Nontuberculous Mycobacteria In Children Research Articles

P060 Impact of elexacaftor/tezacaftor/ivacaftor on eradication of nontuberculous mycobacteria in children with cystic fibrosis: case series from Czech Republic

P060 Impact of elexacaftor/tezacaftor/ivacaftor on eradication of nontuberculous mycobacteria in children with cystic fibrosis: case series from Czech Republic

Treating nontuberculous mycobacteria in children with cystic fibrosis: a multicentre retrospective study

BackgroundRespiratory infection with nontuberculous mycobacteria (NTM) in children with cystic fibrosis (CF) has increased in prevalence. The condition is difficult to diagnose and treatments are complex with limited evidence to...

Non-Tuberculous Mycobacterial Diseases in Children.

Non-tuberculous mycobacteria (NTMs) are ubiquitous and opportunistic emerging bacteria with the potential to colonize and eventually infect either immunocompromised or immunocompetent individuals. In the last three decades, the prevalence of disease caused by NTMs has increased in several countries. The increased prevalence of NTM infection can be explained by an ageing population with rising comorbidities, HIV infection, the common use of immunosuppressive drugs, and improved diagnostic methods. The aim of this review is to demonstrate the clinical relevance of NTMs in children, describing their features and manifestations, diagnostic tools, and therapeutic approaches. We collected data from the literature about NTM infections in young patients over the past five years (2014–2019) using the keywords “non-tuberculous”, “mycobacteria”, “paediatric”, “NTM”, “cystic fibrosis”, and “children”. Recent literature points out that NTMs are ubiquitous, with several species including both those that are pathogens for humans and those that are not. This means that, if a mycobacterium is isolated from a patient’s specimen, we have to distinguish between a simple colonization and an NTM-related disease. The start of treatment depends on many factors that are necessary to consider, such as clinical and imaging features, patient comorbidity and immunocompetence, drug adverse effects, and compliance with a very long therapy that can last many months. Due to the increasing prevalence and clinical relevance of NTMs, guidelines for their optimal management, especially in the presence of chronic underlying disease, are urgently needed.

Risk Factors for Complicated Lymphadenitis Caused by Nontuberculous Mycobacteria in Children.

Nontuberculous mycobacteria (NTM) are an emerging cause of infections, including chronic lymphadenitis in children. To identify risk factors for NTM lymphadenitis, particularly complicated disease, we collected epidemiologic, clinical, and microbiological data on 138 cases of NTM lymphadenitis in children across 13 centers in Germany and Austria. We assessed lifestyle factors but did not identify specific risk behaviors. We noted that more cases of NTM lymphadenitis occurred during cold months than during warm months. Moreover, we noted female sex and age <5.5 years as potential risk factors. Complete extirpation of the affected lymph node appeared to be the best therapeutic measure. We integrated the study data to develop a simple risk score to predict unfavorable clinical outcomes for NTM lymphadenitis.

P161 Treating nontuberculousmycobacteria in children with cystic fibrosis - experience from a paediatric cystic fibrosis centre

P161 Treating nontuberculousmycobacteria in children with cystic fibrosis - experience from a paediatric cystic fibrosis centre

Early detection of non-tuberculous mycobacteria in children with cystic fibrosis using induced sputum at annual review.

Non-tuberculous mycobacteria (NTM) have emerged as an important pathogen in cystic fibrosis (CF). Early detection and treatment of NTM can preserve lung function and maintain good lung health. Many children with CF are not regular sputum producers and cough swabs cannot routinely be used to diagnose NTM. We aimed to test the hypothesis that performing sputum induction at routine annual review results in earlier identification of NTM in non-sputum producing children with CF. We conducted a 5-year prospective observational cohort study involving children with CF aged 5-17 years who had sputum induction with hypertonic saline for microbiological surveillance including NTM at their annual review. Forty-two children (19 males, mean age 11.4 years ± 3.6, mean FEV1 % predicted 94.7 ± 20.6) participated in the study. Forty-one induced sputum samples from 29 children yielded bacterial pathogens. Six samples from six children (14% of the cohort) yielded NTM never previously isolated from the patient. We also detected three isolates of Pseudomonas aeruginosa and one isolate each of Burkholderia cepacia complex and Meticillin resistant Staphylococcus aureus (MRSA), all of which were first time isolates. We conclude that annual induced sputum for microbiological surveillance is useful for early detection of NTM and other important respiratory pathogens, particularly in non-expectorating children. This may lead to earlier identification and help inform initiation of eradication treatment in children with NTM. Children can also be cohorted earlier, before they potentially infect other children in the clinic.

Lymphadenitis by non-tuberculous mycobacteria in children.

Non-tuberculous mycobacteria (NTM) constitute an important cause of cervical lymphadenitis in immunocompetent children. The aims of this study were to estimate the incidence of lymphadenitis due to NTM in children in Cyprus and to describe the characteristics, diagnostic approach, management and outcome of such infections. Children aged 1-5years old, evaluated at Archbishop Makarios III Hospital, Nicosia, Cyprus, from 1 January 2007 to 31 December 2016 for lymphadenopathy, were included in the study. All children had positive lymph node culture for NTM. A total of 22 cases of culture-positive lymphadenitis caused by NTM were reviewed. Patient age ranged from 16 to 55months. Tuberculin skin test produced an induration in 81.0% of cases (diameter, 4-17mm). Mycobacterium avium was isolated in 17 cases (77.3%), M.intracellulare in three (13.6%), M.paraffinicum in one (4.5%) and M.kansasii in one case (4.5%). All 22 patients underwent surgical excision of affected nodes. Additional anti-mycobacterial treatment was given when complete excision was not achieved or for post-surgical recurrence. Complications were few and included scar in three children and one case of transient facial nerve palsy. Surgical excision of NTM-infected lymph nodes is an effective diagnostic and therapeutic approach. When total surgical excision is not feasible, a combination of partial excision with a clarithromycin-including drug regimen appears safe, effective and causes milder and fewer complications than surgery alone.

MYCOBACTERIUM AVIUM COMPLEX MEDIASTINAL LYMPHADENITIS IN AN IMMUNOCOMPETENT ADOLESCENT WITH EROSION INTO THE AIRWAY

SESSION TITLE: Kid cases SESSION TYPE: Fellow Case Reports PRESENTED ON: 10/07/2018 03:30 PM - 04:30 PM INTRODUCTION: Mycobacterium avium complex (MAC) is associated with bronchiectasis and is seen in children with cervical lymphadenitis. It is rarely described in older immunocompetent children. CASE PRESENTATION: A 15-year-old male presented with 4 days of back pain, cough, fever, and pleuritic chest pain. Patient was febrile, 98% SpO2 on room air, tachycardic, with wheezing and rhonchi. D-dimer was elevated. Chest CT revealed a posterior mediastinal soft tissue mass (6.2 cm in diameter) with intra-lesional air abutting the right bronchus intermedius (Figure 1). MRI did not suggest a neurogenic tumor. Empiric IV antibiotics were initiated to treat a presumably infected bronchogenic duplication cyst. The mass was resected via VATS (Figure 2). Post-operatively, a persistent air leak developed. Due to concern for airway injury or bronchial fistula, flexible bronchoscopy was performed, revealing an atypical orifice along the medial wall of the bronchus intermedius (Figure 3). Interrogation revealed a sac like structure. This was presumed to be an accessory cardiac bronchus, a rare anatomic bronchial variant. This structure was in close proximity to the resected tissue and presumably communicated with the pleural space. Histologic evaluation of the resected soft tissue mass identified lymph nodes with necrotizing granulomas without airway or lung tissue. No pathogens were identified and acid-fast bacilli (AFB) smear was negative. A subsequent sputum specimen smear was AFB positive with positive identification of MAC via nucleic acid hybridization. Sputum culture grew MAC at 19 days. Immunologic and infectious evaluations were unremarkable. A treatment course of azithromycin, rifampin, and ethambutol was initiated. Repeat bronchoscopy with BAL performed 2 months after presentation revealed resolution of previous airway abnormality, with negative AFB smear and culture on BAL fluid. Chest CT obtained 3 months after antibiotic therapy revealed resolution of the posterior mediastinal mass. DISCUSSION: Initial bronchoscopy was suggestive of an underlying airway anomaly (cardiac bronchus) as a possible nidus for MAC infection, and subsequent mediastinal erosion. However, given lack of bronchoscopic and imaging evidence supporting a persistent airway anomaly, this case is most consistent with MAC associated mediastinal lymphadenitis complicated by formation of a bronchial fistula. CONCLUSIONS: This case highlights an unusual presentation of MAC mediastinal lymphadenitis with erosion into the airway in an immunocompetent teenager. Although rare in children, MAC mediastinal lymphadenitis needs to be considered in the differential diagnosis of mediastinal masses, especially in patients with respiratory symptoms. If there is evidence on chest imaging of close communication between a mediastinal mass and the airways, clinicians should have a low threshold to perform bronchoscopy to closely evaluate the airways. Reference #1: Nolt, D., Michaels, M. G., & Wald, E. R. (2003). Intrathoracic disease from nontuberculous mycobacteria in children: two cases and a review of the literature. Pediatrics, 112(5), e434-e434. Reference #2: Freeman, A. F., Olivier, K. N., Rubio, T. T., Bartlett, G., Ochi, J. W., Claypool, R. J., … & Holland, S. M. (2009). Intrathoracic nontuberculous mycobacterial infections in otherwise healthy children. Pediatric pulmonology, 44(11), 1051. Reference #3: Desir, A., & Ghaye, B. (2009). Congenital abnormalities of intrathoracic airways. Radiologic clinics of North America, 47(2), 203-225. DISCLOSURES: No relevant relationships by Jason Caboot, source=Web Response No relevant relationships by Benjamin Garren, source=Web Response

Nontuberculous Mycobacteria in Children: A Focus on Bloodstream Infections.

Nontuberculous mycobacteria (NTM) are ubiquitous organisms with variable disease-causing potential. Bloodstream infections caused by NTM in children are poorly described. We describe a retrospective case series of children with culture-confirmed mycobacterial disease managed at the Children's Hospital at Westmead between July 2005 and June 2015. Sixty-five patients had 149 positive NTM cultures; 55 (83.0%) episodes in 54 patients were considered clinically significant. Of the 54 children who met criteria for NTM disease, 25 (46.3%) had lymphadenitis, 13 (24.1%) lung disease, 8 (14.8%) had soft tissue infection or osteomyelitis and 8 (14.8%) had bacteremia. All children with bacteremia had a central venous catheter; those with pulmonary infection had underlying lung disease and all children with soft tissue infection or osteomyelitis had a history of recent penetrating injury. Disease caused by Mycobacterium avium-intracellulare complex was most common, accounting for 19 (76.0%) and 7 (53.8%) lymph node and lung infections, respectively. The most frequently isolated rapid growing mycobacteria were Mycobacterium fortuitum (8; 15%) and Mycobacterium abscessus (6; 11%), with M. fortuitum accounting for the majority (6; 75%) of bloodstream infections. Six (75%) patients with bacteremia had their intravenous catheter removed and all had a favorable outcome. A single disease relapse was reported in 1 of 2 patients with a retained catheter. Lymphadenitis was the most common NTM disease manifestation and not associated with comorbidity. NTM bacteremia was always associated with a central line and catheter removal with cure. We were unable to assess the added value of various antibiotic regimens.

Household proximity to water and nontuberculous mycobacteria in children with cystic fibrosis.

Nontuberculous mycobacteria (NTM) have a particular affinity for patients with cystic fibrosis (CF). Recent studies suggest a possible relationship between acquiring NTM and the level of environmental water in a given area. We sought to determine if there is an association between household proximity to water and NTM in children with CF. An IRB-approved retrospective chart review was completed on 150 children with CF in Florida. Inclusion criteria required regular follow-up, at least two acid-fast bacilli cultures, and a consistent home address over a 3-year period. The distance from each patient's home to the nearest body of water was measured using ArcMap®, a Geographic Information System, and the mean distance to water for NTM-positive and NTM-negative groups were compared. A stepwise backwards logistic regression was used to evaluate for predictors of NTM-positivity. Of the 150 CF patients, 65 met inclusion criteria and 21 (32.3%) tested positive for NTM. Comparison of the mean distance to water for NTM-positive versus NTM-negative groups revealed a cutoff of 500 meters. On the logistic regression, CF patients who lived within 500 meters of water were 9.4 times more likely to acquire NTM (P = 0.013). Other significant predictors included a history of Aspergillus fumigatus (OR 7.9, P = 0.011) and recent history of Pseudomonas aeruginosa (OR 2.5, P = 0.007). In the regions studied, children with CF who live closer to water are more likely to acquire nontuberculous mycobacteria. Future studies in other geographic areas are needed to determine if these results are generalizable. Pediatr Pulmonol. 2017;52:324-330. © 2016 Wiley Periodicals, Inc.

High Rates of Non-Tuberculous Mycobacteria Isolation in Mozambican Children with Presumptive Tuberculosis.

IntroductionNon-tuberculous mycobacteria (NTM) can cause disease which can be clinically and radiologically undistinguishable from tuberculosis (TB), posing a diagnostic and therapeutic challenge in high TB settings. We aim to describe the prevalence of NTM isolation and its clinical characteristics in children from rural Mozambique.MethodsThis study was part of a community TB incidence study in children <3 years of age. Gastric aspirate and induced sputum sampling were performed in all presumptive TB cases and processed for smear testing using fluorochrome staining and LED Microscopy, liquid and solid culture, and molecular identification by GenoType® Mycobacterium CM/AS assays.ResultsNTM were isolated in 26.3% (204/775) of children. The most prevalent NTM species was M. intracellulare (N = 128), followed by M. scrofulaceum (N = 35) and M. fortuitum (N = 9). Children with NTM were significantly less symptomatic and less likely to present with an abnormal chest radiograph than those with M. tuberculosis. NTM were present in 21.6% of follow-up samples and 25 children had the same species isolated from ≥2 separate samples. All were considered clinically insignificant and none received specific treatment. Children with NTM isolates had equal all cause mortality and likelihood of TB treatment as those with negative culture although they were less likely to have TB ruled out.ConclusionsNTM isolation is frequent in presumptive TB cases but was not clinically significant in this patient cohort. However, it can contribute to TB misdiagnosis. Further studies are needed to understand the epidemiology and the clinical significance of NTM in children.

Identification of Immunological Biomarkers Which May Differentiate Latent Tuberculosis from Exposure to Environmental Nontuberculous Mycobacteria in Children

A positive gamma interferon (IFN-γ) response to Mycobacterium tuberculosis early secretory antigenic target-6 (ESAT-6)/culture filtrate protein-10 (CFP-10) has been taken to indicate latent tuberculosis (TB) infection, but it may also be due to exposure to environmental nontuberculous mycobacteria in which ESAT-6 homologues are present. We assessed the immune responses to M. tuberculosis ESAT-6 and cross-reactive responses to ESAT-6 homologues of Mycobacterium avium and Mycobacterium kansasii. Archived culture supernatant samples from children at 3 years post-BCG vaccination were tested for cytokine/chemokine responses to M. tuberculosis antigens. Furthermore, the IFN-γ responses to M. tuberculosis antigens were followed up for 40 children at 8 years post-BCG vaccination, and 15 TB patients were recruited as a control group for the M. tuberculosis ESAT-6 response in Malawi. IFN-γ enzyme-linked immunosorbent assays (ELISAs) on supernatants from diluted whole-blood assays, IFN-γ enzyme-linked immunosorbent spot (ELISpot) assays, QuantiFERON TB Gold-In Tube tests, and multiplex bead assays were performed. More than 45% of the responders to M. tuberculosis ESAT-6 showed IFN-γ responses to M. avium and M. kansasii ESAT-6. In response to M. tuberculosis ESAT-6/CFP-10, interleukin 5 (IL-5), IL-9, IL-13, and IL-17 differentiated the stronger IFN-γ responders to M. tuberculosis ESAT-6 from those who preferentially responded to M. kansasii and M. avium ESAT-6. A cytokine/chemokine signature of IL-5, IL-9, IL-13, and IL-17 was identified as a putative immunological biosignature to differentiate latent TB infection from exposure to M. avium and M. kansasii in Malawian children, indicating that this signature might be particularly informative in areas where both TB and exposure to environmental nontuberculous mycobacteria are endemic.

154 A single centre experience of non-tuberculous mycobacteria in children with cystic fibrosis

154 A single centre experience of non-tuberculous mycobacteria in children with cystic fibrosis

Adénite épitrochléenne à mycobactérie non tuberculeuse

We report the case of a 2-year-old girl referred for unilateral epitrochlear lymphadenitis caused by Mycobacterium avium. Adenitis is the most frequent presentation of non tuberculous mycobacteria in children. Typical locations are the cervical, submandibular, axillar, inguinal, mediastinal, and parotid regions. To our knowledge, this is the first observation of an epitrochlear location. The diagnosis was made by evidencing the causal bacterium but also by the exclusion of other causes such as Bartonella henselae and Mycobacterium tuberculosis infections. Treatment is based on surgical excision, which provides a cure rate of 90%. Macrolides are reserved for extended lesions and/or relapsing lesions despite surgical management.

Cough swabs should not be used to isolate non-tuberculous mycobacteria in children with cystic fibrosis

Non-tuberculous mycobacterium (NTM) account for 13% of cystic fibrosis (CF)-related respiratory infections and present a major therapeutic challenge.1 There is increasing evidence to suggest an adverse prognostic significance of NTM,...

Non‐tuberculous mycobacteria in children with cystic fibrosis: Isolation, prevalence, and predictors

Screening for non-tuberculous mycobacteria (NTM) is recommended for adults with cystic fibrosis (CF). The relevance of this organism in North American pediatric CF patients is unclear as there is limited NTM prevalence data for children. We aimed to determine the prevalence of NTM in children with CF from a single expectorated sputum and identify clinical predictors of NTM isolation. Additionally, we compared two different sputum decontamination methods before mycobacterial culture. From March to November 2004, all sputum-producing patients aged 6-18 years attending the CF clinic at the Hospital for Sick Children in Toronto, Canada, were screened for NTM. Sputum samples were processed by both a single (N-acetyl-l-cysteine + NaOH) and double (N-acetyl-l-cysteine + NaOH + oxalic Acid) decontamination method. Using our CF clinic database and patient charts we analyzed differences in FEV(1), age, sex, pancreatic sufficiency, body mass index, bacterial colonization, and antibiotic use between NTM positive and negative patients. Of 98 study patients, 6 (6.1%) were positive for NTM, 2 with Mycobacterium abscessus, and 4 with Mycobacterium avium complex. One patient with M. abscessus had clinically significant lung disease requiring treatment. We found no predictors of NTM isolation. The double decontamination method allowed detection of only half (3/6) of the positive NTM cultures. As the NTM prevalence rate in children with CF is within the range previously reported in adults and there are no reliable clinical predictors for isolation, annual sputum screening is needed to identify NTM in children. Further research is needed to determine the best sputum decontamination method for NTM culture in pediatric patients.

Isolation of Non-Tuberculous Mycobacteria in Children Investigated for Pulmonary Tuberculosis

ObjectiveTo evaluate the frequency and clinical significance of non-tuberculous mycobacteria (NTM) isolates among children investigated for pulmonary tuberculosis in a rural South African community.MethodsChildren were investigated for pulmonary tuberculosis as part of a tuberculosis vaccine surveillance program (2001–2005). The clinical features of children in whom NTM were isolated, from induced sputum or gastric lavage, were compared to those with culture-proven M. tuberculosis.ResultsMycobacterial culture demonstrated 114 NTM isolates from 109 of the 1,732 children investigated, a crude yield of 6% (95% CI 5–7). The comparative yield of positive NTM cultures from gastric lavage was 40% (95% CI 31–50), compared to 67% (95% CI 58–76) from induced sputum. 95% of children with NTM isolates were symptomatic. Two children were HIV-infected. By contrast, M. tuberculosis was isolated in 187 children, a crude yield of 11% (95% CI 9–12). Compared to those with culture-proven M. tuberculosis, children with NTM isolates were less likely to demonstrate acid-fast bacilli on direct smear microscopy (OR 0.19; 95% 0.0–0.76). Children with NTM were older (p<0.0001), and more likely to demonstrate constitutional symptoms (p = 0.001), including fever (p = 0.003) and loss of weight or failure to gain weight (p = 0.04), but less likely to demonstrate a strongly positive tuberculin skin test (p<0.0001) or radiological features consistent with pulmonary tuberculosis (p = 0.04).DiscussionNTM were isolated in 6% of all children investigated for pulmonary tuberculosis and in more than one third of those with a positive mycobacterial culture. NTM may complicate the diagnosis of PTB in regions that lack capacity for mycobacterial species identification. The association of NTM isolates with constitutional symptoms suggestive of host recognition requires further investigation.

Intrathoracic disease from nontuberculous mycobacteria in children: two cases and a review of the literature.

Pulmonary disease caused by nontuberculous mycobacteria (NTM) is a relatively rare occurrence in immunocompetent children. Two cases of endobronchial NTM infection in immunocompetent children are described. In addition, 41 other children with NTM pulmonary disease reported in the English literature between 1930 and 2003 are reviewed. Clinical manifestations are either purely respiratory or respiratory with more widespread systemic symptoms. Compared with children with only respiratory complaints, children with constitutional symptoms from NTM pulmonary disease 1) had symptoms for a shorter period before presentation (10 vs 28 days), 2) had more radiographic evidence of pulmonary disease, and 3) were treated longer with antimycobacterial agents (11.5 months vs 6 months). The most common causative organism was Mycobacterium avium complex. Pediatricians should be increasingly aware of NTM in the differential diagnosis of persistent pulmonary disease in previously healthy children.

Lymphadenitis due to nontuberculous mycobacteria in children: presentation and response to therapy.

The most common manifestation of infection due to nontuberculous mycobacteria (NTM) in children is cervical lymphadenitis in an otherwise healthy patient. We identified and reviewed 19 cases of proven or presumptive lymphadenitis due to NTM seen at our hospital over the course of 13 months. Nine patients underwent initial surgical excision of involved lymph nodes. Ten children did not have involved lymph nodes excised initially and were treated with macrolide-containing antibiotic regimens. Of these patients, five required subsequent surgical excision and five were cured with combination chemotherapy. Six patients underwent radiographic imaging of the head and neck that revealed asymmetrical adenopathy with ring-enhancing masses but minimal inflammatory stranding of the subcutaneous fat, a finding that may distinguish adenitis caused by NTM from staphylococcal and streptococcal adenitis. Our data suggest that if surgical excision is not considered feasible, antimicrobial therapy for adenitis due to NTM may be beneficial for some patients.

Infections due to nontuberculous mycobacteria in children with leukemia.

We reviewed the spectrum of infections due to nontuberculous mycobacteria (NTM) in children with leukemia. Three children acquired such infections. One patient developed pneumonia after the cessation of chemotherapy when Mycobacterium xenopi was identified in his lung biopsy specimen. He required 2 years of treatment with antituberculous agents and clarithromycin. Cultures of central and peripheral blood specimens from two patients yielded Mycobacterium fortuitum and Mycobacterium chelonae, respectively. Broviac catheters were likely the source of infection. Removal of the catheters and antibiotic treatment resulted in cure. Central venous catheters in leukemic children are potential sources of infection. For febrile neutropenic children with leukemia who do not respond to antibiotic therapy, cultures positive for diphtheroids or negative routine bacterial and fungal cultures should raise a suspicion for infections due to NTM. Systemic infections may require up to 2 years of therapy. Removal of the infected catheters during persistent or recurrent infections in necessary for control of the infection.