Avium Complex Pulmonary Disease Research Articles

Role of ethambutol and rifampicin in the treatment of Mycobacterium avium complex pulmonary disease

BackgroundA three-drug regimen (macrolide, ethambutol, and rifampicin) is recommended for the treatment of Mycobacterium avium complex pulmonary disease (MAC-PD). Although macrolide has proven efficacy, the role of ethambutol and rifampicin in patients without acquired immune deficiency syndrome is not proven with clinical studies. We aimed to clarify the roles of ethambutol and rifampicin in the treatment of MAC-PD.MethodsPatients treated for MAC-PD between March 1st, 2009 and October 31st, 2018 were reviewed retrospectively. Rates of culture conversion, microbiological cure, treatment failure, and recurrence were compared according to the maintenance (≥6 months) of ethambutol or rifampicin with macrolide.ResultsAmong the 237 patients, 122 (51.5%) maintained ethambutol and rifampicin with macrolide, 58 (24.5%) maintained ethambutol and macrolide, 32 (13.5%) maintained rifampicin and macrolide, and 25 (10.6%) maintained macrolide only. Culture conversion was reached for 190/237 (80.2%) patients and microbiological cure was achieved for 129/177 (72.9%) who completed the treatment. Treatment failure despite ≥12 months of treatment was observed in 66/204 (32.4%), and recurrence was identified in 16/129 (12.4%) who achieved microbiological cure. Compared with maintenance of macrolide only, maintenance of ethambutol, rifampicin or both with macrolide were associated with higher odds of culture conversion [odds ratio (OR), 95% confidence interval (CI): 18.06, 3.67–88.92; 15.82, 2.38–105.33; and 17.12, 3.93–74.60, respectively]. Higher odds of microbiological cure were associated with maintenance of both ethambutol and rifampicin with macrolide (OR, 95% CI: 5.74, 1.54–21.42) and macrolide and ethambutol (OR, 95% CI: 5.12, 1.72–15.24) but not macrolide and rifampicin. Maintenance of both ethambutol and rifampicin with macrolide was associated with lower odds of treatment failure (OR, 95% CI: 0.09, 0.01–0.53) compared with macrolide only, while maintenance of one of these with macrolide was not. Maintenance of both ethambutol and rifampicin or one of these with macrolide did not decrease the probability of recurrence when compared with macrolide only.ConclusionsMaintenance (≥6 months) of ethambutol and rifampicin with macrolide was associated with the most favorable treatment outcomes among patients with MAC-PD. Given the association between ongoing ethambutol use and microbiological cure, clinicians should maintain ethambutol unless definite adverse events develop.

Solitary pulmonary nodules caused by Mycobacterium avium complex.

The prevalence of Mycobacterium avium complex (MAC) pulmonary disease (PD) is increasing significantly in Japan. Among the patterns of MAC-PD, a solitary pulmonary nodule (SPN) is less common and often resembles lung cancer. The aim of this study was to identify the clinical features of MAC-SPN. SPNs culture-positive for MAC (definite cases) and culture-negative SPNs showing nucleic acid amplification test (NAAT)-positive status (probable cases) that presented between January 2007 and December 2017 were enrolled. The patients' clinical, laboratory, radiological, and microbiological findings and outcomes were investigated. This study included 28 patients (median age, 66 years; 16 men, 12 women). All patients were asymptomatic when the disease was detected. Median SPN size was 23.5mm. Twenty-six patients underwent video-assisted thoracoscopic surgery, while the others underwent percutaneous needle biopsy for diagnosis. Granulomatous inflammation was confirmed in all cases. Microbiologically, the 28 cases were divided into 17 in the definite group and 11 in the probable group. In both groups, M. avium was predominant. There were no significant differences in clinical and radiological findings and follow-up periods between the 2 groups. After diagnosis, 6 patients received medical treatment, while the others did not. The median follow-up period was 42 months, and no recurrence was observed in both groups. MAC should be considered in the differential diagnosis of SPNs in asymptomatic patients. To overcome the difficulties in diagnosing MAC-SPN, this study underscores the importance of diagnostic interventions and identification of MAC by culture and/or NAAT in biopsied specimens.

Prescribing Patterns for Treatment of Mycobacterium avium Complex and M. xenopi Pulmonary Disease in Ontario, Canada, 2001-2013.

Surveys suggest that clinicians diverge from guidelines when treating Mycobacterium avium complex (MAC) pulmonary disease (PD). To determine prescribing patterns, we conducted a cohort study of adults >66 years of age in Ontario, Canada, with MAC or Mycobacterium xenopi PD during 2001-2013. Using linked laboratory and health administrative databases, we studied the first treatment episode (>60 continuous days of >1 of a macrolide, ethambutol, rifamycin, fluoroquinolone, linezolid, inhaled amikacin, or, for M. xenopi, isoniazid). Treatment was prescribed for 24% MAC and 15% of M. xenopi PD patients. Most commonly prescribed was the recommended combination of macrolide, ethambutol, and rifamycin, for 47% of MAC and 36% of M. xenopi PD patients. Among MAC PD patients, 20% received macrolide monotherapy and 33% received regimens associated with emergent macrolide resistance. Although the most commonly prescribed regimen was guidelines-recommended, many regimens prescribed for MAC PD were associated with emergent macrolide resistance.

Application of a commercial serodiagnostic kit that measures the serum anti-glycopeptidolipid core IgA antibody in Mycobacterium avium complex pulmonary disease.

The diagnosis of Mycobacterium avium complex (MAC) pulmonary disease is occasionally cumbersome and time-consuming because the MAC species is ubiquitous, and therefore its detection is not necessarily indicative of a definitive diagnosis. A serodiagnostic method specific for MAC pulmonary disease that measures the serum anti-glycopeptidolipid core antigen IgA has been developed and is commercially available. Meta-analysis revealed that the test showed a good diagnostic accuracy. The estimated sensitivity and specificity values were 69.6% (95% confidence interval 62.1-76.1) and 90.6% (95% confidence interval 83.6-95.1), respectively. As antibody levels may reflect the disease activity, their serial measurement can also be used in the management of MAC disease. To justify its routine use in clinical practice, further validation in various regions and studies addressing whether serodiagnosis combined with present diagnostic criteria facilitate more rapid accurate diagnosis of MAC pulmonary disease are necessary.

Retrospective evaluation of natural course in mild cases of Mycobacterium avium complex pulmonary disease.

BackgroundThere is no proven management for mild cases of Mycobacterium avium complex (MAC) pulmonary disease, who do not immediately receive treatment and are managed with observation alone, because its long term-natural course, factors predictive of deterioration, and the effect of treating the disease remain unclear. Thus, we sought to investigate the natural course of mild cases of MAC pulmonary disease.MethodsWe conducted a multicenter retrospective study. Sixty-five patients with mild MAC pulmonary disease in whom treatment was withheld for at least 6 months after diagnosis were retrospectively recruited after a review of 747 medical records. Longitudinal changes in clinical features were evaluated by using a mixed effects model.ResultsMean follow-up was 6.9 ± 5.7 years. During the follow-up period, 15 patients (23%) required treatment and 50 (77%) were managed with observation alone. At diagnosis, 65 patients had nodular bronchiectatic disease without fibrocavitary lesions. Among clinical features, mean body mass index (BMI), forced expiratory volume in 1 second as percent of forced vital capacity (%FEV1), nodular lung lesions, and bronchiectasis worsened significantly in the observation group during follow-up. In the treatment group, BMI, and %FEV1 were stable, but bronchiectasis significantly worsened. At diagnosis, the polyclonal MAC infection rate in the treatment group was higher than that in the observation group. Other microbiological factors, such as insertion sequences, did not differ significantly between the groups.ConclusionsMild MAC pulmonary disease progresses slowly but substantially without treatment. Treatment prevents the deterioration of the disease but not the progression of bronchiectasis. Polyclonal MAC infection is a predictor of disease progression.

Mycobacterium avium complex pulmonary disease in multidrug-resistant tuberculosis-suspected patients in Mali

Background The incidence of nontuberculous mycobacteria is increasing, among them Mycobacterium avium complex (MAC) strains are the most frequently isolated. In countries endemic for tuberculosis, these infections pose a differential diagnosis challenge due to their clinical similarities. Patients and methods The main goal of this study was to describe the epidemiological, clinical aspects, and outcome of patients infected with MAC who met the American thoracic society (ATS) 2007 criteria for MTN disease’s definition. We conducted a 4-year retrospective evaluation from January 2009 to December 2012 at the Pneumophtisiology Department of the Point G University Teaching Hospital in Bamako. Results A total of 17 patients met the criteria for MAC disease, 16 men and one woman with a mean age of 50.4 years. All patients had at least two antituberculosis treatment courses without success. The signs and symptoms were a febrile alteration of physical condition in 41.7% (seven cases), chronic cough in 94.1% (16 cases), dyspnea in 68.7% (11 cases), and hemoptysis in 11.7% (two cases). The sputum smear was positive in 94.1% (16 cases) and the chest radiography showed constant cavitary images associated with nodular lesions in 52.9% (nine cases) or pleurisy in 11.7% (two cases). The evolution was marked by six deaths occurred within an average of 10 months and 10 were loss to follow-up. Conclusion The occurrence of MAC pulmonary disease poses diagnosis and treatment problems with less favorable outcome. Availability of early diagnosis with sputum culture will allow an accurate treatment regimen, which will improve patient outcomes.

Antibody response against Mycobacterium avium complex in cystic fibrosis patients measured by a novel IgG ELISA test

BackgroundEarly signs of Mycobacterium avium complex pulmonary disease can be missed in patients with cystic fibrosis due to subclinical infection or delays in mycobacterial culture. The aim of this study was to determine the diagnostic accuracy of a novel enzyme linked immunosorbent assay for immunoglobulin G against Mycobacterium avium complex, which could help stratify patients according to risk. MethodsA retrospective cross sectional analysis of serum samples from the Copenhagen Cystic Fibrosis Center was performed. Corresponding clinical data were reviewed and patients with cystic fibrosis were assigned to one of four groups based on their mycobacterial culture results. In addition, anti-Mycobacterium avium complex immunoglobulin G levels were measured longitudinally before and after first positive culture in the period 1984–2015. ResultsThree-hundred and five patients with cystic fibrosis were included with a median of five nontuberculous mycobacterial cultures. Four individuals had Mycobacterium avium complex pulmonary disease at the time of cross sectional testing and their median antibody level was 22-fold higher than patients with no history of infection (1820 vs. 80 IgG units; p < 0.001). Test sensitivity was 100% (95% CI 40–100) and specificity 77% (95% CI 72–81). Longitudinal kinetics showed rising antibodies prior to first positive culture suggesting diagnostic delay. ConclusionsAntibody screening for Mycobacterium avium complex may be used as a supplement to culture. Although confirmation in a larger cohort is needed, our findings suggest that stratifying a cystic fibrosis population into high- and low-risk groups based on antibody levels may help clinicians identify patients in need of more frequent culture.

CAVITARY LUNG DISEASE: ADENOCARCINOMA IN SITU OF THE LUNG WITH CONCOMITANT MYCOBACTERIUM AVIUM COMPLEX INFECTION

SESSION TITLE: Lung Cancer 1 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Adenocarcinoma in situ (AIS) of the lung usually presents on computed tomography (CT) of the chest as solid nodules, although part-solid or groundglass nodules are also often seen. In the case of cavitary lesions on CT in combination with nodular opacities, the diagnosis of Mycobacterium avium complex (MAC) infection is more readily considered. Herein is a case in which AIS with concurrent MAC infection presented on CT with multifocal cavitary lesions. CASE PRESENTATION: A 60-year-old Caucasian female with a history of former tobacco use presented with chronic cough productive of white sputum for four months as well as dyspnea on exertion. She was diagnosed on two separate occasions with pneumonia thirteen and three months prior to presentation. Evaluation of her cough included chest CT, which revealed dense consolidation with air bronchograms and widespread interstitial infiltration with groundglass opacities highlighting numerous cysts in the right upper lobe; a 6-cm cavitary lesion in the superior segment of the right lower lobe; and bilateral nodularity with both groundglass and cavitary components in a centrilobular, non-hematogenous distribution in the central lung zone regions. The clinical presentation and the radiologic findings were initially concerning for MAC infection. Bronchoscopy with transbronchial lung cryobiopsy (TBLC) was performed to confirm the diagnosis. However, cytology revealed malignant glandular cells consistent with adenocarcinoma, and surgical pathology revealed moderately-differentiated, non-mucinous neoplastic epithelium with papillary architecture consistent with AIS. Sputum smear initially revealed no acid-fast bacilli, but three weeks later cultures grew Mycobacterium avium-intracellulare. DISCUSSION: The pathology results of this patient are consistent with a diagnosis of lepidic-predominant, non-mucinous adenocarcinoma, which has rarely, if ever, been shown to present with cavitary lesions. In contrast, MAC infections routinely exhibit multiple small nodules and fibrocavitary lesions. In addition to radiologic evidence, the patient’s demographics and clinical presentation gave further reason to suspect a diagnosis of MAC infection, so the initial diagnosis of adenocarcinoma in situ was unexpected. Because diagnostic criteria for MAC infection includes radiologic evidence and bronchial washing, biopsy might not always be considered to rule out malignancy, especially with cavitation evident on CT scan. However, without biopsy, the significant diagnosis of adenocarcinoma could be missed. It is also notable to mention that it is necessary to follow up on sputum culture results that could modify treatment if resulted positive. CONCLUSIONS: When considering MAC infection as a diagnosis for cavitary lesions, it may be appropriate to consider biopsy of lesions to rule out malignancy, especially if suggested by the clinical presentation. Reference #1: Austin J, et al. Radiologic Implications of the 2011 Classification of Adenocarcinoma of the Lung. Radiology. 2013;266(1):62-71. Reference #2: Field S, Fisher D, Cowie R. Mycobacterium Avium Complex Pulmonary Disease in Patients Without HIV Infection. Chest. 2004;126(2):566-581. Reference #3: Travis W, et al. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma. Journal of Thoracic Oncology. 2011;6(2):244-285. DISCLOSURES: No relevant relationships by Andrew Astin, source=Web Response No relevant relationships by Ezmin George, source=Web Response No relevant relationships by Jeff Hon, source=Web Response No relevant relationships by Vikas Pathak, source=Web Response No relevant relationships by Christine Zhou, source=Web Response

Microbiologic outcome of interventions against Mycobacterium avium complex pulmonary disease: A systematic review

Microbiologic outcome of interventions against Mycobacterium avium complex pulmonary disease: A systematic review

Low body mass index and lymphocytopenia associate with Mycobacterium avium complex pulmonary disease in patients with rheumatoid arthritis

Objectives: Patients with rheumatoid arthritis (RA) are at an increased risk of Mycobacterium avium complex pulmonary disease (MAC-PD). We aimed to identify factors associated with MAC-PD in RA patients, and investigate their clinical significance for diagnosis of this disease.Methods: We examined 396 patients with RA for the presence of MAC-PD, using the criteria of the American Thoracic Society and conducted three years of follow-up on these patients. Multivariate logistic analyses were employed for selecting factors associated with MAC-PD. We developed a point system based on these factors which we call MAC-PD score to improve diagnosis of MAC-PD.Results: During this study, 14 out of 396 patients were newly diagnosed with MAC-PD. Multivariate analyses revealed body mass index (BMI) <18.0 kg/m2 and lymphocyte count <1500/μl were associated with MAC-PD in RA patients. Points were assigned to them and totalled to provide the MAC-PD score. Among 20 patients with high-resolution computer tomography images consistent with MAC-PD, the scores were significantly higher in 14 patients with MAC-PD than those in six patients without MAC-PD.Conclusion: Using these data, in the forms of the MAC-PD score, could help to identify patients who should be considered for bronchoscopy more selectively.

Mycobacterium avium complex pulmonary disease: new epidemiology and management concepts.

The prevalence of Mycobacterium avium complex (MAC)-related pulmonary disease has been increasing because of environmental factors, changes in organism virulence, and evolving host susceptibility. Treatment is often complicated by adverse effects, development of drug resistance, and refractory disease, with recurrence rates as high as 25-45%. Aerosolization of water, soil, or dusts are the likely sources of MAC-related pulmonary disease in susceptible individuals. The management of MAC-related pulmonary disease requires a multimodality approach, including antimicrobial therapy in appropriate patients, employment of mucus clearance techniques, instituting changes in the individual's home environment and personal habits to reduce environmental exposure to MAC, prevention of reflux, and maintenance of a healthy body weight. When the standard treatment for MAC-related pulmonary disease is not possible because of drug intolerance, antibiotic resistance, or progression of disease, second-line agents such as inhaled amikacin, clofazimine, bedaquiline, and delamanid must be considered, despite limited experience and few studies to guide their use. Individuals who have proven to be susceptible to MAC-related pulmonary disease should institute measures to reduce exposure to environmental sources of infection. Further research is needed to assess the impact of such preventive strategies on the incidence of new infection and disease recurrence. The efficacy of new medications for MAC-related pulmonary disease and their use in different combinations also requires further study.

Multiple Segmental Lung Lavages in the Treatment of Secondary Alveolar Proteinosis

SESSION TITLE: Pulmonary Manifestations of Systemic Disease 4 SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Pulmonary alveolar proteinosis (PAP) is characterized by the accumulation of periodic acid-Schiff (PAS)-positive material in the lungs. We present a case of multiple segmental lung lavages (MSLL) in the treatment of secondary PAP where whole-lung lavage (WLL) was precluded due to severe refractory hypoxemia. CASE PRESENTATION: A 34-year-old man with history of myelodysplastic syndrome (MDS) status post allogeneic bone marrow transplant was admitted to the intensive care unit (ICU) due to acute on chronic hypoxemic respiratory failure. He was afebrile, hemodynamically stable, his oxyhemoglobin saturation was 92% on 10L of oxygen via non-rebreather mask, and coarse breath sounds were present bilaterally. He had a history of Mycobacterium avium complex (MAC) pulmonary disease and a recent bone marrow biopsy showed MDS recurrence with positive familial GATA2 mutation. Computer tomography (CT) of the chest showed diffuse bilateral groundglass and interstitial opacities. Except for sputum culture positive for MAC, his infectious workup was negative. He was intubated and mechanically ventilated. A bronchoalveolar lavage demonstrated a milky fluid sample with proteinaceous sediment positive for PAS, suggesting PAP. MonoMac syndrome1 was suspected given his MAC pulmonary infections, MDS/GATA2 mutation, and PAP. With severe refractory hypoxemia, WLL was precluded and MSLL were considered as an alternative. Initially, the right lower lobe was lavaged with sequential instillations of saline 35mL-aliquots until the fluid became clear. Within 24 hours, FiO2 requirements decreased from ~0.8-1.0 to 0.65. Segmental lavages of the left lower lobe, and the right upper and middle lobes were completed within the next 48 hours. Unfortunately, the patient developed multiple organ system failure (MOSF) and his family opted for comfort cares. DISCUSSION: Secondary PAP can be found in association with MonoMac syndrome. This case was a diagnostic and therapeutic challenge due to the patient’s comorbidities, decreased functional status at baseline, and atypical findings for PAP on CT of the chest. MSLL resulted in decreased oxygen requirements; however, the impact of these interventions on the final outcome was lessened by the development of MOSF in this case. CONCLUSIONS: When severe hypoxemia among patient with PAP precludes WLL as a therapeutic intervention, multiple segmental lung lavages could be an alternative treatment option, or a temporizing method allowing clinical improvement prior to WLL. Reference #1: 1.Blood.2011;118:2656-2658 DISCLOSURE: The following authors have nothing to disclose: Gustavo Cortes Puentes, Darlene Nelson, James Utz No Product/Research Disclosure Information

Treatment and outcome of non-tuberculous mycobacterial pulmonary disease in a predominantly fibro-cavitary disease cohort.

The incidence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) has increased in the Netherlands. The fibro-cavitary disease manifestation predominates, as elsewhere in Europe. We studied treatment and outcome of this disease manifestation, as such data are scarce. We conducted a retrospective study of all patients diagnosed with NTM-PD according to the American Thoracic Society statement between 2008 and 2013 in a reference clinic. Sixty-three patients were included. Thirty-two (51%) were females and mean age was 60.8 years. Most patients had underlying COPD (73%). M.avium complex pulmonary disease (MAC-PD) was most frequent (n=38, 60.3%), followed by M.malmoense (n=7) and M.kansasii (n=6). Twenty-two patients had fibro-cavitary MAC-PD, 14 had nodular-bronchiectatic MAC-PD and 2 had other manifestations. Thirty-two (94%) patients treated for MAC-PD received a rifamycin-ethambutol-macrolide based regimen. Microbiological cure rates were lower for fibro-cavitary (52.4%) than for nodular bronchiectatic MAC-PD (100%; p=0.03). Sixty-nine percent of treated patients experienced adverse events, most frequently gastrointestinal discomforts (71%), tinnitus (18%), hearing impairment (16%) and hepatotoxicity (18%). Fibro-cavitary NTM-PD remains predominant, but is now diagnosed more frequently in women. Fibro-cavitary disease is harder to cure than nodular-bronchiectatic disease. Adverse events are frequent and can necessitate cessation of treatment.

Hsa-miR-346 is a potential serum biomarker of Mycobacterium avium complex pulmonary disease activity.

MicroRNA (miRNA) has been recently recognized as a biomarker of various diseases; however, there are no known miRNAs associated with Mycobacterium avium complex (MAC) pulmonary disease. In addition, there are no known biomarkers to precisely reflect disease activity after the diagnosis of MAC pulmonary disease. Thus, we sought to identify a miRNA which is a candidate biomarker of MAC pulmonary disease activity. Serum hsa-miR-346 concentrations of 16 patients with M.avium pulmonary disease were significantly higher than those of 16 healthy controls (p=0.047). The secretion of hsa-miR-346 increased in a multiplicity of infection-dependent manner in M.avium-infected macrophages. Serum hsa-miR-346 levels of 5 patients with bacterial conversion at the end of follow-up were significantly lower than those at the beginning of the follow-up (p=0.043). In addition, the longitudinal change in serum hsa-miR-346 concentration correlated with bacterial load in 2 patients with M.avium pulmonary disease. Based on our results, it is supposed that MAC-infected macrophages in pulmonary lesions produce hsa-miR-346, which is then secreted into the bloodstream. The magnitude of this process could be quantitatively controlled by the bacterial load, suggesting that serum hsa-miR-346 is a potentially useful biomarker of MAC pulmonary disease activity.

Mycobacterium avium MAV2054 protein induces macrophage apoptosis by targeting mitochondria and reduces intracellular bacterial growth

Mycobacterium avium complex induces macrophage apoptosis. However, the M. avium components that inhibit or trigger apoptosis and their regulating mechanisms remain unclear. We recently identified the immunodominant MAV2054 protein by fractionating M. avium culture filtrate protein by multistep chromatography; this protein showed strong immuno-reactivity in M. avium complex pulmonary disease and in patients with tuberculosis. Here, we investigated the biological effects of MAV2054 on murine macrophages. Recombinant MAV2054 induced caspase-dependent macrophage apoptosis. Enhanced reactive oxygen species production and JNK activation were essential for MAV2054-mediated apoptosis and MAV2054-induced interleukin-6, tumour necrosis factor, and monocyte chemoattractant protein-1 production. MAV2054 was targeted to the mitochondrial compartment of macrophages treated with MAV2054 and infected with M. avium. Dissipation of the mitochondrial transmembrane potential (ΔΨm) and depletion of cytochrome c also occurred in MAV2054-treated macrophages. Apoptotic response, reactive oxygen species production, and ΔΨm collapse were significantly increased in bone marrow-derived macrophages infected with Mycobacterium smegmatis expressing MAV2054, compared to that in M. smegmatis control. Furthermore, MAV2054 expression suppressed intracellular growth of M. smegmatis and increased the survival rate of M. smegmatis-infected mice. Thus, MAV2054 induces apoptosis via a mitochondrial pathway in macrophages, which may be an innate cellular response to limit intracellular M. avium multiplication.

Macrolide-Resistant Mycobacterium avium Complex Lung Disease: Analysis of 102 Consecutive Cases.

The management of macrolide-resistant Mycobacterium avium complex (MR-MAC) pulmonary disease is difficult and is thought to be analogous to that of multidrug-resistant tuberculosis (MDR-TB). This study aimed to clarify the cause of MR-MAC, to see how its management affected outcome, and to compare its prognosis with that of MDR-TB. The medical records of 102 consecutive cases with MR-MAC pulmonary disease at three tertiary hospitals for mycobacteriosis in metropolitan Tokyo and one in Aichi prefecture from 2005 to 2014 were reviewed. The data of 311 consecutive cases with MDR-TB were extracted from the medical data at Fukujuji Hospital. Of the 90 patients who met the criteria, 53 (58.9%) received inappropriate first-line treatment, and 28 (31.1%) deviated from the standard treatment because of the adverse effects of ethambutol. The survival rates for MR-MAC disease and MDR-TB were not significantly different (P = 0.6). Multivariate analysis showed that the combination of aminoglycoside and surgery resulted in the best treatment outcome (P = 0.02), although neither of the two factors reached significance by themselves. The continuation of clarithromycin and the addition of fluoroquinolones did not improve the outcome for the treatment of disease caused by MR-MAC. Inappropriate prescription patterns and deviations from the standard treatment because of adverse drug reactions appeared to be the main causes of macrolide resistance in this patient series. Drug sensitivity testing should be performed at diagnosis to identify macrolide resistance and patients who may benefit from other therapy.

Relapse versus Reinfection of Mycobacterium avium Complex Pulmonary Disease. Patient Characteristics and Macrolide Susceptibility.

Clinical recurrence of Mycobacterium avium complex (MAC) pulmonary disease occurs in 10 to 40% of patients treated for this disease process. Episodes of clinical recurrence may represent true relapse from the same MAC strain or reinfection with a new strain. The purpose of this study was to investigate the clinical implications of separating patients into these two groups. This retrospective study evaluated patients with a clinical recurrence of MAC pulmonary disease at our institution from 2000 to 2012. Isolates were genotyped using pulsed-field gel electrophoresis to differentiate relapse versus reinfection. Change in macrolide susceptibility was also analyzed. In our cohort, 25% of patients suffered a clinical recurrence. Of the 46 included patients, 25 (54%) suffered a true relapse and 21 (46%) had a reinfection. Median time between completion of therapy and clinical recurrence was significantly lower in the relapse group compared with the reinfection group (210 d vs. 671 d; P = 0.004). The measured convalescent macrolide minimum inhibitory concentrations were significantly more likely to increase in the relapse group compared with the reinfection group (80 vs. 33%; P = 0.002). No differences in clinical outcomes were observed between the two groups at conclusion of the study. Our findings suggest that patients with true relapse of MAC pulmonary disease present earlier than those with reinfection. Routine use of pulsed-field gel electrophoresis in the management of clinical recurrences may be beneficial, as those suffering a relapse are more likely to have increasing macrolide minimum inhibitory concentrations than those with reinfection.

Evaluation of a bovine antibody test for diagnosing Mycobacterium avium complex in patients with cystic fibrosis.

The aim of this study was to test a commercial bovine enzyme-linked immunosorbent assay for investigating antibody activity against Mycobacterium avium complex. All patients at the Copenhagen Cystic Fibrosis (CF) Center who had culture for nontuberculous mycobacteria performed were included. A commercially available antibody test used in veterinary medicine, was adjusted for human use, and applied to patient sera in a cross sectional test. The test positivity threshold was determined using a receiver operating curve (ROC). A longitudinal analysis of antibody kinetics before and after culture conversion was performed in case patients. Out of 286 included subjects, six had clinical M. avium complex pulmonary disease at the time of sera sampling. These patients presented with higher antibody test values (P-value <0.01). A test cut point of 0.78 was chosen, corresponding to a sensitivity of 100% (54-100), specificity of 66% (60-72), a positive predictive value of 6% (2-13), and negative predictive value of 100% (98-100). While not suited for direct diagnosis of M. avium complex due to a high number of false positive subjects, the assay proved useful at ruling out pulmonary disease. Screening sera from patients with CF could guide clinicians to focus attention on patients at higher risk of M. avium complex pulmonary disease. Pediatr Pulmonol. 2017;52:34-40. © 2016 Wiley Periodicals, Inc.

Diagnostic test accuracy of anti-glycopeptidolipid-core IgA antibodies for Mycobacterium avium complex pulmonary disease: systematic review and meta-analysis.

Currently, an anti-glycopeptidolipid (GPL)-core IgA antibody assay kit for diagnosing Mycobacterium avium complex (MAC) is commercially available. We conducted this systematic review and meta-analysis to reveal the precise diagnostic accuracy of anti-GPL-core IgA antibodies for MAC pulmonary disease (MAC-PD). We systematically searched reports that could provide data for both sensitivity and specificity by anti-GPL-core IgA antibody for clinically diagnosed MAC-PD. Diagnostic test accuracy was estimated using the bivariate model. Of the 257 articles that we had found through primary search, we finally included 16 reports consisted of 1098 reference positive subjects and 2270 reference negative subjects. The diagnostic odds ratio was 24.8 (95% CI 11.6–52.8, I2 = 5.5%) and the area under the hierarchical summary receiver operating characteristic curves was 0.873 (95% CI 0.837–0.913). With a cutoff value of 0.7 U/mL, the summary estimates of sensitivity and specificity were 0.696 (95% CI 0.621–0.761) and 0.906 (95% CI 0.836–0.951), respectively. The positive and negative likelihood ratios were 7.4 (95% CI 4.1–13.8) and 0.34 (95% CI 0.26–0.43), respectively. The demanding clinical diagnostic criteria may be a cause of false positive of the index test. The index test had good overall diagnostic accuracy and was useful to ruling in MAC-PD with the cutoff value.

Bronchial artery embolization to control hemoptysis in patients with Mycobacterium avium complex.

Hemoptysis frequently develops in patients with Mycobacterium avium complex (MAC) pulmonary disease. Bronchial artery embolization (BAE) has been established as one of the useful treatments of massive and persistent hemoptysis. We evaluated the efficacy and safety of BAE for controlling hemoptysis in MAC patients, and identified the risk factors of rebleeding after BAE. Among the 529 patients with MAC who were admitted to our institution from January 2007 to December 2012, we retrospectively reviewed the demographic data, imaging, sputum, and angiographic findings, and the clinical course of 43 patients who underwent BAE using coils, due to hemoptysis. Among the 43 patients enrolled in the study, rebleeding developed in 13 cases (30.2%) with a mean follow-up period of 18 months. Median rebleeding-free time after BAE was 29.9 months and the cumulative hemoptysis control rates were 79.1%, 73.8%, and 63.3% in one, two, and three years, respectively. Rebleeding-free time significantly correlated with comorbid chronic pulmonary aspergillosis (CPA). When limited to 35 MAC patients without CPA, the rate increased to 88.6%, 82.1%, and 70.4%, respectively. Factors such as coexisting CPA, multiple embolized vessels at BAE, longer length of time from the diagnosis of MAC to BAE, and an administration of antibiotics for MAC at the time of hemoptysis, indicated statistically significant correlations with rebleeding. Major complications concerning BAE were not encountered. BAE using coils is an effective and safe method for controlling hemoptysis in patients with MAC pulmonary disease. However, it is important to carefully observe patients with risk factors for rebleeding after BAE.