Evaluation of Mycobacterium avium complex lung disease in women

Mycobacterium avium complex (MAC) is a ubiquitous organism responsible for most pulmonary and disseminated disease caused by non-tuberculosis (NTM) mycobacteria. Though MAC lung disease without predisposing factors is uncommon, in recent years it has been increasingly described in middle-aged and elderly women. Recognition and correct diagnosis, is often delayed due to the indolent nature of the disease. It is unclear if these women have significant clinical disease as or if their airways are simply colonized by the bacterium. This study describes the clinical presentation, identifies risk factors, and describes the clinical significance of MAC lung disease in HIV-negative women aged 50 or greater. ^ A hybrid study design utilizing both cross-sectional and case-control methodologies was used. A comparison population was selected from previously identified tuberculosis suspects found throughout Harris County. The study population had at least one acid fast bacillus pulmonary culture performed between 1/1/1998 and 12/31/2000 from a pulmonary source. Clinical presentation and symptoms were analyzed using a cross-sectional design. Past medical history and other risk factors were evaluated using a traditional case-control study design. Differences in categorical variables were estimated with the Chi Square or Fisher's Exact test as appropriate. Odds ratios and 95% confidence intervals were utilized to evaluate associations. Multivariate logistic regression was used to identify predictive factors for MAC. All statistical tests were two-sided and P-values <0.05 were considered statistically significant. ^ Culture confirmed MAC pulmonary cases were more likely to be white, have bronchiectasis, scoliosis, evidence of cavitation and pleural changes on chest radiography and granulomas on histopathologic examination than women whose pulmonary cultures were AFB negative. After controlling for selected risk factors, white race continued to be significantly associated with MAC lung disease (OR = 4.6, 95% CI = 2.3, 9.2). In addition, asthma history, smoking history and alcohol use were less likely to be evident among MAC cases in a multivariate analysis. Right upper and right middle lobe disease was further noted among clinically significant cases. Based on population data, MAC lung disease appears to represent a significant clinical syndrome in HIV-negative women thus supporting the theory of the Lady Windermere Syndrome. ^

Role of {\it Mycobacterium avium-intracellulare\/} complex infection in AIDS mortality

Disseminated MAC (dMAC) is the third most prevalent opportunistic infection in AIDS patients. In order to understand the role MAC infection plays in affecting survival of AIDS patients, a cohort of 203 suspected dMAC veterans seen at the Houston Veterans Affairs Medical Center between August 14, 1987 and December 31, 1991 were analyzed. The criteria for suspected dMAC infection was HIV+ men having a CD4+ level $\le$200 cells/mm$\sp3,$ on zidovudine treatment $\ge$1 month and who had any of the following: (a) a confirmed respiratory MAC infection, (b) fever $\ge$101$\sp\circ\rm F$ for $\ge$48 hours, (c) unexplained weight loss of 10 lbs or $\ge$10% BW over 3 months or (d) Hgb $\le$7.5 g/dl or decrease in Hgb $\ge$3.0 g/dl, while on 500-600 mg/day AZT. The study was conducted before the commencement of an effective MAC anti-mycobacterial therapy, so the true course of MAC infection was seen without the confounder of a therapeutic regimen. Kaplan-Meier and Cox regression survival analysis was used to compare 45 MAC culture positive and 118 MAC culture negative veterans. The 1 year survival rate of veterans with documented dMAC infection was 0.37 compared to 0.50 for veterans not acquiring dMAC infection. Significant differences between subgroups were also seen with the variables: PCP prophylaxis, the AIDS indicator disease Candida esophagitis, CD4+ lymphocyte level, CD4 percent lymphocyte level, WBC level, Hgb and Hct levels. Using multivariate modeling, it was determined that PCP prophylaxis (RR = 6.12, CI 2.24-16.68) was a predictor of survival and both CD4% lymphocytes $\le$6.0% (RR = 0.33, CI 0.17-0.68) and WBC level $\le$3000 cells/mm$\sp3$ (RR = 0.60, CI 0.39-0.93) were predictors of mortality. CD4+ level $\le$50 cells/mm$\sp3$ was not a significant predictor of mortality. Although MAC culture status was a significant predictor of mortality in the univariate model, a positive dMAC culture was not a significant predictor of AIDS mortality in the multivariate model. A positive dMAC culture, however, did affect mortality in a stratified analysis when baseline laboratory values were: CD8+ lymphocytes $>$600 cells/mm$\sp3,$ Hgb $>$11.0 g/dl, Hct $>$31.0% and WBC level $>$3000 cells/mm$\sp3.$ ^

Epidemiology of tuberculosis and nontuberculous mycobacterial infections in Houston children

Background. Nontuberculous mycobacteria (NTM) are environmentally ubiquitous organisms whose epidemiology is poorly understood. Species differ with respect to disease presentation, prognosis, and antimicrobial susceptibility. We reviewed one Texas pediatric hospital's experience with NTM and tuberculosis (TB) disease.^ Methods. This was a retrospective case series of children with culture-confirmed mycobacterial infections seen at a children's hospital from 2003-2008.^ Results. One hundred sixty-two isolates were identified from 150 children; 132 (81.5%) had NTM species isolated, and 30 (18.5%) had M. tuberculosis isolated; 2 children had both NTM and M. tuberculosis isolated. The most common species were Mycobacterium avium complex (MAC) (29%), M. tuberculosis (18.5%), M. abscessus (13%), M. fortuitum (11.7%), and M. chelonae-abscessus (9.9%). TB was the most common organism isolated from respiratory specimens. MAC and M. simiae were significantly more likely to be associated with lymphadenopathy than other NTM species (p < 0.001). Mycobacterium fortuitum was significantly more likely to be associated with soft tissue infections than other NTM species (p < 0.001). Seventy-five children met criteria for NTM disease (30 lymphadenopathy, 17 pulmonary, 17 soft tissue infections, 11 bacteremia). Children with NTM lymphadenopathy were more likely to be Hispanic (OR 24, CI 2.8-1063), younger (3.3 years vs. 10.6 years, p < 0.001), and previously healthy (OR 0.004, CI 0-0.06) than children with NTM pulmonary disease. Children with NTM disease were less likely to be previously healthy (OR 0.30, 95% CI 0.09-0.88) and foreign-born (OR 0.09, CI 0.03-0.29) than children with TB.^ Conclusions. Children with NTM lymphadenopathy were younger and more likely to be healthy than children with NTM pulmonary disease. Tuberculosis comprised a large proportion of mycobacterial disease in this series. Children with NTM pulmonary disease were less likely to be previously healthy and born abroad when compared to children with TB. There was wide variation in antimicrobial susceptibility patterns among NTM species. This, together with the large percentage of disease caused by TB, emphasizes the importance of securing a specific microbiologic diagnosis in children with pulmonary or lymph node disease caused by mycobacteria.^

EPIDEMIOLOGIC TRENDS OF LUNG DISEASE DUE TO MYCOBACTERIA KANSASII AND AVIUM-INTRACELLULARE IN TEXAS, 1977-1983

This study compared the reported isolations of Mycobacterium kansasii (MK) and Myobacterium avium-intracellulare (MAI) with Mycobacterium tuberculosis (MTB) between 1977-1983 in Texas. A total of 15,395 mycobacterial cases were identified of which 1,352 (8.8%) were MK or MAI. The incidence of MK was higher in urban areas than nonurban areas (p < .005). The incidence of MAI has increased in the Dallas metroplex from 34 cases to 251 for the same time period. Although the number of MK cases previously reported has always exceeded those of MAI, the numbers were equal in the last year (1983) of the study.^ More than 75% of patients with MK or MAI were Caucasians compared to only 18% of patients with MTB. Male to female ratios for MK and MAI are 3:1 and 3:2, respectively. The age distribution of MK patients were an average of 5 years younger than patients with MAI, a finding which concurs with previous studies. MK and MAI pulmonary infections continue to be absent among children and relatively absent among Hispanics.^ MK appears to be associated with occupations in construction, whereas MAI is more often associated with farm work. ^