Continuous high-grade mycobacterium avium-intracellulare bacteremia in patients with the acquired immune deficiency syndrome

Wong, Brian; Edwards, F F; Kiehn, Timothy E.; Whimbey, Estella; Donnelly, Harrison J.; Bernard, Edward M.; Gold, Jonathan W. M.; Armstrong, Donald

doi:10.1016/0002-9343(85)90458-9

Cited by 166 publications

(56 citation statements)

References 16 publications

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“…The presence of a positive blood culture for mycobacteria in these circumstances, however, makes the diagnosis of tuberculosis somewhat less likely. Blood cultures are positive in 86 to 98% of patients with disseminated MAC, often within 14 days (reflecting the high level of bacteremia), but are rarely positive in patients with tuberculosis (202,342,466,485). While sputum smears are much more likely to be positive in patients with tuberculosis than in those with MAC infection (83 versus 16%), both organisms are isolated with fairly equal frequency from lymph node, bone marrow, and stool specimens (342).…”

Section: Delayed Confirmation Of Clinical Diagnosismentioning

confidence: 99%

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The Mycobacterium avium complex

1993

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Mycobacterium avium complex (MAC) disease emerged early in the epidemic of AIDS as one of the common opportunistic infections afflicting human immunodeficiency virus-infected patients. However, only over the past few years has a consensus developed about its significance to the morbidity and mortality of AIDS. M. avium was well known to mycobacteriologists decades before AIDS, and the MAC was known to cause disease, albeit uncommon, in humans and animals. The early interest in the MAC provided a basis for an explosion of studies over the past 10 years largely in response to the role of the MAC in AIDS opportunistic infection. Molecular techniques have been applied to the epidemiology of MAC disease as well as to a better understanding of the genetics of antimicrobial resistance. The interaction of the MAC with the immune system is complex, and putative MAC virulence factors appear to have a direct effect on the components of cellular immunity, including the regulation of cytokine expression and function. There now is compelling evidence that disseminated MAC disease in humans contributes to both a decrease in the quality of life and survival. Disseminated disease most commonly develops late in the course of AIDS as the CD4 cells are depleted below a critical threshold, but new therapies for prophylaxis and treatment offer considerable promise. These new therapeutic modalities are likely to be useful in the treatment of other forms of MAC disease in patients without AIDS. The laboratory diagnosis of MAC disease has focused on the detection of mycobacteria in the blood and tissues, and although the existing methods are largely adequate, there is need for improvement. Indeed, the successful treatment of MAC disease clearly will require an early and rapid detection of the MAC in clinical specimens long before the establishment of the characteristic overwhelming infection of bone marrow, liver, spleen, and other tissue. Also, a standard method of susceptibility testing is of increasing interest and importance as new effective antimicrobial agents are identified and evaluated. Antimicrobial resistance has already emerged as an important problem, and methods for circumventing resistance that use combination therapies are now being studied.

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Section: Delayed Confirmation Of Clinical Diagnosismentioning

confidence: 99%

“…Quantitative blood cultures were first used in the mid1980s as a marker of microbiologic efficacy (202,485). In these studies, mycobacteria were cleared from the blood of only two patients with varied combinations of clofazimine, ethambutol, ethionamide, rifampin, rifabutin, and INH.…”

Section: Treatment Of Disease In Patients With Aidsmentioning

confidence: 99%

The Mycobacterium avium complex

1993

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“…to release intracellular organisms. Weighed specimens of organs were homogenized at a dilution of 1:10 (by weight) in 0.1% sodium deoxycholate in saline (24). Serial dilutions of homogenates or blood were incubated on 7H11 plates at 37°C, and the colonies were counted after 7 and 14 days.…”

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confidence: 99%

Azithromycin, rifabutin, and rifapentine for treatment and prophylaxis of Mycobacterium avium complex in rats treated with cyclosporine

Brown

Edwards

Bernard

et al. 1993

Antimicrob Agents Chemother

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Azithromycin, rifabutin, and rifapentine were used to treat or prevent disseminated Mycobacterium avium complex (MAC) infections produced in rats immunosuppressed with cyclosporine. Animals with bacteremic infections were treated 1 week after intravenous inoculation with 107 CFU of MAC with azithromycin, 100 mg/kg of body weight administered subcutaneously for 5 days and then 75 mg/kg on Monday, Wednesday, and Friday, or with rifabutin or rifapentine, 20 mg/kg administered intraperitoneally on Monday through Friday. All three drugs showed efficacy after 1 and 2 months. Rifabutin cleared the organisms from tissues more rapidly than azithromycin or rifapentine. To approximate prophylaxis, treatment was started 2 weeks before intravenous inoculation with 104 organisms. MAC infections were undetectable in treated animals after 4 months, while control animals had disseminated infections. These findings support the rationale for clinical trials of treatment and prophylaxis with these agents. The cyclosporine-treated rat appears to be a useful model in which to evaluate compounds for the treatment and prophylaxis of disseminated MAC infections.Disseminated infection with the Mycobacterium avium complex (MAC) is the most common cause of bacteremia in patients with AIDS, occurring in up to 50% of these patients (14). Survival of MAC-and human immunodeficiency virusinfected patients is half that of those with similar stages of human immunodeficiency virus infection but who do not have disseminated MAC infections (13). Treatment regimens with significant activity against MAC have been described, but relapses have occurred and none of the regimens have reliably eradicated the infection (9,10,11,20,25). Thus, there is an urgent need for more effective agents and approaches to the treatment and prevention of MAC infections.Successful treatment of established infections probably requires combination therapy with two or more effective drugs having different mechanisms of action (17). Rifabutin and rifapentine are new rifamycin analogs which demonstrate significant in vitro activity against MAC isolates.Studies of treatment with these agents in animal models have produced contradictory results (4,5,15,16). Azithromycin is a new azilide antibiotic which, despite its low in vitro activity against MAC, has shown promise as a treatment in animal studies (12) and early human trials (26). This efficacy may stem from its unusual pharmacokinetic profile, which can result in high concentrations in tissues (6).A new model of disseminated MAC infection has recently been described in Sprague-Dawley rats immunosuppressed with cyclosporine (CsA) (2). We evaluated the response to treatment with azithromycin, rifabutin, or rifapentine in CsA-treated rats with bacteremic MAC infections. As a model of prophylaxis, we also tested whether these drugs prevent the progression of low-grade infection.(Results of the studies described here were presented in MATERIALS AND METHODSDrugs. Azithromycin was provided by Pfizer Central Research, Groton, Conn. ...

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“…Blood cultures prepared from such patients may be the only effective means of diagnosis since these lung infections seldom result in cavitary disease (14,61). Blood cultures also provide a useful means for monitoring the effectiveness of any chemotherapeutic regimen since the blood will be rendered culture negative long before the systemic infection begins to decline (10,206).…”

Section: Nontuberculous Mycobacterial Infections and Aidsmentioning

confidence: 99%

“…Because of the profound immunodepression which develops in the AIDS patient, the presence of even a few acid-fast bacilli within lung or intestinal biopsy specimens should be accorded the utmost pathological significance (60,206,212). Early detection of MAC involvement in the ARC patient is a technically difficult problem for the diagnostic bacteriologist (24,69,165,188), and most of the available tests are slow, tedious, time-consuming, and expensive (122).…”

Section: Nontuberculous Mycobacterial Infections and Aidsmentioning

confidence: 99%

Mycobacterial disease, immunosuppression, and acquired immunodeficiency syndrome

Collins

1989

Clin Microbiol Rev

132

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The mycobacteria are an important group of acid-fast pathogens ranging from obligate intracellular parasites such as Mycobacterium leprae to environmental species such as M. gordonae and M. fortuitum. The latter may behave as opportunistic human pathogens if the host defenses have been depleted in some manner. The number and severity of such infections have increased markedly with the emergence of the acquired immunodeficiency syndrome (AIDS) epidemic. These nontuberculous mycobacteria tend to be less virulent for humans than M. tuberculosis, usually giving rise to self-limiting infections involving the cervical and mesenteric lymph nodes of young children. However, the more virulent serovars of M. avium complex can colonize the bronchial and intestinal mucosal surfaces of healthy individuals, becoming virtual members of the commensal gut microflora and thus giving rise to low levels of skin hypersensitivity to tuberculins prepared from M. avium and M. intracellulare. Systemic disease develops when the normal T-cell-mediated defenses become depleted as a result of old age, cancer chemotherapy, or infection with human immunodeficiency virus. As many as 50% of human immunodeficiency virus antibody-positive individuals develop mycobacterial infections at some time during their disease. Most isolates of M. avium complex from AIDS patients fall into serotypes 4 and 8. The presence of these drug-resistant mycobacteria in the lungs of the AIDS patient makes their effective clinical treatment virtually impossible. More effective chemotherapeutic, prophylactic, and immunotherapeutic reagents are urgently needed to treat this rapidly increasing patient population.

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Continuous high-grade mycobacterium avium-intracellulare bacteremia in patients with the acquired immune deficiency syndrome

Cited by 166 publications

References 16 publications

The Mycobacterium avium complex

The Mycobacterium avium complex

Azithromycin, rifabutin, and rifapentine for treatment and prophylaxis of Mycobacterium avium complex in rats treated with cyclosporine

Mycobacterial disease, immunosuppression, and acquired immunodeficiency syndrome

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