Amikacin Liposome Inhalation Suspension in the Real-World Management of Refractory Mycobacterium avium Complex Pulmonary Disease.

The increasing prevalence of Mycobacterium avium complex (MAC) pulmonary disease poses a significant therapeutic challenge, particularly due to the limited efficacy and systemic toxicity associated with conventional guideline-based therapy. Amikacin liposome inhalation suspension (ALIS) has been developed, yet its real-world application remains underreported. This retrospective analysis, conducted from March 2021 to February 2024, examined ALIS's clinical use in patients aged 20 years or older with refractory MAC pulmonary disease at our institution. The primary objective of this study is to describe the patient characteristics and clinical trajectories associated with the initiation of ALIS therapy in real-world settings for individuals diagnosed with MAC pulmonary disease. Of 11 patients initiated on ALIS, one was excluded due to financial constraints impacting continuation. The analysis proceeded with the remaining 10 subjects. The mean age of participants was 70.2 years, with a predominance of female patients (n = 7, 70%) and a higher incidence of M. avium infections (n = 6, 60%). Forty percent of the cohort (n = 4) had a history of ethambutol-induced optic neuritis leading to the cessation of the drug. The average interval from the initiation of guideline-based therapy to the start of ALIS was 8.5 ± 6.9 years (mean ± standard deviation). The majority (80%) presented with positive Gaffky scores at ALIS initiation, and a significant proportion exhibited resistance to clarithromycin and ethambutol. Comorbid conditions, including diabetes and previous cancer, were noted. The study also observed elevated anti-MAC antibody levels. Treatment duration varied, with fatigue leading to discontinuation in two cases. Treatment-emergent adverse events were documented in individual patients, each presenting with grade 1 severity: hemoptysis (n = 1, 10%), elevated creatinine levels (n = 1, 10%), and dysphonia (n = 2, 20%) were observed, respectively. Correlation analysis revealed a significant inverse relationship between body mass index (BMI) and ALIS discontinuation due to fatigue, and a positive correlation between Gaffky scores and C-reactive protein (CRP) levels. These results underscore the potential benefits and limitations of ALIS, suggesting that timely intervention and comprehensive healthcare support are crucial for optimal outcomes in the treatment of advanced MAC pulmonary disease.

Successful management of Mycobacterium abscessus pneumonia in a 53-day-old immunocompetent infant.

Pulmonary infection due to Mycobacterium abscessus complex (MABC) usually occurs in children with underlying risk factors including cystic fibrosis (CF), chronic lung disease, and immunocompromised status, but rarely in immunocompetent children without underlying lung disease, especially in infants. We present a case of MABC pulmonary disease (MABC-PD) in an otherwise healthy 53-day-old male infant with one week of cough and respiratory distress. Computed tomography showed multiple masses across both lungs. Isolated mycobacteria from his bronchoalveolar lavage fluid were identified as MABC. We describe our complete evaluation, including immunodeficiency evaluation incorporating whole exome sequencing and our therapeutic process given complicated susceptibility pattern of the M. abscessus isolate, and review literature for MABC-PD in immunocompetent children. The infant was successfully treated through prolonged treatment with parenteral Amikacin, Cefoxitin, Linezolid, and Clarithromycin, combined with inhaled Amikacin.

Lipoarabinomannan modification as a source of phenotypic heterogeneity in host-adapted Mycobacterium abscessus isolates.

Mycobacterium abscessus is increasingly recognized as the causative agent of chronic pulmonary infections in humans. One of the genes found to be under strong evolutionary pressure during adaptation of M. abscessus to the human lung is embC which encodes an arabinosyltransferase required for the biosynthesis of the cell envelope lipoglycan, lipoarabinomannan (LAM). To assess the impact of patient-derived embC mutations on the physiology and virulence of M. abscessus, mutations were introduced in the isogenic background of M. abscessus ATCC 19977 and the resulting strains probed for phenotypic changes in a variety of in vitro and host cell-based assays relevant to infection. We show that patient-derived mutational variations in EmbC result in an unexpectedly large number of changes in the physiology of M. abscessus, and its interactions with innate immune cells. Not only did the mutants produce previously unknown forms of LAM with a truncated arabinan domain and 3-linked oligomannoside chains, they also displayed significantly altered cording, sliding motility, and biofilm-forming capacities. The mutants further differed from wild-type M. abscessus in their ability to replicate and induce inflammatory responses in human monocyte-derived macrophages and epithelial cells. The fact that different embC mutations were associated with distinct physiologic and pathogenic outcomes indicates that structural alterations in LAM caused by nonsynonymous nucleotide polymorphisms in embC may be a rapid, one-step, way for M. abscessus to generate broad-spectrum diversity beneficial to survival within the heterogeneous and constantly evolving environment of the infected human airway.

Formation of Mycobacterium abscessus colonies in cellular culture in an in vitro infection model.

Mycobacterium abscessus is one of the most important nontuberculous mycobacteria that cause lung diseases. In vitro infection models developed to analyze the immune response are frequently based on the addition of mycobacteria to mononuclear cells or neutrophils from peripheral blood. An important requirement of these assays is that most cells phagocytose mycobacteria, only accomplished by using large multiplicities of infection (1 or more bacteria per cell) which may not adequately reflect the inhalation of a few mycobacteria by the host. We propose modifications that try to mimic some of the conditions in which immune cells deal with mycobacteria. For the preparation of the inoculum mycobacteria are grown in solid media followed by preparation to a single cell suspension. Multiplicities of infection (number of bacteria per cell) are below 0.01. Serum-free cellular media is used to allow the growth of M. abscessus. After several days of incubation Bacterial Colonies in Cellular Culture (BCCC) develop, which are enumerated directly under an inverted microscope. These colonies may represent biofilm formation during chronic infections. •Low multiplicity of infection (below 0.01 bacteria per cell) reflects more realistically conditions encountered by immune cells in the lungs.•The surface of mycobacteria prepared for infection assays that are grown in solid media are less affected than that of mycobacteria grown in liquid media with detergents.•Colony formation in the infected cells may reflect the aggregation and biofilm formation in the lungs during chronic infection.

An early and trustable indicator suggestive of non-tuberculosis mycobacteria isolation in a high tuberculosis burden setting.

BACKGROUND: Distinguishing between nontuberculous mycobacterial (NTM) lung infections and pulmonary tuberculosis becomes challenging due to their similar clinical manifestations and radiological images. Consequently, instances of delayed diagnosis or misdiagnosis are highly frequent. A feasible and reliable indicator of the existence of NTM in the early stages of the disease would help to solve this dilemma. METHODS: In this study, we evaluated the potential of smear-positive and Xpert assay (Cepheid, USA) negative outcomes as an early indicator of possible NTM infection in a high TB-burden setting retrospectively and prospectively. RESULTS: During the study period, 12·77% (138/1081) of the smear-positive cases yielded negative outcomes with the simultaneous Xpert assay. From the 110 patients who yielded smear-positive/Xpert-negative outcomes and cultivated strain as well, 105 (95·45%) were proved to have NTM isolated. By incorporating an additional criterion of a negative result from the Interferon-gamma release assay, the accuracy of the screening method reached 100%. Regarding the NTM presence prediction value, smear-positive/Xpert-negative has a sensitivity of 24·86% (45/181) in all NTM isolated cases but 93·75-96·55% accuracy in retrospective study or 93·75% accuracy in prospective study in smear-positive NTM isolated cases. In addition, the specificity was ∼99·47% (943/948) in smear-positive tuberculosis cases. CONCLUSION: The clue of the presence of NTM could be obtained on the first day of the hospital visit due to the point of care (POC) feature of smear testing and Xpert assay. About one-fourth of the NTM-isolated patients would benefit from this rapid, convenient, and reliable screening strategy in the given circumstance. Smear-positive/Xpert-negative outcome is an early, trustable indicator that is indicative of NTM isolation.

Improvement in Health-Related Quality of Life Following Antibiotic Treatment in Nontuberculous Mycobacterial Pulmonary Disease: Initial Analysis of the NTM-KOREA Cohort.

BACKGROUND: Improving health-related quality of life (HRQOL) has emerged as a priority in the management of nontuberculous mycobacterial pulmonary disease (NTM-PD). We aimed to evaluate HRQOL and its changes after 6 months' treatment in patients with NTM-PD. METHODS: The NTM-KOREA is a nationwide prospective cohort enrolling patients initiating treatment for NTM-PD in 8 institutions across South Korea. We conducted the Quality of Life-Bronchiectasis (QOL-B) at 6-month intervals and evaluated baseline scores (higher scores indicate better quality of life) and changes after 6 months' treatment. Multivariate logistic regression was performed to identify factors associated with improvement in the QOL-B physical functioning and respiratory symptoms domains. RESULTS: Between February 2022 and August 2023, 411 patients were included in the analysis. Baseline scores (95% confidence interval [CI]) for physical functioning and respiratory symptoms were 66.7 (46.7-86.7) and 81.5 (70.4-92.6), respectively. Among 228 patients who completed the QOL-B after 6 months' treatment, improvements in physical functioning and respiratory symptoms were observed in 61 (26.8%) and 71 (31.1%) patients, respectively. A lower score (adjusted odds ratio; 95% CI) for physical functioning (0.93; 0.91-0.96) and respiratory symptoms (0.92; 0.89-0.95) at treatment initiation was associated with a greater likelihood of physical functioning and respiratory symptom improvement, respectively; achieving culture conversion was not associated with improvement in physical functioning (0.62; 0.28-1.39) or respiratory symptoms (1.30; 0.62-2.74). CONCLUSIONS: After 6 months of antibiotic treatment for NTM-PD, HRQOL improved in almost one-third, especially in patients with severe initial symptoms, regardless of culture conversion. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT03934034.

Non-pharmacological Treatment for Nontuberculous Mycobacterial Pulmonary Disease.

Nontuberculous mycobacterial pulmonary disease (NTM-PD) arises from the exposure of susceptible hosts to a diverse group of environmental mycobacteria. The emphasis on non-pharmacological strategies is motivated by widespread presence of nontuberculous mycobacteria (NTM) in various environments and the inconsistent success rates of pharmacological treatments. Modifiable factors contributing to NTM-PD development include impaired airway clearance, low body mass index, gastroesophageal reflux disease, and exposure to NTM habitats. This suggests that lifestyle and environmental modifications could affect disease development and progression. The review highlights several modalities that can modify the risk factors. Airway clearance techniques, informed by the "gel-on-brush" model of the bronchial epithelium, aims at enhancing mucociliary clearance and have potential in alleviating symptoms and potentially improving lung function. The impact of nutritional status is also examined, with a lower body mass index linked to an increased risk and progression of NTM-PD, indicating the importance of targeted nutritional support. Additionally, the theoretical and epidemiological links between gastroesophageal reflux disease and NTM-PD advocates for careful management of reflux episodes. Understanding the risk of NTM transmission through environmental exposure to contaminated water and soil is also crucial. Strategies to mitigate this risk, including effective water management and minimizing soil contact, are presented as vital preventive measures. In conclusion, the review supports the inclusion of non-pharmacological treatments within a comprehensive NTM-PD management strategy, alongside conventional pharmacological therapies. This integrated approach seeks to improve the overall understanding and handling of NTM-PD.

Prominent transcriptomic changes in Mycobacterium intracellulare under acidic and oxidative stress.

BACKGROUND: Mycobacterium avium complex (MAC), including Mycobacterium intracellulare is a member of slow-growing mycobacteria and contributes to a substantial proportion of nontuberculous mycobacterial lung disease in humans affecting immunocompromised and elderly populations. Adaptation of pathogens in hostile environments is crucial in establishing infection and persistence within the host. However, the sophisticated cellular and molecular mechanisms of stress response in M. intracellulare still need to be fully explored. We aimed to elucidate the transcriptional response of M. intracellulare under acidic and oxidative stress conditions. RESULTS: At the transcriptome level, 80 genes were shown [FC] ≥ 2.0 and p < 0.05 under oxidative stress with 10 mM hydrogen peroxide. Specifically, 77 genes were upregulated, while 3 genes were downregulated. In functional analysis, oxidative stress conditions activate DNA replication, nucleotide excision repair, mismatch repair, homologous recombination, and tuberculosis pathways. Additionally, our results demonstrate that DNA replication and repair system genes, such as dnaB, dinG, urvB, uvrD2, and recA, are indispensable for resistance to oxidative stress. On the contrary, 878 genes were shown [FC] ≥ 2.0 and p < 0.05 under acidic stress with pH 4.5. Among these genes, 339 were upregulated, while 539 were downregulated. Functional analysis highlighted nitrogen and sulfur metabolism pathways as the primary responses to acidic stress. Our findings provide evidence of the critical role played by nitrogen and sulfur metabolism genes in the response to acidic stress, including narGHIJ, nirBD, narU, narK3, cysND, cysC, cysH, ferredoxin 1 and 2, and formate dehydrogenase. CONCLUSION: Our results suggest the activation of several pathways potentially critical for the survival of M. intracellulare under a hostile microenvironment within the host. This study indicates the importance of stress responses in M. intracellulare infection and identifies promising therapeutic targets.

In vitro activity of gepotidacin and comparator antimicrobials against isolates of nontuberculous mycobacteria (NTM).

Novel antimicrobials are needed to treat rising nontuberculous mycobacteria (NTM) infections. Using standard broth microdilution methods, 68 NTM isolates were tested against gepotidacin, a new, first-in-class, oral triazaacenaphthylene bacterial topoisomerase inhibitor. MICs varied (0.25 to >64 µg/mL) with the lowest being M. fortuitum complex (0.25-8 µg/mL), M. mucogenicum complex (1-2 µg/mL), M. kansasii (0.25-8 µg/mL), and M. marinum (4-16 µg/mL). Testing greater numbers of some species is suggested to better understand gepotidacin activity against NTM.

Epidemiological Characteristics of Nontuberculous Mycobacterial Pulmonary Disease in South Korea: A Meta-Analysis of Individual Participant Data.

Rationale: Despite the global increase in nontuberculous mycobacterial pulmonary disease (NTM-PD), there are geographical variations in clinical characteristics. We investigated the clinical characteristics of patients with NTM-PD in South Korea. Methods: We systematically reviewed articles about patients with NTM-PD in South Korea until February 2022. Individual participant data, regardless of treatment, were collected using a standard case report form. Results: The data of 6,489 patients from 11 hospitals between 2002 and 2019 were analyzed. The mean age was 61.5 ± 11.7 years, and 57.7% were women. Mycobacterium avium (41.4%) and Mycobacterium intracellulare (38.4%) comprised most of the causative species, followed by Mycobacterium abscessus subspecies abscessus (8.6%) and Mycobacterium abscessus subspecies massiliense (7.8%). Bronchiectasis (59.4%) was the most common pulmonary comorbidity. Reported cases of NTM-PD increased over the years, but the proportions of causative species and radiologic forms remained similar. Distinct clinical characteristics were observed according to age and sex. Men were older at the time of diagnosis (median 63.8 vs. 59.9 years, P<0.001) and had more cavitary lesions than women (38.8% vs. 21.0%, P<0.001). The older group (≥65 years) had a higher proportion of patients with body mass index <18.5 kg/m2 (27.4% vs. 18.6%, P<0.001) and cavitary lesions (29.9% vs. 27.6%, P=0.009) than the younger group. Conclusion: We performed a meta-analysis of the clinical characteristics of patients with NTM-PD in South Korea. We found age- and sex-related differences in disease-specific severity. Further investigation would enhance our comprehension of the disease's nature and inherited and acquired host factors.

Mycobacterium porcinum Disseminated Infection in Non-severely Immunocompromised Host.

Mycobacterium porcinum is a nontuberculous mycobacteria (NTM) recently identified to cause human infection. Correct speciation of NTMs can be difficult and result in misdiagnosis and delayed treatment. Because of the paucity of the literature, there is a lack of awareness of the possibility of serious infections caused by M. porcinum. Although severe infections tend to occur in individuals with certain risk factors, the primary being an immunocompromised state, our case illustrates that it can also be possible in non-severely immunocompromised individuals. A 65-year-old male with a medical history of diabetes mellitus (DM), end-stage renal disease (ESRD) on hemodialysis (HD), congestive heart failure (CHF), and chronic obstructive pulmonary disease (COPD) was admitted to the emergency room due to a laceration on his right lower leg following a fall. He reported shortness of breath but denied other respiratory symptoms. On examination, he showed signs of infection and increased oxygen requirement compared to baseline. Blood culture was positive for acid-fast bacilli (AFB), initially reported as M. avium complex (MAC) and later confirmed as M. porcinum through gene sequencing and morphology analysis. Interval blood cultures taken a week later confirmed true M. porcinum bacteremia. Treatment initially involved intravenous antibiotics- imipenem and ciprofloxacin before transitioning to oral linezolid and ciprofloxacin based on sensitivities. Following 10 days of antibiotic therapy, subsequent blood cultures returned negative, and treatment with oral antibiotics was advised, with continued outpatient follow-up with infectious disease in two weeks. M. porcinum, typically considered a contaminant in healthy individuals, was identified as the causative agent of a disseminated infection in a non-severely immunocompromised patient. This case underscores the importance of accurately identifying the specific mycobacterial species, confirming true infection, and conducting antibiotic susceptibility testing due to the distinct antibiotic susceptibility profile of M. porcinum compared to other NTM like MAC.

Metagenomic next-generation sequencing assistance in identifying Mycobacterium avium meningoencephalitis: A case report and literature review.

Nontuberculous mycobacteria associated intracranial infection is a rare disease that mainly occurs in HIV-infected patients. The disease has a poor prognosis. The authors report a case of non-tuberculous mycobacterial meningoencephalitis in a non-AIDS patient, but long history of poorly controlled type 2 diabetes mellitus. A 55-year-old, right-handed, male patient presented with an 8-day history of fever, episodes of severe headache with signs of meningeal irritation. MRI showed hyperintensities/contrast enhancement in the visual pathways, basal ganglia sellar region and leptomeninges. No etiological diagnosis was reached until metagenomic next-generation sequencing (mNGS) was used, showing the presence of Mycobacterium avium. The patient was cured with aggressive antimycobacterial therapy. The authors discuss the clinical manifestations and drug therapy of nontuberculous mycobacteria-related intracranial infections by reviewing relevant literature. As meningoencephalitis by Mycobacterium avium has a high mortality an early diagnosis and appropriate therapeutic interventions are warranted. For this reason, the use of mNGS can be helpful to avoid therapeutic delay.

Biofilm prevention concentration of clarithromycin against clinically relevant species of nontuberculous mycobacteria.

OBJECTIVE: Mycobacterium avium complex (MAC) and Mycobacterium abscessus are a group of nontuberculous mycobacteria (NTM) that have been described as human pathogens. Their ability to develop biofilms in tissues and medical devices is one of the most important pathogenicity factors, with important implications in diagnosis and treatment. Macrolides are usually considered one of the bases of this treatment. METHODS: Here we have studied the biofilm prevention concentration (BPC) of 16 strains (n=16) with clarithromycin to avoid the biofilm development by these NTM. RESULTS: In this study, all M. abscessus strains have similar BPC, while MAC strains showed different values. For MAC the concentrations ranged between 1-16 mg/L, while for M. abscessus the concentration was 32 mg/L for all strains except one that was 64 mg/L. CONCLUSIONS: These results open the possibility of using macrolides for the prevention of biofilm development in patients with a risk of developing NTM disease.

Retrospective and prospective evaluation of the FluoroType®-Mycobacteria VER 1.0 assay for the identification of mycobacteria from cultures in a French center.

PURPOSE: Rapid, reliable identification of mycobacteria from positive cultures is essential for patient management, particularly for the differential diagnosis of Mycobacterium tuberculosis complex (MTBC) and nontuberculous mycobacteria (NTM) species. The aim of the present study was to evaluate a new "In-Vitro-Diagnostic"-certified PCR kit, FluoroType®-Mycobacteria VER 1.0 (Hain Lifescience GmbH) for NTM and MTBC identification from cultures. METHODS: Mycobacteria identification isolated from positive cultures during routine practice at the Lyon university hospital mycobacteria laboratory obtained by hsp65 amplification/sequencing were compared retrospectively and prospectively to those obtained by and the FluoroType®-Mycobacteria VER 1.0 kit. RESULTS: The overall agreement between hsp65 amplification/sequencing and the FluoroType®-Mycobacteria VER 1.0 kit was 88.4% (84/95); 91.2% (52/57) for the retrospective period and 84.2% (32/38) for the prospective period. There were 9 (9.5%) minor discrepancies (species in the FluoroType®-Mycobacteria VER 1.0 database and identified at genus level): 4 during the retrospective period, 5 during the prospective period; and 2 (2.1%) major discrepancies (species in the FluoroType®-Mycobacteria VER 1.0 database and identified incorrectly to species level): 1 during the retrospective period (M. kumamotonense identified as M. abscessus subsp massiliense by the kit) and 1 during the prospective period (M. chimaera identified as M. smegmatis by the kit). Including concordant results at genus level and minor discrepancies, 17.9% (17/95) of strains were identified as Mycobacterium sp. by the FluoroType®-Mycobacteria-VER 1.0 kit. CONCLUSION: The good performance of the FluoroType®-Mycobacteria-VER 1.0 kit with few major discrepancies could enable its use for first-line identification of positive mycobacteria cultures. However, an alternative identification method at least for reference laboratories is needed owing to the non-negligible proportion of NTM strains were identified at genus level.

Beyond Symptoms: Radiologic identification of asymptomatic Mycobacterium avium complex pulmonary infections.

BACKGROUND: Although international nontuberculous mycobacterial pulmonary disease (NTM-PD) guidelines highlight symptom presence at diagnosis, the clinical characteristics of asymptomatic Mycobacterium avium complex pulmonary infection (MAC-PI) patients remain understudied. We clarified the clinical characteristics and course of asymptomatic MAC-PI patients. METHODS: We retrospectively analyzed 200 consecutive patients with MAC-PIs and adequate available data who newly met the microbiological and radiological criteria for NTM-PD at Fukujuji Hospital from January 2018 to June 2020. We compared the clinical characteristics and course of asymptomatic patients with symptomatic patients and evaluated factors influencing treatment initiation through multivariate analysis. RESULTS: 111 patients were symptomatic and 89 were asymptomatic at diagnosis. While the proportion was significantly lower than that in the symptomatic group (28.8 %), 15.7 % of asymptomatic group patients had cavitary lesions (P = 0.042). In the asymptomatic group, treatments were initiated in 38 (42.7 %) patients, and cavitary lesions, a positive acid-fast bacilli smear, and younger age were independent risk factors for treatment initiation. Among 22 (57.9 %) patients who experienced disease progression necessitating treatment during follow-up, 13 (34.2 %) displayed radiological progression without any worsening of symptoms. Agents used for treatment were consistent across the groups, with no significant differences in culture conversion, microbiological recurrence rates, or spontaneous culture conversion rates. CONCLUSION: Routine health checkups and radiological examinations can detect clinically important MAC-PIs even in the absence of symptoms. Considering that the clinical course of asymptomatic MAC-PI patients is largely similar to that of symptomatic patients, timely and appropriate management and intervention are essential for all MAC-PI patients.

Medical Tourism in Plastic Surgery: A Case Series of Complications.

Background: Medical tourism in plastic surgery has grown exponentially over the last decade. The rise in the number of cases is multifactorial but is mostly driven by reduced cost. While this may seem attractive to patients, it is not without risk. Even under the best circumstances, complications can arise, and patients may be put at increased risk of atypical infections due to different sterilization standards. Lack of customary follow-up and accessibility can lead to delays in diagnosing infections and cause patients to seek care locally. We present our experience in managing atypical infections resulting from cosmetic surgery tourism in a tertiary care system. Methods: We report a case series of 3 patients who underwent cosmetic procedures abroad who presented to our institutions with postoperative complications and infections. Results: Our cohort consist of 3 female patients ranging from 26 to 48 years of age who had cosmetic surgery abroad. All 3 presented with nontuberculous mycobacteria (NTM) infections. Conclusions: Cosmetic surgery tourism is luring patients with advertised all-inclusive surgery and vacation packages at reduced cost. This attracts vulnerable patients and puts them at risk of devastating long-term physical and financial sequalae. NTM infections should be considered early in this population, especially when they are not responding to other therapies. More widespread information about the consequences of traveling for medical procedures is needed to help inform and empower patients to make educated decisions when choosing where to seek care.

Gene knock-out in Mycobacterium abscessus using Streptococcus thermophilus CRISPR/Cas.

The CRISPRi system using dCas9Sth1 from Streptococcus thermophilus developed for Mycobacterium tuberculosis and M. smegmatis was modified to allow gene knock-out in M. abscessus. Efficacy of the knock-out system was evaluated by applying deletions and insertions to the mps1 gene. A comparative genomic analysis of mutants and wild type validated the target specificity.

Rates and Risk Factors of Progression in Patients With Nontuberculous Mycobacterial Pulmonary Disease: Secondary Analysis of a Prospective Cohort Study.

BACKGROUND: The clinical course of nontuberculous mycobacterial pulmonary disease (NTM-PD) is varied, and a watchful waiting management strategy is appropriate for a subset of patients. Understanding disease progression and risk factors for progression is essential for deciding on an appropriate follow-up strategy. RESEARCH QUESTION: What is the rate of NTM-PD progression, and what are the predictors of progression? STUDY DESIGN AND METHODS: Patients with NTM-PD who were enrolled in a prospective observational cohort study between July 1, 2011, and December 31, 2022, were included in this analysis. Clinical, bacterial, laboratory, and radiographic data were collected at enrollment and then regularly during follow-up. NTM-PD progression was defined as either the initiation of treatment or the clinician's intention to treat. The rate of progression was calculated and the predictors for progression were analyzed. RESULTS: Of the 477 patients enrolled, NTM-PD progressed in 192 patients over a median follow-up of 5.4 years. The incidence of NTM-PD progression was 11.0 cases per 100 person-years (95% CI, 9.5-12.7 cases per 100 person-years). The proportion of patients experiencing disease progression was 21.4% at 1 year, 33.8% at 3 years, and 43.3% at 5 years. The final multivariable analysis model identified female sex (adjusted hazard ratio [aHR], 1.69; 95% CI, 1.19-2.39), elevated erythrocyte sedimentation rate (aHR, 1.79; 95% CI, 1.31-2.43), FEV1 % predicted (aHR, 0.89; 95% CI, 0.82-0.96), and the presence of a cavity (aHR, 2.78; 95% CI, 2.03-3.80) as predictors of progression. INTERPRETATION: About half of patients with NTM-PD experienced progression during an observation period of > 5 years. Patients with risk factors for progression should be observed closely. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01616745; URL: www. CLINICALTRIALS: gov.

Shower dehumidification to reduce nontuberculous mycobacteria aerosolization.

OBJECTIVE: Nontuberculous mycobacteria (NTM) are environmentally acquired opportunistic pathogens that can cause recalcitrant lung disease. Prior reports have demonstrated links between shower use and infections, yet the aerosolization of NTM from showerheads, as well as the humidity levels that may modulate NTM aerosolization from showerheads is less studied. The objective of the current study was to investigate the role of humidity in NTM aerosolization among showers in homes located in a geographic area with high lung disease incidence, Hawai'i, and test whether deployment of a dehumidifier in well-ventilated bathrooms reduce NTM exposure. RESULTS: Across two sampling events and five showers, existing NTM showerhead biofilms along with shower air were sampled at three points: pre-shower, post-shower, and post-dehumidification. In each of the sampling events, respiratory relevant NTM species were identified from shower biofilms, which were also detected in aerosolized shower air after showering events, but not after the shower was dehumidified and bathrooms vented. While sample size was small, these data suggest running a shower is a possible source of NTM aerosolization and using a commercial household dehumidifier in conjunction with opening bathroom doors and windows may be simple, cost-effective interventions to reduce environmental NTM exposures.

Nontuberculous mycobacteria testing and culture positivity in the United States.

BACKGROUND: Nontuberculous mycobacteria (NTM) are environmental bacteria which may cause chronic lung disease. The prevalence of NTM pulmonary infection and disease has been increasing in the United States and globally. The predominant clinically relevant species of NTM in the United States are Mycobacterium avium complex (MAC) species and Mycobacterium abscessus. With the development of rapid species identification methods for NTM (e.g. PCR probes), more testing for NTM is being conducted through commercial labs, such as Laboratory Corporation of America (Labcorp), which provides deidentified real-time testing data to the Centers for Disease Control (CDC) pursuant to a data sharing agreement. Because NTM lung infections are not reportable in most states, other data sources are key to understanding NTM testing patterns, positivity rates, and species distributions to track infection trends and identify clinical care needs. METHODS: We obtained national Labcorp data for the period January 2019 through mid-April 2022. We subset the data to only respiratory samples sent for Acid Fast Bacilli (AFB) cultures. NTM positive results were defined as those which identified an NTM species and are not Mycobacterium tuberculosis, Mycobacterium bovis, or Mycobacterium gordonae. RESULTS: Overall, 112,528 respiratory samples were sent for AFB testing during the study period; 26.3% were from the Southeast U.S., identified as HSS Region IV in the Labcorp dataset, and 23.0% were from the Pacific and South Pacific region (Region IX). The culture positive prevalence ranged from 20.2% in the Southeast to 9.2% in the East North Central region (Region V). In the Southeast US, M. abscessus prevalence was 4.0%. For MAC, the highest prevalence was observed in the Mountain region (Region VII) (13.5%) and the lowest proportion was in the East South Central region (7.3%, Region III). Among positive tests, the proportion which was MAC varied from 61.8% to 88.9% and was highest in the Northeast U.S. The proportion of positive samples which were M. abscessus ranged from 3.8% to 19.7% and was highest in the Southeast. CONCLUSIONS: The Southeastern region of the U.S. has the highest rate of culture positivity in Labcorp tests for total NTM and, of all positive tests, the highest proportion of M. abscessus. These estimates may underrepresent the true number of M. abscessus infections because M. absesscus-specific probes are not commercially available and not all NTM testing in the United States is done by Labcorp. Analysis of real-time testing data from commercial laboratories may provide insights into risk factors for NTM culture positivity in 'hotspot' areas.