Mycobacterium avium complex and Mycobacterium tuberculosis in patients infected with the human immunodeficiency virus

Primary care physicians play an important role in identifying and treating bacterial infections in adults infected with the human immunodeficiency virus (HIV). Mycobacterium avium complex and Mycobacterium tuberculosis are pathogens that can cause systemic or local infection in these patients. We review the epidemiology, pathogenesis, clinical presentation, and principles of treatment for these two mycobacterial pathogens. Because M tuberculosis disease is preventable and curable and yet communicable, physicians should maintain a high degree of suspicion for tuberculosis in HIV-infected adults. In comparison, the goal of treating M avium complex in patients with advanced HIV disease is to reduce constitutional symptoms and improve survival.     

Mycobacterium avium complex in macaques with AIDS is associated with a specific strain of simian immunodeficiency virus and prolonged survival after primary infection

Mycobacterium avium complex (MAC) in simian immunodeficiency virus (SIV)-infected macaques is a frequent opportunistic infection that shares many features with the condition in human AIDS patients. A retrospective analysis of necropsies on 135 macaques with SIV-induced simian AIDS that received neither antiretroviral nor antimicrobial therapy revealed that 17% (23/135) were infected with MAC. MAC developed in 31.3% (21/67) of the animals inoculated with uncloned SIVmac251 versus 1.9% (1/53) and 6.7% (1/15) of the animals inoculated with the molecular clones SIVmac239 and SIVmac239/316EM, respectively (P = .001). This is the first example in which the risk of infection with a specific opportunistic organism was affected by the infecting strain of immunodeficiency virus. In addition, animals with MAC had a longer mean survival after primary infection and lower CD4 cell counts at death than animals that did not develop this opportunistic infection. The SIV-inoculated macaque is a valuable model in which to study the pathogenesis of MAC in the immunocompromised host.     

Clinical and bacteriologic impact of rifabutin prophylaxis for Mycobacterium avium complex infection in patients with human immunodeficiency virus infection

Carcinoma of the oesophagus is the seventh most common malignancy worldwide. It is a disease with a poor prognosis; more than half of the patients present with surgically irresectable tumours. For such patients, palliative therapy is directed towards the relief of dysphagia. Expandable metallic stents have recently been developed for use in the oesophagus. These have the advantage of being introduced through small diameter delivery catheters. Once released, they can expand to as much as 25 mm in diameter, potentially allowing patients to consume a normal diet. The current designs of metallic stents include the Strecker stent, the Wallstent endoprosthesis, and the Gianturco-Rosch stent. The Strecker is an uncovered stent while the other two are covered on the outside of the stent with plastic to prevent tumour ingrowth. A review of the literature indicates that deployment of these stents is associated with a high technical success rate. Improvement in swallowing function is seen in 83% to 100% of these patients. The overall complication rates are low. However, covered stents are prone to migration while uncovered stents are vulnerable to tumour ingrowth. Further improvements in design promise to expand the role of these endoprostheses in the management of oesophageal carcinoma.     

Randomized, open-label trial of azithromycin plus ethambutol vs. clarithromycin plus ethambutol as therapy for Mycobacterium avium complex bacteremia in patients with human immunodeficiency virus infection. Veterans Affairs HIV Research Consortium

Disseminated Mycobacterium avium complex (MAC) infection continues to be a common opportunistic infection in patients infected with human immunodeficiency virus (HIV). The optimal therapy for disseminated MAC infection is unclear. We compared azithromycin plus ethambutol with clarithromycin plus ethambutol in the treatment of disseminated MAC infection in HIV type 1-infected patients, examining the frequency of bacteremia clearance, time to clearance, and study drug tolerance after 16 weeks of therapy. Fifty-nine patients for whom blood cultures were positive for MAC were enrolled in the study from 10 university-affiliated Veterans Affairs Medical Centers. Thirty-seven patients were evaluable for determination of quantitative bacteremia and clinical outcomes. Clearance of bacteremia was seen at the final visit in 37.5% of azithromycin-treated patients and in 85.7% of clarithromycin-treated patients (P = .007). The estimated median time to clearance of bacteremia was also significantly different between the two treatment arms: 4.38 weeks for clarithromycin recipients vs. > 16 weeks for azithromycin recipients (P = .0018). Only one isolate developed macrolide resistance during therapy. Abatement of symptoms, other laboratory-evident abnormalities, and adverse effects were similar in the two groups. At the doses used in this study, clarithromycin/ethambutol produced a more rapid resolution of bacteremia than did azithromycin/ethambutol, and clarithromycin/ethambutol was more effective at sterilization of blood cultures after 16 weeks of therapy.     

Genetic diversity among Mycobacterium avium complex strains recovered from children with and without human immunodeficiency virus infection

The genetic diversity and molecular epidemiology of Mycobacterium avium complex (MAC) infections in children with and without human immunodeficiency virus (HIV) infection were evaluated. Isolates recovered from 136 children were subtyped by sequence analysis of a 360-bp region of the gene (hsp65) encoding a 65-kDa heat-shock protein. Twenty-one distinct hsp65 alleles were identified. On the basis of hsp65 genotype, 6 isolates were not MAC organisms. Of the remaining 130 samples, 61% were M. avium, 37% were Mycobacterium intracellulare, and 2% were species nonspecific MAC. Eighty-eight percent of the isolates obtained from HIV-infected children were M. avium. In contrast, only 38% of the isolates obtained from children without HIV infection were M. avium (chi2 test, P < .001). M. avium isolates were further subtyped by Southern blot analysis with insertion element IS1245. Taken together, no evidence for a single clonal M. avium strain causing infection was detected.     

Mycobacterium avium complex common-source or cross-infection in AIDS patients attending the same day-care facility

To delineate the epidemiology of Mycobacterium avium complex (MAC) infection in acquired immunodeficiency syndrome patients, we studied 32 case patients with disseminated MAC infection who attended the same daycare facility during a period of 13 months. Pulsed-field gel electrophoresis analysis showed very low similarity between MAC strains, suggesting that, despite close contacts between the patients, nosocomial cross-transmission or exposure to a common source of MAC did not occur.     

Polyclonal Mycobacterium avium complex infections in patients with nodular bronchiectasis

P2X purinoceptors have been suggested to participate in transduction of painful stimuli in nociceptive neurons. In the current experiments, ATP (1-10 mM), alpha,beta-methylene-ATP (10-30 microM) and capsaicin (10 nM-1 microM) were applied to neurons impaled with high resistance microelectrodes in rat dorsal root ganglia (L4 and L5) isolated in vitro together with the sciatic nerve and dorsal roots. The agonists were either bath applied or focally applied using a picospritzer. GABA (100 microM) and 40-80 mM K+ solutions gave brisk responses when applied by either technique. Only three of 22 neurons with slowly conducting axons (C cells) showed evidence of P2X-purinoceptor-mediated responses. Only two of 13 cells which responded to capsaicin (putative nociceptors), and none of 29 cells with rapidly conducting axons (A cells), responded to the purinergic agonists. When acutely dissociated dorsal root ganglion cells were studied using patch-clamp techniques, all but four of 30 cells of all sizes responded with an inward current to either ATP or alpha,beta-methylene-ATP (both 100 microM). Our data suggest that few sensory cell bodies in intact dorsal root ganglia express functional purinoceptors.     

Determinants of rifabutin-associated uveitis in patients treated with rifabutin, clarithromycin, and ethambutol for Mycobacterium avium complex bacteremia: a multivariate analysis. Canadian HIV Trials Network Protocol 010 Study Group

Two patients with the Kennedy's disease (KD) mutation have been identified in the Newcastle Brain Tissue Bank. One of these patients had presenile dementia as a prominent clinical feature, previously undescribed in KD. The pathologic substrate underlying the cognitive changes in this patient included neuronal depletion and gliosis in the hippocampus and subcortical gliosis in the prefrontal region. Immunostaining for macrophage markers showed evidence for subtle corticospinal tract pathology in both cases. In contrast to the molecular pathologic features found in ALS, surviving motor neurons in the two KD cases showed no evidence of ubiquitinated inclusions or alterations in neurofilament phosphorylation.     

Protection from Mycobacterium avium complex disease in human immunodeficiency virus-infected persons with a history of tuberculosis

Risk of Mycobacterium avium complex disease was examined in human immunodeficiency virus (HIV)-infected patients with and without a history of tuberculosis. Information was obtained by retrospective review of charts of patients in HIV clinics in 10 US cities. Among 1363 patients with <200 CD4 cells/mm3 seen at Grady Memorial Hospital (GMH), 11 (17%) of 66 with a history of a positive purified protein derivative (PPD) skin test acquired M. avium infection, while 29 (16%) of 185 who were PPD-negative (but not anergic) did not (P = .85). Only 4 (8%) of 49 GMH patients with a history of tuberculosis acquired M. avium infection compared with 252 (19%) of 1314 GMH patients without a history of tuberculosis (P = .05). Proportional hazards analysis of risk factors for M. avium infection among 441 persons with and 8702 persons without a history of tuberculosis in 9 other cities confirmed protection from M. avium infection in persons with a history of tuberculosis (relative risk, 0.52; 95% confidence interval, 0.36-0.76; P < .001). Prior tuberculosis provides protection against M. avium infection in HIV-infected persons, possibly by stimulation of antimycobacterial immunity.     

A case of AIDS with disseminated Mycobacterium kansasii infection in which Mycobacterium, avium complex was also detected from his sputum repeatedly

A 43 year-old Japanese male was admitted to our hospital because of productive cough and fever. He was diagnosed as acquired immunodeficiency syndrome (AIDS) in 1994. Laboratory findings were as follows: WBC was 3200/microliter, CD4+ T lymphocyte count was 22/microliter. His chest X-ray film taken on admission showed infiltration with small cavity lesion in middle left lung field. Tuberculin skin reaction was negative. He was treated with isoniazid 0.4 g, rifampicin 0.45 g, and ethambutol 0.75 g each daily. Sputum smear was positive for acid fast bacilli. The cultured isolates were identified as Mycobacterium kansasii (M. kansasii) and Mycobacterium avium complex (MAC). Urine smear was also positive for acid fast bacilli. The cultured isolates were identified as M. kansasii. He was diagnosed as disseminated M. kansasii infection and suspected MAC infection. About one hundred days later, his chest X-ray film showed reticular shadow. His clinical symptoms improved and the sputum smear and culture converted to negative for acid fast bacilli. Based on these findings, his MAC discharge was considered not as MAC infection, but MAC colonization. He returned to the former hospital for AIDS treatment, and he died in August 1996.     

Mycobacterium avium complex strains from AIDS patients belong to a homogeneous group ascribed by rRNA typing methods

16S rRNA RFLP analysis of Mycobacterium avium complex (MAC) strains isolated from 25 AIDS patients led to identification of seven ribotypes. The same ribotype was determined for strains from 19 patients with and without disseminated disease. When isolates representing the seven ribotypes were examined for their internal transcribed spacer (ITS) between the 16S and 23S rRNA gene nucleotide sequence, four different sequences, including a new ITS type, were recovered. All isolates with the most common ribotype belonged to the sequevar Mav-B. When MAC strains from AIDS patients were compared by ITS sequencing and ribotyping, a significant degree of homogeneity was observed. The discriminatory level reached with ribotyping might be useful for grouping isolates from different clinical sources.     

Once weekly azithromycin therapy for prevention of Mycobacterium avium complex infection in patients with AIDS: a randomized, double-blind, placebo-controlled multicenter trial

We conducted a randomized, double-blind, placebo-controlled multicenter trial of azithromycin (1,200 mg once weekly) for the prevention of Mycobacterium avium complex (MAC) infection in patients with AIDS and a CD4 cell count of < 100/mm3. In an intent-to-treat analysis through the end of therapy plus 30 days, nine (10.6%) of 85 azithromycin recipients and 22 (24.7%) of 89 placebo recipients developed MAC infection (hazard ratio, 0.34; P = .004). There was no difference in the ranges of minimal inhibitory concentrations of either clarithromycin or azithromycin for the five breakthrough (first) MAC isolates from the azithromycin group and the 18 breakthrough MAC isolates from the placebo group. Of the 76 patients who died during the study, four (10.5%) of 38 azithromycin recipients and 12 (31.6%) of 38 placebo recipients had a MAC infection followed by death (P = .025). For deaths due to all causes, there was no difference in time to death or number of deaths between the two groups. Episodes of non-MAC bacterial infection per 100 patient years occurred in 43 azithromycin recipients and 88 placebo recipients (relative risk, 0.49; 95% confidence interval, 0.33-0.73). The most common toxic effect noted during the study was gastrointestinal, reported by 78.9% of azithromycin recipients and 27.5% of placebo recipients. Azithromycin given once weekly is safe and effective in preventing disseminated MAC infection, death due to MAC infection, and respiratory tract infections in patients with AIDS and CD4 cell counts of < 100/mm3.     

Preventing Mycobacterium avium complex in patients who are using protease inhibitors: a cost-effectiveness analysis

Recombinant human interleukin-11 (rhIL-11) is a pleiotropic cytokine with effects on multiple cell types. In addition to thrombopoietic activity, rhIL-11 has demonstrated anti-inflammatory activity in vitro and in vivo. rhIL-11 treatment reduces clinical signs and histologic lesions of colitis in transgenic rats expressing the human major histocompatibility complex (MHC) Class I allele, HLA-B27. We have investigated the effects of rhIL-11 at the molecular and cellular level in this model of inflammatory bowel disease. RT-PCR analysis of colonic RNA revealed that treatment with rhIL-11 down-regulated expression of proinflammatory cytokines including TNF-alpha, IL-1beta, and IFN-gamma. rhIL-11 also reduced the level of myeloperoxidase activity in the cecum indicating reduced inflammation. After stimulation in vitro with anti-CD3 antibody, spleen cell cultures derived from rhIL-11-treated rats produced less IFN-gamma, TNF-alpha, and IL-2 than cultures derived from vehicle-treated rats. These molecular and cellular effects correlated with amelioration of disease as measured by stool character and histologic lesion scores. These findings suggest that rhIL-11 acts to reduce inflammation through modulation of multiple proinflammatory mediators including products of activated T cells. This study has identified pharmacodynamic markers of rhIL-11 anti-inflammatory activity in vivo and supports rhIL-11 therapy to treat inflammatory bowel disease.     

Resistant Mycobacterium tuberculosis: its relation with coinfection with human immunodeficiency virus. 5-year study

BACKGROUND: To analyze the situation of resistance to antituberculous drugs among strains of Mycobacterium tuberculosis recovered in our environment during a five-year period and its relationship with HIV co-infection. PATIENTS AND METHODS: Review of the Mycobacterium tuberculosis strains recovered from patients aged older than 14 years in Hospital Joan March from 1992 to 1996 of which a susceptibility testing study by means of the multiple proportions method was available. The initial or secondary resistance was considered according to the previous antituberculosis treatment antecedent. RESULTS: The susceptibility testing was available from 179 cases (136 males and 43 females) out of a total of 214. The overall resistance rate to any of the tested drugs was 10.1% (18 cases) with a 4% (6 cases) of initial and 38.7% (12 cases) secondary resistances. Co-infection with HIV showed not to be a risk factor for the development of resistance. No significant increase was observed analyzing the temporal trend through the five years studied. CONCLUSIONS: At present, the situation of resistance to Mycobacterium tuberculosis seems not to be alarming in our environment. Co-infection with HIV has not been shown to be associated with an increase in resistance rates.