Treatment of Mycobacterium avium-intracellulare complex lung disease with a macrolide, ethambutol, and clofazimine

BACKGROUND: Mycobacterium avium-intracellulare (MAC) causes progressive lung disease. Recommended treatment regimens include a macrolide and a rifamycin, but drug intolerance and relapse after treatment is completed often limit successful therapy. METHODS: Consecutive individuals referred for treatment of MAC lung disease were treated with a regimen that included either clarithromycin, 500 mg bid, or azithromycin, 250 mg/d, on weekdays; ethambutol, 15 mg/kg/d; and clofazimine, 100 mg/d. The intention was to treat patients for a minimum of 12 months. The diagnosis of MAC lung disease was confirmed by multiple positive sputum culture findings in patients with typical symptoms and radiologic findings. RESULTS: Thirty patients (27 women and 3 men; mean age, 70 +/- 9.4 years [SD]) were treated. A total of 22 of the patients reported adverse effects from clarithromycin or azithromycin. Intolerance of clarithromycin resulted in the withdrawal of four patients before sputum conversion. The remaining patients continued treatment for an average of 10 months, and sputum findings converted to negative in all 26 patients (87%). One patient died of unrelated causes while still receiving therapy, and five patients (19%) relapsed an average of 17 months after treatment was completed. CONCLUSIONS: Treatment with a macrolide, ethambutol, and clofazimine was successful in 20 of 30 patients (67%) with MAC lung disease and is a reasonable alternative to rifamycin-containing regimens.     

Repeat positive cultures in Mycobacterium intracellulare lung disease after macrolide therapy represent new infections in patients with nodular bronchiectasis

The genomic DNA patterns (genotypes) of 55 episodes of late positive sputum isolates, collected after >or=4 consecutive months of negative sputum cultures, in prospective macrolide treatment trials of Mycobacterium avium complex (MAC) lung disease were assessed by pulsed-field gel electrophoresis (PFGE). Having >or=2 cultures positive for MAC after completion of therapy was documented 23 times; of 20 episodes studied by PFGE, 17 (85%) represented new genotypes (i.e., new infections), and 87% occurred in patients with nodular bronchiectasis. With >or=2 positive cultures after therapy was stopped prematurely, 6 (86%) of 7 episodes were relapses. Single positive cultures after completion of therapy occurred 16 times; only 1 (6%) was predictive of a subsequent relapse. No late isolates were macrolide resistant. Thus, relapses of MAC lung disease with these macrolide regimens are unusual, and most infections after completing therapy resulted from new strains in patients with nodular bronchiectasis.     

Overview of respiratory infection caused by nontuberculous mycobacteria

Recently, the clinical importance of nontuberculous mycobacteria (especially, Mycobacterium avium complex [MAC] respiratory infection) has been increasing. In addition, an official ATS/IDSA statement about diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases has been published in February, 2007. In this review article, essence of this official statement will be introduced. In MAC respiratory infection, (i) primarily fibrocavitary disease, (ii) nodular/bronchiectatic disease, and (iii) hypersensitivity-like disease are identified, and (i) and (ii) are clinically important. Primarily fibrocavitary disease is characterized by cavitary lesions in upper lung fields in elderly subjects, smoking patients, or patients with pneumoconiosis. Nodular/bronchiectatic disease is characterized by centrilobular nodules and diffuse bronchiectases in the right middle lobe and the left lingula in middle-aged women. In addition, disseminated MAC disease in patients with acquired immunodeficiency syndrome should be considered. Further studies concerning transmission route as well as mechanism of MAC disease should be performed.     

Clinical and molecular analysis of macrolide resistance in Mycobacterium avium complex lung disease

RATIONALE: The clinical features and outcome of macrolide-resistant Mycobacterium avium complex (MAC) lung disease are not known. OBJECTIVES: Characterize patients, treatment, and isolates in macrolide-resistant MAC lung disease. METHODS: Retrospective chart review, susceptibility testing, molecular fingerprinting, and DNA sequence analyses of resistant MAC isolates. MEASUREMENTS AND MAIN RESULTS: We identified 51 patients over a 15-yr period with clarithromycin-resistant MAC (minimum inhibitory concentration (MIC)>or=32 microg/ml) lung disease at a single referral center. Twenty-four (47%) patients had nodular disease with bronchiectasis and 27 (53%) had upper lobe cavitary disease. Most patients (77%) had M. intracellulare. Sequencing of the 23S r-RNA gene showed 49 of 51 isolates (96%) with the expected mutation in adenine 2058 or 2059. Risk factors for resistance included macrolide monotherapy or combination with a quinolone only (39/51 or 76%). Macrolide resistance developed in 12 of 303 (4.0%) patients started on the American Thoracic Society-recommended two companion drugs, with no risk difference in clarithromycin versus azithromycin and daily versus intermittent therapy. Sputum conversion with macrolide-resistant MAC occurred in 11 of 14 (79%) patients who received more than 6 mo of injectable aminoglycoside therapy and lung resection, compared with 2 of 37 (5%) who did not. The 1-yr mortality in patients who remained culture positive was 34% (13/38) compared with 0% (0/13) of patients who became culture negative (converted). CONCLUSIONS: Macrolide resistance rarely occurs in patients also receiving ethambutol and a rifamycin. Macrolide-resistant MAC lung disease requires aggressive drug and surgical therapy for cure.     

The expanding spectrum of Mycobacterium avium complex-associated pulmonary disease

Nontuberculous mycobacteria (NTM) are increasingly recognized as important pulmonary pathogens. Mycobacterium avium intracellulare complex (MAC) causes most lung infections due to NTM. Patients with preexisting lung disease or immunodeficiency are at greatest risk for developing MAC infection. The majority of MAC pulmonary cases, however, occur in immunocompetent elderly women in association with nodular infiltrates and bronchiectasis. More recently, pulmonary disease has also been described in immunocompetent patients after exposure to MAC-contaminated hot tubs. We describe a case of aggressive MAC lung disease in a young immunocompetent female patient without preexisting lung disease whose clinical and pathologic characteristics do not fit into any of these categories and may represent a unique manifestation of MAC lung disease.     

Four cases of pulmonary Mycobacterium avium intracellulare complex presenting as a solitary pulmonary nodule and a review of other cases in Japan

OBJECTIVE: To evaluate clinical findings of patients with a solitary pulmonary nodule in Japan caused by pulmonary Mycobacterium avium complex (MAC) disease. METHODS: The authors investigated the clinical features of 12 patients diagnosed as having pulmonary MAC disease who had presented with a solitary pulmonary nodule. RESULTS: The causative microorganisms were M. avium in seven patients, Mycobacterium intracellulare in two and MAC in three. The diagnostic methods were bronchoscopic biopsy or percutaneous lung biopsy in three patients and surgical operations in the remaining nine. Eleven patients had a complete surgical resection of the nodule and antituberculous drugs were administered to eight. On X-ray, there was an absence of calcification, satellite lesions, cavities, or bronchoectasis that are often thought to be characteristic of pulmonary mycobacterial disease. Differentiation from lung cancer was thought necessary in five patients. There was no microbiological or radiological relapse in those who underwent complete surgical resection. CONCLUSIONS: Because treatment is often poorly effective for patients with pulmonary non-tuberculous mycobacterial disease, it is important to identify the causative microorganisms by performing a culture examination of resected lung tissue especially if there is a solitary pulmonary nodule.     

Relationship between mitral annular calcification and severity of carotid atherosclerosis in patients with symptomatic ischemic cerebrovascular disease

OBJECTIVES: Many studies have reported the association between mitral annular calcification (MAC) and stroke. MAC has been speculated to be a direct embolic source of stroke. Recently, the association between MAC and atherosclerosis in the coronary artery, aorta, and carotid artery has been reported. This prospective study investigated the association between MAC and severity of carotid atherosclerosis in patients with symptomatic ischemic cerebral disease to evaluate the association between MAC and atherosclerosis as a cause of stroke. METHODS: We studied 377 patients with ischemic cerebral disease (253 men, 124 women, mean age 68 +/- 11 years) who underwent echocardiography to determine the presence of MAC and carotid ultrasonography to determine the severity of carotid atherosclerosis. Plaque score was the sum of the maximum intimamedia thickness in the common carotid region, the bifurcation bulb region, and the internal carotid artery region, including both right and left arteries. RESULTS: MAC was found in 86 patients, and was more frequent in women, the elderly, and patients with diabetes or hyperlipidemia (p < 0.05). Plaque score was higher in patients with than without MAC (8.3 +/- 5.8 vs 5.2 +/- 5.2 mm, p < 0.001). Multivariate regression analysis identified MAC (r = 0.26, p < 0.0001), female sex (r = -0.12, p = 0.03), and age (r = 0.23, p < 0.0001) as independently associated with plaque score. CONCLUSIONS: MAC is independently associated with severity of carotid atherosclerosis in patients with symptomatic ischemic cerebral disease. This association suggests MAC may be indirectly related to cerebrovascular disease as a marker of the presence of progressive arteriosclerosis for thromboemboli causing stroke.     

Resumption/efficacy and safety of an azithromycin-containing regimen against Mycobacterium avium complex lung disease in patients who experienced adverse effects with a clarithromycin-containing regimen

BackgroundAntibiotic therapy, including clarithromycin (CLR), has been widely used for the management of Mycobacterium avium complex (MAC) lung disease in clinical settings. When patients develop adverse events (AEs) during CLR-based treatment, the treatment regimen is modified or chemotherapy itself is discontinued. The need for alternative macrolide treatment strategies is emphasized due to the high rate of AEs possibly caused by CLR. Thus, the current study aimed to examine the efficacy and safety of azithromycin (AZM) in patients with MAC lung disease whose treatment was switched from CLR to AZM.MethodsWe performed a retrospective study of patients with MAC lung disease. The inclusion criteria were as follows: (1) patients who experienced AEs during treatment with antibiotics, including CLR, between December 2012 and November 2017, and (2) those who had antimicrobial therapy that was switched from CLR to AZM. The efficacy and safety of AZM during the clinical course of the disease after switching the regimen from CLR to AZM were investigated.ResultsAntibiotic therapy was switched in 31 patients who presented with AEs including drug-induced fever, rash, dysgeusia, liver dysfunction, and neutropenia during treatment with CLR-containing regimens. After switching to AZM, the median duration of treatment was 1286 (364–4615) days. During follow-up, 13 patients had a negative conversion of sputum culture.ConclusionsAZM may be safe and effective for patients with MAC lung disease who have difficulty tolerating CLR. In patients who experienced AEs possibly caused by CLR, switching from CLR to AZM might be an appropriate strategy.     

Nontuberculous mycobacteriosis; the present status of epidemiology and clinical studies]

In Japan, The Mycobacteriosis Research Group at the Japanese National Chest Hospitals has continuously made the clinico-epidemiological study of nontuberculous mycobacteriosis (NTM) since early 1970s. The prevalence rate was determined as 0.82, 0.91, 1.22, 1.74 and 2.43 per 100,000 population per year in 1971, 1975, 1980, 1985 and in 1990 respectively. The newest datum in 1997 was 3.52. These data indicates the prevalence rate has continuously increased and became 3.8 times than 25 years ago. While on the other hand, the prevalence rate of lung tuberculosis has decreased from 133.1 to 15.2, becoming one nines in the same period. The numbers of newly detected patients of lung mycobacteriosis in 1996 were also studied at 12 hospitals in Kinki district. The rate of NTM was 16.6% in 4 sanatorium hospitals, being about the same to the datum of The Mycobacteriosis Research Group. The rate of NTM in 8 general hospitals was surprisingly high, 40.0%. The 70% of NTM patients were infected with Mycobacterium avium complex (MAC). The 24% were with M. kansasii, and the only 6% were with other miscellaneous species. That is, the about one thirds or more of total NTM patients were female MAC desease patients, another one thirds or less were male MAC patients, and the more than 90% of M. kansasii patients (about one fourth of total patients) were male. These 3 groups took the most part of NTM patients. The rate of female MAC patients with small non-cavitary lesion without underlying diseases showed a tendency to increase, and the rate of male MAC patients with cavitary lesions with underlying lung or systemic diseases decreased. In 1997, American Thoracic Society (ATS) published the official statement about the diagnosis and treatment of NTM disease. The table-1 in that statement showed the new criteria for diagnosis of NTM pulmonary disease. It is useful for precise diagnosis of lung NTM disease, and the old criteria made by The Mycobacteriosis Research Group of the Japanese National Chest Hospitals is also useful for rough diagnosis. In the ATS statement, for adult HIV-negative MAC patients, minimum three drug regimen of clarithromycin (or azithromycin), rifabutin (or rifampin) and ethambutol, with intermittent streptomycin which is option for extensive disease, is recommended. This regimen is the same that most of the Japanese specialists for NTM disease recommended. The follow-up study of 47 Japanese MAC patients treated by the regimen contained clarithromycin with other anti-tuberculous drugs revealed that 80% of cases converted into bacilli negative and that the regimen had durable effect for at least 24 months. The resectional surgery may be considered for localized disease, and supportive nutritional treatment must also be considered for the MAC patients to whom the drug therapy was not effective, as if for the tuberculosis patients of multi-drug resistant.     

Successful treatment of acquired immunodeficiency syndrome-related Mycobacterium avium complex disease with a multiple drug regimen including amikacin

Disease due to Mycobacterium avium complex (MAC) in patients with the acquired immunodeficiency syndrome (AIDS) typically occurs late in the course of AIDS and is usually disseminated with evidence of multiorgan involvement. Most patients are persistently bacteremic. Previously published studies have noted a poor response to antimycobacterial chemotherapy. We describe successful treatment of MAC disease in an AIDS patient with a multiple drug regimen, including amikacin, clofazimine, rifampin, ethambutol, and ciprofloxacin. This patient, whose presentation and MAC disease course distinctly differ from most published experience, remains clinically and microbiologically MAC-disease free 25 months after initiation of therapy. We describe four additional AIDS patients with MAC disease who had a favorable clinical and microbiological response to this regimen without developing serious adverse effects after periods ranging from 4 to 12 months. We suggest a prospective, controlled clinical trial using this regimen for treatment of MAC disease in patients with AIDS may be warranted.     

A study on clinical features of Mycobacterium kansasii pulmonary disease in women

OBJECTIVES: To clarify clinical features of M. kansasii pulmonary disease in women. METHODS: We performed a retrospective analysis of M. kansasii pulmonary disease in women compairing with that in men. We focused on 8 female cases of M. kansasii pulmonary disease during the past 7 years from June 1998 to August 2005. RESULTS: The cases of M. kansasii pulmonary disease in women have increased in the latter few years. The mean age of female cases was higher than that of male cases, 65.6 and 53.1 years old, respectively. The number of female cases with smoking history was lower than that of male cases, 37.5% and 90.0%, respectively. Two female cases had underlying pulmonary diseases, as compared with 10 male cases, 25.0% and 33.3%, respectively. The radiological findings in female cases included 2 cavitary opacities, 1 infiltrative opacity and 5 nodular, bronchiectatic opacities, as compared with 27 cavitary opacities, 1 infiltrative opacity, 1 solitary nodular opacity and 1 nodular, bronchiectatic opacity in male cases. MAC was also detected in 2 female cases, who presented with nodular, bronchiectatic opacities. On the other hand, there were 6 female cases, in which no other NTM was detected. 3 cases showed cavitary or infiltrative opacities, which improved with the following 3 tuberculous drugs INH, RFP, and EB (HRE), while others showed nodular, bronchiectatic opacities, in which 2 cases showed radiological exacerbations without any treatment and another one revealed an improvement with HRE. CONCLUSIONS: M. kansasii pulmonary disease in women tends to be identified in elderly who smoke less and have no underlying pulmonary diseases, and most of radiological findings in female cases revealed nodular, bronchiectatic opacities. Summing up all these findings, clinical features of M. kansasii pulmonary disease in women was considered to resemble that of MAC infection, and it was speculated that the increase of M. kansasii pulmonary disease in women has some relationship with that of MAC infection in middle or lingular lobe. However, it was confirmed that some cases of M. kansasii pulmonary disease in women might primarily present with nodular, bronchiectatic lesions, regardless of MAC infection.     

Diagnosis and treatment of infections due to Mycobacterium avium complex

MYCOBACTERIUM AVIUM complex (MAC) consists of nontuberculous mycobacteria that cause disease in immunocompromised and immunocompetent hosts. The organisms are ubiquitous in the environment, and acquisition occurs through ingestion or inhalation of aerosols from soil, water, or biofilms. Disease may manifest as disseminated infection, soft tissue infection, chronic pneumonia, or hypersensitivity pneumonitis. Nontuberculous mycobacteria are increasingly associated with pulmonary disease, with MAC being the most common nontuberculous mycobacteria to cause pulmonary disease in the United States. Pulmonary symptoms, nodular or cavitary opacities on a chest radiograph or high-resolution computed tomographic scan with multifocal bronchiectasis and multiple small nodules, plus positive culture results from two sputum specimens or one bronchoscopic specimen are consistent with MAC pulmonary disease. Treatment consists of a macrolide, rifamycin, and ethambutol given three times weekly for noncavitary disease and daily with or without an aminoglycoside for cavitary disease.     

Causes and presenting features of pulmonary infarctions in 43 cases identified by surgical lung biopsy

BACKGROUND: Although pulmonary infarction is usually associated with pulmonary thromboembolism, it can occur with other disorders such as vasculitis, angioinvasive infections, sickle-cell disease, tumor embolism, and pulmonary torsion. STUDY OBJECTIVE: To identify causes and presenting features of pulmonary infarctions diagnosed by surgical biopsy in a consecutive series of patients encountered at a single institution. DESIGN: Retrospective review. SETTING: Tertiary care, referral medical center. PATIENTS: Forty-three patients with pulmonary infarction identified on surgical lung biopsy over a period of 7 years, January 1996 through December 2002. RESULTS: The median age of these 43 patients was 55 years (range, 22 to 85 years); 17 patients (40%) were women, and 26 patients (60%) were men. Thirty-five patients (81%) had a smoking history. Twenty-eight patients (65%) presented with solitary or multiple lung nodules/masses of undetermined etiology. The underlying cause was identifiable in 31 cases (72%) based on a review of clinical, laboratory, radiologic, and histopathologic data. The two most common causes were pulmonary thromboembolism (18 cases, 42%) and pulmonary infections (5 cases, 12%). Thromboembolic pulmonary infarctions typically presented as solitary or multiple nodules located in the subpleural regions. Other causes included diffuse alveolar damage in two cases (5%), pulmonary torsion in two cases (5%), and one case each of lung cancer, amyloidosis, embolotherapy, and catheter embolism. In 12 cases (28%), the underlying cause was not directly identifiable but was probably due to previous pulmonary thromboembolism. CONCLUSION: We conclude that although pulmonary thromboembolism is the most common cause of pulmonary infarction identified by surgical lung biopsy, a variety of other causes are clinically encountered, including infections, inflammatory or infiltrative lung diseases, pulmonary torsion, malignancy, and nonthrombotic embolism. Pulmonary infarction should be considered in the differential diagnosis of peripheral lung nodules or masses.     

Obstructive granulomatous bronchiolitis due to Mycobacterium avium complex in an immunocompetent man.

While the development of pulmonary disease due to Mycobacterium avium complex (MAC) infection is most commonly associated with underlying predisposing factors, this organism occasionally causes symptomatic disease in otherwise normal individuals. Patients with MAC pulmonary disease most often present with cavitating granulomas, but a spectrum of pathologic changes has been described. The authors present a case of MAC pulmonary disease in an immunocompetent, middle-aged man with no identified predisposing factors. The diagnostic biopsy disclosed the unusual finding of noncaseating granulomas with predominant involvement of bronchioles, corresponding to the patient's obstructive and restrictive pulmonary dysfunction.     

Mycobacterium avium-avium-Associated Typhlitis Mimicking Appendicitis in an Immunocompetent Host

Mycobacterium avium-intracellulare complex (MAC) primarily causes respiratory infection in patients with underlying lung disease or disseminated disease in immunocompromised patients. We report a unique case of MAC disease in the terminal ileum of a healthy patient, mimicking appendicitis. This case emphasizes the need to further explore MAC pathogenesis in immunocompetent hosts.     

Paraneoplastic vasculitis in patients with solid tumors: report of 15 cases

OBJECTIVE: To review all cases of concurrent vasculitis and solid tumors diagnosed at our Department over a 15-year period and explore evidence that would support the notion of vasculitis being a true paraneoplastic syndrome. METHODS: We reviewed the records of all patients diagnosed with vasculitis and solid tumors within 12 months of each other and prospectively followed until death or our report. We analyzed the main features and outcome of vasculitis in this setting. We also reviewed all cases published in the French-English literature. RESULTS: Fifteen patients (9 men and 6 women) in whom both vasculitis and solid tumor occurred within the same 12 months were identified. Mean age was 72.5 years (range 58-84). In 7 cases the diagnosis of vasculitis antedated that of cancer, in 6 both processes were synchronously diagnosed, and in 2 vasculitis appeared after cancer diagnosis. The most common vasculitis was cutaneous leukocytoclastic vasculitis (n = 9). Other vasculitides included Henoch-Sh?nlein purpura (n = 2), polyarteritis nodosa (n = 1), and giant cell arteritis (n = 3). The commonest malignancies were carcinomas of urinary organs (40%), lung (26.7%), and gastrointestinal tract (26.7%). The median followup was 28.4 months (range 1-96). Thirteen of the 15 patients demonstrated concordance of disease activity and treatment response for both cancer and vasculitis. Vasculitis flared heralding tumor recurrence or progression in 7 (46.6%) cases. CONCLUSION: In our patients, resolution of vasculitis following effective treatment of the putatively linked malignancy, and recurrence of vasculitis heralding tumor recurrence or progression, provide strong evidence for vasculitis being a true paraneoplastic syndrome. Chronic or persistent vasculitis with poor response to usually effective therapy, especially in elderly patients, should raise questions about underlying malignancy.     

Infektionen mit nichttuberkul?sen Mykobakterien bei Patienten mit Immundefekten

Infections caused by nontuberculous mycobacteria (NTM) cause a variety of clinical pictures, like nodular or cavitary lung infiltrations, lymphadenitis or lesions of the skin and soft tissue. In patients with innate or acquired immune deficiencies, an increase of disseminated but also local, atypical disease manifestations is observed. Detailed knowledge about underlying immune defects and the current immune status of patients with suspected NTM infections is indispensable to verify the detection of NTM in clinical specimens which does not necessarily account for a direct disease association. Differences in the growth kinetics of bacteria from the M. avium complex (MAC) which primarily cause lung diseases in contrast to the rapidly growing M. fortuitum and M. chelonae (RGM) involved in skin and soft tissue infections have to be considered in the diagnostics of NTM infections. Emergence of treatment strategies including biologicals in chronic inflammatory diseases resulted in an increase of local and disseminated NTM infections in the past. The duration of NTM treatment may be prolonged in patients with underlying immune deficiencies and disseminated infections. NTM prophylaxis should be discussed in HIV/AIDS patients with severe immune deficiency (CD4 ?<?50/??l) starting with antiretroviral therapy (cART) as NTM infections presenting as lymphadenitis are frequently observed in patients with immune reconstitution inflammatory syndrome (IRIS).     

Sentinel-site surveillance of Mycobacterium avium complex pulmonary disease.

The incidence of Mycobacterium avium complex (MAC) pulmonary disease in HIV-negative patients was studied prospectively from January 1, 2000 to December 31, 2002 through 32 sentinel sites distributed all over France. Among the 275 patients who yielded MAC isolates from respiratory clinical specimens, 101 (36.7%) met the bacteriological, radiographical and clinical criteria established by the American Thoracic Society for nontuberculous mycobacterial respiratory disease. Of these 101 patients, 81 had underlying lung disease, mainly previous tuberculosis, bronchectasis or chronic obstructive pulmonary disease. Among the 20 patients with no underlying lung disease, 12 had a predisposing factor such as leukaemia or immunosuppressive treatment and eight had no predisposing factor. All patients with MAC respiratory disease had clinical symptoms, commonly cough and fatigue, and 52 (51.5%) were sputum smear positive for acid-fast bacillus. The ratio of patients with Mycobacterium avium complex pulmonary disease to patients with pulmonary tuberculosis in France was estimated to be 3% and the incidence of Mycobacterium avium complex pulmonary disease in France was 0.2 per 100,000 inhabitants.     

Mycobacterial infections in AIDS patients, with an emphasis on the Mycobacterium avium complex

Serious infections caused by the Mycobacterium avium complex (MAC) have been increasingly recognized over the last three decades. However, the epidemic of the acquired immunodeficiency syndrome (AIDS) has increased interest in these infections. Disseminated mycobacterial disease is common in patients with AIDS, and MAC is the predominant bacterial isolate. Indeed, at UCLA Medical Center, MAC organisms are now the predominant isolates in both AIDS- and non-AIDS-associated mycobacterial disease. MAC lung infections have been difficult to treat. Complex regimens employing four to six drugs are not clearly effective and are usually associated with considerable toxicity. Treatment of MAC infections in patients with AIDS has been particularly frustrating, and evidence that treatment can either eradicate disease or prolong life is limited. MAC organisms are invariably resistant to traditional antituberculosis medications. We have examined a variety of other compounds, and our findings, based on both in vitro and animal-model studies, have identified drugs which, when used in combination, are potentially of therapeutic utility.     

When and how to treat pulmonary non-tuberculous mycobacterial diseases

Non-tuberculous mycobacteria are ubiquitous environmental organisms that have been recognized as a cause of pulmonary infection for over 50 years. Traditionally patients have had underlying risk factors for development of disease; however, the proportion of apparently immunocompetent patients involved appears to be rising. Not all patients culture-positive for mycobacteria will have progressive disease, making the diagnosis difficult, though criteria to aid in this process are available. The two main forms of disease are cavitary disease (usually involving the upper lobes) and fibronodular bronchiectasis (predominantly middle and lingular lobes). For patients with disease, combination antibiotic therapy for 12–24 months is generally required for successful treatment, and this may be accompanied by drug intolerances and side-effects. Published success rates range from 30% to 82%. As the progression of disease is variable, for some patients, attention to pulmonary hygiene and underlying diseases without immediate antimycobacterial therapy may be more appropriate. Surgery can be a useful adjunct, though is associated with risks. Randomized controlled trials in well-described patients would provide stronger evidence-based data to guide therapy of non-tuberculous mycobacteria lung diseases, and thus are much needed.