Mycobacterium Avium Complex Disease Research Articles

Development of a rapid detection method for the macrolide resistance gene in Mycobacterium avium using the amplification refractory mutation system-loop-mediated isothermal amplification method.

Macrolide antibiotics such as clarithromycin (CLR) and azithromycin are the key drugs used in multidrug therapy for Mycobacterium avium complex (MAC) diseases. For these antibacterial drugs, drug susceptibility has been correlated with clinical response in MAC diseases. We have previously demonstrated the correlation between drug susceptibility and mutations in the 23S rRNA gene, which confers resistance to macrolides. Herein, we developed a rapid detection method using the amplification refractory mutation system (ARMS)-loop-mediated isothermal amplification (LAMP) technique to identify mutations in the 23S rRNA gene of M. avium. We examined the applicability of the ARMS-LAMP method to genomic DNA extracted from six genotypes of M. avium clinical isolates. The M. avium isolates were classified into 21 CLR-resistant and 9 CLR-susceptible strains based on the results of drug susceptibility tests; the 23S rRNA genes of these strains were sequenced and analyzed using the ARMS-LAMP method. Sequence analysis revealed that the 9 CLR-sensitive strains were wild-type strains, whereas the 21 CLR-resistant strains comprised 20 mutant-type strains and one wild-type strain. Using ARMS-LAMP, no amplification from genomic DNAs of the 10 wild-type strains was observed using the mutant-type mismatch primer sets (MTPSs); however, amplification from the 20 mutant-type strain DNAs was observed using the MTPSs. The rapid detection method developed by us integrates ARMS-LAMP with a real-time turbidimeter, which can help determine drug resistance in a few hours. In conclusion, ARMS-LAMP might be a new clinically beneficial technology for rapid detection of mutations.IMPORTANCEMultidrug therapy for pulmonary Mycobacterium avium complex disease is centered on the macrolide antibiotics clarithromycin and azithromycin, and resistance to macrolides is an important prognosticator for clinical aggravation. Therefore, it is important to develop a quick and easy method for detecting resistance to macrolides. Drug resistance is known to be correlated with mutations in macrolide resistance genes. We developed a rapid detection method using amplification refractory mutation system (ARMS)-loop-mediated isothermal amplification (LAMP) to identify a mutation in the 23S rRNA gene, which is a macrolide resistance gene. Furthermore, we examined the applicability of this method using M. avium clinical isolates. The rapid method developed by us for detection of the macrolide resistance gene by integrating ARMS-LAMP and a real-time turbidimeter can help in detection of drug resistance within a few hours. Since this method does not require expensive equipment or special techniques and shows high analytical speed, it would be very useful in clinical practice.

Challenging Case of Mycobacterium Avium Complex (MAC) Disease in a Malnourished Non-HIV Patient

Challenging Case of Mycobacterium Avium Complex (MAC) Disease in a Malnourished Non-HIV Patient

Serum Cell-free DNA-based Detection of Mycobacterium Avium Complex Infection.

Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial pulmonary disease (NTM-PD), which exhibits increasing global incidence. Current microbiologic methods routinely used in clinical practice lack sensitivity and have long latencies, leading to delays in diagnosis and treatment initiation and evaluation. A CRISPR-based assay that measures MAC cell-free DNA (MAC-cfDNA) levels in serum could provide a rapid means to detect MAC infection and monitor response to antimicrobial treatment. To develop and optimize a CRISPR-MAC assay for MAC infection detection and to evaluate its diagnostic and prognostic performance in two MAC disease cohorts. MAC-cfDNA serum levels were measured in individuals diagnosed with MAC disease or who had bronchiectasis or COPD diagnoses without a history of NTM-PD or NTM-positive sputum cultures. Diagnostic performance was analyzed with pre-treatment serum from two cohorts. Serum MAC-cfDNA changes during MAC-PD treatment were evaluated in a subset of MAC-PD patients who received macrolide-based multi-drug regimens. CRISPR-MAC assay detected MAC-cfDNA in MAC-PD with 97.6% (91.6 - 99.7%) sensitivity and 97.6% (91.5 - 99.7%) specificity overall. Serum MAC-cfDNA levels markedly decreased after MAC-directed treatment initiation in MAC-PD patients that demonstrated MAC culture conversion. This study provides preliminary evidence for the utility of a serum-based CRISPR-MAC assay to rapidly detect MAC infection and monitor their response to treatment.

Disseminated Mycobacterium avium Infection with Different Clinical Presentation in Two Human Immunodeficiency Virus-positive Patients

Abstract Microorganisms belonging to the Mycobacterium avium complex (MAC) are ubiquitous in the environment, but only a minority of infected persons develop disease. An underlying lung disease or immune deficiency is a prerequisite for clinical manifestation. However, disseminated MAC disease primarily manifests in people living with human immunodeficiency virus (HIV) in the severe immunodeficiency stage with a whole host of clinical symptoms. We present two cases of disseminated M. avium infection in people living with HIV in the stage of severe immunodeficiency. Both patients exhibited distinct disease progression, with the absence of pulmonary symptoms being a common characteristic. The first patient predominantly experienced high fever, accompanied by diarrhea and severe anemia. The normothermia in the second patient was incongruent with the presence of marked cachexia, severe abdominal pain, and magnetic resonance imaging evidence of abdominal lymph node involvement. The causative agent was isolated from both sputum and stools. The patients underwent treatment that comprised aminoglycoside, macrolide, ethambutol, and rifampicin. Although both patients achieved optimal viral suppression of HIV, the immunologic response to antiretroviral therapy was suboptimal. The first patient died in the setting of severe immunodeficiency due to the development of decompensated liver cirrhosis, while the second patient demonstrated a slight reverse course of the disease.

Comparing minimum inhibitory concentrations of amikacin for pulmonary Mycobacterium avium complex disease: An analysis of culture media differences

Mycobacterium avium complex (MAC) is considered a paramount microbe, especially in East Asia, including Japan. The commonly used commercial Minimum Inhibitory Concentrations (MIC) assay using Middlebrook 7H9 (7H9) medium deviates from the latest Clinical and Laboratory Standards Institute (CLSI) guidelines. Alternatively, measurement with cation-adjusted Mueller-Hinton broth (CAMHB) that conforms to CLSI standards is not yet widely available. Following the approval and commercialization of amikacin liposome inhalation suspension (ALIS) in 2021, a more precise evaluation of amikacin (AMK) susceptibility in MAC is necessary for treatment decisions. In the present study, 33 sputum samples were extracted from 27 patients, and MICs of AMK were compared between the frequently used 7H9 and the recommended CAMHB of the isolated MAC strains. The history of exposure to aminoglycosides for each sample was also added as clinical information. The findings indicated that there was only an 18% concordance rate in MIC between the two media, with 19 samples (58%) indicating lower MICs in 7H9 relative to CAMHB. The 17 samples had a history of exposure to aminoglycosides for periods ranging from 1.5 to 28 months. Specifically, 10 samples were exposed to amikacin by inhalation and intravenous injection, and the remaining seven samples had a history of ALIS inhalation. Samples with a prior utilization of aminoglycosides were significantly predisposed to developing resistance to ALIS compared to those without such a history (P = 0.046). Physicians are encouraged to scrutinize the findings of susceptibility testing utilizing CLSI-endorsed MIC assay using CAMHB medium to ascertain the optimal therapeutic approach.

Longitudinal changes in radiographic features of pulmonary Mycobacterium avium complex diseases

BackgroundThe radiographic features of Mycobacterium avium complex pulmonary disease (MAC-PD), a major component of nontuberculous mycobacteria, consist of a variety of lesions; however, the responsiveness of each type of radiographic factor to treatment is unclear. Thus, we evaluated the longitudinal changes of each factor in serial computed tomography (CT) images using a mixed-effects model, and investigated the radiographic transition in patients with MAC-PD whose progress could be followed. MethodsIn this retrospective study, eighty-four patients diagnosed with MAC-PD and with yearly CT records were recruited after a review of 328 medical records with culture-positive MAC in respiratory specimens. The study participants were divided into two groups: treatment (n = 43) and no-treatment (n = 41) groups. Radiographic images were scored using the nodule (N), infiltration (I), cavity (C), ectasis (E) scoring system. Longitudinal changes in each radiographic lesion factor were analyzed using a mixed-effects model in treated and untreated patients. ResultsAll factors tended to progress without treatment, and significant longitudinal changes were observed in the N, I, and E factors (N: p = 0.010, I: p = 0.004, E: p < 0.001). Although treatment tended to improve N and I in radiographic images (N: p = 0.006, I: p = 0.203), cavities and ectasis progressed, regardless of treatment (C: p = 0.057 and E: p = 0.033). ConclusionRadiographic changes of MAC-PD can be categorized into reversible (nodules and infiltrations) and irreversible (cavities and ectasis) lesions. Early treatment may prevent the accumulation of irreversible factors.

Monotherapy: Key cause of macrolide-resistant Mycobacterium avium complex disease

BackgroundMacrolide-resistant Mycobacterium avium complex (MAC) disease is very difficult to cure. Macrolide-resistance emerges in patients and is largely preventable by appropriate screening and treatment practices. MethodsPatients with macrolide-resistant MAC isolates between March 2019 and March 2022 were retrieved from the mycobacteriology reference laboratory database at Radboudumc, Nijmegen, the Netherlands. Clinical consultation reports were extracted from the database to assess the cause of macrolide resistance. ResultsSixteen patients with macrolide-resistant MAC disease were included, from a total of 815 patients with MAC isolates (2%); Macrolide monotherapy in bronchiectasis or CF was the most frequent cause of development of macrolide-resistance MAC disease (n = 8; 50%). Short (n = 3; mean duration 9 months, range 6–12) or guideline non-compliant (n = 2) treatment regimens and patient non-adherence (n = 2) were other key causes of macrolide-resistance. ConclusionsMacrolide monotherapy after inappropriate screening is the most frequent cause of macrolide-resistant Mycobacterium avium complex disease in the Netherlands. Educational efforts are needed to prevent this.

Antigen-specific cytokine profiles for pulmonary Mycobacterium avium complex disease stage diagnosis.

Controlling pulmonary Mycobacterium avium complex (MAC) disease is difficult because there is no way to know the clinical stage accurately. There have been few attempts to use cell-mediated immunity for diagnosing the stage. The objective of this study was to characterize cytokine profiles of CD4+T and CD19+B cells that recognize various Mycobacterium avium-associated antigens in different clinical stages of MAC. A total of 47 MAC patients at different stages based on clinical information (14 before-treatment, 16 on-treatment, and 17 after-treatment) and 17 healthy controls were recruited. Peripheral blood mononuclear cells were cultured with specific antigens (MAV0968, 1160, 1276, and 4925), and the cytokine profiles (IFN-γ, TNF-α, IL-2, IL-10, IL-13, and IL-17) of CD4+/CD3+ and CD19+ cells were analyzed by flow cytometry. The response of Th1 cytokines such as IFN-γ and TNF-α against various antigens was significantly higher in both the on-treatment and after-treatment groups than in the before-treatment group and control (P < 0.01-0.0001 and P < 0.05-0.0001). An analysis of polyfunctional T cells suggested that the presence of IL-2 is closely related to the stage after the start of treatment (P = 0.0309-P < 0.0001) and is involved in memory function. Non-Th1 cytokines, such as IL-10 and IL-17, showed significantly higher responses in the before-treatment group (P < 0.0001 and P < 0.01-0.0001). These responses were not observed with purified protein derivative (PPD). CD19+B cells showed a response similar to that of CD4+T cells. There is a characteristic cytokine profile at each clinical stage of MAC.

Prevalence of systemic and local risk factors for pulmonary non-tuberculous mycobacterial disease in Japan: a single-institution study.

Objective: To identify the prevalence of risk factors for pulmonary non-tuberculous mycobacterial (NTM) disease in a Japanese population. Patients and Methods: We reviewed 337 consecutive Japanese patients (210 women) with pulmonary NTM disease, including 225 patients with Mycobacterium avium complex (MAC) disease (95.8%) at our hospital during 2006-2017. We calculated the prevalence of risk factors reported in Western countries among mycobacterial species. Results: Pulmonary MAC disease cases comprised 78.2% of pulmonary NTM patients in their 40s, increasing to 100% at age ≥80 years. Body mass index (BMI) was <18.5 in approximately 40% of patients, which was significantly higher than the prevalence of underweight in the Japanese population. The percentage of male heavy smokers (Brinkman index ≥600) was 58.2% of pulmonary NTM disease and was high for all mycobacterial species. In pulmonary MAC disease, systemic factors were observed in the order of malignant tumors (other than lung cancer), diabetes, rheumatoid arthritis, and tuberculosis. Local factors were observed in the order of bronchiectasis, chronic obstructive pulmonary disease, lung cancer, and bronchial asthma. Conclusion: The risk factors reported in Western countries were relatively highly prevalent among Japanese pulmonary NTM disease patients. This observation may help elucidate disease onset mechanisms.

Disseminated Mycobacterium avium Complex Infection in a Patient Treated With Immunosuppressants

Mycobacterium avium complex (MAC) is an important cause of opportunistic infections in immunosuppressed hosts, such as patients with HIV infection and solid organ transplant recipients. MAC disease usually presents in 4 distinct clinical categories: chronic pulmonary disease, disseminated disease, skin/soft-tissue infection, and superficial lymphadenitis. However, clinical reports on gastrointestinal (GI) MAC disease are rare, especially in patients without HIV infection or a history of organ transplantation. We describe a case of non-HIV-associated GI MAC disease in a patient with long-term mycophenolate mofetil use. In this case, MAC organisms in the GI tract and ascites were observed. Endoscopy revealed a unique colonic image with large, deep epithelial denudations. This suggests that apart from patients with HIV infection or transplant recipients, those treated with immunosuppressants can have disseminated MAC. Therefore, internal physicians need to monitor patients undergoing mycophenolate mofetil immunosuppressant therapy.

Cumulative antimicrobial susceptibilities for respiratory clinical isolates of Mycobacterium avium Complex, Mycobacterium kansasii, and Mycobacterium abscessus from Pakistan 2018 to 2022.

Nontuberculous mycobacteria (NTM) are increasingly identified as causes of protracted pulmonary infections. Antibiotic susceptibility testing requires microdilution methods, which are often unavailable in laboratories in resource-poor settings. We report cumulative antibiograms for the most frequently isolated clinical pulmonary NTM from Pakistan to inform empiric antibiotic management of initial NTM infections. We analyzed data from 2018 to 2022 for the most frequently isolated and clinically relevant NTM isolated from respiratory specimens, i.e., Mycobacterium avium complex (MAC), Mycobacterium abscessus group (MAG), and Mycobacterium kansasii (MK). Antibiograms were developed using the Clinical Laboratory Standards Institute's M39ED5 standard. Percentage susceptibilities and 95% confidence intervals (CI) were calculated. Over 4 years, 529 NTM, comprising 209 MAC, 249 MAG, and 71 MK were analyzed. For MAC and MAG, where clarithromycin (CLR)-based regimens are recommended, CLR was active for 94.8% (95% CI 91.3-96.9), and 77.5% (95% CI 71.4-82.7) isolates, respectively. Combination regimens comprising 3 active drugs CLR + linezolid (LZD) + moxifloxacin for MAC and CLR + LZD + Amikacin for MAG had 98.4% (95% CI 95.9-99.4) and 68.9% (95% CI 62.3-74.8) coverage for pulmonary disease, respectively. For MK, 91.5% (95% CI 82.8-96.1) isolates were susceptible to rifampin (RIF), with a combination of RIF + CLR covering 88.7% (95% CI 79.3-94.2) of MK pulmonary infections, respectively. These data can inform empiric treatment guidance for the most common NTM pulmonary infections, i.e., for MAC, MAG, and MK disease in Pakistan.

Esophageal Monkeypox lesion

A 30-year-old cis-man living with well-controlled HIV infection presented with a 6-day history of perianal and tongue lesions and 2 days of fever, sweats, and odynophagia manifested as retrosternal chest pain when consuming fluids. His past medical history included HIV, treated with abacavir-dolutegravir-lamivudine and darunavir-cobicistat, with recent CD4 count of 192 and an undetectable viral load, and previously treated Mycobacterium avium complex disease with lymph node involvement. His other medications include trimethoprim-sulfamethoxazole, azithromycin, moxifloxacin, and ethambutol.

Analysis of adverse drug events in pulmonary Mycobacterium avium complex disease using spontaneous reporting system

BackgroundIn Japan, Mycobacterium avium complex lung disease (MAC-LD) is the most common in nontuberculous mycobacterial lung disease. Patients often experience adverse events, resulting in the discontinuation of treatment, which causes treatment failure. The JADER (Japanese Adverse Drug Event Report) database is a database of adverse events that allows us to collect real-world data on adverse events. We can collect large-scale data cost-effectively and detect signals of potential adverse events such as reporting odds ratio (ROR) by using spontaneous reporting systems. In this study, we aimed to elucidate the adverse events of clarithromycin (CAM), ethambutol (EB), and rifampicin (RFP) using the JADER database.MethodsWe included cases of MAC-LD between April 2004 and June 2017. We investigated sex, age, and medications that may have caused the adverse events, outcomes, and time of onset. We calculated the safety signal index as the ROR. Time-to-event analysis was performed using the Weibull distribution.ResultsThe total number of adverse events of CAM, EB, and RFP was 2780, with 806 patients. In the overall adverse events, hematologic and lymphatic disorders were the most common adverse events, with 17.3%, followed by eye disorders (16.6%), and hepatobiliary disorders (14.0%). The outcomes were as follows: recovery, 40.0%; remission, 27.1%; non-recovery, 11.2%; and death, 7.1%. Regarding the most common onset time of CAM, EB, and RFP was within 120 days at 40%, 181–300 days at 43.6%, and within 120 days at 88.5%. For CAM, the RORs of infections and infestations, hepatobiliary system disorders, and immune system disorders were 4.13 (95% confidence interval [CI], 2.3–7.44), 2.61 (95% CI, 1.39–4.91), and 2.38 (95% CI, 1.04–5.44). For EB, the ROR of eye disorders was 215.79 (95% CI, 132.62–351.12). For RFP, the RORs of renal and urinary tract disorders and investigations were 7.03 (95% CI, 3.35–14.77) and 6.99 (95% CI, 3.22–15.18). The β value of EB was 2.07 (95% CI, 1.48–2.76), which was classified as a wear-out failure type.ConclusionsFor MAC-LD, the adverse event which has the highest ROR is infections and infestations in CAM, eye disorders in EB, renal and urinary tract disorders in RFP. Adverse events of EB occur after 180 days, whereas the adverse events of CAM and RFP occur early in the course of treatment.

Impact of chronic co-infection in pulmonary Mycobacterium avium complex disease after treatment initiation

BackgroundThe impact of co-infection with other pathogenic microorganisms after initiation of treatment for Mycobacterium avium complex pulmonary disease (MAC-PD) has not been clearly described. This study sought to clarify the clinical outcomes of co-infection with MAC after antimycobacterial therapy for MAC.MethodsCo-infection status was defined as the detection of pathogenic microorganisms other than MAC in at least two consecutive sputum cultures 6–24 months after initiation of treatment. Chest computed tomography (CT) findings and culture results were compared between co-infection and MAC alone groups.ResultsThe co-infection and MAC alone groups comprised 12 and 36 patients, respectively. The proportion of patients with sputum culture positive for MAC after 24 months of therapy did not differ significantly between the two groups [25% (3/12) vs. 16.7% (6/36); p = 0.671]. The proportion of patients with improved chest CT score after 24 months of starting treatment compared to baseline was significantly lower for the co-infection group than for the MAC alone group [16.7% (2/12) vs. 79.4% (27/34); p < 0.001]. In the co-infection group, median CT score values at 12 and 24 months did not differ from baseline. However, the MAC alone group showed significant improvement at 12 and 24 months compared with baseline.ConclusionsIn the patient group with co-infection of other pathogenic microorganisms after treatment initiation for MAC there was no impact on therapeutic efficacy compared to the MAC alone group. However, therapeutic intervention interfered with improvement in chest CT findings such as nodule formation, bronchiectasis, infiltration, and cavitary lesions.

A Case of Disseminated Mycobacterium Avium Complex Disease Associated with Immunodeficiency Suspected of Bilateral Adrenal Tumors

A Case of Disseminated Mycobacterium Avium Complex Disease Associated with Immunodeficiency Suspected of Bilateral Adrenal Tumors

Omadacycline efficacy in the hollow fibre system model of pulmonary Mycobacterium avium complex and potency at clinically attainable doses.

ObjectivesThe standard of care (SOC) for the treatment of pulmonary Mycobacterium avium complex (MAC) disease (clarithromycin, rifabutin, and ethambutol) achieves sustained sputum conversion rates of only 54%. Thus, new treatments should be prioritized.MethodsWe identified the omadacycline MIC against one laboratory MAC strain and calculated drug half life in solution, which we compared with measured MAC doubling times. Next, we performed an omadacycline hollow fibre system model of intracellular MAC (HFS-MAC) exposure–effect study, as well as the three-drug SOC, using pharmacokinetics achieved in patient lung lesions. Data was analysed using bacterial kill slopes (γ-slopes) and inhibitory sigmoid Emax bacterial burden versus exposure analyses. Monte Carlo experiments (MCE) were used to identify the optimal omadacycline clinical dose.ResultsOmadacycline concentration declined in solution with a half-life of 27.7 h versus a MAC doubling time of 16.3 h, leading to artefactually high MICs. Exposures mediating 80% of maximal effect changed up to 8-fold depending on sampling day with bacterial burden versus exposure analyses, while γ-slope-based analyses gave a single robust estimate. The highest omadacycline monotherapy γ-slope was −0.114 (95% CI: −0.141 to −0.087) (r2 = 0.98) versus −0.114 (95% CI: −0.133 to −0.094) (r2 = 0.99) with the SOC. MCEs demonstrated that 450 mg of omadacycline given orally on the first 2 days followed by 300 mg daily would achieve the AUC0-24 target of 39.67 mg·h/L.ConclusionsOmadacycline may be a potential treatment option for pulmonary MAC, possibly as a back-bone treatment for a new MAC regimen and warrants future study in treatment of this disease.

Laryngitis after inhalation of liposomal amikacin.

A 56‐year‐old woman with pulmonary Mycobacterium avium complex disease was started on inhalation liposomal amikacin. One month later, she developed hoarseness and was diagnosed with laryngitis. The laryngitis healed immediately after treatment discontinuation, and no recurrence occurred even after resuming intermittent inhalation.

The diagnostic yield and characteristics of bronchoalveolar lavage in suspected nontuberculous mycobacterial pulmonary disease.

Bronchoalveolar lavage (BAL) has widely been used to manage respiratory diseases including respiratory infections. The aim of this study was to evaluate the diagnostic yield of BAL for detecting nontuberculous Mycobacterium (NTM). We retrospectively reviewed the records of 54 patients who underwent bronchoscopy due to suspected NTM pulmonary disease. Positive culture results of respiratory specimens were defined as NTM pulmonary disease. For BAL, two or three aliquots of 50 mL (total 100 or 150 mL) of sterile normal saline were instilled through bronchoscope. NTM was detected in 31 of 54 (57.4%) patients. The detection rates were not different between the patients who underwent bronchoscopy with BAL (24 of 39, 61.5%) and those without (7 of 15, 46.7%) (P = 0.437). BAL fluid was mostly neutrophil dominant in both positive and negative NTM culture groups. In the subgroup analysis of 33 patients who underwent both the BAL and anti- glycopeptidolipid (GPL)-core immunoglobulin A (IgA) antibody measurements, 12 of 19 (63.2%) positive Mycobacterium avium complex (MAC) culture patients and 8 of 14 (57.1%) negative MAC culture patients were positive for anti-GPL-core IgA antibody (seropositive) (P = 0.991). There was no severe complication related to BAL. The diagnostic yield of BAL with ≥100 mL sterile saline was not superior to that of bronchial wash or sputum aspiration in patients with suspected NTM pulmonary disease. Patients with seropositive but negative culture results for MAC suggest pseudonegative for pulmonary MAC disease.

Long-term good outcome of the fibrocavitary form of pulmonary Mycobacterium avium complex disease with concomitant abatacept monotherapy in a patient with rheumatoid arthritis

A 53-year-old woman diagnosed with rheumatoid arthritis (RA) demonstrated thick-walled large cavities with consolidation in the left upper lobe on chest computed tomography (CT). Mycobacterium avium was isolated from sputum cultures, and she was diagnosed as having the fibrocavitary (FC) form of pulmonary Mycobacterium avium complex (MAC) disease. Clarithromycin-containing, multidrug, anti-MAC chemotherapy was started immediately. After 7 months, the cavitary lesions improved, and sputum cultures showed negative conversion. Thereafter, abatacept monotherapy was started due to high RA disease activity. Clinical remission of RA has been sustained and cavitary lesions disappeared by concomitant abatacept and anti-MAC therapy for more than 5 years. Immediate initiation of anti-MAC therapy and prior confirmed efficacy are needed for the treatment of the FC form. Abatacept and anti-MAC therapy could be continued, leading to the withdrawal of prednisolone, along with careful observation by strict chest CT evaluation and repeated sputum cultures. Biologics are generally contraindicated for pulmonary MAC disease, particularly the FC form. When there is a pre-existing lung lesion apparently of FC type, abatacept cannot be started without prior anti-MAC chemotherapy. This case suggests that abatacept may be carefully used to avoid progressive joint destruction after FC lesions of pulmonary MAC disease are resolved.

Spouses with Pulmonary Mycobacterium Avium Complex Infections: A Case Report

Introduction: Mycobacterium avium complex (MAC) is the most common cause of pulmonary infections due to nontuberculous mycobacterium in the United States. While there have been reports of geographic variations in incidence as well as disease clusters among genetically related individuals, there have been no published reports describing clusters of co-occurring pulmonary MAC disease among genetically unrelated individuals. Clinical Findings: Patient 1 was a 56-year-old male with worsening asthma exacerbations associated with recurrent bronchitis. Patient 2 was a 55-year-old female with worsening asthma exacerbations, progressive dyspnea, and recurrent bronchitis. The 2 patients lived together, were immunocompetent, and genetically unrelated. They were frequently exposed to aerosolized soil and inadequately heated water. Clinical Course: Patient 1 had normal imaging and his sputum grew out MAC. He responded quickly to treatment with azithromycin, rifampin, and ethambutol. Patient 2 had computed tomographic imaging that revealed tree-in-bud and ground-glass opacities. Her sputum samples did not grow out acid-fast bacillus; however, 14 months after Patient 1 was diagnosed, her bronchoscopy samples ultimately grew out MAC. Patient 2 clinically responded quickly to the same treatment as Patient 1, with resolution of her dyspnea, bronchitis, and radiographic abnormalities. Conclusions: We describe 2 cohabitating, genetically unrelated, immunocompetent patients with pulmonary MAC infections. The likely cause of these infections was a common exposure to aerosolized soil and inadequately heated water. We report the unusual co-occurrence of pulmonary MAC among genetically unrelated individuals living together.