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Nontuberculous mycobacteria (NTM) and, in particular, the Mycobacterium abscessus group are recognized as emerging respiratory pathogens among patients with cystic fibrosis. Reports from the United States, France, and Israel have [...]

Symptoms of chronic rhinosinusitis (CRS) often persist despite treatment. Because nontuberculous mycobacteria (NTM) are resistant to commonly used antimicrobial drugs and are found in drinking water that patients may use [...]

Infections caused by members of the Mycobacterium chelonae-abscessus complex remain a serious public health problem, and their role has expanded, with growing numbers of therapeutic interventions that disrupt the competency [...]

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. Author summary: To determine how nontuberculous mycobacteria (NTM) infection is established and how NTM disease progresses, we established a chronic NTM mouse model by intranasal inoculation of M. intracellulare, one of the most frequently isolated strains in NTM patients. The bacteria persistently grew in the lungs and caused fibrotic lung damage with over 50% mortality over 39 weeks. Neutrophils and IL-17A rapidly increased in the lung during early (1–2 weeks) infection, and neutrophils reappeared at 39 weeks postinfection. Depletion of neutrophils during early (0–2 weeks) and chronic (32–34 weeks) infection had no effect on mortality or lung damage in chronically infected mice. Neutralization of IL-17A during early (0–2 weeks) infection significantly reduced mortality, bacterial burden, fibrotic lung damage, and lung matrix metalloproteinase (MMP)-3 at 39 weeks postinfection. Exogenous IL-17A exaggerated the production of MMP-3, but not MMP-9, by lung epithelial cells upon M. intracellulare infection. This study demonstrates that early IL-17A production contributes to established M. intracellulare infection in mice. [ABSTRACT FROM AUTHOR]

Recent studies have characterized a dominant clone (Clone 1) of Mycobacterium abscessus subspecies massiliense (M. massiliense) associated with high prevalence in cystic fibrosis (CF) patients, pulmonary outbreaks in the United States (US) and United Kingdom (UK), and a Brazilian epidemic of skin infections. The prevalence of Clone 1 in non-CF patients in the US and the relationship of sporadic US isolates to outbreak clones are not known. We surveyed a reference US Mycobacteria Laboratory and a US biorepository of CF-associated Mycobacteria isolates for Clone 1. We then compared genomic variation and antimicrobial resistance (AMR) mutations between sporadic non-CF, CF, and outbreak Clone 1 isolates. Among reference lab samples, 57/147 (39%) of patients with M. massiliense had Clone 1, including pulmonary and extrapulmonary infections, compared to 11/64 (17%) in the CF isolate biorepository. Core and pan genome analyses revealed that outbreak isolates had similar numbers of single nucleotide polymorphisms (SNPs) and accessory genes as sporadic US Clone 1 isolates. However, pulmonary outbreak isolates were more likely to have AMR mutations compared to sporadic isolates. Clone 1 isolates are present among non-CF and CF patients across the US, but additional studies will be needed to resolve potential routes of transmission and spread. [ABSTRACT FROM AUTHOR]

Rationale: Patients with refractory Mycobacterium avium complex (MAC) lung disease have limited treatment options. In the CONVERT study, amikacin liposome inhalation suspension (ALIS) added to guideline-based therapy (GBT) increased culture conversion rates versus GBT alone by Month 6. Limited data are available regarding >6-month treatment in a refractory population.Objectives: Evaluate 12-month safety, tolerability, and efficacy of ALIS+GBT.Methods: Adults with refractory MAC lung disease not achieving culture conversion by CONVERT Month 6 could enroll in this open-label extension (INS-312) to receive 590 mg once-daily ALIS+GBT for 12 months. Two cohorts enrolled: the "ALIS-naive" cohort included patients randomized to GBT alone in CONVERT, and the "prior-ALIS" cohort included those randomized to ALIS+GBT in CONVERT. Safety and tolerability of ALIS over 12 months (primary endpoint) and culture conversion by Months 6 and 12 were assessed.Results: In the ALIS-naive cohort, 83.3% of patients (n = 75/90) experienced respiratory treatment-emergent adverse events (TEAEs), and 35.6% (n = 32) had serious TEAEs; 26.7% (n = 24) achieved culture conversion by Month 6 and 33.3% (n = 30) by Month 12. In the prior-ALIS cohort, 46.6% of patients (n = 34/73) experienced respiratory TEAEs, and 27.4% (n = 20) had serious TEAEs; 9.6% (n = 7) achieved culture conversion by Month 6 (≤14 mo ALIS exposure) and 13.7% (n = 10) by Month 12 (≤20 mo ALIS exposure). Nephrotoxicity-related TEAEs and measured hearing decline were infrequent in both cohorts.Conclusions: In up to 20 months of ALIS use, respiratory TEAEs were common, nephrotoxicity and hearing decline were infrequent, and culture conversion continued beyond 6 months of therapy.Clinical trial registered with www.clinicaltrials.gov (NCT02628600). [ABSTRACT FROM AUTHOR]

INTRODUCTION The first clinical and laboratory description of Mycobacterium fortuitum was reported by da Costa Cruz in 1936 (26). This was also the first case of nosocomial disease proved to [...]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background. Nontuberculous mycobacteria (NTM) commonly colonize municipal water supplies and cause healthcare-associated outbreaks. We investigated a biphasic outbreak of Mycobacterium abscessus at a tertiary care hospital. Methods. Case patients had recent hospital exposure and laboratory-confirmed colonization or infection with M. abscessus from January 2013 through December 2015. We conducted a multidisciplinary epidemiologic, field, and laboratory investigation. Results. The incidence rate of M. abscessus increased from 0.7 cases per 10 000 patient-days during the baseline period (January 2013-July 2013) to 3.0 cases per 10 000 patient-days during phase 1 of the outbreak (August 2013-May 2014) (incidence rate ratio, 4.6 [95% confidence interval, 2.3-8.8]; P < .001). Thirty-six of 71 (51%) phase 1 cases were lung transplant patients with positive respiratory cultures. We eliminated tap water exposure to the aerodigestive tract among high-risk patients, and the incidence rate decreased to baseline. Twelve of 24 (50%) phase 2 (December 2014-June 2015) cases occurred in cardiac surgery patients with invasive infections. Phase 2 resolved after we implemented an intensified disinfection protocol and used sterile water for heater-cooler units of cardiopulmonary bypass machines. Molecular fingerprinting of clinical isolates identified 2 clonal strains of M. abscessus; 1 clone was isolated from water sources at a new hospital addition. We made several water engineering interventions to improve water flow and increase disinfectant levels. Conclusions. We investigated and mitigated a 2-phase clonal outbreak of M. abscessus linked to hospital tap water. Healthcare facilities with endemic NTM should consider similar tap water avoidance and engineering strategies to decrease risk of NTM infection. [ABSTRACT FROM AUTHOR]

Abstract: Background: Actinomycetoma caused by Nocardia usually responds well to antibiotics. Emerging species of Nocardia, such as N. wallacei, can be a therapeutic challenge. Aims: Confirm the therapeutic effectivity of linezolid in multidrug resistant Nocardia Wallacei actinomycetoma. Materials and Methods: We evaluated the medical management of an 18‐year‐old man with multidrug resistant actinomycetoma of the left leg caused by N. transvalensis complex treated 17 years ago with linezolid 1200 mg a day. This bacteria was recently reclassified as Nocardia Wallacei by specific molecular biology technique. Results: The infection was cured after 3 months of treatment; the patient remained asymptomatic for the past 17 years. No adverse effects were found. Discussion: Frequently, strains of N. transvalensis complex have aminoglycoside resistance; in this case, we highlight the effectiveness of linezolid for the successful medical management of multidrug resistant actinomycetoma. Conclusion: Linezolid can be an alternative for the treatment of multidrug resistant Nocardia Wallacei. [ABSTRACT FROM AUTHOR]

Rationale: Microbiologically based criteria such as sputum culture conversion to negative have traditionally been used to define treatment success for mycobacterial diseases. There are, however, limited data regarding whether nontuberculous mycobacterial sputum culture conversion or semiquantitative culture analysis correlates with subjective or nonmicrobiologic objective indices of treatment response.Objectives: To determine whether a semiquantitative mycobacterial culture scale correlated with clinical disease status and was predictive of long-term sputum mycobacterial culture conversion to negative in a cohort of patients with nodular/bronchiectatic Mycobacterium avium complex lung disease undergoing therapy.Methods: One hundred and eighty patients undergoing standard macrolide-based therapy for M. avium complex lung disease were monitored at standard frequent intervals with symptomatic, radiographic, and microbiologic data collected, including semiquantitative mycobacterial culture analysis. Analyses were used to evaluate clinical and microbiologic predictors of long-term sputum conversion to culture negative.Measurements and Main Results: After 12 months of therapy, 148 (82%) patients had sputum conversion to culture negative. Baseline semiquantitative sputum culture scores did not differ between patients with sputum conversion and those without. The change in sputum culture semiquantitative score from baseline to Month 3 was highly predictive of subsequent sputum long-term conversion status indicative of treatment success, as was improvement in cough, and especially early radiographic improvement.Conclusions: Early semiquantitative sputum agar plate culture results can be used to predict symptomatic and radiographic improvement as well as long-term sputum culture conversion to negative in this population. We suggest that semiquantitative sputum culture scores can be a useful tool for evaluating new nontuberculous mycobacterial lung disease therapies. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined the potential clinical and microbiologic activity of bedaquiline in patients with advanced Mycobacterium avium complex (MAC) and Mycobacterium abscessus (Mab) lung disease. Topics discussed include the common side effects of Bedaquiline and the findings which indicate a modest favorable clinical response following six months of therapy with a bedaquiline-containing treatment regimen.

The article discusses a study which aims to discover the clinical significance of isolating Mycobacterium abscessus subspecies abscessus (MAA) during the lung disease therapy for Mycobacterium avium complex (MAC). Topics discussed include the collection of sputum for acid-fast bacilli (AFB) analysis, and the composition and parameters of the two groups of patients with MAA isolates. A case study of a 78-year-old woman positive for MAC is also presented.

Background: There is no large study validating the appropriateness of current treatment guidelines for Mycobacterium avium complex (MAC) lung disease. This is a retrospective single-center review evaluating the efficacy of macrolide/azalide-containing regimens for nodular/bronchiectatic (NB) MAC lung disease.Methods: Patients were treated according to contemporary guidelines with evaluation of microbiologic responses. Macrolide susceptibility of MAC isolates was done at initiation of therapy, 6 to 12 months during therapy, and on the first microbiologic recurrence isolate. Microbiologic recurrence isolates also underwent genotyping for comparison with the original isolates.Results: One hundred eighty patients completed > 12 months of macrolide/azalide multidrug therapy. Sputum conversion to culture negative occurred in 154 of 180 patients (86%). There were no differences in response between clarithromycin or azithromycin regimens. Treatment regimen modification occurred more frequently with daily (24 of 30 [80%]) vs intermittent (2 of 180 [1%]) therapy (P = .0001). No patient developed macrolide resistance during treatment. Microbiologic recurrences during therapy occurred in 14% of patients: 73% with reinfection MAC isolates, 27% with true relapse isolates (P = .03). Overall, treatment success (ie, sputum conversion without true microbiologic relapse) was achieved in 84% of patients. Microbiologic recurrences occurred in 74 of 155 patients (48%) after completion of therapy: 75% reinfection isolates, 25% true relapse isolates.Conclusions: Current guidelines for macrolide/azalide-based therapies for NB MAC lung disease result in favorable microbiologic outcomes for most patients without promotion of macrolide resistance. Intermittent therapy is effective and significantly better tolerated than daily therapy. Microbiologic recurrences during or after therapy are common and most often due to reinfection MAC genotypes. [ABSTRACT FROM AUTHOR]

The article presents a study evaluating the use of macrolide/azalide-containing regimens in treating nodular/bronchiectatic (NB) Mycobacterium avium complex (MAC) lung disease. Topics include the use of contemporary guidelines to evaluate the biologic responses of patients, the complicating factors that emerged during or after therapy and the results of a consistent protocol for treatment of MAC lung disease at a single center. It explains why it recommends intermittent versus daily therapy.

Background: Hypersensitivity pneumonitis has been described with exposure to aerosolized Mycobacterium avium complex (MAC) in indoor hot tubs (hot tub lung). Objectives: To describe a case of MAC-associated hypersensitivity pneumonitis-like reaction possibly from showering and review previous hot tub lung reports. Methods: For the case report, we investigated a patient with histologically diagnosed hypersensitivity pneumonitis and MAC-positive sputum culture findings. Mycobacterial cultures were obtained from his home and workplace. Isolates were typed using pulsed-field gel electrophoresis. For the review, MEDLINE and EMBASE were searched for hot tub lung reports, which were reviewed and summarized. Results: A 50-year-old man had progressive dyspnea and episodic fever and myalgias. Pulmonary function testing results revealed obstruction and impaired diffusion; a chest CT scan found diffuse, centrilobular, ground-glass nodules, and air trapping, and a lymphocytic alveolitis with an elevated CD4/CD8 ratio. Transbronchial biopsy showed multiple wellformed nonnecrotizing granulomas. Multiple respiratory samples and shower and bathtub specimens grew MAC, with matching pulsed-field gel electrophoresis patterns. The patient changed from showering to tub bathing. Prednisone and antimycobacterial drugs were administered for approximately 1 year. His symptoms, pulmonary function abnormalities, and CT scan findings resolved. The literature review yielded 36 cases of hot tub lung. Clinical features included dyspnea (97%), cough (78%), and fever (58%). Pulmonary function testing showed obstruction (67%), restriction (55%), and impaired diffusion (75%). A chest CT scan showed ground-glass opacification (95%) and nodules (67%). Granulomas were well-formed in 95%. Treatments included discontinuation of hot tub use and prednisone, antimycobacterial drugs, or both. Outcomes were favorable. Conclusions: A hypersensitivity pneumonitis-like reaction to mycobacteria can occur from exposures other than hot tubs. There are key differences between classic hypersensitivity pneumonitis and MAC-associated hypersensitivity pneumonitis. Antimycobacterial therapy may be required. The possibility of MAC hypersensitivity pneumonitis from showering raises potential implications in the investigation of patients with hypersensitivity pneumonitis. [ABSTRACT FROM AUTHOR]

We initiated a prospective trial of an intermittent clarithromycin-containing regimen for the treatment of patients with Mycobacterium kansasii lung disease. Eighteen patients (10 men and 8 women) with M. kansasii lung disease received a regimen consisting 500–1000 mg of clarithromycin, 25 mg/kg ethambutol, and 600 mg of rifampin 3 times per week. The primary treatment end point was a 12-month period during which sputum cultures were sterile while the patient was receiving therapy. Four male patients were lost to follow-up, but all of the remaining patients successfully completed therapy without significant drug-related adverse events. The mean time (± standard deviation [SD] to sputum conversion was 1.0 ± 0.9 months, and the mean duration (±SD) of therapy was 13.4 ± 0.9 months. No patient who successfully completed therapy had relapsed after a mean (±SD) of 46 ± 8.0 months. Clarithromycin- and rifampin-containing regimes offer the possibility of effective short-course and intermittent treatment of M. kansasii lung disease. [ABSTRACT FROM AUTHOR]