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.     

Malignant fibrous histiocytoma in a child''s hand

Mycobacterium szulgai is a rare cause of human infections, and when present it is mostly known to cause lung infection. We report the first case of isolated Mycobacterium szulgai osteomyelitis in a 68-year-old woman on chronic immunosuppressive therapy. Review of the literature revealed a total of three other cases of M. szulgai osteomyelitis. In all these cases there was evidence of hematogenous or contiguous spread, including one with extensive dissemination. Pulmonary M. szulgai infections tend to occur in patients with chronic lung disease and/or concomitant lung infections, whereas osteomyelitis tends to occur in patients who have severe immunosuppression secondary to disease or drugs.     

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.     

Pulmonary hypertension. Response of vasoactive peptides to a nonionic contrast medium in patients undergoing pulmonary angiography

A 46-years-old male was admitted to our hospital because of productive cough and infiltrates on the chest roentogenogram. The patient had a history of left upper bullectomy ten years prior to the admission. The CT scan of the chest on admission showed infiltrats with cavitation in the left apex and multiple bullae in almost whole lung. Microscopical examination of smears of sputum and bronchoalveolar lavage fluid revealed acid-fast bacilli. They were identified as Mycobacterium szulgai by DNA-DNA hybridization method. The patient was treated with isoniazid, streptomycin and rifampicin. After treatment for about a month, the culture of sputum converted to negative for M. szulgai. After about three months hospitalization, the infiltrates decreased and the cavity wall became thin, and no recurrence sign has been observed after the discharge. There are a few case reports of pulmonary infection due to M. szulgai associated with bullous disease of the lung in Japan.     

Simulating binocular visual field status in glaucoma

A 73-year-old male was admitted to our hospital because of productive cough and infiltrate on the chest roentogenogram. The underlying diseases was found to be multiple myeloma. He received a physical examination in June, 1996. The chest X-ray and CT scan on admission showed an infiltrative shadow with multiple bulla in the left upper lung field. Internal use of antibiotics and drip infusion of IPM/CS were ineffective. The chest X-ray showed air-fluid level in left upper peripheral bullous lesion and a percutaneus needle aspiration of the lung was performed. The specimen was pus with blood and microscopical examination of smears revealed no acid-fast bacilli, but Mycobacterium szulgai was isolated and identified by DNA-DNA hybridization method. The patient was treated with isoniazid and rifampicin, and improved in a few months. There are a few case reports of pulmonary infection due to M. szulgai associated with emphysematous bulla of the lung in Japan. M. szulgai infection of the lung is similar to M. kansasii infection in respect to clinical features (improvement of chest abnormal shadow, efficacy of drug).     

Nontuberculous mycobacterial infections

The acquired immunodeficiency syndrome (AIDS) pandemic has led to greater understanding and respect for the pathogenic potential of non-tuberculous mycobacteria. Mycobacterium avium complex (MAC) has emerged as the most common systemic bacterial infection in AIDS, causing debilitating disseminated disease in late-stage HIV-infected patients. With the release of the macrolide antibiotics, clarithromycin and azithromycin, effective and well-tolerated therapeutic regimens for MAC have been developed which prolong survival and increase quality of life. The macrolides and rifabutin are also effective as preventive therapy for MAC in patients with AIDS. Mycobacterium kansasii, which causes pulmonary disease similar to tuberculosis as well as disseminated disease in AIDS, is treatable with isoniazid, rifampin and ethambutol. Clinical syndromes and therapeutic options for other non-tuberculous mycobacteria in AIDS are also reviewed.     

Differentiation between Mycobacterium tuberculosis and Mycobacterium avium by amplification of the 16S-23S ribosomal DNA spacer

Differentiation between Mycobacterium tuberculosis and M. avium is helpful for the treatment of disseminated mycobacterial infection in AIDS patients. This can traditionally be done by time-consuming biochemical tests or with Accuprobe. Previously, PCR restriction enzyme analysis (PCR-REA) of the 16S-23S rRNA gene spacer was shown to be able to identify a limited number of strains of Mycobacterium. In this study the method was improved by using more specific primers and was tested with 50 clinical isolates of M. tuberculosis and 65 clinical isolates of M. avium complex. Probes specific to the spacers of M. tuberculosis and M. avium were also tested. Both M. tuberculosis and M. avium could be reliably identified either by PCR-REA or by PCR-hybridization, with the results completely agreeing with those obtained by biochemical tests and with the Accuprobe, respectively. The method may therefore be useful as an alternative in-house method for identification of the bacteria.     

Atypical mycobacteriosis (Mycobacterium xenopi) with "initial aggravation"

A 66-year-old man was admitted to Nara Medical University Hospital because of sputum production and fevre. A chest X-ray film obtained on admission revealed many cysts and an infiltrative shadow in the right upper lung field. The patient was treated with antimycobacterial drugs (isoniazid 400 mg, streptomycin 0.75 g, and rifampicin 450 mg) because acid-fast bacilli were detected in his sputum. Although the symptoms and laboratory data improved, a new infiltrative shadow developed in the right lower lung field two months after the start of treatment. Transbronchial biopsy specimens showed intraluminal organizing exudate and alveolitis. The new lesion resolved when treated with the same antimycobacterial drugs. Mycobacterium xenopi was cultured from the sputum 80 days later. This is the third reported case of atypical mycobacteriosis (non-tuberculous mycobacteriosis) due to M. xenopi in Japan with the "initial aggravation" seen in some patients with typical pulmonary tuberculosis.     

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.     

Prolonged fever due to Mycobacterium avium complex (MAC) disease in advanced HIV infection: a public health concern

From March 1997 to June 1998, infectious etiologies of prolonged fever was prospectively investigated in 104 advanced human immunodeficiency virus (HIV) infected patients admitted to Siriraj Hospital. The etiology could be identified in 91 cases (87.5%). Of these, blood cultures from 68 patients yielded mycobacteria and fungi. Mycobacterium avium complex was the most common blood isolate in 24 per cent of the patients; followed by Mycobacterium tuberculosis in 20.2 per cent, Cryptococcus neoformans in 5.8 per cent, Penicillium marneffei in 5.8 per cent. During the course of febrile illness, 79 of the 91 patients (86.8%) exhibited focal lesions. Weight loss, elevated serum alkaline phosphatase were often found to be significantly more associated with MAC bacteremia (P < 0.05). Pulmonary involvement significantly correlated more with M. tuberculosis bacteremia than MAC bacteremia (P < 0.05). No cause could be identified in 13 cases. Mycobacterium blood culture alone established the etiologies in 68 cases (65.4%). Of the 25 patients with disseminated MAC (DMAC) infection, nine patients died during hospitalization. Another three cases died within a few months of appropriate anti-MAC chemotherapy. We concluded that the risk of DMAC infection in advanced AIDS patients in Thailand is high when low CD4 lymphocyte count is established. The prolonged fever resulted from DMAC in advanced HIV infection is warrant to be public health concern. Mycobacterium blood culture is a most valuable tool contributing to the diagnosis of infectious agents in this condition. The guidelines of 1997 USPHS/IDSA should be followed to give chemoprophylaxis against DMAC disease in patients with advanced HIV infection and a CD4 count less than 50 cells/mm3.     

Pulmonary disease caused by Mycobacterium avium presenting as a solitary cavity with a thickened wall]

A 46-year-old man was admitted for evaluation of a solitary pulmonary cavity in the apey of the left lung. Because two transbronchial biopsies followed by brushing and washing and sputum cytology did not yield any diagnostic findings, the patient was treated with INH, RFP and SM under a tentative diagnosis of pulmonary tuberculosis. The shadow decreased over two months with combination therapy, but increased again after the dose of SM was decreased. We performed a left upper lobectomy to diagnose either multi-drug-resistant pulmonary tuberculosis or lung cancer. Pathological examination of the resected lung revealed epitheloid cell granulomas with areas of caseous necrosis. Smooth chromophoric colonies were isolated on an Ogawa egg medium, and were identified as M. avium by PCR and DDH. A diagnosis of pulmonary M. avium was made. A chest X-ray film taken two years later was normal. Pulmonary M. avium disease developed in this patient, who had no predisposing lung pathologies.     

Effect of anesthetic technique on cardiac morbidity following carotid artery surgery

Clarithromycin and rifabutin are among the most promising drugs for the therapy of infections caused by Mycobacterium avium or other atypical mycobacteria. Since synergism of combined drugs is important in order to achieve strong antimycobacterial activity, the combined inhibitory effects of antibacterial agents should also be investigated when agents are evaluated for possible use in antimycobacterial drug therapy. In the present study we examined the antimycobacterial activity of clarithromycin, rifabutin, and their combination against 51 clinical isolates of the M. avium complex from patients with acquired immune deficiency syndrome (AIDS) with disseminated mycobacteriosis. A concentration-dependent inhibition was seen for each drug. The antibacterial effect was significantly more pronounced for the combined drugs than for the agents tested separately. Synergism, against up to 88% of the strains tested, was seen for the tested drugs combined at different concentrations. All 51 M. avium strains were susceptible to the combination of 4 mg/l clarithromycin and 2 mg/l rifabutin.     

Pyrrolnitrin and related pyrroles endowed with antibacterial activities against Mycobacterium tuberculosis

During development of nitroheterocycles with potential antimycobacterial activities we have tested against Mycobacterium tuberculosis a number of pyrroles strictly related to pyrrolnitrin, an antifungal antibiotic isolated from Streptomyces pyrrocinia. Some of the tested arylpyrrole derivatives and pyrrolnitrin have shown appreciable inhibiting activity against M. tuberculosis and M. avium. SAR studies well correlate antimycobacterial potency with the presence of halogens in the phenyl ring and a nitro group at position 3 of pyrrole.     

Disseminated Mycobacterium genavense infection: clinical and microbiological features and response to therapy

OBJECTIVE: Mycobacterium genavense is a newly described pathogen that causes disseminated infection in AIDS. It is difficult to detect and identify due to its slow growth and fastidious nature. There is little information available about therapy for this new pathogen. We describe clinical and laboratory features and response to therapy in four patients with advanced AIDS complicated by disseminated M. genavense infection from Denver, Colorado, USA. DESIGN AND METHODS: Retrospective analysis of four cases identified in an AIDS clinic affiliated with a municipal hospital in Denver, Colorado. Clinical samples were inoculated onto BACTEC 12B, Lowenstein-Jensen, and Middlebrook 7H11 media. RESULTS: The clinical features mimicked those of disseminated M. avium complex infection, with invasion of liver, spleen and lymph nodes with acid-fast bacilli (AFB). Acid-fast smears of blood and lymph nodes were positive; there was a modest increase in the growth index in BACTEC broth and tiny colonies appeared on Middlebrook agar. Patients were treated with combinations of antimycobacterial agents. Blood smears and cultures reverted to negative in treated patients. The best clinical response was associated with clarithromycin therapy. CONCLUSIONS: Disseminated disease due to M. genavense should be suspected among patients with the clinical presentation of disseminated M. avium complex infection and low growth index on BACTEC cultures for AFB. The diagnosis of M. genavense may be facilitated by performing acid-fast stains of samples from BACTEC bottles in such individuals. Clarithromycin therapy is associated with clinical improvement and clearance of bacteremia.     

Bacteriology of mycobacteria: taxonomic and morphological characteristics

Bacteriological characteristics of organisms belonging to Genus Mycobacterium which involves more than 60 species are described. Mycobacterial organisms can be divided into the following groups having differential characteristics, on the basis of the results of biological, biochemical, and genetic investigations, including lipid analysis, DNA probe test, and comparative 16S ribosomal RNA sequencing. First, Mycobacterium tuberculosis complex (M. tuberculosis, M. bovis, M. africanum, etc.). Second, cultivable but slowly growing nontuberculous mycobacteria, including photochromogens (Runyon Group I) such as M. kansasii, M. marinum, M. simiae, M. intermedium, and M. asiaticum, scotochromogens (Runyon Group II) such as M. scrofulaceum, M. szulgai, M. injectum, M. lentiflavum, and M. gordonae, nonphotochromogenens (Runyon Group III) such as M. avium, M. intracellulare, M. xenopi, M. malmoense, M. genavense, M. celatum, and M. gastri. Third, cultivable rapidly growing nontuberculous mycobacteria (Runyon Group IV) including M. fortuitum, M. chenolae, M. abscessus, M. phlei, and M. smegmatis. Fourth, noncultivable mycobacteria including M. leprae. About 30 species of Mycobacterium cause pulmonary, dermal, lymphatic, and disseminated infections in human beings. This paper mainly deals with the taxonomic, morphological, and other biological characteristics of these mycobacterial organisms.     

Number of days required for recovery of mycobacteria from blood and other samples

From 1991 to 1996, 541 blood samples were tested for the presence of mycobacteria; 56 were positive (30 patients, 26 human immunodeficiency virus positive). The species found were Mycobacterium avium (41 samples from 18 patients), Mycobacterium tuberculosis (12 samples from 9 patients), and three other species (1 sample each). The average time to detection was 25.23 days (22.65 for M. avium and 35.33 for M. tuberculosis). For 10 patients, the blood isolate was the only mycobacterium detected (4 M. tuberculosis).     

Breast cancer five-year survival, by New South Wales regions, 1980 to 1991

Mycobacterium xenopi is one of the most frequently isolated nontuberculous mycobacteria in Ontario, Canada. We reviewed the records of 28 human immunodeficiency virus (HIV)-infected patients from whom M. xenopi was isolated between 1982 and 1995. M. xenopi was recovered from respiratory specimens from 24 patients, most of whom had clinical and radiographic evidence of pulmonary disease. However, coexistent pulmonary infection due to other pathogens was found in 17 patients: Pneumocystis carinii (9 patients), cytomegalovirus (5), Haemophilus influenzae (2), Mycobacterium avium complex (2), Streptococcus pneumoniae (1), Staphylococcus aureus (1), Aspergillus species (1), and Histoplasma capsulatum (1). Three patients had bacteremia with M. xenopi, including two patients with pulmonary infection. Two of the bacteremic patients had chronic fever and a wasting syndrome. Twenty-one (75%) of the 28 patients were thought to be colonized, and seven patients (25%; of whom four had CD4 cell counts of < or = 50/mm3) were thought to have significant infection due to M. xenopi. Sixteen patients died, but in no case was death attributable to M. xenopi infection. In a region where M. xenopi is a relatively common mycobacterial isolate, the organism frequently colonizes HIV-infected patients. Significant disease occurs in those patients with more advanced HIV infection.     

The present situation, treatment and prognosis of drug-resistant pulmonary tuberculosis. Cooperative Study Unit of Chemotherapy of Tuberculosis of the National Sanitoria in Japan

We studied 266 patients with drug-resistant pulmonary tuberculosis at national sanatoria in Japan. The patients included 218 men (mean age, 58 years) and 48 women (mean age, 62 years). The levels of isoniazid and rifampicin resistance were determined at 1 mcg/mL and 50 mcg/mL, respectively. The results were as follows. (1) Most patients with drug-resistant pulmonary tuberculosis were middle-aged or past middle-aged. (2) There were many cases of drug-resistant pulmonary tuberculosis in previously treated tuberculosis patients with active disease and several cases in previously untreated pulmonary tuberculosis patients. However, in some previously untreated patients active tuberculosis was convert relatively easily to inactive tuberculosis. (3) Concerning life style, bachelors who drank heavily were more likely to develop drug-resistant pulmonary tuberculosis. (4) Most cases of drug-resistant pulmonary tuberculosis had at least one cavity on chest radiographs. (5) Several patients with drug-resistant tuberculosis left the hospital against the advice of their attending doctors; therefore, it was difficult to treat their illnesses. (6) In more than half the cases in which Mycobacterium tuberculosis was resistant to isoniazid and rifampicin, tolerance to streptomycin and ethanbutol was also seen. (7) When patients with drug-resistant pulmonary tuberculosis continued to have tuberculous bacilli in their sputum after 3 months of chemotherapy, there was a tendency for them to expectorate tuberculous bacilli in their sputum. For these drug-resistant tuberculosis patients, we must pay attention not only to the medical aspects but also to the social aspects of their disease.     

Lack of a docking mechanism for neurotransmitter release in the aganglionic segment of bowel in patients with Hirschsprung''s disease

To evaluate the patterns of drug resistance of Mycobacterium tuberculosis in Taiwan, a total of 1,091 isolates collected from patients from January 1996 through December 1996 were tested for drug susceptibility using the absolute concentration method at the Taiwan Provincial Chronic Disease Control Bureau. The overall drug rate of resistance to at least one drug was 35.5%. Among the 249 isolates from patients who had never been treated for tuberculosis, 16.1% were resistant to one or more drugs; 1.6% were resistant to at least isoniazid and rifampin. Of 200 patients with prior antituberculosis treatment, 67.0% had isolates resistant to one or more drugs and 46.0% had isolates resistant to at least isoniazid and rifampin. We conclude that drug-resistant M. tuberculosis is an important issue in tuberculosis treatment in Taiwan, especially when dealing with patients with a prior history of antituberculosis treatment. More aggressive interventions, such as directly observed therapy, short-course, are needed to improve the cure rate of pulmonary tuberculosis and to decrease resistance rates.     

New beginnings: the National Blood Data Resource Center

A case of pulmonary Mycobacterium avium (M. avium) disease associated with idiopathic CD4+ T lymphocytopenia is reported. A rapidly growing pulmonary nodule was detected on a chest roentgenogram in a young man. Bronchoscopic examination revealed M. avium infection. Hematological studies showed a low CD4+ cell count in the absence of any identifiable immunodeficiency, including human immunodeficiency virus (HIV) infection. With the combination of chemotherapy and surgery, he had a good clinical outcome. Idiopathic CD4+ T lymphocytopenia should be considered in patients with unexplained opportunistic infection.