Mycobacterium Avium Complex Bacteremia Research Articles

Geographic and Seasonal Variation in Mycobacterium avium Bacteremia Among North American Patients With AIDS

AbstractAnalysis of geographic risk was performed for Mycobacterium avium complex (MAC) bacteremia among North American patients with AIDS. Monthly mycobacterial blood cultures were taken from patients who were placebo recipients in a prospective evaluation of MAC prophylaxis. Of 571 patients, 102 (17.9%) acquired MAC bacteremia during an average follow-up of 256 days. The area with the highest risk for MAC was the South Central region (27.9%; P <0.02), whereas the area with the lowest risk was Canada (11.3%; P = 0.12). When the southern states were combined and compared with the northern states and Canada, the incidence of MAC bacteremia was higher in the southern states (21.6% versus 14.0%, P < 0.03). Proportional hazards analysis was performed for the difference between the North and South and controlled for baseline CD4 cell count. In this analysis, time to MAC was significantly longer in the North (hazard ratio = 0.587,95% confidence interval 0.390 to 0.883, P = 0.01). Although overall variation in seasonality was not marked, there was a significant decrease in cases in the North during the summer months (P < 0.01). We conclude that geographic location is a risk factor for MAC bacteremia in patients with advanced AIDS, with decreased risk in northern North America.

Triple therapy cleared M. avium complex infection better than quadruple therapy in HIV infection

Source Citation Shafran SD, Singer J, Zarowny DP, et al., for the Canadian HIV Trials Network Protocol 010 Study Group. A comparison of two regimens for the treatment of Mycobacterium avium complex bacteremia in AIDS: rifabutin, ethambutol, and clarithromycin versus rifampin, ethambutol, clofazimine, and ciprofloxacin. N Engl J Med. 1996 Aug 8;335:377-83.

Impact of Mycobacterium avium complex prophylaxis on the incidence of mycobacterial infections and transfusion-requiring anemia in an HIV-positive population.

Disseminated Mycobacterium avium complex (MAC) infection is common in persons with advanced HIV infection and can be prevented by prophylactic use of rifabutin; however, routine prophylaxis is costly and incompletely effective. Chronic anemia is a common manifestation of MAC infection. We conducted a retrospective population study of the annual incidence of MAC bacteremia and blood transfusion for anemia in a regional HIV-positive population before and after the introduction of rifabutin to determine the effect of MAC prophylaxis on the incidence of transfusion-requiring anemia. The HIV-infected patient populations in 1992 and 1993 were comparable in number, severity of immunodeficiency, and zidovudine (ZDV) use. The use of rifabutin for MAC prophylaxis for those with CD4 T-lymphocyte counts < 100/microl increased from 17.2% in 1992 to 33.7% in 1993 (p < 0.001), whereas diagnostic surveillance for MAC bacteremia was stable. In 1993, there was a decrease in the number of HIV-infected persons from whom MAC was isolated (10 vs. 26, p = 0.004), and a significant decrease in the number of patients transfused for anemia (15 vs. 35, p = 0.002), number of transfusion episodes, and numbers of units transfused, associated with significant cost and resource savings. Adoption of MAC prophylaxis was followed by a significant decrease in the number of diagnosed MAC infections and in transfusion requirements in an HIV-positive population with sustained surveillance and similar levels of immunodeficiency, which may represent a health and economic benefit of effective [correction of defective] MAC prophylaxis in a population at risk.

Natural history of opportunistic disease in an HIV-infected urban clinical cohort.

To determine the effect of contemporary clinical care on the natural history of opportunistic disease in an urban population infected with human immunodeficiency virus (HIV). Urban university HIV clinic. Retrospective and prospective observational study. 1246 HIV-infected patients with CD4+ counts of 300 cells/mm3 or less. Incidence rates and Kaplan-Meier estimates of the probability of developing opportunistic disease with time, distribution of the CD4+ counts at which opportunistic disease develops, survival after the development of opportunistic disease, and the association between preventive drug therapies and the occurrence of opportunistic infection. The most common opportunistic disease was Candida esophagitis, which had an incidence of 13.3 events per 100 person-years and a 3-year Kaplan-Meier probability of 0.30. Pneumocystis carinii pneumonia, Mycobacterium avium complex bacteremia, cytomegalovirus, and the acquired immunodeficiency syndrome dementia complex occurred at rates of 5 to 9 events per 100 person-years and 3-year Kaplan-Meier probabilities of 0.15 to 0.22. Toxoplasmosis, cryptococcal meningitis, herpes zoster, the wasting syndrome, and Kaposi sarcoma occurred at rates of about 2 to 4 events per 100 person-years and with 3-year Kaplan-Meier probabilities of 0.05 to 0.10. Non-Hodgkin lymphoma, M. tuberculosis infection, progressive multifocal leukoencephalopathy, and cryptosporidiosis were the least common disorders, with an incidence of about 1 to 2 events per 100 person-years and a 3-year Kaplan-Meier probability less than 0.05. Only the incidences of cryptococcal meningitis, secondary P. carinii pneumonia, and herpes zoster decreased (P < 0.05) between 1989-1992 and 1993-1995. Fluconazole use was associated with a decreased relative rate of 0.49 (P = 0.06) for cryptococcal meningitis and a decreased relative rate of 0.61 (P = 0.005) for esophageal candidiasis. Rifabutin use was associated with a decreased relative rate of 0.37 (P = 0.002) for M. avium complex bacteremia, and trimethoprim-sulfamethoxazole use was associated with decreased relative rates of 0.33 (P = 0.02) for secondary P. carinii pneumonia and 0.55 (P = 0.08) for primary P. carinii pneumonia. Candidiasis, herpes zoster, and M. tuberculosis infection first occurred at a median CD4+ count greater than 100 cells/mm3, but all other opportunistic diseases first occurred at a median CD4+ count less than 50 cells/mm3. Median survival after diagnosis varied from 35 days for non-Hodgkin's lymphoma to 680 days for herpes zoster. In the patients studied, the incidences of secondary P. carinii pneumonia, cryptococcal meningitis, and herpes zoster have declined in the past 5 years. The incidences of primary P. carinii pneumonia and Kaposi sarcoma appear to be declining compared with historical estimates. However, although these and other opportunistic diseases continue to be relatively frequent complications of HIV infection, they are first occurring at more advanced immunosuppression than in the past. Continued efforts are needed to develop effective strategies for preventing opportunistic disease in very advanced HIV infection.

The Clinical Pharmacokinetics of Rifabutin

Rifabutin is structurally similar to rifampin, but there are important pharmacokinetic differences between the two drugs. Rifabutin is more lipid soluble than is rifampin, resulting in more-extensive tissue uptake, a larger volume of distribution, lower maximum plasma concentrations, lower trough concentrations, a longer terminal half-life, and higher tissue-to-plasma drug concentration ratios. The oral bioavailability of rifabutin is low. Like rifampin, rifabutin induces its own metabolism during multiple dosing. Rifabutin is extensively metabolized. The two major metabolites of rifabutin contribute to its antimicrobial activity. Rifabutin induces hepatic metabolism but is not as potent an inducer as is rifampin. Rifabutin does not affect the pharmacokinetics of antiretroviral drugs that are excreted in the urine. Although rifabutin decreases plasma concentrations of zidovudine, this finding does not appear to be clinically relevant. When administered during rifabutin prophylaxis, fluconazole decreases the incidence of Mycobacterium avium complex bacteremia. The coadministration of clarithromycin and rifabutin results in increased plasma concentrations of rifabutin and decreased plasma concentrations of clarithromycin; however, the plasma concentration of clarithromycin's active metabolite is increased.

Disseminated Mycobacterium avium complex: correlation between blood and tissue burden.

To determine the relationship between levels of Mycobacterium avium complex (MAC) in blood and tissues, histopathologic examination and quantitative MAC cultures were done on blood samples and tissue samples of 7 organs at autopsy of 10 AIDS patients who had been treated for MAC bacteremia. Blood and tissue cultures were negative for MAC for 3 of the patients and positive for 7. The numbers of MAC colony-forming units in the blood and tissues were highly correlated. The highest concentrations of MAC were observed in the reticuloendothelial organs, with a maximum of 6.9 log10 cfu/g in mesenteric lymph nodes and 6.8 log10 cfu/g in spleen. Histopathologic findings paralleled quantitative cultures and were consistent with entry of MAC via lymphatics through the gastrointestinal tract, followed by hematogenous dissemination.

Rifabutin prophylaxis for Mycobacterium avium complex infection in patients with AIDS.

Rifabutin, a macrophage-penetrating lipophilic rifamycin, has a long half-life and activity in vitro against Mycobacterium avium complex (MAC). Preliminary studies of patients with AIDS and those with AIDS-related complex defined dose-limiting toxic effects (arthralgia/arthritis and uveitis) and suggested that rifabutin alone might reduce the incidence of MAC infections. Two double-blind, randomized, placebo-controlled trials involving 1,100 subjects confirmed the safety and efficacy of low doses of rifabutin; this therapy halved the rate of MAC bacteremia and significantly reduced symptoms associated with disseminated MAC infections. Subsequent experience with rifabutin as prophylaxis for and treatment of MAC infections has generally supported its safety profile. Emergence of drug-resistant MAC causing infection in patients receiving rifabutin therapy has not been reported. Interactions with azoles and macrolides increase blood levels of rifabutin and have led to the development of uveitis in certain patients. Studies of the cost-effectiveness of rifabutin prophylaxis for MAC infection suggest that it is comparable with other preventive interventions employed in clinical practice.

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.

Survival analysis of two controlled trials of rifabutin prophylaxis against Mycobacterium avium complex in AIDS

Rifabutin prophylaxis has been shown to significantly decrease the incidence of Mycobacterium avium complex (MAC) bacteremia in two randomized controlled clinical trials, but a survival benefit has not been observed. An analysis of complete follow-up of these patients through August 1992 was performed to assess subsequent survival, because although follow-up in the previous trials was limited at the time of initial analysis, the analysis did suggest that a survival benefit might be emerging. Data from 1146 AIDS patients with CD4+ counts < or = 200 x 10(6)/l enrolled at 73 US and Canadian sites in two clinical trials of MAC prophylaxis were analyzed using Cox proportional hazards analysis with rifabutin use modeled as a time-dependent covariate, taking into account the initial randomized double-blind phase of the trials and the subsequent open-label phase of follow-up of those patients. Survival from date of enrollment was analyzed. Other covariates adjusted for in the analysis were CD4+ lymphocytes count, Karnofsky performance score and hospitalization for opportunistic complications of AIDS. Patients who received open-label rifabutin may have had a better prognosis than those who did not, based on Karnofsky score and occurrence of opportunistic disease. Adjusting for these variables and for use of rifabutin as time-dependent covariates, the relative hazard (RH) of dying while receiving rifabutin prophylaxis was 0.74 for the entire cohort [95% confidence interval (CI), 0.60-0.91; P < 0.004]. For patients with an enrollment CD4+ count < or = 50 x 10(6)/l (n = 655), the RH was 0.75 (95% CI, 0.58-0.98), and for patients with an enrollment CD4+ count of > 50 x 10(6)/l (n = 491), the RH was 0.69 (95% CI, 0.49-0.99). An analysis of the combined double-blind and open-label follow-up of two clinical trials of rifabutin prophylaxis for MAC supports the suggestion of the double-blind study that rifabutin improves survival of AIDS patients.

Preventing disseminated Mycobacterium avium complex disease in patients infected with human immunodeficiency virus.

Disseminated Mycobacterium avium complex (MAC) infection is an important late-stage complication of infection with the human immunodeficiency virus. Since MAC is widely dispersed in the environment, the source of infection for patients with disseminated MAC generally cannot be determined. Therefore, specific recommendations for avoiding exposure are not supported at this time. Routine screening of stools and sputum to detect MAC colonization as a means of targeting prophylaxis for disseminated disease is also not recommended at present. Two randomized, placebo-controlled trials have demonstrated that prophylactic use of rifabutin in persons with low CD4 lymphocyte counts results in a 50% decrease in MAC bacteremia as well as a reduction in some signs, symptoms, and laboratory abnormalities associated with MAC disease. Thus a prophylactic daily dose of rifabutin (300 mg) should be considered for adults who have had a previous AIDS-defining opportunistic illness and who have a CD4 lymphocyte count of < 75/microL. Many experts would consider prophylaxis appropriate only when the CD4 lymphocyte count is < 50/microL, particularly when there has not been a previous AIDS-defining opportunistic infection. Clinicians should be aware of drug interactions and potential adverse effects associated with the use of rifabutin. Preliminary reports of randomized, placebo-controlled trials suggest that chemoprophylaxis with clarithromycin is also effective in the prevention of disseminated MAC disease, and evaluation of other agents is under way. Prophylaxis for disseminated MAC infection in children has not been evaluated but is presumed to be as effective as that in adults. Decisions regarding initiation of MAC chemoprophylaxis should be individualized.

Autopsy Findings In Aids Patients With Mycobacterium avium Complex Bacteremia

To study the pathogenesis of Mycobacterium avium complex (MAC) bacteremia, the extent of organ involvement was determined in a retrospective cohort of 44 AIDS patients with MAC bacteremia and complete autopsies between 1988 and 1992. Clinical and microbiologic histories were reviewed and lymph nodes, spleen, liver, bone marrow, small intestine, and colon from each autopsy were systematically evaluated for the presence of mycobacteria or foamy histiocytes. Of the patients, 30% had no histologic evidence of MAC. In the remaining 70%, reticuloendothelial and gastrointestinal involvement was most common, but the number and distribution of involved sites was highly variable. The risk of developing detectable histologic involvement was related to the duration of bacteremia. In contrast to the prevailing concept, our data suggest that MAC bacteremia may precede widespread tissue disease.

Mycobacterium avium complex: Advances in therapy

Disseminated Mycobacterium avium complex (MAC) is one of the most common opportunistic infections in AIDS patients and is increasingly recognized as a significant pathogen in chronic pulmonary disease in nonimmunocompromised patients. Important progress in therapy has occurred over the last several years. In AIDS patients, multidrug therapy has been shown to be beneficial in terms of reducing circulating bacteremia and improving clinical symptoms. Clarithromycin and azithromycin, two broad-spectrum antimicrobials with minimal activity against Mycobacterium tuberculosis, have emerged as potent, well tolerated agents pivotal to treatment regimens. In AIDS patients, rifabutin prophylaxis reduced the frequency of MAC bacteremia by 50% in two placebo controlled trials. Despite these advances, there remains a need for determining the optimal combination regimens for therapy, and more effective drugs for prophylaxis which are beneficial both in terms of survival and functional capacity of patients.

Predicting Mycobacterium avium complex bacteremia in patients infected with human immunodeficiency virus: a prospectively validated model.

In cases of advanced infection with human immunodeficiency virus, mycobacterial blood cultures are frequently used to diagnose disseminated infection with the Mycobacterium avium complex (MAC). However, no prospectively validated guidelines exist for the use of such cultures. In this study, a two-part model for predicting MAC bacteremia was developed and then validated prospectively. First, a CD4+ cell count of < or = 50/microL was used to predict bacteremia. Then, among patients with < or = 50 CD4+ cells/microL, the documentation of fever on more than 30 days during the preceding 3 months, a hematocrit of < 30%, or a serum albumin concentration of < 3.0 g/dL was used to predict bacteremia. This model had a sensitivity of 89% and positive and negative predictive values of 30% and 98%, respectively, for the identification of patients with bacteremia. Had the model been applied to patients in this study, the number of blood cultures performed would have decreased by 61%, but 11% of the positive cultures would have been missed. In short, this model can predict MAC bacteremia and can potentially guide the use of mycobacterial blood cultures.

The Impact Of Mycobacterium AviumComplex Bacteremia And Its Treatment On Survival Of Aids Patients-A Prospective Study

It is currently recommended that patients with AIDS and Mycobacterium avium complex (MAC) bacteremia receive antimycobacterial treatment. However, no study has prospectively evaluated the impact of this infection and its treatment on survival. This study prospectively followed a cohort of 367 AIDS patients with < or = 50 CD4+ cells/microL and found that MAC bacteremia was independently associated with an increased risk of death (relative hazard [RH] = 1.8, 95% confidence interval [CI] = 1.3-2.4, P < .001). Patients with MAC bacteremia who were treated had a longer median survival than those who were not (263 vs. 139 days, P < .001); treatment was independently associated with a lower risk of death (RH = 0.45, 95% CI = 0.23-0.89, P < .001). However, 23% of patients with bacteremia died within 28 days of that diagnosis; few were treated. MAC bacteremia contributes to the death of patients with AIDS, and treatment increases survival. However, many patients will not survive long enough to receive treatment. These results underscore the importance of early diagnosis and chemoprophylaxis for MAC bacteremia.

Disseminated Mycobacterium avium Complex Disease in Patients with AIDS

Disseminated Mycobacterium avium complex (MAC) infection is a common complication of advanced HIV disease that is associated with significant morbidity. After diagnosis of MAC by recovery of organisms from blood or other normally sterile sites, specific treatment with multiple-drug regimens is appropriate and may reduce morbidity. Multiple-drug regimens with agents active against MAC should be employed to reduce the development of drug resistance. Unfortunately, as most clinical trials of anti-MAC agents have lasted 12 weeks or less and have not compared specific agents, the most effective multiple-drug regimen has not been established. The U.S. Public Health Service Task Force on Prophylaxis and Therapy of MAC recommends treatment of disseminated disease with at least two antimycobacterial agents, one of which should be clarithromycin or possibly azithromycin. Ethambutol, which may have an additive or synergistic effect in combination with other anti-MAC agents, is a reasonable second drug. Other agents with activity include rifampin or rifabutin, clofazimine, ciprofloxacin, or parenteral amikacin. A microbiological response may require up to 2 to 8 weeks. The clinical response generally parallels the microbiological response. Rifabutin, which is licensed for prophylaxis of MAC, reduces the incidence of and delays the time to MAC bacteremia. Individuals at highest risk of MAC bacteremia (i.e., CD4+ cell counts of < 75-100 cells/microliters) had the most benefit from rifabutin prophylaxis. Tuberculosis must be ruled out before rifabutin prophylaxis is initiated. Careful observation without prophylaxis is an acceptable alternative for those who are not able to take rifabutin or alternative agents.

Efficacy of Rifabutin in the Treatment of Disseminated Infection Due to Mycobacterium avium Complex

The incidence of infection with Mycobacterium avium complex (MAC) is increasing among patients with AIDS. Although numerous antimicrobial regimens have been proposed as treatment for this infection, it is unclear which therapy is most effective. For this reason, we prospectively evaluated rifabutin (600 mg/d) vs. a placebo, each in combination with clofazimine and ethambutol, for the treatment of MAC bacteremia. Patients in the rifabutin group had a significantly higher rate of microbiological response (defined as either sterilization of the blood or at least a 2-log10 reduction in mycobacterial titers). By week 4 of therapy, 7 of 11 patients receiving rifabutin, vs. 0 of 13 in the placebo group, had responded (P < .001). Similar results were seen at later time points (7 of 10 vs. 1 of 8 responded to rifabutin by week 8, and 6 of 9 vs. 1 of 7 responded to a placebo by week 12). These results indicate that, in combination with other antimicrobial agents, rifabutin may be effective in the treatment of disseminated MAC infection.

Prophylaxis of Mycobacterium avium Complex Bacteremia in Patients with AIDS

Prevention of opportunistic infections is an integral part of caring for patients infected with human immunodeficiency virus. Mycobacterium avium complex (MAC) bacteremia can cause severe morbidity and excess mortality among these patients. Controlled trials of rifabutin for the prophylaxis of MAC bacteremia have been completed. Rifabutin reduced the incidence of MAC bacteremia by approximately one-half and, when disseminated disease due to MAC (DMAC) did develop, reduced the frequency of associated clinical symptoms. Moreover, prophylaxis with rifabutin was well tolerated. Prophylaxis of MAC bacteremia with macrolide antibiotics is currently being investigated, but no data from large-scale prospective trials are yet available. On the basis of trials completed thus far, the U.S. Public Health Service has recently recommended the use of rifabutin (300 mg/d) as prophylaxis for MAC bacteremia in patients with fewer than 100 CD4+ lymphocytes/mm3. The widespread use of this prophylactic regimen could reduce the rates of morbidity and mortality caused by DMAC. However, rifabutin must be administered only after careful consideration of the circumstances of individual patients. Potential drug interactions, cost, and compliance are important factors in the decision about which patients should receive prophylaxis.

Disease due to the Mycobacterium avium complex in patients infected with human immunodeficiency virus: diagnosis and susceptibility testing.

Because the symptoms and laboratory abnormalities associated with disseminated disease due to the Mycobacterium avium complex (MAC) are nonspecific, diagnosis requires recovery of the organism from blood or other normally sterile body sites. Isolation of MAC by conventional mycobacterial culture on tubed solid medium generally takes 3-4 weeks. This interval can be decreased to 5-12 days with the radiometric BACTEC TB system and to 12-19 days with Septi-Chek AFB. For diagnosis of MAC bacteremia, blood is inoculated directly into a BACTEC TB 13A blood culture vial. For quantitative cultures, blood is collected in an Isolator lysis-centrifugation tube, and the sediment of the processed sample is inoculated onto agar plates. MAC is identified by conventional biochemical tests, which take several weeks or months, or with commercial DNA probes or chromatography, each of which provides results in a few hours. No standardized reference method for antimicrobial susceptibility testing exists, and no correlation between in vitro results and clinical efficacy is clear. Isolates appear more sensitive in broth than on agar. Evaluation of susceptibility in macrophage and animal models is helpful because drugs concentrated in cells may be more efficacious against MAC--an intracellular pathogen--than would be predicted by results in cell-free systems.

Mycobacterium avium complex in the respiratory or gastrointestinal tract and the risk of M. avium complex bacteremia in patients with human immunodeficiency virus infection.

Mycobacterium avium complex (MAC) is frequently isolated from the respiratory or gastrointestinal tract of patients with advanced human immunodeficiency virus (HIV) infection. Whether they are at increased risk of MAC bacteremia and whether culture of respiratory tract or stool specimens is useful for predicting bacteremia are unclear. HIV-infected patients with < or = 50 CD4+ cells/microL were prospectively studied. The risk of MAC bacteremia was approximately 60% within 1 year for patients with MAC in either the respiratory or gastrointestinal tract and was greater than for those without MAC in these sites (relative hazards for respiratory and gastrointestinal tract, 2.3 and 6.0; 95% confidence intervals, 1.1-4.6 and 2.5-14.6, respectively). Both respiratory tract specimen and stool culture had poor sensitivities (22% and 20%, respectively) but good positive predictive values (approximately 60%) for bacteremia. Symptomatic HIV-infected patients with MAC in the respiratory or gastrointestinal tract are at a substantial risk for developing MAC bacteremia; culture of these sites has limited usefulness as a screening test.

Reproducibility of lysis-centrifugation cultures for quantification of Mycobacterium avium complex bacteremia.

While quantitative mycobacterial blood cultures have been accepted as the standard for evaluating response to various Mycobacterium avium complex (MAC) treatment regimens, variability in this methodology has not been evaluated in a rigorous fashion. We thus studied the reproducibility of quantitative MAC cultures by a lysis-centrifugation culture system within and among five institutions. To measure the intralaboratory variation in mycobacterial colony counts, colony counts from duplicate blood specimens collected from 52 AIDS patients with MAC bacteremia were determined. Colony counts ranged from 0 to 50,000 CFU/ml. Nonparametric analyses revealed there was no significant difference in colony counts between the 52 duplicate specimens. The agreement between the intralaboratory paired specimens, as measured by the intraclass correlation coefficient, was 0.997. To measure the interlaboratory variation, multiple 10-ml aliquots from 12 patients were distributed to five institutions and processed within 24 to 32 h by lysis-centrifugation. For the 12 specimens distributed to the five laboratories, two-way analysis of variance for repeated measures revealed no significant difference in an individual patient's colony counts between laboratories (P > 0.2). We conclude that quantitation of mycobacterial colony counts by the lysis-centrifugation system is reproducible within and between institutions. Clinical trials evaluating response to therapeutic interventions for MAC can use multiple laboratories for quantitation of mycobacteremia. Furthermore, a 24- to 32-h delay in processing appeared to have no impact on reproducibility.