Long-term results of medical treatment in mycobacterium intracellulare infection

doi:10.1016/0002-9343(79)90792-7

The American Journal of Medicine

Volume 67, Issue 3, September 1979, Pages 449-453

https://doi.org/10.1016/0002-9343(79)90792-7 Get rights and content

Abstract

Mycobacterium avium-intracellulare (the “Battey bacillus”) was deemed to be pathogenic in 85 cases of pulmonary disease and in five cases of extrapulmonary lesions in which the patients were treated in local chest clinics of the Arkansas Department of Health's tuberculosis program from 1970 to 1975. Multiple drug chemotherapy was initially successful in converting the sputum cultures to negative in 68 (80 per cent) of the 85 cases of pulmonary disease and in healing in all five cases of the extrapulmonary lesions. In 17 (25 per cent) of the 85 cases of pulmonary disease, the initial regimen of therapy failed to convert the bacteriology to negative. Relapse occurred in 16 (23 per cent) of the 68 cases in which conversion occurred, either during or following therapy, and in only seven (44 per cent) did the patients respond to a subsequent course of therapy. Ultimately, 39 (46 per cent) of the 85 cases of pulmonary disease and all five cases of extrapulmonary disease, remained bacteriologically negative at the end of three to eight years of observation. The drugs most likely to produce a therapeutic effect are ethambutol, ethionamide and cycloserine. However, because of the uncertain pathogenicity of this organism in many patients and the considerable morbidity from the multiple-drug regimens that must be employed, great care should be exercised to be certain that the organism is truly behaving as a pathogen: i.e., repeatedly present in significant numbers in culture and associated with a lesion that is producing illness.

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Microbiological Cure at Treatment Completion Is Associated With Longer Survival in Patients With Mycobacterium avium Complex Pulmonary Disease
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Morbidity and mortality from nontuberculous mycobacterial pulmonary disease (NTM-PD) are increasing. Mycobacterium avium complex (MAC) is the most common cause of NTM-PD. Microbiological outcomes are widely used as the primary end point of antimicrobial treatment, but their long-term impact on prognosis is uncertain.
Do patients who achieve microbiological cure at the end of treatment have longer survival than those who do not?
We retrospectively analyzed adult patients who met the diagnostic criteria for NTM-PD, were infected with MAC species, and were treated with a macrolide-based regimen for ≥ 12 months per guidelines between January 2008 and May 2021 at a tertiary referral center. Mycobacterial culture was performed during antimicrobial treatment to assess the microbiological outcome. Patients with three or more consecutive negative cultures collected ≥ 4 weeks apart and no positive cultures until treatment completion were considered to have achieved microbiological cure. To assess the impact of microbiological cure on all-cause mortality, we performed multivariable Cox proportional hazards regression analysis adjusted for age, sex, BMI, presence of cavitary lesions, erythrocyte sedimentation rate, and underlying comorbid conditions.
Among 382 patients enrolled, 236 (61.8%) achieved microbiological cure at completion of treatment. These patients were younger, had lower erythrocyte sedimentation rates, were less likely to use four or more drugs, and had shorter treatment duration than those who failed to achieve microbiological cure. During a median follow-up of 3.2 (first quartile to third quartile, 1.4-5.4) years after treatment completion, 53 patients died. Microbiological cure was significantly associated with reduced mortality after adjustment for major clinical factors (adjusted hazard ratio, 0.52; 95% CI, 0.28-0.94). The association between microbiological cure and mortality was maintained in a sensitivity analysis that included all patients treated < 12 months.
Microbiological cure at completion of treatment is associated with longer survival in patients with MAC-PD.
OTHER MYCOBACTERIA
2009, Feigin and Cherry's Textbook of Pediatric Infectious Diseases, Sixth Edition
Mycobacterium avium complex pulmonary disease in patient without HIV infection
2004, Chest
Citation Excerpt :
The drugs primarily used in these reports were isoniazid, PAS, and streptomycin. Rifampin and ethambutol were used in most of the 19 treatment studies published between 1974 and 1993 and in the British Thoracic Society (BTS) trial (Table 4).2697374133134135136137138139140141142143144145146147 Clarithromycin or azithromycin were included in the 12 studies published after 1993 (Table 5).148149150151152153154155156157158159
Mycobacterium avium complex (MAC) is ubiquitous. It is found in various freshwater and saltwater sources around the world, including hot water pipes. Although the organism was identified in the 1890s, its potential to cause human disease was only recognized 50 years later. Only a minority of people exposed to the organism will acquire MAC lung disease, usually those with underlying lung disease or immunosuppression. MAC may, however, cause progressive parenchymal lung disease and bronchiectasis in patients without underlying lung disease, particularly in middle-aged and elderly women. Preliminary data suggest that the interferon-γ pathways may be deficient in elderly women with MAC lung disease. Other groups of patients who are more likely to harbor MAC in their lungs include patients with a cystic fibrosis or an abnormal α₁-antiproteinase gene and patients with certain chest wall abnormalities. Treatment results continue to be disappointing, and the mortality of patients with MAC lung disease remains high. A PubMed search identified 38 reports of the treatment of MAC lung disease. Apart from the British Thoracic Society study, the only published controlled investigation, the studies published since 1994 have included a macrolide, either clarithromycin or azithromycin, usually in combination with ethambutol and a rifamycin. If success is defined as eradication of the organism without relapse over a period of several years after treatment has been discontinued, the reported treatment success rate with the macrolide containing regimens is approximately 55%. The prolonged treatment period, side effects, and possibly reinfection rather than relapse are responsible for the high failure rate.
Radiology of pulmonary Mycobacterium avium-intracellulare complex
2002, Clinics in Chest Medicine
Imaging of non-tuberculous (atypical) mycobacterial pulmonary infection
2002, Clinical Radiology
Pulmonary infections due to mycobacterial organisms are increasing in incidence. Non-tuberculous (atypical) mycobacteria (NTM) represent a significant proportion of mycobacterial infections and may prove difficult to diagnose due to their non-specific clinical and radiographic presentations. An increasing volume of radiological data is now available for the more common non-tuberculous mycobacterial infections, and we have summarized the imaging features found in such cases, identifying radiographic features that would favour the diagnosis of a non-tuberculous mycobacterium and that, in some cases, suggest a specific organism. Ellis, S. M. and Hansell, D. M. (2002). Clinical Radiology57, 661–669.
Nontuberculous mycobacteria
2001, American Journal of the Medical Sciences
Citation Excerpt :
In the premacrolide era, long-term success rates for treatment of pulmonary MAC infection ranged from 44 to 80% and were not clearly related to or aided by determination of in vitro susceptibilities. Dutt and Stead40 reported on 85 cases of pulmonary and 5 cases of extrapulmonary MAC infection from Arkansas in the era before macrolides. Sixty-five percent of their population had underlying pulmonary disease and 31% were women.
The nontuberculous mycobacteria are for the most part ubiquitous environmental organisms that only rarely cause disease in humans. Therefore, the normal host defense against these organisms must be quite robust, as exposure is universal and disease is rare. The organisms that are most commonly encountered in clinical practice, Mycobacterium avium, M intracellulare, M kansasii, M fortuitum, M abscessus, and M chelonae, are frequently found in water sources and soil.¹ These organisms share significant structural and biochemical similarities with their more pathogenic relative, M tuberculosis (MTB). Because they are of significantly lower pathogenicity than MTB, patients with abnormal susceptibility to these infections should include those with defects that may be identifiable. Study of these patients should lead to determination of the mechanisms underlying resistance to these organisms, which in turn are likely to be highly informative regarding host defense against these infections and their more virulent relative MTB. Furthermore, recognition of host factors that permit infection with nontuberculous mycobacteria in otherwise normal hosts will identify pathways that can be targeted for therapeutic intervention. Thus, the search for genetic and acquired susceptibility to nontuberculous mycobacteria is also a search for susceptibility factors for MTB as well as an opportunity to recognize endogenous pathways that can be exploited therapeutically.

View all citing articles on Scopus

^☆: Presented in part at the 58th annual session of the American College of Physicians in Dallas, Texas, April 18–21, 1977.

¹: From the Tuberculosis Program, Arkansas Department of Health, Little Rock, Arkansas.

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Clinical studyLong-term results of medical treatment in mycobacterium intracellulare infection☆

Abstract

Med Clin North Am

Dis Chest

J Thorac Cardiovasc Surg

Chest

A clinical study of the chronic lung disease due to nonphotochromogenic acid-fast bacilli

Ann Intern Med

A study of pulmonary disease associated with mycobacteria other than Mycobacterium tuberculosis: clinical characteristics

Am Rev Respir Dis

Atypical mycobacteria in Western Australia

Am Rev Respir Dis

Atypical pulmonary tuberculosis caused by unclassified mycobacteria

Ann Intern Med

Treatment of unclassified mycobacterial infection of the lungs

Thorax

A study of diseases caused by atypical mycobacteria in Japan

Am Rev Respir Dis

Infections with atypical mycobacteria. Five years' experience at the National Jewish Hospital

Am Rev Respir Dis

Infection with the Avian-Battey group of mycobacteria in England and Wales

Br Med J

Clinical aspects of atypical mycobacterial infection

Can Med Assoc J

Atypical mycobacteria: a factor to consider in lung disease

Postgrad Med

Atypical mycobacteria. Their clinical, laboratory, and epidemiologic significance

Medicine (Baltimore)

Clinical study
Long-term results of medical treatment in mycobacterium intracellulare infection☆