Information from the National Library of Medicine To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor. Please refer to this study by its ClinicalTrials. Layout table for location contacts Contact: Andie Hendrick hendrmic ohsu.
More Information. Ann Am Thorac Soc. Nontuberculous mycobacterial lung disease prevalence at four integrated health care delivery systems. Epub Jun Pulmonary nontuberculous mycobacterial disease prevalence and clinical features: an emerging public health disease. Epub May Dosage error in article text. Ethambutol ocular toxicity in treatment regimens for Mycobacterium avium complex lung disease. Epub Apr Once-daily dosing of amikacin for treatment of Mycobacterium abscessus lung disease.
Int J Tuberc Lung Dis. Aminoglycoside toxicity: daily versus thrice-weekly dosing for treatment of mycobacterial diseases. Clin Infect Dis. Epub May 5. The tolerability of linezolid in the treatment of nontuberculous mycobacterial disease. Eur Respir J. Epub Jan Efficacy of clarithromycin and ethambutol for Mycobacterium avium complex pulmonary disease.
A preliminary study.
21 years old with MAC
A double-blind randomized study of aminoglycoside infusion with combined therapy for pulmonary Mycobacterium avium complex disease. Respir Med. Epub Jun 5. Lack of adherence to evidence-based treatment guidelines for nontuberculous mycobacterial lung disease. Outcomes of Mycobacterium avium complex lung disease based on clinical phenotype.
Print Sep. Per-Protocol Analyses of Pragmatic Trials. N Engl J Med. Adherence adjustment in the Coronary Drug Project: A call for better per-protocol effect estimates in randomized trials. Reinfection was observed in only 3 patients with cavitary upper lobe disease, and this same previous PFGE study showed that patients with this form of disease are infected with a single strain [ 1 ]. All the relapse isolates identified to date occurred within 10 months of stopping therapy. Relapse isolates were seen in 4 cultures.
Three of these cultures were AFB smear negative, with positive cultures in the broth only, and were not followed by any subsequent positive cultures. Perhaps equally surprising, none of the relapse isolates tested was macrolide resistant. Another important observation was the significance of a single positive culture of the infecting strain during the therapy period after sputum conversion.
When this culture usually a liquid medium bottle only with no growth on the solid media was ignored, all patients subsequently experienced relapse. This also points out the importance of using liquid media broth in patient follow-up during therapy and the need to do routine cultures after sputum conversion. An important issue raised by these observations is whether DNA strain comparison is needed to make quality decisions about therapy of MAC lung disease. We believe that the availability of methods for strain comparison, such as PFGE, in patients with nodular bronchiectasis is helpful, if not essential.
We recommend that at least 1 pretreatment isolate from all patients with MAC should be saved for at least 3 years from the start of therapy and that this isolate be compared to any subsequent positive cultures that may affect treatment. This presumes that subsequent cultures over a 6-month period after the single positive are negative. Several features of the reinfections are disturbing. One is that they were often polymicrobial i. One would have expected a single strain or genotype to have been identified. In 2 patients, however, 2 distinct episodes involving different strains were identified table 1.
The observation that many episodes of positive cultures may be followed by periods of negative cultures suggests that the latter possibility is more likely. The second surprising feature is how close the new infections in patients with nodular bronchiectasis occurred after stopping therapy, with a mean of only 24 months. This might support the concept that they were present all along in the patient, but just not active.
Yet, true relapses of the identified original strains or genotypes were rare and all occurred within the first year after stopping therapy. It is most likely, in our opinion, that MAC infection is not the primary disease in patients with nodular bronchiectasis. We suspect that reinfections in patients with nodular bronchiectasis will continue to be seen and will not just be clustered close to the time that therapy was stopped. Longer follow-up appears to be most important for patients with upper lobe fibrocavitary disease, where relapses occurred a mean of 4 years after stopping therapy.
It seems likely that more reinfections of this type will be seen, but may require many years more follow-up. The other potential pathogens seen in these patients, primarily Pseudomonas aeruginosa and Mycobacterium abscessus bear a striking resemblance to the microbial flora seen in some patients with cystic fibrosis CF. No genetic defect has been described in these patients with nodular bronchiectasis as it has in patients with CF, but it is a strong possibility. The most logical common denominator showed by the 2 groups would seem to be their bronchiectasis, but more studies are needed to help address this issue.
We would like to acknowledge the support of the clinical mycobacteriology laboratory of the University of Texas Health Center Tyler and Joanne Woodring, for her help in preparation of the manuscript. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide.
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21 years old with MAC | NTM Info and Research Inc.
Volume Article Contents. Patients, Materials, and Methods. Wallace, Jr. Reprints or correspondence: Dr. Oxford Academic. Google Scholar. Yansheng Zhang. Barbara A. Mitchell A. Rebecca W. Linda Mann. Leslie Couch. William M. David E. Article history. Revision Received:. Cite Citation. Permissions Icon Permissions. View large Download slide. Polyclonal Mycobacterium avium complex infections in patients with nodular bronchiectasis. Search ADS. Diagnosis and treatment of disease caused by nontuberculous mycobacteria: official statement of the American Thoracic Society.
Mycobacterium avium complex pulmonary disease presenting as an isolated lingular or middle lobe pattern: the Lady Windermere syndrome. Computed tomographic diagnosis of Mycobacterium avium—intracellulare complex in patients with bronchiectasis. Initial clarithromycin monotherapy for Mycobacterium avium—intracellulare complex lung disease.
Clarithromycin regimens for pulmonary Mycobacterium avium complex: the first 50 patients. Azithromycin activity against Mycobacterium avium complex lung disease in patients who were not infected with human immunodeficiency virus. Denmark, [ 20 ]. Canada, [ 21 ]. Japan, [ 22 ]. USA [ 23 ] ,a. USA, [ 23 ] ,a. UK and Scandinavia, [ 24 ]. UK, Denmark, Sweden and Italy, [ 25 ] ,a.
Analysis of five-year mortality in selected data sets. MAC-related five-year mortality and cavitary disease in selected data sets. Yeager [ 12 ]. Hayashi [ 13 ]. Ito [ 14 ]. Yamakawa [ 15 ]. Morimoto [ 16 ]. Zoumot [ 17 ]. Gochi [ 18 ]. Kumagai [ 19 ] a.
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Marras [ 21 ]. Asakura [ 22 ] a.
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Novosad [ 23 ] a. Research Committee of the British Thoracic Society [ 24 ]. Adding clarithromycin vs. Jenkins [ 25 ]. One study also analysed the relationship between radiologic types of MAC lung disease and all-cause five-year mortality [ 13 ]. This demonstrated that patients with fibrocavitary disease have a substantially greater risk of death compared with nodular disease Fig. We performed a sensitivity analysis using the geographic region in which the selected studies were conducted Additional file 1 : Table S1.
Several publications have demonstrated the incremental impact of NTM infection on patient mortality. Here, the mortality was Diel et al. These studies indicate that NTM-PD increases mortality risk at a population level, independent of underlying comorbidities. Although predictors of mortality varied between studies, some common features were observed.
A worse prognosis was noted with male sex, comorbidities e. The latter was found to be associated with increased MAC-related mortality rate in two studies [ 13 , 18 ], and in one, all-cause mortality [ 13 ]. This is in line with results from Fleshner and colleagues who identified fibrocavitary disease as a predictor of mortality in NTM-PD after controlling for possible confounders adjusted hazard ratio [aHR] 3.
Fleshner and colleagues also documented pulmonary hypertension as a risk factor for mortality aHR 2. Similarly, five-year age-adjusted mortality rates were slightly higher for patients meeting However, all patients with disease considered bad enough to be recorded by investigators, and hence included in studies, are at some increased risk of death. Furthermore, whereas all-cause mortality is an objective measure, the proportion of deaths attributed to MAC lung infection depends largely on how clinicians determine the cause of death.
This may be unclear, particularly in long-term follow up studies where underlying comorbidities may progress; it a pertinent issue in MAC lung disease as many patients are elderly and often have a number of comorbidities [ 2 , 29 ]. Thus, the impact of MAC lung disease on mortality at a population level is more appropriately reflected in studies using matched control groups.
Our sensitivity analysis identified a lower mortality rate in Asian studies, particularly those from Japan. A similar trend has previously been observed [ 30 ]. The present study has several limitations. We were keen to include a range of studies reflecting the published literature and so did not use a complex set of stringent-pre-specified criteria. Thus, our analysis is influenced by the design of the selected studies. Specifically, only two prospective studies including three data sets are included in our analysis [ 24 , 25 ].
This is challenging for the field as a whole, and further prospective studies of mortality in MAC-PD patients, which could support identification of additional prognostic factors, are warranted.
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Furthermore, we could not account for the potential effects of patient immunosuppression e. HIV or heterogeneity of treatment regimens between studies as the selected studies did not report outcomes for different subgroups. The authors suggested that this may be due to inconsistency among treatment protocols and in the reporting of key patient and study characteristics [ 9 ], preventing identification of clear factors related to treatment success.
Managing the Disease
It is important to note that, as many reported studies are frequently based on population-level data for example, [ 21 ] , they can contain limited clinical information. This inevitably means that one must be careful to not over-interpret their findings. Most of our selected studies do not explicitly identify patients with macrolide-resistant pulmonary disease.
This is a concern, as recent work from Korea reported a five-year mortality of This is much higher than the pooled estimate from our analysis indicating that macrolide resistance increases mortality risk, and should be specifically identified in future studies. Most i. Substantial heterogeneity in study characteristics was found, with male sex, presence of cavitary disease and high comorbidity levels predicting worse survival outcomes. Further prospective studies using appropriately matched controls may contribute to a better understanding of long-term survival in MAC-related pulmonary disease.
Cystic fibrosis. Confidence interval. Chronic obstructive pulmonary disease. Mycobacterium avium complex. Nontuberculous mycobacterium. Nontuberculous mycobacteria pulmonary disease.