Pulmonary Mycobacterium avium complex disease without dissemination in HIV-infected patients

Pulmonary disease due to Mycobacterium avium complex (MAC) without evidence of dissemination is uncommon in HIV-infected patients. Five cases were observed over a 2-year period. All patients had AIDS and the median CD4 cell count at the time of presentation was 90 x 10(6)/L. Radiographic patterns included unilobar alveolar infiltrates or diffuse alveolar densities. All patients had a favorable clinical response to antimycobacterial chemotherapy with a median follow-up period of 10 months. MAC should be considered in HIV-infected patients with positive respiratory samples for acid-fast bacilli and pulmonary infiltrates. Patients with such findings in whom presumptive therapy for tuberculosis has failed should receive broad-spectrum antimycobacterial chemotherapy until final identification is available.     

New trends in the drug therapy of localized and disseminated Mycobacterium avium complex infection

Recent advances in the drug therapy of localized and disseminated infection with Mycobacterium avium complex (MAC) are reviewed. MAC infection is the most commonly reported bacterial infection in patients with AIDS, and the frequency of this infection in patients negative for the human immunodeficiency virus (HIV) is increasing. The main portals of entry for MAC are the gastrointestinal and respiratory tracts. Localized MAC infection is more common in HIV-negative than HIV-infected patients. The symptoms of disseminated MAC disease are those typical of advanced HIV disease. The most reliable diagnosis is provided by blood cultures; radiometric culturing techniques are favored. The overall treatment of MAC infection has improved greatly with the introduction of new agents during the past 15 years; survival time has been extended. Clarithromycin and azithromycin have proven effective against both localized and disseminated MAC infection. Clarithromycin is the cornerstone of therapy for disseminated infection. Ciprofloxacin has been successfully used to treat disseminated infection as part of a four-drug regimen including rifampin, ethambutol, and clofazimine. Rifabutin has substantial efficacy when combined with other agents. Liposomal aminoglycosides, such as amikacin, and interferon gamma have shown some initial promise. Rifabutin is currently recommended for the prevention of MAC disease in HIV-infected patients. Clarithromycin and azithromycin have also shown efficacy for prophylaxis, and fluoroquinolones may play a preventive role as well. New drug therapies are improving the outlook for persons infected with MAC.     

The Mycobacterium avium complex

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.     

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.     

Molluscum contagiosum-like papules within the scope of disseminated infection with Mycobacterium avium complex in an AIDS patient

A 38-year-old HIV-positive man had several attacks of high fever associated with extensive perspiration over a 10-week period. Simultaneously, he developed molluscum contagiosum-like papules and an erythematous plaque on the face, ulcerated papules on both shoulders and buttocks and subcutaneous nodules on the arms. Histological examination of biopsy specimens revealed a diffuse, histiocytic infiltrate with abundant rod-shaped bacteria. Mycobacterium avium complex was cultured from the tissue and Mycobacterium avium complex DNA was detected by the polymerase chain reaction. The diagnosis of disseminated disease was additionally confirmed by culturing Mycobacterium avium complex from blood, sputum and stool. The skin lesions healed completely within 10 weeks by a multiagent as the patient was treated with a drug therapy. We describe the differential diagnosis, diagnostic procedures and therapy of disseminated infection with Mycobacterium avium complex.     

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.     

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.     

Pathobiological significance of colony morphology in Mycobacterium avium complex

There have been considerable political and organizational moves to involve 'consumers' (patients, carers, service users, potential users, local communities and the public at large) in the provision, planning and monitoring of health services. Such developments beg the question 'what constitutes good practice in user involvement?'. Taking user views into account relates not only to obtaining feedback on 'hotel' aspects of care (issues such as food and cleanliness) but also to the potential for patient input to clinical audit and the standards by which care itself is measured. Recent policy statements specifically advocate involving users in the process and product of clinical audit. In practice, 'involvement' has meant anything from passing on information to full and active participation in partnership with professionals. This paper outlines some of the issues raised in the published literature on user involvement in clinical audit. Suggesting that real involvement refers to users as active participants, not passive recipients, the paper documents the increasing policy commitment to user involvement and considers issues that influence how the rhetoric is put into practice.     

Sequence-based differentiation of strains in the Mycobacterium avium complex

The complete 16S-23S rDNA internal transcribed spacer (ITS) was sequenced in 35 reference strains of the Mycobacterium avium complex. Twelve distinct ITS sequences were obtained, each of which defined a "sequevar"; a sequevar consists of the strain or strains which have a particular sequence. ITS sequences were identified which corresponded to M. avium (16 strains, four ITS sequevars) and Mycobacterium intracellulare (12 strains, one ITS sequevars). The other seven M. avium complex strains had ITS sequences which varied greatly from those of M. avium and M. intracellulare and from each other. The 16S-23S rDNA ITS was much more variable than 16S rDNA, which is widely used for genus and species identification. Phylogenetic trees based on the ITS were compatible with those based on 16S rDNA but were more detailed and had longer branches. The results of ITS sequencing were consistent with the results of hybridization with M. avium and M. intracellulare probes (Gen-Probe) for 30 of 31 strains tested. Serologic testing correlated poorly with ITS sequencing. Strains with the same sequence were different serovars, and those of the same serovar had different sequences. Sequencing of the 16S-23S rDNA ITS should be useful for species and strain differentiation for a wide variety of bacteria and should be applicable to studies of epidemiology, diagnosis, virulence, and taxonomy.     

A phase II/III trial of antimicrobial therapy with or without amikacin in the treatment of disseminated Mycobacterium avium infection in HIV-infected individuals. AIDS Clinical Trials Group Protocol 135 Study Team

OBJECTIVE: To determine the clinical and microbiologic benefit of adding amikacin to a four-drug oral regimen for treatment of disseminated Mycobacterium avium infection in HIV-infected patients. DESIGN: A randomized, open-labeled, comparative trial. SETTING: Outpatient clinics. PATIENTS: Seventy-four patients with HIV and symptomatic bacteremic M. avium infection. INTERVENTIONS: Rifampin 10 mg/kg daily, ciprofloxacin 500 mg twice daily, clofazimine 100 mg every day, and ethambutol 15 mg/kg orally daily for 24 weeks, with or without amikacin 10 mg/kg intravenously or intramuscularly 5 days weekly for the first 4 weeks. MAIN OUTCOME MEASURE: Clinical and microbiologic response at 4 weeks; quantitative level of bacteremia with M. avium. RESULTS: No difference in clinical response was noted with the addition of amikacin to the four-drug oral regimen, and only 25% in either group had a complete or partial response at 4 weeks. A comparable quantitative decrease in bacteremia was noted in both treatment groups, with 16% of patients being culture-negative at 4 weeks and 38% at 12 weeks. Toxicities were mainly gastrointestinal. Amikacin was well tolerated. Median survival was 30 weeks in both groups. CONCLUSIONS: The addition of amikacin to a four-drug oral regimen of rifampin, ciprofloxacin, clofazimine, and ethambutol did not provide clinical or microbiologic benefit.     

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.     

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.