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.

Early IL-17A production helps establish Mycobacterium intracellulare infection in mice.

Nontuberculous mycobacteria (NTM) infection is common in patients with structural lung damage. To address how NTM infection is established and causes lung damage, we established an NTM mouse model by intranasal inoculation of clinical isolates of M. intracellulare. During the 39-week course of infection, the bacteria persistently grew in the lung and caused progressive granulomatous and fibrotic lung damage with mortality exceeding 50%. Lung neutrophils were significantly increased at 1 week postinfection, reduced at 2 weeks postinfection and increased again at 39 weeks postinfection. IL-17A was increased in the lungs at 1-2 weeks of infection and reduced at 3 weeks postinfection. Depletion of neutrophils during early (0-2 weeks) and late (32-34 weeks) infection had no effect on mortality or lung damage in chronically infected mice. However, neutralization of IL-17A during early infection significantly reduced bacterial burden, fibrotic lung damage, and mortality in chronically infected mice. Since it is known that IL-17A regulates matrix metalloproteinases (MMPs) and that MMPs contribute to the pathogenesis of pulmonary fibrosis, we determined the levels of MMPs in the lungs of M. intracellulare-infected mice. Interestingly, MMP-3 was significantly reduced by anti-IL-17A neutralizing antibody. Moreover, in vitro data showed that exogenous IL-17A exaggerated the production of MMP-3 by lung epithelial cells upon M. intracellulare infection. Collectively, our findings suggest that early IL-17A production precedes and promotes organized pulmonary M. intracellulare infection in mice, at least in part through MMP-3 production.

Genetic relationships between behavioral traits and feed efficiency traits in lactating Holstein cows.

The evaluation of dairy cow feed efficiency using residual feed intake accounts for known energy sinks. However, behavioral traits may also contribute to the variation in feed efficiency. Our objective was to estimate the heritability and repeatability of behavioral traits and their genetic correlations with feed efficiency and its components in lactating Holstein cows. The first data set consisted of 36,075 daily rumination and lying time records collected using a SMARTBOW ear tag accelerometer (Zoetis, Parsippany, NJ) and 6,371 weekly feed efficiency records of 728 cows from the University of Wisconsin-Madison. The second data set consisted of 59,155 daily activity records, measured as number of steps, recorded by pedometers (AfiAct; S.A.E. Afikim, Kibbutz Afikim, Israel), and 8,626 weekly feed efficiency records of 635 cows from the University of Florida. Feed efficiency and its components included dry matter intake, change in body weight, metabolic body weight, secreted milk energy, and residual feed intake. The statistical models included the fixed effect of cohort, lactation number, and days in milk, and the random effects of animal and permanent environment. Heritability estimates for behavioral traits using daily records were 0.19 ± 0.06 for rumination and activity, and 0.37 ± 0.07 for lying time. Repeatability estimates for behavioral traits using daily data ranged from 0.56 ± 0.02 for activity to 0.62 ± 0.01 for lying time. Both heritability and repeatability estimates were larger when weekly records instead of daily records were used. Rumination and activity had positive genetic correlations with residual feed intake (0.40 ± 0.19 and 0.31 ± 0.22, respectively) while lying time had a negative genetic correlation with this residual feed intake (-0.27 ± 0.11). These results indicate that more efficient cows tend to spend more time lying and less time active. Additionally, less efficient cows tend to eat more and therefore also tend to ruminate longer. Overall, sensor-based behavioral traits are heritable and genetically correlated with feed efficiency and its components and, therefore, they could be used as indicators to identify feed efficient cows within the herd.

Geographic Barriers to Indexing: Examining Appalachia.

The objective of this study was to examine the accuracy of indexing for "Appalachian Region"[Mesh]. Researchers performed a search in PubMed for articles published in 2019 using "Appalachian Region"[Mesh] or "Appalachia" or "Appalachian" in the title or abstract. Only 17.88% of the articles retrieved by the search were about Appalachia according to the ARC definition. Most articles retrieved appeared because they were indexed with state terms that were included as part of the mesh term. Database indexing and searching transparency is of growing importance as indexers rely increasingly on automated systems to catalog information and publications.

Epidemiology, management, and clinical outcomes of extrapulmonary Mycobacterium abscessus complex infections in heart transplant and ventricular assist device recipients.

Nontuberculous mycobacteria are emerging pathogens, yet data on the epidemiology and management of extrapulmonary nontuberculous mycobacteria infections in orthotopic heart transplantation (OHT) and ventricular assist device (VAD) recipients are scarce. We retrospectively reviewed records of OHT and VAD recipients who underwent cardiac surgery at our hospital and developed Mycobacterium abscessus complex (MABC) infection from 2013 to 2016 during a hospital outbreak of MABC linked to heater-cooler units. We analyzed patient characteristics, medical and surgical management, and long-term outcomes. Ten OHT patients and 7 patients with VAD developed extrapulmonary M. abscessus subspecies abscessus infection. The median time from presumed inoculation during cardiac surgery to the first positive culture was 106 days in OHT and 29 days in VAD recipients. The most common sites of positive cultures were blood (n = 12), sternum/mediastinum (n = 8), and the VAD driveline exit site (n = 7). The 14 patients diagnosed when alive received combination antimicrobial therapy for a median of 21 weeks, developed 28 antibiotic-related adverse events, and underwent 27 surgeries. Only 8 (47%) patients survived longer than 12 weeks after diagnosis, including 2 patients with VAD who experienced long-term survival after an explantation of infected VADs and OHT. Despite aggressive medical and surgical management, OHT and VAD patients with MABC infection experienced substantial morbidity and mortality.

Emergence of Inducible Macrolide Resistance in Mycobacterium chelonae Due to Broad-Host-Range Plasmid and Chromosomal Variants of the Novel 23S rRNA Methylase Gene, erm(55).

Macrolides are a mainstay of therapy for infections due to nontuberculous mycobacteria (NTM). Among rapidly growing mycobacteria (RGM), inducible macrolide resistance is associated with four chromosomal 23S rRNA methylase (erm) genes. Beginning in 2018, we detected high-level inducible clarithromycin resistance (MICs of ≥16µg/mL) in clinical isolates of Mycobacterium chelonae, an RGM species not previously known to contain erm genes. Using whole-genome sequencing, we identified a novel plasmid-mediated erm gene. This gene, designated erm(55)P, exhibits <65% amino acid identity to previously described RGM erm genes. Two additional chromosomal erm(55) alleles, with sequence identities of 81% to 86% to erm(55)P, were also identified and designated erm(55)C and erm(55)T. The erm(55)T is part of a transposon. The erm(55)P allele variant is located on a putative 137-kb conjugative plasmid, pMchErm55. Evaluation of 133 consecutive isolates from 2020 to 2022 revealed 5 (3.8%) with erm(55). The erm(55)P gene was also identified in public data sets of two emerging pathogenic pigmented RGM species: Mycobacterium iranicum and Mycobacterium obuense, dating back to 2008. In both species, the gene appeared to be present on plasmids homologous to pMchErm55. Plasmid-mediated macrolide resistance, not described previously for any NTM species, appears to have spread to multiple RGM species. This has important implications for antimicrobial susceptibility guidelines and treatment of RGM infections. Further spread could present serious consequences for treatment of other macrolide-susceptible RGM. Additional studies are needed to determine the transmissibility of pMchErm55 and the distribution of erm(55) among other RGM species.

In Vitro Susceptibility Testing of Eravacycline against Nontuberculous Mycobacteria.

Nontuberculous mycobacteria (NTM) infections are increasing worldwide. Mycobacterium avium complex (MAC) and the M. abscessus species are the most commonly cultured NTM and treatment options are limited, especially for the M. abscessus species. In this study, the in vitro activity of eravacycline, a new tetracycline derivative, was tested against 110 clinical isolates of NTM. MIC testing was performed as recommended by the Clinical and Laboratory Standards Institute against 60 isolates of rapidly growing mycobacteria (RGM), of which ~70% were tetracycline resistant. These included M. abscessus subsp. abscessus (8 isolates), M. abscessus subsp. massiliense (5), M. chelonae (10), M. immunogenum (3), M. fortuitum group (20) including 12 doxycycline-resistant isolates, and M. mucogenicum group (10) including three doxycycline-resistant isolates. Due to trailing, eravacycline MICs were read at 80% and 100% inhibition. Eravacycline was active against all RGM species, with MIC50 ranges of ≤0.015 to 0.5 and ≤0.015 to 0.12 µg/mL for 100% and 80% inhibition, respectively. For M. abscessus subsp. abscessus, MIC50 values were 0.12 and 0.03 µg/mL with 100% and 80% inhibition, respectively. MICs for tigecycline were generally within 1 to 2 dilutions of the 100%-inhibition eravacycline MIC values. Fifty isolates of slowly growing mycobacteria (SGM) species, including 16 isolates of MAC, were also tested. While there was no trailing observed in most SGM, the eravacycline MICs were higher (MIC range of >8 µg/mL), except for M. kansasii and M. marinum which had MIC50 values of 1 µg/mL. This study supports further evaluation of eravacycline, including clinical trials for the development of RGM treatment regimens, especially for M. abscessus.

Genomic Analysis of a Hospital-Associated Outbreak of Mycobacterium abscessus: Implications on Transmission.

Whole-genome sequencing (WGS) has recently been used to investigate acquisition of Mycobacterium abscessus. Investigators have reached conflicting conclusions about the meaning of genetic distances for interpretation of person-to-person transmission. Existing genomic studies were limited by a lack of WGS from environmental M. abscessus isolates. In this study, we retrospectively analyzed the core and accessory genomes of 26 M. abscessus subsp. abscessus isolates collected over 7 years. Clinical isolates (n = 22) were obtained from a large hospital-associated outbreak of M. abscessus subsp. abscessus, the outbreak hospital before or after the outbreak, a neighboring hospital, and two outside laboratories. Environmental M. abscessus subsp. abscessus isolates (n = 4) were obtained from outbreak hospital water outlets. Phylogenomic analysis of study isolates revealed three clades with pairwise genetic distances ranging from 0 to 135 single-nucleotide polymorphisms (SNPs). Compared to a reference environmental outbreak isolate, all seven clinical outbreak isolates and the remaining three environmental isolates had highly similar core and accessory genomes, differing by up to 7 SNPs and a median of 1.6% accessory genes, respectively. Although genomic comparisons of 15 nonoutbreak clinical isolates revealed greater heterogeneity, five (33%) isolates had fewer than 20 SNPs compared to the reference environmental isolate, including two unrelated outside laboratory isolates with less than 4% accessory genome variation. Detailed genomic comparisons confirmed environmental acquisition of outbreak isolates of M. abscessus subsp. abscessus. SNP distances alone, however, did not clearly differentiate the mechanism of acquisition of outbreak versus nonoutbreak isolates. We conclude that successful investigation of M. abscessus subsp. abscessus clusters requires molecular and epidemiologic components, ideally complemented by environmental sampling.

Vestibular Rehabilitation for Peripheral Vestibular Hypofunction: An Updated Clinical Practice Guideline From the Academy of Neurologic Physical Therapy of the American Physical Therapy Association.

BACKGROUND: Uncompensated vestibular hypofunction can result in symptoms of dizziness, imbalance, and/or oscillopsia, gaze and gait instability, and impaired navigation and spatial orientation; thus, may negatively impact an individual's quality of life, ability to perform activities of daily living, drive, and work. It is estimated that one-third of adults in the United States have vestibular dysfunction and the incidence increases with age. There is strong evidence supporting vestibular physical therapy for reducing symptoms, improving gaze and postural stability, and improving function in individuals with vestibular hypofunction. The purpose of this revised clinical practice guideline is to improve quality of care and outcomes for individuals with acute, subacute, and chronic unilateral and bilateral vestibular hypofunction by providing evidence-based recommendations regarding appropriate exercises. METHODS: These guidelines are a revision of the 2016 guidelines and involved a systematic review of the literature published since 2015 through June 2020 across 6 databases. Article types included meta-analyses, systematic reviews, randomized controlled trials, cohort studies, case-control series, and case series for human subjects, published in English. Sixty-seven articles were identified as relevant to this clinical practice guideline and critically appraised for level of evidence. RESULTS: Based on strong evidence, clinicians should offer vestibular rehabilitation to adults with unilateral and bilateral vestibular hypofunction who present with impairments, activity limitations, and participation restrictions related to the vestibular deficit. Based on strong evidence and a preponderance of harm over benefit, clinicians should not include voluntary saccadic or smooth-pursuit eye movements in isolation (ie, without head movement) to promote gaze stability. Based on moderate to strong evidence, clinicians may offer specific exercise techniques to target identified activity limitations and participation restrictions, including virtual reality or augmented sensory feedback. Based on strong evidence and in consideration of patient preference, clinicians should offer supervised vestibular rehabilitation. Based on moderate to weak evidence, clinicians may prescribe weekly clinic visits plus a home exercise program of gaze stabilization exercises consisting of a minimum of: (1) 3 times per day for a total of at least 12 minutes daily for individuals with acute/subacute unilateral vestibular hypofunction; (2) 3 to 5 times per day for a total of at least 20 minutes daily for 4 to 6 weeks for individuals with chronic unilateral vestibular hypofunction; (3) 3 to 5 times per day for a total of 20 to 40 minutes daily for approximately 5 to 7 weeks for individuals with bilateral vestibular hypofunction. Based on moderate evidence, clinicians may prescribe static and dynamic balance exercises for a minimum of 20 minutes daily for at least 4 to 6 weeks for individuals with chronic unilateral vestibular hypofunction and, based on expert opinion, for a minimum of 6 to 9 weeks for individuals with bilateral vestibular hypofunction. Based on moderate evidence, clinicians may use achievement of primary goals, resolution of symptoms, normalized balance and vestibular function, or plateau in progress as reasons for stopping therapy. Based on moderate to strong evidence, clinicians may evaluate factors, including time from onset of symptoms, comorbidities, cognitive function, and use of medication that could modify rehabilitation outcomes. DISCUSSION: Recent evidence supports the original recommendations from the 2016 guidelines. There is strong evidence that vestibular physical therapy provides a clear and substantial benefit to individuals with unilateral and bilateral vestibular hypofunction. LIMITATIONS: The focus of the guideline was on peripheral vestibular hypofunction; thus, the recommendations of the guideline may not apply to individuals with central vestibular disorders. One criterion for study inclusion was that vestibular hypofunction was determined based on objective vestibular function tests. This guideline may not apply to individuals who report symptoms of dizziness, imbalance, and/or oscillopsia without a diagnosis of vestibular hypofunction. DISCLAIMER: These recommendations are intended as a guide to optimize rehabilitation outcomes for individuals undergoing vestibular physical therapy. The contents of this guideline were developed with support from the American Physical Therapy Association and the Academy of Neurologic Physical Therapy using a rigorous review process. The authors declared no conflict of interest and maintained editorial independence.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A369).

Invasive Mycobacterium abscessus Complex Infection After Cardiac Surgery: Epidemiology, Management, and Clinical Outcomes.

BACKGROUND: We recently mitigated a clonal outbreak of hospital-acquired Mycobacterium abscessus complex (MABC), which included a large cluster of adult patients who developed invasive infection after exposure to heater-cooler units during cardiac surgery. Recent studies have detailed Mycobacterium chimaera infections acquired during cardiac surgery; however, little is known about the epidemiology and clinical courses of cardiac surgery patients with invasive MABC infection. METHODS: We retrospectively collected clinical data on all patients who underwent cardiac surgery at our hospital and subsequently had positive cultures for MABC from 2013 through 2016. Patients with ventricular assist devices or heart transplants were excluded. We analyzed patient characteristics, antimicrobial therapy, surgical interventions, and clinical outcomes. RESULTS: Ten cardiac surgery patients developed invasive, extrapulmonary infection from M. abscessus subspecies abscessus in an outbreak setting. Median time from presumed inoculation in the operating room to first positive culture was 53 days (interquartile range [IQR], 38-139 days). Disseminated infection was common, and the most frequent culture-positive sites were mediastinum (n = 7) and blood (n = 7). Patients received a median of 24 weeks (IQR, 5-33 weeks) of combination antimicrobial therapy that included multiple intravenous agents. Six patients required antibiotic changes due to adverse events attributed to amikacin, linezolid, or tigecycline. Eight patients underwent surgical management, and 6 patients required multiple sternal debridements. Eight patients died within 2 years of diagnosis, including 4 deaths directly attributable to MABC infection. CONCLUSIONS: Despite aggressive medical and surgical management, invasive MABC infection after cardiac surgery caused substantial morbidity and mortality. New treatment strategies are needed, and compliance with infection prevention guidelines remains critical.

Management of Drug Toxicity in Mycobacterium avium Complex Pulmonary Disease: An Expert Panel Survey.

Adverse events are frequent in nontuberculous mycobacteria pulmonary disease treatment, but evidence to support their management is scarce. An expert panel survey on management of adverse events shows consistent opinions on management of hepatoxicity, ocular toxicity, ototoxicity, tinnitus, and gastrointestinal upset. These opinions can provide assistance in individual patient management decisions.

Comparison of In Vitro Susceptibility of Delafloxacin with Ciprofloxacin, Moxifloxacin, and Other Comparator Antimicrobials against Isolates of Nontuberculous Mycobacteria.

Nontuberculous mycobacterial (NTM) infections are increasing globally. Mycobacterium avium complex (MAC) and M. abscessus complex are the most commonly reported NTM. Oral treatment options are limited, especially for the M. abscessus complex. We tested delafloxacin, a new oral fluoroquinolone, against 131 isolates of NTM. Delafloxacin microdilution MICs were performed as recommended by the Clinical and Laboratory Standards Institute using cation adjusted Mueller-Hinton broth. The rapidly growing mycobacteria tested included M. abscessus subsp. abscessus (n = 16) and subsp. massiliense (n = 5), M. chelonae (n = 11), M. immunogenum (n = 5), M. fortuitum group (n = 13), M. porcinum (n = 7), M. senegalense (n = 7), M. mucogenicum group (n = 5), and M. goodii (n = 1). For the slowly growing NTM (SGM), M. avium (n = 16), M. intracellulare (n = 13), M. chimaera (n = 9), M. arupense (n = 5), M. simiae (n = 5), M. lentiflavum (n = 4), M. kansasii (n = 6), and M. marinum (n = 3) were tested. Delafloxacin was most active in vitro against the M. fortuitum and M. mucogenicum groups and M. kansasii, with MIC50 values of 0.12 to 0.5 µg/ml (MIC range, 0.001 to 4 µg/ml) compared to ≤0.06 to >4 µg/ml for ciprofloxacin and ≤0.06 to >8 µg/ml for moxifloxacin. For other SGM (including MAC), and the M. abscessus/M. chelonae, the delafloxacin MIC range was 8 to >16 µg/ml compared to ciprofloxacin and moxifloxacin of 0.5 to >4 µg/ml and ≤0.06 to 8 µg/ml, respectively. To our knowledge, this is the first MIC study with delafloxacin to use Clinical and Laboratory Standards Institute (CLSI) recommended methods. This study illustrates the potential utility of delafloxacin in treatment of infections due to some NTM.

In Vitro Susceptibility Testing of Omadacycline against Nontuberculous Mycobacteria.

Infections caused by nontuberculous mycobacteria (NTM) are increasing globally. Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex are the most frequently encountered NTM, and oral treatment options are extremely limited for these pathogens, especially for the M. abscessus complex. In this study, the in vitro potency of omadacycline, a new tetracycline derivative, was tested against 111 isolates of NTM. MIC testing was performed as recommended by the Clinical and Laboratory Standards Institute against 70 isolates of rapidly growing mycobacteria (RGM), of which >90% were tetracycline resistant. These included M. abscessus subsp. abscessus (20 isolates), M. abscessus subsp. massiliense (3), Mycobacterium chelonae (15 isolates), Mycobacterium immunogenum (7 isolates), the Mycobacterium fortuitum group, including six doxycycline-resistant isolates (12 isolates), and the Mycobacterium mucogenicum group, including four doxycycline-resistant isolates (10 isolates). Forty-one isolates of slowly growing mycobacteria (SGM), including 16 isolates of MAC, were also tested. Omadacycline was active against all RGM species, with MIC50 ranges of 0.004 to 0.25 and 0.06 to 1 µg/ml for 80% and 100% inhibition, respectively. For M. abscessus subsp. abscessus, MIC50s were 0.06 and 0.12 µg/ml with 80% and 100% inhibition, respectively. There was considerable trailing of the omadacycline endpoint with the RGM. MICs of tigecycline exhibited no trailing and were generally within 1 to 2 dilutions of the 100% inhibition omadacycline MICs. While there was no trailing observed in SGM, omadacycline MICs were higher (MIC range, 8 to >16 µg/ml; n = 41), as previously noted with tigecycline. This study supports further research of omadacycline, including clinical trials, for the treatment of RGM infections, especially M. abscessus.

Treatment of Nontuberculous Mycobacterial Pulmonary Disease: An Official ATS/ERS/ESCMID/IDSA Clinical Practice Guideline.

Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites. This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi among the slowly growing NTM and Mycobacterium abscessus among the rapidly growing NTM. A panel of experts was carefully selected by leading international respiratory medicine and infectious diseases societies (ATS, ERS, ESCMID, IDSA) and included specialists in pulmonary medicine, infectious diseases and clinical microbiology, laboratory medicine, and patient advocacy. Systematic reviews were conducted around each of 22 PICO (Population, Intervention, Comparator, Outcome) questions and the recommendations were formulated, written, and graded using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Thirty-one evidence-based recommendations about treatment of NTM pulmonary disease are provided. This guideline is intended for use by healthcare professionals who care for patients with NTM pulmonary disease, including specialists in infectious diseases and pulmonary diseases.

Treatment of Nontuberculous Mycobacterial Pulmonary Disease: An Official ATS/ERS/ESCMID/IDSA Clinical Practice Guideline.

Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites. This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi among the slowly growing NTM and Mycobacterium abscessus among the rapidly growing NTM. A panel of experts was carefully selected by leading international respiratory medicine and infectious diseases societies (ATS, ERS, ESCMID, IDSA) and included specialists in pulmonary medicine, infectious diseases and clinical microbiology, laboratory medicine, and patient advocacy. Systematic reviews were conducted around each of 22 PICO (Population, Intervention, Comparator, Outcome) questions and the recommendations were formulated, written, and graded using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Thirty-one evidence-based recommendations about treatment of NTM pulmonary disease are provided. This guideline is intended for use by healthcare professionals who care for patients with NTM pulmonary disease, including specialists in infectious diseases and pulmonary diseases.

Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline.

Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites. This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi among the slowly growing NTM and Mycobacterium abscessus among the rapidly growing NTM. A panel of experts was carefully selected by leading international respiratory medicine and infectious diseases societies (ATS, ERS, ESCMID, IDSA) and included specialists in pulmonary medicine, infectious diseases and clinical microbiology, laboratory medicine, and patient advocacy. Systematic reviews were conducted around each of 22 PICO (Population, Intervention, Comparator, Outcome) questions and the recommendations were formulated, written, and graded using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Thirty-one evidence-based recommendations about treatment of NTM pulmonary disease are provided. This guideline is intended for use by healthcare professionals who care for patients with NTM pulmonary disease, including specialists in infectious diseases and pulmonary diseases.

Mycobacterium avium in Community and Household Water, Suburban Philadelphia, Pennsylvania, USA, 2010-2012.

Attention to environmental sources of Mycobacterium avium complex (MAC) infection is a vital component of disease prevention and control. We investigated MAC colonization of household plumbing in suburban Philadelphia, Pennsylvania, USA. We used variable-number tandem-repeat genotyping and whole-genome sequencing with core genome single-nucleotide variant analysis to compare M. avium from household plumbing biofilms with M. avium isolates from patient respiratory specimens. M. avium was recovered from 30 (81.1%) of 37 households, including 19 (90.5%) of 21 M. avium patient households. For 11 (52.4%) of 21 patients with M. avium disease, isolates recovered from their respiratory and household samples were of the same genotype. Within the same community, 18 (85.7%) of 21 M. avium respiratory isolates genotypically matched household plumbing isolates. Six predominant genotypes were recovered across multiple households and respiratory specimens. M. avium colonizing municipal water and household plumbing may be a substantial source of MAC pulmonary infection.

In Vitro Susceptibility Testing of Bedaquiline against Mycobacterium abscessus Complex.

We performed bedaquiline broth microdilution susceptibility testing using Clinical and Laboratory Standards Institute (CLSI) guidelines on 104 nonduplicate isolates of Mycobacterium abscessus complex [M. abscessus subsp. abscessus (76); M. abscessus subsp. massiliense (10); M. abscessus subsp. bolletii (2); and M. abscessus subsp. abscessus-M. abscessus subsp. massiliense hybrid, i.e., M. abscessus subsp. abscessus by rpoB gene and M. abscessus subsp. massiliense by erm(41) gene (16)]. All isolates from patients not known to have been on bedaquiline prior had MIC values of ≤0.25 µg/ml. The bedaquiline MIC50 value for all 76 isolates of M. abscessus subsp. abscessus and 16 isolates of M. abscessus subsp. abscessus-M. abscessus subsp. massiliense hybrid was 0.06 µg/ml. The MIC50 and MIC90 values for 10 isolates of M. abscessus subsp. massiliense were 0.12 µg/ml. Only two isolates of M. abscessus subsp. bolletii were tested with bedaquiline MICs of 0.06 µg/ml. Our study suggests that oral bedaquiline may have potential use in the treatment of disease caused by the M. abscessus complex. Combination therapy with other agents (imipenem, cefoxitin, amikacin, and/or tigecycline) is recommended.

Mycobacterium talmoniae, a Potential Pulmonary Pathogen Isolated from Multiple Patients with Bronchiectasis in the United States, Including the First Case of Clinical Disease in a Patient with Cystic Fibrosis.

We characterize three respiratory isolates of the recently described species Mycobacterium talmoniae recovered in Texas, Louisiana, and Massachusetts, including the first case of disease in a patient with underlying cystic fibrosis. The three isolates had a 100% match to M. talmoniae NE-TNMC-100812T by complete 16S rRNA, rpoB region V, and hsp65 gene sequencing. Core genomic comparisons between one isolate and the type strain revealed an average nucleotide identity of 99.8%. The isolates were susceptible to clarithromycin, amikacin, and rifabutin, while resistance was observed for tetracyclines, ciprofloxacin, and linezolid. M. talmoniae should be added to the list of potential pulmonary pathogens, including in the setting of cystic fibrosis.