory infections due to Haemophilus influenzae and Moraxella catarrhalis. Except for its cost, it is now the preferred therapy for urethritis caused by Chlamydia trachomatis. Its activity against Mycobacterium avium intracellulare complex has not proven to be clinically important, except in AIDS patients with disseminated infections. 

Perlman DC, El Sadr WM, Heifets LB, Nelson ET, Matts JP, Chirgwin K, Salomon N, Telzak EE, Klein O, Kreiswirth BN, Musser JM, Hafner R. Susceptibility to levofloxacin of Mycobacterium tuberculosis isolates from patients with HIV-related tuberculosis and characterization of a strain with levofloxacin monoresistance. AIDS 1997 11 1473-1478. 

The incidence of disseminated Mycobacterium avium complex (MAC) infection has increased dramatically with the AIDS epidemic. 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 X 10 /1 (5). In a randomized, open trial in 37 patients with HIV-associated disseminated MAC infection, treatment with clarithromycin -I- ethambutol produced more rapid resolution of bacteremia, and was more effective at sterilization of blood cultures after 16 weeks than azithromycin -I- ethambutol (6). 

Mycobacterium hemophilum is a pathogen that is found in immunosuppressed patients, such as those with malignancy, AIDS, and organ transplants. Systemic lupus erythematosus can make patients more susceptible to infection. 

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