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The diagnosis of nontuberculous mycobacterial infections is challenging in pediatric solid organ transplant and hematopoietic cell transplant recipients due to the absence of specific clinical manifestations, limitations of sampling, prolonged times for culture and identification, and difficulty discerning colonization from clinical disease. Treatment is dependent on the nontuberculous mycobacterial species, disease type, and pattern of drug resistance. Treatment of nontuberculous mycobacterial infections involves prolonged durations of therapy using multiple medications, which are limited by toxicities and drug–drug interactions. [ABSTRACT FROM AUTHOR]

Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause significant disease in both immunocompromised and immunocompetent individuals. The incidence of NTM pulmonary disease (NTM-PD) is rising globally. Diagnostic challenges persist and treatment efficacy is variable. This article provides an overview of NTM-PD for clinicians. We discuss how common it is, who is at risk, how it is diagnosed and the multidisciplinary approach to its clinical management. [ABSTRACT FROM AUTHOR]

Non-tuberculous mycobacteria (NTM) infections predominantly present as pulmonary disease. Although relatively rare, 20--30 % originate from extrapulmonary sites resulting in a wide range of clinical syndromes. Immunocompromised individuals are particularly susceptible. Clinical manifestations include skin and soft-tissue infections, lymphadenitis, musculoskeletal infections and disseminated disease. Diagnosing extrapulmonary NTM is challenging, and management is complex, often involving multiple radiological and microbiological investigations, long courses of combination antibiotic regimens and may require adjuvant surgical interventions. We highlight both the importance of involving NTM experts at an early stage and the role of a multidisciplinary approach in the diagnosis and management of these infections. [ABSTRACT FROM AUTHOR]

Background: Globally, the prevalence of nontuberculous mycobacterial pulmonary disease (NTM-PD) has significantly increased. Consequently, interest in non-pharmacological treatment approaches has risen. Current Concepts: Nutritional and immunological status plays a pivotal role in the onset, treatment, and prognosis of NTM-PD. A lower body mass index is associated with an increased disease risk. Reduced abdominal fat and hypoalbuminemia have also been linked to the progression of NTM-PD. As a result, nutritional therapy aims to overcome underweight and meet energy, protein, and micronutrient requirements. In addition, exercise, and respiratory rehabilitation are essential for patients. Moderate aerobic and strength training is recommended, while strenuous activities need to be avoided, especially in cases of hemoptysis. Environmental management includes minimizing exposure to potential NTM sources like aerosols from showers, public baths, and gardening. Recommendations include regular cleaning of showerheads, adequate bathroom ventilation, and avoiding public baths and indoor swimming. For patients with gastroesophageal reflux disease, consuming water boiled for at least 10 minutes is advised. Discussion and Conclusion: Although antibiotics remain central to NTM-PD treatment, they may not be suitable for every patient due to their potential side effects. Therefore, a comprehensive approach encompassing nutritional management, exercise, and environmental control is essential. Continued research into developing non-pharmacological interventions remains vital for holistic treatment strategies to address NTM-PD. [ABSTRACT FROM AUTHOR]

Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic inflammatory lung disease caused by infection with non-tuberculous mycobacteria (NTM). International guidelines provide evidence-based recommendations on appropriate diagnosis and treatment strategies, but there is a need for sharing day-to-day best practice between treatment centers to optimize patient care. This is particularly valuable for rare diseases like NTM-PD. In this cross-sectional analysis of NTM-PD management in Germany, medical and administrative staff from seven treatment centers were interviewed to identify best practice in the diagnosis, treatment, and ongoing management of patients with NTM-PD, including related hospital infrastructure and administration processes. A prioritization led to a collection of best practices for the management of patients with NTM-PD in Germany, which is presented here. Selected current best practices included performance of regular sputum tests for diagnosis, use of medical reports, and regular follow-up visits as well as increased interaction between physicians across different specialties. Future best practices that may be implemented to overcome current barriers comprised disease awareness activities, patient empowerment, and new approaches to enhance physician interaction. Challenges related to their implementation are also discussed and will help to raise disease awareness. The presented best practices may guide and optimize patient management in other centers. [ABSTRACT FROM AUTHOR]

Rifampicin is a first-line drug used in the management of tuberculosis (TB) due to its sterilizing effect that targets the bacteria responsible for the disease. This study modified and validated a method for quantitatively determining rifampicin plasma drug concentration of TB patients through High Performance Liquid Chromatography Ultraviolet-Visible detection. The analytic method modified from a standard method was validated for linearity, coefficient of variation, intra-day and inter-day precision, and recovery rate. The retention time of rifampicin was reduced from 18.3 to 3.1 minutes after the method was modified. To validate the method, the coefficient of determination was determined for the linearity to be between 0.975 and 0.998, the coefficient of variation ranged between 2.8% to 15.5% for both intra-day and inter-day precision. Recovery rates ranged between 87% and 125%. The results indicated that the analytical method developed was valid, precise and feasible, and could be useful for quantitatively determining rifampicin plasma drug concentration in TB patients. [ABSTRACT FROM AUTHOR]

Background Lymphadenitis is the most common manifestation of non-tuberculous mycobacteria (NTM) infection in children. We describe the epidemiology and clinical characteristics of NTM lymphadenitis, determine diagnostic yield from tissue sampling, and review management and outcomes. Methods This was a 10-year retrospective review of children aged 0–16 years diagnosed with NTM cervicofacial lymphadenitis who were seen in a pediatric infectious disease clinic in a tertiary public hospital. Data relating to patient demographics, clinical features, surgical and antimicrobial treatment, complications, and outcomes were retrieved from patients' electronic medical records and analyzed. Results There were 48 episodes of NTM cervicofacial lymphadenitis in 45 children (17 males and 28 females). Of these episodes, 43.7% manifested as a unilateral single node, mostly parotid (39.6%) and submandibular (29.2%). All patients underwent diagnostic fine-needle aspiration or surgery. Surgical excision more frequently yielded positive histological findings (P =.016). NTM was identified in 22/48 episodes (45.8%) via culture or molecular sequencing. Mycobacterium abscessus was most commonly found (47.8%). Thirty-eight children (79.2%) received antibiotics. Outcomes in 43 episodes revealed full resolution in 69.8%, while 25.6% had de novo disease and 4.6% experienced recurrence at the same site. Overlying skin changes and multiple or bilateral nodal diseases were significantly associated with de novo disease or recurrence (P =.034 and.084, respectively). Complications occurred in 11/70 (15.7%) procedures. Antibiotic-associated adverse effects occurred in 14/38 (36.8%) episodes. Conclusions NTM lymphadenitis remains a challenging condition. More aggressive management with surgical excision and antibiotics is recommended for those with overlying skin changes and extensive nodal disease. [ABSTRACT FROM AUTHOR]

Among 1038 participants with pulmonary Mycobacterium avium complex and 120 with Mycobacterium abscessus enrolled in the US Bronchiectasis and NTM Research Registry, less than half received antibiotic therapy in the 24 months before registry enrollment, of which less than half were guideline based. Adverse effects occurred in 21% of therapy recipients, of whom 33% discontinued therapy. [ABSTRACT FROM AUTHOR]

A 69-year-old Chinese man presented with proptosis was found to suffer from orbital mycobacterial infection. As acid-fast bacilli were identified from orbital excisional biopsy, the patient was treated with an anti-tuberculous regimen. He responded well and was asymptomatic at 13-month follow-up. This case is documented for its rarity. [ABSTRACT FROM AUTHOR]

Background: Non‐tuberculous mycobacteria (NTM) can cause chronic lung infection particularly in patients who have structural lung disease such as cystic fibrosis (CF). We evaluated the incidence and management of NTM infections in patients with CF in our center. Methods: A retrospective cohort study was carried out on CF patients having at least one positive NTM isolate between 2012 and 2020. Results: Ten patients (2.1%) had at least one positive NTM culture from respiratory samples. All of them were vaccinated with Bacille Calmette–Guérin (BCG) vaccine, which is in the national vaccination program in our country. Eight patients had the Mycobacteriumabscessus complex, one had Mycobacterium avium, and one had Mycobacterium szulgai growth in their respiratory samples. Three patients had transient NTM infection, two had persistent, and five had active NTM infection (NTM pulmonary disease). Patients with NTM pulmonary disease received antibiogram‐directed antimycobacterial therapy. In patients with NTM pulmonary disease, the median ppFEV1 and BMI decreased by 17% and 1%, respectively, at the time of the first NTM isolation when compared with the values one year before the first NTM isolation. Culture conversion was not seen in any patient infected with Mycobacteriunm abscessus complex. Conclusions: The NTM infection incidence is lower in our country than in those countries where the BCG vaccine is not routinely applied. The BCG vaccine may be a protective factor for NTM infection. Further studies are needed about the prevalence of NTM infections, facilitating and protective factors, and appropriate management of NTM infections in patients with CF. [ABSTRACT FROM AUTHOR]

Mycobacterium paratuberculosis causes Johne's disease in cattle, a chronic granulomatous enteritis for which a killed vaccine is commercially available. We present a case of a veterinarian who had an unintended needle-stick with injection of vaccine material. He developed a granulomatous dermatitis with acid-fast bacilli identified on pathology of affected tissue. It is important for health-care providers who care for patients at risk for unintended vaccine exposure to be aware of the possible sequelae after exposure and provide appropriate treatment based on the severity of the injury and subsequent tissue response. [ABSTRACT FROM AUTHOR]

Rationale: The clinical features and prognosis of nontuberculous mycobacterial (NTM) pleuritis and pleural effusion combined with NTM lung disease remain unclear. Objectives: To investigate the clinical features and prognosis of NTM pleuritis. Methods: This retrospective observational study included patients with NTM pleuritis from January 2001 to June 2018 across eight hospitals in Japan. NTM pleuritis was defined by a positive NTM culture of pleural effusion samples. We matched patients with Mycobacterium avium complex (MAC) lung disease (MAC-LD) without pleuritis by sex and age to obtain comparative data and investigated the association between clinical parameters and the prognosis. Results: We identified 64 patients with NTM pleuritis (median age, 73 yr; 37 female patients). The median follow-up duration was 11 months, and 27 patients died. Patients with MAC pleuritis had a significantly lower survival rate than matched patients with MAC-LD without pleuritis. Multivariate analysis revealed that pleuritis (adjusted hazard ratio, 6.99; 95% confidence interval [CI], 2.58-19.00) and underlying pulmonary diseases (adjusted hazard ratio, 3.01; 95% CI, 1.44-6.28) were independently associated with all-cause mortality in patients with MAC-LD. Conclusions: The prognosis of MAC pleuritis is poorer than that of MAC-LD without pleuritis. Pleuritis is an independent prognostic factor in patients with MAC-LD. [ABSTRACT FROM AUTHOR]

Background Lymphopenia has been reported as a risk factor for poor prognosis in various infectious diseases, including Mycobacterium avium complex lung disease (MAC-LD), and recurrence in several infectious diseases. However, the association between lymphopenia and the risk of redeveloping nontuberculous lung disease (NTM-LD) after completed treatment for MAC-LD is unknown. Methods We performed a retrospective cohort study with 147 patients with MAC-LD who successfully completed guideline-based therapy. Lymphopenia was defined as an absolute lymphocyte count (ALC) <1000 cells/μL based on commonly accepted reference values. Results During the median follow-up period of 41.9 months after treatment completion, 59 (40.1%) patients redeveloped NTM-LD. Patients with NTM-LD redevelopment had significantly lower posttreatment ALCs (median, 1260 vs 1420 cells/μL) than those without, and the univariate Cox proportional hazard analysis identified posttreatment ALC as a predictive factor for redevelopment (hazard ratio,.94 [95% confidence interval,.89–.99] for every increase of 100 cells/μL; P =.04). In the multivariate analysis, posttreatment ALC and the extent of bronchiectasis were independently associated with NTM-LD redevelopment. The cumulative rate of NTM-LD redevelopment was significantly higher in patients with posttreatment lymphopenia than in those without (P =.008). Conclusions Posttreatment lymphopenia could predict an increased risk of NTM-LD redevelopment after completed treatment for MAC-LD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The author reflects on the physiotherapy for patients with non-tuberculous mycobacterial disease, which causes various infections in humans like chronic pulmonary illnesses. Topics include the susceptibility risk factors for the disease like bronchi anatomical alteration, bronchiectasis in non-tuberculous mycobacterial disease, and oscillatory positive expiratory pressure.

Rationale: Because the prognosis of nontuberculous mycobacterial pulmonary disease varies, a scoring system predicting mortality is needed.Objectives: We aimed to develop a novel scoring system to predict mortality among patients with nontuberculous mycobacterial pulmonary disease.Methods: We included patients age ≥20 years with newly diagnosed nontuberculous mycobacterial pulmonary disease, with Mycobacterium avium, M. intracellulare, M. abscessus subsp. abscessus, or M. abscessus subsp. massiliense. Cox proportional hazards models were used to identify predictors of mortality in a derivation cohort, and a scoring system was developed. It was validated in an independent prospective cohort.Measurements and Main Results: A total 1,181 and 377 patients were included in the derivation and validation cohorts, respectively. In the final model, body mass index <18.5 kg/m2 (1 point), age ≥65 years (1 point), presence of cavity (1 point), elevated erythrocyte sedimentation rate (1 point), and male sex (1 point) were selected as predictors for mortality. We named this novel scoring system BACES (body mass index, age, cavity, erythrocyte sedimentation rate, and sex). Harrell's C-index for the BACES score was 0.812 (95% confidence interval, 0.786-0.837) in the derivation cohort and 0.854 (95% confidence interval, 0.797-0.911) in the validation cohort, indicating excellent discrimination performance. The estimated 5-year risk of mortality was 1.2% with BACES score 0 and 82.9% with BACES score 5.Conclusions: We developed the BACES score, which could accurately predict mortality among patients with nontuberculous mycobacterial pulmonary disease caused by M. avium, M. intracellulare, M. abscessus subsp. abscessus, or M. abscessus subsp. massiliense. [ABSTRACT FROM AUTHOR]

The emergence of multi-drug resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis creates the urgency for new anti-tuberculosis drugs to improve the efficiency of current tuberculosis treatment. In the search for a new potential tuberculosis drug, we synthesized an isoindole based chemical library and screened a potential candidate with significant anti-tuberculosis activity. The compound named 2-hydroxy-4-(4-nitro-1,3-dioxoisoindolin-2-yl) benzoic acid (IDD-B40) showed strong activity against all the tested drug-susceptible and drug-resistant strains of M. tuberculosis, with the 50% minimum inhibitory concentrations (MIC50) of 0.39 μg/ml both in culture broth and inside Raw 264.7 cells. Also, IDD-B40, in combination with rifampicin, exhibited a direct synergistic effect against both XDR and H37Rv M. tuberculosis. Besides, IDD-B40 showed a better post-antibiotic effect (PAE) than did some first-line drugs and showed no significant cytotoxicity to any cell line tested, with a selectivity index of ≥ 128. Although IDD-B40 showed a result similar to isoniazid in the preliminary mycolic acid inhibition assay, it did not exhibit any effect against other mycolic acid-producing nontuberculous mycobacterial strains (NTM), and different non-mycobacterial pathogenic strains, so further studies are required to confirm the mode of action of IDD-B40. Considering its results against M. tuberculosis, IDD-B40 is a potential anti-tuberculosis drug candidate. However, further studies are required to evaluate its potential in vivo effect and therapeutic potential. [ABSTRACT FROM AUTHOR]

Background: Fat grafting is a standard method for soft augmentation. However, occasionally Mycobacterium abscessus infection can be seen secondary to fat grafting. The aim of this study was to report experience with and propose standard treatment. Patients and Methods: From 2006 to 2018, 12 women who had received fat grafting for facial soft augmentation in different Chinese private clinics were reviewed. Results: The patients presented with local swelling and skin ulceration. They patients received primary infusion of antibiotic agents; however, the results were poor. After being admitted to our hospital, cultures were taken and sent to the specialized examination center. Mycobacterium abscessus was diagnosed in all of the patients. According to drug sensitivity results, targeted antibiotic agent treatment was implemented for 12 months. Local proper conservative debridement was conducted as needed. When the patients were discharged from the hospital, they were advised to continual oral medication for six months. After three to nine years of follow-up, no recurrence was found. On the basis of this, a corresponding standard treatment was proposed. Conclusions:Mycobacterium abscessus infection after fat grafting should be diagnosed and treated accurately. Our experience and proposed treatment may be beneficial. [ABSTRACT FROM AUTHOR]

Left ventricular assist devices (LVADs) are integral for the management of medically refractory heart failure, and LVAD infections are common following device placement. Most infections are caused by Staphylococcal spp. and Gram-negative enteric bacteria but nontuberculous mycobacterial (NTM) infections have been reported. We present the second-ever reported case of a driveline infection caused by Mycobacterium fortuitum in a 75-year-old male with a continuous-flow LVAD. After receiving meropenem, azithromycin, and ciprofloxacin, he underwent device exchange and ultimately died after failing to recover neurologically. Management of NTM infections presents a clinical challenge due to the propensity for rapidly growing mycobacterial species to form biofilms and the possibility of negative cultures delaying diagnosis. To address the literature gap surrounding NTM infections in LVAD patients, we performed a systematic review and present all previously reported cases. [ABSTRACT FROM AUTHOR]

The incidence of primary cutaneous Mycobacterium intracellulare infection is very low. We report a case of primary cutaneous M. intracellulare infection which presented as painful erythematous swelling of the right upper limb without systemic involvement. A novel technique of vacuum sealing drainage was successfully implemented after antimycobacterial treatment proved ineffective at the end of 3 months. Our technique also revealed some additional practical advantages. [ABSTRACT FROM AUTHOR]

Background: The cystic fibrosis (CF) pathogen, Mycobacterium abscessus complex, covers three subspecies: M. abscessus, M. massiliense, and M. bolletii. There are no clinical outcome data concerning M. bolletii. Our aim was to characterize M. bolletii lung infections in patients with CF.Methods: We included patients with M. bolletii lung infection recorded between 1994 and 2012 in France. Data were collected from the CF registry, medical records, and questionnaires submitted to the CF primary physician. Strains were typed by multilocus sequence typing analysis.Results: Fifteen cases were identified in nine CF centers. Nine patients (60%) presented with nontuberculous mycobacterial pulmonary disease. Follow-up of 13 patients showed a trend to more rapid decline in FEV1 in the first year of colonization (-9.4%; SD 19.3) in comparison with noninfected control subjects (-2.3%; SD 12.1) (P = .16). Twelve patients were treated, and 11 received oral macrolides. Treatment-induced eradication occurred in five patients (41.7%). Four patients died (26.7%), including one patient with fatal nontuberculous mycobacterial pulmonary disease. Inducible macrolide resistance was demonstrated in all strains. Patients always harbored unique strains.Conclusions: Our study reports the largest study cohort of CF patients infected with M. bolletii. M. bolletii infection affects both children and young adults, is most often symptomatic, and may be fatal. Macrolide-based therapies have poor effectiveness. There is no evidence of patient-to-patient transmission. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 6-year-old girl having interleukin-12 receptor β-1 deficiency, with mycobacterial infection by Mycobacterium genavense infection. It notes the empirical treatment with oral rifampicin, ethambutol, amikacin, with active infection confirmed by F-fluorodeoxyglucose positron emission tomography.

We are in the midst of a global outbreak of Mycobacterium chimaera infections related to a point source contamination of a widely used surgical device, the 3T heater–cooler unit. More than 250000 heart bypass procedures using heater–cooler devices are performed in the United States every year. It is estimated that 60% of these operations use the device associated with this outbreak. Most of the reported cases present with a disseminated infection that is striking in both the latency of presentation and the high mortality. The diagnosis can be elusive due to intermittent bacteremia and normal echocardiography. Therapy includes several months of antibiotics, and surgical intervention appears to be critical for successful outcomes. Here, we review diagnostic methods and treatment options to guide clinicians in the management of this complicated infection. [ABSTRACT FROM AUTHOR]

Mycobacterium fortuitum is a rare, opportunistic pathogen most frequently contracted through contact with a contaminated source. An immunocompetent 26-year-old female patient presented to our institution with an infected lumboperitoneal (LP) shunt presenting as continued nonhealing wounds. After multiple debridements, shunt revisions, and wound closure failures, infectious disease specialists were consulted. The wound cultures returned positive for M. fortuitum and the shunt was removed. Cerebrospinal fluid studies revealed significant pleocytosis with normal opening pressure, and the patient was diagnosed as having secondary meningitis. After shunt removal, the patient was treated with intravenous and oral antibiotics, resulting in infection resolution. Five months later, a new LP shunt was placed without infection recurrence. Although M. fortuitum was previously reported in neurosurgical patients with ventriculoperitoneal shunts, which are summarized here, to date this is the first case in the literature of M. fortuitum meningitis from an LP shunt. This case demonstrates the importance of clinicians considering uncommon and slow-growing pathogens, as well as consulting infectious disease specialists for patients with persistent, unexplained infections. [ABSTRACT FROM AUTHOR]

The potential use of clinically approved beta-lactams for Buruli ulcer (BU) treatment was investigated with representative classes analyzed in vitro for activity against Mycobacterium ulcerans. Beta-lactams tested were effective alone and displayed a strong synergistic profile in combination with antibiotics currently used to treat BU, i.e. rifampicin and clarithromycin; this activity was further potentiated in the presence of the beta-lactamase inhibitor clavulanate. In addition, quadruple combinations of rifampicin, clarithromycin, clavulanate and beta-lactams resulted in multiplicative reductions in their minimal inhibitory concentration (MIC) values. The MIC of amoxicillin against a panel of clinical isolates decreased more than 200-fold within this quadruple combination. Amoxicillin/clavulanate formulations are readily available with clinical pedigree, low toxicity, and orally and pediatric available; thus, supporting its potential inclusion as a new anti-BU drug in current combination therapies. [ABSTRACT FROM AUTHOR]

The mycobacterial type VII secretion system ESX-1 is responsible for the secretion of a number of proteins that play important roles during host infection. The regulation of the expression of secreted proteins is often essential to establish successful infection. Using transcriptome sequencing, we found that the abrogation of ESX-1 function in Mycobacterium marinum leads to a pronounced increase in gene expression levels of the espA operon during the infection of macrophages. In addition, the disruption of ESX-1-mediated protein secretion also leads to a specific down-regulation of the ESX-1 substrates, but not of the structural components of this system, during growth in culture medium. This effect is observed in both M. marinum and M. tuberculosis. We established that down-regulation of ESX-1 substrates is the result of a regulatory process that is influenced by the putative transcriptional regulator whib6, which is located adjacent to the esx-1 locus. In addition, the overexpression of the ESX-1-associated PE35/PPE68 protein pair resulted in a significantly increased secretion of the ESX-1 substrate EsxA, demonstrating a functional link between these proteins. Taken together, these data show that WhiB6 is required for the secretion-dependent regulation of ESX-1 substrates and that ESX-1 substrates are regulated independently from the structural components, both during infection and as a result of active secretion. [ABSTRACT FROM AUTHOR]

Abstract Spectinamides are a novel class of antibiotics under development for the treatment of MDR- and XDR-tuberculosis, with 1599 and 1445 as early lead candidates within this group. In order to evaluate and differentiate the pharmacological properties of these compounds and assist in candidate selection and design of optimal dosing regimens in animal models of Mtb infection, time kill curve assessments were performed in a previously established in vitro PK/PD model system. The performed studies and subsequent pharmacometric analysis indicate that the anti-mycobacterial activity of 1599 exhibits concentration-dependent killing whereas 1445 shows time-dependent killing. These findings are supported by the fact that the PKPD index that best describes bacterial killing is T > MIC for 1445, but fC max /AUC for 1599. The differential killing behavior among the lead candidates can be rationalized by the differences in post-antibiotic effect: 15.7 h for 1445 compared the 133 h for 1599. Overall, the PK/PD based analysis of the in vitro pharmacologic killing profile of spectinamides 1599 and 1445 on mycobacteria provided valuable insights that contributed to lead candidate selection and preclinical development of these compounds. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Background: Nontuberculous mycobacteria (NTM) lung diseases are increasingly recognized as chronic opportunistic infections, occurring in individuals with a wide variety of underlying conditions. In the absence of systemic immunodeficiency, decision of NTM lung disease treatment must relies on a careful risk/benefit assessment, given the requirement of long-term administration of multidrug therapies supported by limited evidence. The primary objective was to identify the factors associated with anti-NTM treatment initiation. Clinical and radiological outcome upon treatment were studied.Methods: This retrospective, single center study (2013-2016, 45 months) addressed the criteria supporting treatment decision among adults with NTM lung disease without systemic immunodeficiency at our institution, with the assigned goal to harmonize the practice. All patients matched the current international definitions of NTM lung disease according to the American Thoracic Society criteria. Factors associated with anti-NTM treatment were investigated by conditional logistic regression. Clinical and radiological outcomes of treated and untreated NTM-disease cases were examined. Mortality rate was assessed. An expert radiologist conducted a blinded computed tomography (CT)-scan review of the treated and untreated patients.Results: Among 51 cases of NTM lung diseases, 25 (49%) received anti-NTM treatment. In univariate analysis, a body mass index (BMI) < 18 kg/m2 (odds ratio (OR), 4.2 [95% confidence interval (CI) 1.2-15.2]; p = 0.042), hemoptysis (OR, 11.8 [95% CI 1.35-12.9]; p = 0.026), excavation(s) (OR, 4.8 [95% CI 1.4-16.4], p = 0.012), prior anti-NTM treatment (OR, 5.65 [95% CI 1.06-29.9]; p = 0.042), Aspergillus spp. co-infection (OR, 6.3 [95% CI 1.8-22.2]; p = 0.004) were associated with treatment initiation. In multivariate analysis, Aspergillus spp. co-infection was the only independent determinant of treatment initiation (OR, 5.3 [95% CI 1.1-25.4]; p = 0.036). Twenty-one (81%) patients received ≥3 anti-NTM drugs. Median treatment duration and follow-up were 36.3 (interquartile range [IQR], 13.1-64.4) weeks and 17.1 (IQR, 8.7-27.1) months, respectively. Regarding radiological outcome, 85 CT-scans were reviewed, showing similar rates of regression or stabilization in treated and untreated patients. Overall mortality rate was not different in treated and untreated patients.Conclusion: The most relevant variable associated with anti-NTM treatment initiation was Aspergillus spp. co-infection. Radiological regression or stabilization of pulmonary lesions was not different between the treated and untreated patients. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Interactions between hydrophobic drugs and endogenous gastrointestinal substances have the potential to manipulate drug concentration in the human gastrointestinal system, and thus likely play an important role in determining the rate of absorption for hydrophobic drugs. The effects of phospholipids, bile salts and digestive proteins on the solution behaviour of clofazimine in biorelevant media was demonstrated here using dissolution experiments and solid state analytical techniques. Clofazimine is a hydrophobic, anti-mycobacterial agent with virtually no detectable water solubility in its free base form. Salt forms of the drug offer improved aqueous solubility but are unstable in solutions at low pH (pH 1.6) or high pH (pH 6.5). At low pH and high chloride ion concentrations, CFZ in solution experiences a high driving force to crystallize from solution as a hydrochloride salt, which is insoluble, while at high pH CFZ does not dissolve to any extent. In this study, it is demonstrated that amphipathic compounds present in the gastric and intestinal systems can overcome the instability experienced by CFZ at these pH values. This is done by encapsulation of the hydrophobic drug in mixed bile salt phospholipid micelles in both the gastric and intestinal fluid, and by the drug actively binding with the digestive enzyme pepsin in the gastric system. Pepsin binds and solubilises the drug at even relatively low concentration (0.1 mg/mL). When pepsin concentration is increased in the gastric media, a corresponding increase in the solution stability of CFZ is observed. [ABSTRACT FROM AUTHOR]

Nontuberculous mycobacteria (NTM) are a diverse group of organisms that are ubiquitous in the environment, and the incidence of cutaneous infections due to NTM has been steadily increasing. Cutaneous infections due to NTM can be difficult to diagnose, due to their wide spectrum of clinical presentations and histopathological findings that are often nonspecific. A variety of modalities including tissue culture and polymerase chain reaction (PCR) assays may be necessary to identify the organism. Treatment can also be challenging, as it can depend on multiple factors, including the causative organism, the patient’s immunological status, and the extent of disease involvement. In this review, we discuss the common presentations of cutaneous NTM infections, diagnostic tools, and treatment recommendations. A multi-disciplinary approach that involves good communication between the clinician, the histopathologist, the microbiologist, and infectious disease specialists can help lead to successful diagnosis and management. [ABSTRACT FROM AUTHOR]

A series of novel thiazolo pyrimidine derivatives were designed, synthesized, and assessed for their in vitro anti‐mycobacterial activities. All hybrids displayed considerable antitubercular activities against primary Mycobacterium smegmatis mc2 155 screening and successive Mycobacterium tuberculosis H37Rv. In particular, the hybrid entities 13 and 14 (minimum inhibitory concentration: 47 and 39 μg/mL) were found to be equipotent candidates with first‐line antitubercular agent rifampicin, which could act as a lead for further optimization. [ABSTRACT FROM AUTHOR]

We report herein the design, synthesis, and in vitro anti‐mycobacterial activities of 11 pyrrolidine‐containing or piperazine‐containing nitrofuranylamides. Results revealed that all derivatives 3a–k endowed with excellent activity [minimum inhibitory concentration (MIC): <0.016–0.482 μg/mL] against Mycobacterium tuberculosis (MTB) H37Rv strain and more than half of them were more potent than the first‐line anti‐tuberculosis agents isoniazid (MIC: 0.078 μg/mL) and rifampicin (MIC: 0.078 μg/mL). The most active six derivatives were further evaluated against two clinically isolated multidrug‐resistant MTB strains resistant to both of isoniazid and rifampicin. In particular, four of them 3a, 3c, 3d, and 3j (MIC: 1.412–3.230 μg/mL) showed promising activity against the two clinically isolated multidrug‐resistant MTB strains and could act as starting points for further investigation. [ABSTRACT FROM AUTHOR]

We report herein the design, synthesis, and in vitro anti‐mycobacterial activities of a series of 1,2,3‐triazole‐tetraethylene glycol tethered isatin dimers. Our results indicated that all the synthesized isatin dimers showed weak to moderate anti‐mycobacterial activities against both Mycobacterium tuberculosis H37Rv and multidrug‐resistant tuberculosis strains. Dimer 7g was found to be most active against the tested two strains with minimum inhibitory concentration of 128 and 64 μg/mL, which was eightfold more potent than INH (minimum inhibitory concentration: 512 μg/mL) against multidrug‐resistant tuberculosis. Moreover, dimer 7g (CC50: 62.5 μg/mL) also showed acceptable cytotoxicity against VERO cell line, could act as a lead for further investigation. The enriched structure–activity relationship may pave the way to find more effective anti‐mycobacterial candidates. [ABSTRACT FROM AUTHOR]

A new class of istain dimers tethered by tetraethylene glycol was designed, synthesized, and evaluated for their in vitro anti‐mycobacterial activities against Mycobacterium tuberculosis H37Rv and multidrug‐resistant M. tuberculosis strains. Our results indicated that all the synthesized hybrids exhibited promising anti‐mycobacterial activities against the tested strains and the enriched structure–activity relationship may pave the way to further rational development of istain dimers with a unique mechanism of action different from that of the currently used drugs to overcome the resistance. [ABSTRACT FROM AUTHOR]

Mycobacterium marinum is a nontuberculous mycobacterium responsible of infections in humans, ranging from skin infection to disseminated infection in immunocompromised hosts. Clinical suspicion and prompt diagnosis are crucial to prescribe appropriate antimycobacterial treatment and avoid sequelae. [ABSTRACT FROM AUTHOR]

Background: While nontuberculous mycobacterial (NTM) pleuritis rarely complicates pulmonary NTM infection, high mortality has been reported in case reports and small studies. Objectives: The purpose of this study was to clarify the clinical features and treatment outcomes of pulmonary NTM infection cases accompanied by NTM pleuritis. Methods: Medical records of 1,044 patients with pulmonary NTM disease were retrospectively reviewed to select patients complicated by NTM-proven pleuritis. We investigated clinical characteristics, pathogens, pleural effusion examinations, radiographic findings, treatments, and clinical course of the NTM pleuritis patients. Results: Among 1,044 cases with pulmonary NTM, NTM pleuritis occurred in 15 cases (1.4%). The mean age was 69 years with a performance status of mostly 2 or better (80.0%), and 6 cases (40.0%) were complicated by pneumothorax. Subpleural cavities were radiologically detected in 11 cases (73.3%), and extrapulmonary air-fluid level was detected in 14 cases (93.3%). Eleven patients were treated with combinations of 2–4 antimycobacterial drugs, including clarithromycin, and 2 patients were treated with isoniazid, rifampicin, and ethambutol. Chest tube drainage was performed in 11 cases, and surgical approach was added in 6 cases. The pleural effusion of 2 patients treated with only antimycobacterial medications gradually deteriorated. Two patients died from NTM pleuritis, and 1 patient died from pneumonitis during a mean of 1.8 years of follow-up. Conclusions: Comorbid NTM pleuritis was difficult to treat by medical therapy alone and resulted in a poor prognosis. In addition to antimycobacterial agents, chest tube drainage and surgical procedures in the early stages should be considered to treat NTM pleuritis. [ABSTRACT FROM AUTHOR]

Abstract Background and Objectives To treat organ transplant patients with mycobacterial infection, physicians need to pay attention to interaction between drugs used against mycobacteria and immunosuppressants. The purpose of this report is to describe the clinical features of and treatment for mycobacterial infection in lung transplant (LTx) recipients. Methods To investigate the incidence, treatment, and outcome for mycobacterial infection, we retrospectively reviewed 100 LTx recipients in our program since 2000. Results Four recipients (4.0%) developed mycobacterial infection. Three recipients took tacrolimus, and 1 received cyclosporine with mycophenolate mofetil and a steroid for immunosuppression. Tuberculosis (TB) was isolated from 2 recipients, and non-tuberculous mycobacteriosis (NTM) was detected in the other 2. We treated the patients with levofloxacin + isoniazid + pyrazinamide + ethambutol (EB) for TB and clarithromycin (CLM) + EB for NTM to avoid interaction of calcineurin inhibitors (CNI: 8-10 ng/mL in trough level) with rifampicin (RFP). In treating the patients with NTM, we were able to maintain an adequate blood concentration of CNI by decreasing the dosage from one-half to one-quarter. All mycobacterial infections were controlled with treatment. In 1 patient with chronic obstructive pulmonary disease (COPD) infected with TB in the native lung, the forced expiratory volume in 1 second (FEV1) unexpectedly increased from 1890 mL before infection to 2320 mL possibly due to organization of the native lung. Conclusions We were able to manage the mycobacterial infections using drugs other than RFP without any cases of acute rejection under adequate immunosuppression. Organization of the native lung with TB infection unexpectedly resulted in improvement of FEV1 in a COPD patient. Highlights • Physicians need to consider potential drug interactions when treating mycobacterial infection in transplant recipients. • Organization in the native lung may affect pulmonary function test results. • We were able to manage mycobacterial infection with drugs other than rifampicin. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) causes oxidative stress in patients contracting it while antioxidant vitamins such as ascorbic acid (AA) demonstrated antimycobacterial (anti-MTB) effects. Ascorbate's anti-MTB effect in 7H9 media depended on high iron concentration. However, high iron concentration in vivo rather favored mycobacterial growth. Iron dynamics in TB infected macrophages is also complex making it difficult to extrapolate ascorbate's in vivo effect based on observations in 7H9 media. To address this issue, we assessed ascorbate's anti- MTB effect in human macrophage cell culture model. Methods: We collected 20 ml blood from HIV negative subjects, isolated Peripheral Blood Mononuclear Cells (PBMCs) and separated monocytes from the PBMCs. Monocytes were allowed to mature, were infected with Mycobacterium TB (MTB) and were incubated in RPMI plus autologous serum after adding different concentrations of ascorbate. Colony Forming Units (CFU) were counted and compared among cultures incubated with different ascorbate concentrations. Ascorbate's anti-MTB effect was also assessed in 7H9 media for comparison. Results: At concentrations of 10-1 mM, 1 mM and 10 mM, ascorbate reduced MTB CFU in cell culture model by 13%, 53% and 71% respectively while in 7H9 medium CFU reductions were 2.8%, 58.7% and 99.3% respectively. Conclusions: Despite low iron concentration in human cell culture, ascorbate showed dose dependent anti-MTB effect in the cell culture and hence ascorbate can be further investigated in clinical trials to assess its use as an adjunct to anti- TB drugs [ABSTRACT FROM AUTHOR]

Objectives: To describe a safe and effective treatment for endobronchial Mycobacterium avium complex. Methods: Case report and literature review. Results: We present a case of endobronchial M. avium complex in a healthy child treated with serial carbon-dioxide laser excisions and antibiotic triple therapy using azithromycin, rifampin, and ethambutol. No current guideline for the treatment of these lesions in the pediatric population exists. Conclusions: In patients with airway impingement, serial endoscopic surgical resection combined with antibiotics can provide safe and effective management. [ABSTRACT FROM AUTHOR]

Mycobacterial spindle cell pseudotumor (MSP) is a rare benign spindle cell lesion containing acid-fact mycobacteria. These lesions are most commonly identified in the lymph nodes, skin, spleen, or bone marrow of immunocompromised patients and only rarely involve the lungs. We report 3 cases of pulmonary MSP, which include 2 patients who are known to be HIV-positive. The histopathological diagnosis of MSP in the lung lends itself to many challenges due to its rare incidence and its spindled tumor-like appearance. The differential diagnosis is broad and includes both benign and malignant entities. We highlight the importance of the clinical context in which these lesions typically present and the morphologic spectrum of features seen, and we offer a practical approach to the workup of pulmonary mycobacterial pseudotumor. Appropriate recognition of this entity should lead to an accurate diagnosis of a treatable benign condition despite the clinical presentation often favoring malignancy. [ABSTRACT FROM AUTHOR]

β-lactams, the most widely used class of antibiotics, are well-tolerated, and their molecular mechanisms of action against many bacteria are well-documented. Mycobacterium abscessus (Mab) is a highly drug-resistant rapidly-growing nontuberculous mycobacteria (NTM). Only in recent years have we started to gain insight into the unique relationship between β-lactams and their targets in Mab. In this mini-review, we summarize recent findings that have begun to unravel the molecular basis for overall efficacy of β-lactams against Mab and discuss emerging evidence that indicates that we have yet to harness the full potential of this antibiotic class to treat Mab infections. [ABSTRACT FROM AUTHOR]

Yifei Tongluo (YFTL) is a traditional Chinese medicine (TCM) formulation which has been shown clinical efficacy in treatment of patients with multidrug-resistant tuberculosis in China. However, the underlying mechanisms of the effects of YFTL are lacking. This study investigated the effects of YFTL on immune regulation with a mouse lung infection model with Bacille Calmette-Guérin (BCG). We found that compared with untreated mice, the lung mycobacterial load in YFTL-treated mice was significantly reduced, accompanied by alleviated pulmonary inflammation with reduction of pro-inflammatory cytokines and increase of prostaglandin E2 (PGE2). Flow cytometry analyses showed that Th1 cells were significantly higher in the lungs of YFTL-treated mice at early infection time. The results suggest that YFTL-treatment down-regulates pulmonary inflammation, which facilitates a rapid infiltration of Th1 cells into the lungs. Moreover, the Th1 cells in the lungs were resolved faster at later time concomitant with increased the regulatory T cells (Tregs). The reduction of mycobacterial burden associated with improved tissue pathology, faster Th1 cell trafficking, and accelerated resolution of Th1 cells in the lungs of YFTL-treated mice indicates that YFTL improves mycobacterial clearance by maintaining lung homeostasis and dynamically regulating T cells in the lung parenchyma, and suggests that YFTL can be used as host-directed therapies that target immune responses to mycobacterial infection. [ABSTRACT FROM AUTHOR]

Abstract: Bacterial persistence, the ability of bacteria to survive high concentrations of antibiotics for extended periods of time, is an important contributing factor to therapy failure and development of chronic and recurrent infections. Several recent studies have suggested that this persistence is mediated primarily by (p)ppGpp, through its interactions with toxin–antitoxin modules and polyphosphates. In this study, we address whether these key players play a role in mycobacterial persistence against antibiotics. We targeted these specific pathways in Mycobacterium smegmatis by constructing deletion strains of (p)ppGpp synthetase/hydrolase (relA), polyphosphate kinases (ppk1 and ppk2), exopolyphosphatases (ppx1 and ppx2), and the lon protease. None of these mutant strains exhibited altered levels of persisters against isoniazid and ciprofloxacin, when compared with wild‐type strain. Even under conditions in which the stringent response usually gets activated, these strains displayed wild‐type persister levels. Interestingly, we also found that unlike Escherichia coli, maintaining M. smegmatis in exponential phase by repeated passaging does not eliminate persisters suggesting that at least against the antibiotics tested, stationary‐phase dependent persisters (type I) are not the major contributors. Thus, our data demonstrate that multiple mechanisms of antibiotic persistence exist and that these vary widely among different bacterial species. © 2018 IUBMB Life, 70(9):836–844, 2018 [ABSTRACT FROM AUTHOR]

A series of novel tetraethylene glycol tethered heteronuclear bis‐isatin derivatives 7a–l were designed, synthesized, and evaluated for their in vitro anti‐mycobacterial activities against Mycobacterium tuberculosis (MTB) H37Rv and multidrug‐resistant TB (MDR‐TB) as well as cytotoxicity in VERO cell line. All hybrids exhibited potential anti‐mycobacterial activities against MTB H37Rv and MDR‐TB, and acceptable cytotoxicity. Among them, the heteronuclear bis‐isatin 7l [minimum inhibitory concentration (MIC): 16 and 16 μg/mL] was found to be most active against MTB H37Rv and MDR‐TB strains, which was 2‐fold and >8‐fold, respectively, more potent than were the first‐line anti‐tubercular agents rifampicin (MIC: 32 μg/mL) and isoniazid (MIC: >128 μg/mL) against MDR‐TB, also demonstrated acceptable cytotoxicity profile (CC50: 62.5 μg/mL), could act as a starting point for further optimization. [ABSTRACT FROM AUTHOR]

In recent years, several small natural cyclopeptides and cyclodepsipeptides were reported to have antimycobacterial activity. Following this lead, a synthetic pathway was developed for a small series of 12-membered ring compounds with one amide and two ester bonds (cyclotridepsipeptides). Within the series, the ring system proved to be necessary for growth inhibition of Mycobacterium smegmatis and Mycobacterium tuberculosis in the low micromolar range. Open-chain precursors and analogues were inactive. The compounds modulated autophosphorylation of the mycobacterial protein kinase B (PknB). PknB inhibitors were active at µM concentration against mycobacteria while inducers were inactive. PknB regulates the activity of the mycobacterial reductase InhA, the target of isoniazid. The activity of the series against Mycobacterium bovis BCG InhA overexpressing strains was indistinguishable from that of the parental strain suggesting that they do not inhibit InhA. All substances were not cytotoxic (HeLa > 5 µg/ml) and did not show any significant antiproliferative effect (HUVEC > 5 µg/ml; K-562 > 5 µg/ml). Within the scope of this study, the molecular target of this new type of small cyclodepsipeptide was not identified, but the data suggest interaction with PknB or other kinases may partly cause the activity. [ABSTRACT FROM AUTHOR]

Nontuberculous mycobacterial (NTM) pulmonary infections are emerging as a global health problem and pose a threat to susceptible individuals with structural or functional lung conditions such as cystic fibrosis, chronic obstructive pulmonary disease and bronchiectasis. Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MABSC) species account for 70–95% of the pulmonary NTM infections worldwide. Treatment options for these pathogens are limited, involve lengthy multidrug regimens of 12–18 months with parenteral and oral drugs, and their outcome is often suboptimal. Development of new drugs and improved regimens to treat NTM infections are thus greatly needed. In the last 2 years, the screening of compound libraries against M. abscessus in culture has led to the discovery of a number of different chemotypes that target MmpL3, an essential inner membrane transporter involved in the export of the building blocks of the outer membrane of all mycobacteria known as the mycolic acids. This perspective reflects on the therapeutic potential of MmpL3 in Mycobacterium tuberculosis and NTM and the possible reasons underlying the outstanding promiscuity of this target. It further analyzes the physiological and structural factors that may account for the apparent looser structure-activity relationship of some of these compound series against M. tuberculosis compared to NTM. [ABSTRACT FROM AUTHOR]

Nontuberculous mycobacteria (NTM) can cause chronic pulmonary infection in susceptible hosts. Individuals with cystic fibrosis (CF), a multisystem disease predominated by progressive structural lung disease, are particularly vulnerable. Only recently have NTM been recognized for their potential to cause lung deterioration in CF patients. The reported prevalence varies widely from 4 to 40%, significantly more common than in the general population, but this varies because of multiple factors including inconsistent screening practices. Mycobacterium abscessus complex and Mycobacterium avium complex are the two most common species recovered. Defining NTM pulmonary disease in a CF patient can present challenges as it can be difficult to distinguish from the other potentially pathogenic organisms in the lung microbiome. In general, treatment regimens do not differ from the non-CF population but the clinician should be aware of potential interactions with other CF therapies. Recent population-level genomics has raised serious concern for indirect person-to-person transmission of several dominating NTM clones worldwide, raising awareness for increase prevention strategies when CF patients potentially congregate, such as clinic visits. Lung transplantation is controversial in those with NTM present in sputum culture but the available evidence suggests that this is not an absolute contraindication. [ABSTRACT FROM AUTHOR]

Nontuberculous mycobacteria (NTM) are numerous, and for the vast majority of them, randomized studies are lacking and data regarding optimal treatment are limited. When Mycobacterium avium complex (MAC) and M. abscessus are excluded, the main NTM are M. xenopi, M. kansasii, M. malmoense, M. szulgai, and M. simiae. Treatment is long (at least 12 months after culture conversion according to recommendations by scientific societies) and difficult (at least three drugs are required, each of which have potential adverse events). Moreover, optimal treatment is unknown for the vast majority of NTM and efficacy of treatment is not 100%. That is why, balance between benefit and risk is fundamental. For M. xenopi, the second most common NTM isolated in Europe, treatment is classically based on macrolides or fluoroquinolones, associated with ethambutol and rifampicin. For M. kansasii, the cornerstone of treatment is rifampicin, which should be associated with two other drugs: ethambutol plus isoniazid or clarithromycin. M. malmoense, which is common in Northern Europe, can be treated by rifampicin, ethambutol, and clarithromycin and/or fluoroquinolones. [ABSTRACT FROM AUTHOR]

Of the nontuberculous mycobacteria (NTMs) causing lung disease, members of the Mycobacterium abscessus complex (MABc) present a formidable obstacle to successful management. This challenge starts from a poorly understood pathogenesis, continues with complicated subspecies variation in treatment response, and extends to the multidrug-resistant nature of these organisms. The disease often necessitates the use of intravenous therapy, toxic drug combinations, and, in some cases, lung resection. Like many NTMs, MABc treatment requires prolonged therapy with multiple medications, and pulmonary disease in some subspecies can be impossible to eradicate or cure. This disease also represents a frequent and unique problem in certain populations, including cystic fibrosis and lung transplant recipients, and providers who manage such patients should be familiar with how MABc disease influences management. Because of the rising prevalence of the MABc, especially in patients with complicated underlying pulmonary disease, it is increasingly necessary for infectious diseases and pulmonary medicine clinicians to understand the unique aspects of MABc management and understand when to obtain expert consultation in the care of these patients. [ABSTRACT FROM AUTHOR]

Extrapulmonary disease occurs in a minority of nontuberculous mycobacterial (NTM) infections. The pattern of disease tends to be multifocal in immunocompromised individuals and localized in the immunocompetent. There is increasing recognition of disseminated Mycobacterium chimaera infection, as a complication of cardiac surgery, and focal infections due to rapidly growing mycobacteria. Microbiologic diagnosis requires detection of NTM in blood or tissue samples by microscopy, culture, or molecular methods. Management of extrapulmonary NTM infection requires prolonged, targeted multiple-drug therapy and, in some cases, aggressive surgical intervention. The optimal treatment approach is often unknown. Despite combined medical and surgical therapy, outcomes may be poor. A high degree of clinical suspicion and early diagnosis are required to maximize chances of a positive outcome. [ABSTRACT FROM AUTHOR]