Duplex real-time PCR assay for the simultaneous detection of Achromobacter xylosoxidans and Achromobacter spp.

Microb Genom. 2020 Jul 15;:

Authors: Price EP, Soler Arango V, Kidd TJ, Fraser TA, Nguyen TK, Bell SC, Sarovich DS

Abstract
Several members of the Gram-negative environmental bacterial genus Achromobacter are associated with serious infections, with Achromobacter xylosoxidans being the most common. Despite their pathogenic potential, little is understood about these intrinsically drug-resistant bacteria and their role in disease, leading to suboptimal diagnosis and management. Here, we performed comparative genomics for 158 Achromobacter spp. genomes to robustly identify species boundaries, reassign several incorrectly speciated taxa and identify genetic sequences specific for the genus Achromobacter and for A. xylosoxidans. Next, we developed a Black Hole Quencher probe-based duplex real-time PCR assay, Ac-Ax, for the rapid and simultaneous detection of Achromobacter spp. and A. xylosoxidans from both purified colonies and polymicrobial clinical specimens. Ac-Ax was tested on 119 isolates identified as Achromobacter spp. using phenotypic or genotypic methods. In comparison to these routine diagnostic methods, the duplex assay showed superior identification of Achromobacter spp. and A. xylosoxidans, with five Achromobacter isolates failing to amplify with Ac-Ax confirmed to be different genera according to 16S rRNA gene sequencing. Ac-Ax quantified both Achromobacter spp. and A. xylosoxidans down to ~110 genome equivalents and detected down to ~12 and ~1 genome equivalent(s), respectively. Extensive in silico analysis, and laboratory testing of 34 non-Achromobacter isolates and 38 adult cystic fibrosis sputa, confirmed duplex assay specificity and sensitivity. We demonstrate that the Ac-Ax duplex assay provides a robust, sensitive and cost-effective method for the simultaneous detection of all Achromobacter spp. and A. xylosoxidans and will facilitate the rapid and accurate diagnosis of this important group of pathogens.

PMID: 32667877 [PubMed - as supplied by publisher]

Predictors of long-term employment among patients with cystic fibrosis undergoing lung transplantation.

Swiss Med Wkly. 2020 Jul 13;150:w20286

Authors: Radtke T, Königs A, Chen X, Braun J, Dressel H, Benden C

Abstract
AIMS OF THE STUDY: Lung transplantation is an established therapy in selected patients with advanced cystic fibrosis lung disease. Resumption of employment after lung transplantation is generally supported. In Switzerland, there are no data on long-term employment in people with cystic fibrosis undergoing lung transplantation.
METHODS: In a single-centre, cross-sectional study at a Swiss university hospital, clinical data from lung transplant recipients with cystic fibrosis, covering the transplantation period from January 1996 to December 2016, were analysed retrospectively. The potential influence of pre-lung transplantation factors (age, sex, lung function, body mass index, six-minute walk test distance, lung transplantation wait list time, paid employment on the wait list, education, relationship status, housing situation) and post-lung transplantation factors (chronic allograft dysfunction [CLAD], dialysis, cancer diagnosis [except skin cancer]) on paid employment and work percentage after lung transplantation were investigated using mixed logistic and linear regression models. Descriptive analyses of paid employment were performed for various periods after lung transplantation (<1, 1–3, 3–5, 5–10, >10 years). Data are reported as odds ratios (ORs) or coefficients (β) with their 95% confidence intervals (CIs).
RESULTS: Eighty-four subjects (46.4% female) with a mean ± SD age of 29.9 ± 8.4 years were included in the study. Mean wait time for lung transplantation was 42.7 ± 40.2 weeks. The number (percentage) of subjects employed <1 year, 1–3 years, 3–5 years, 5–10 years and >10 years after lung transplantation was n = 23 (28%), n = 51 (65%), n = 44 (75%), n = 30 (68%) and n = 21 (75%), respectively. In mixed logistic regression models, pre-lung transplantation paid employment (OR 24.03, 95% CI 6.08 to 164.39, p <0.0001), academic education (OR 7.81, 95% CI 1.66 to 48.66, p = 0.01) and time post lung transplantation (on log scale, OR 5.81, 95% CI 3.15 to 12.78, p <0.0001) were the main factors influencing post-lung transplantation paid employment status. In mixed linear regression models, pre-lung transplantation paid employment (β = 21.40, 95% CI 10.98 to 31.81, p = 0.00014), academic education (β = 12.54, 95% CI 0.48 to 24.55, p = 0.05) and time post lung transplantation (on log scale, β = 8.96, 95% CI 6.17 to 11.82, p <0.0001) were the main factors influencing work percentage post lung transplantation. No evidence for an influence of clinical factors such as CLAD, cancer or dialysis on post-lung transplantation employment and work percentage was found.
CONCLUSION: Pre-transplant employment is the dominant factor influencing lung transplantation employment in people with cystic fibrosis. People with cystic fibrosis undergoing lung transplantation should be encouraged to work for as long as their health status permits. Professional reintegration after successful lung transplantation should be supported by a multi-disciplinary lung transplant team.

PMID: 32667678 [PubMed - as supplied by publisher]

Sphingolipids and plasma membrane hydrolases in human primary bronchial cells during differentiation and their altered patterns in cystic fibrosis.

Glycoconj J. 2020 Jul 14;:

Authors: Loberto N, Mancini G, Bassi R, Carsana EV, Tamanini A, Pedemonte N, Dechecchi MC, Sonnino S, Aureli M

Abstract
Human primary bronchial epithelial cells differentiated in vitro represent a valuable tool to study lung diseases such as cystic fibrosis (CF), an inherited disorder caused by mutations in the gene coding for the Cystic Fibrosis Transmembrane Conductance Regulator. In CF, sphingolipids, a ubiquitous class of bioactive lipids mainly associated with the outer layer of the plasma membrane, seem to play a crucial role in the establishment of the severe lung complications. Nevertheless, no information on the involvement of sphingolipids and their metabolism in the differentiation of primary bronchial epithelial cells are available so far. Here we show that ceramide and globotriaosylceramide increased during cell differentiation, whereas glucosylceramide and gangliosides content decreased. In addition, we found that apical plasma membrane of differentiated bronchial cells is characterized by a higher content of sphingolipids in comparison to the other cell membranes and that activity of sphingolipids catabolic enzymes associated with this membrane results altered with respect to the total cell activities. In particular, the apical membrane of CF cells was characterized by high levels of ceramide and glucosylceramide, known to have proinflammatory activity. On this basis, our data further support the role of sphingolipids in the onset of CF lung pathology.

PMID: 32666337 [PubMed - as supplied by publisher]

Deoxyribonucleases and Their Applications in Biomedicine.

Biomolecules. 2020 Jul 11;10(7):

Authors: Lauková L, Konečná B, Janovičová Ľ, Vlková B, Celec P

Abstract
Extracellular DNA, also called cell-free DNA, released from dying cells or activated immune cells can be recognized by the immune system as a danger signal causing or enhancing inflammation. The cleavage of extracellular DNA is crucial for limiting the inflammatory response and maintaining homeostasis. Deoxyribonucleases (DNases) as enzymes that degrade DNA are hypothesized to play a key role in this process as a determinant of the variable concentration of extracellular DNA. DNases are divided into two families-DNase I and DNase II, according to their biochemical and biological properties as well as the tissue-specific production. Studies have shown that low DNase activity is both, a biomarker and a pathogenic factor in systemic lupus erythematosus. Interventional experiments proved that administration of exogenous DNase has beneficial effects in inflammatory diseases. Recombinant human DNase reduces mucus viscosity in lungs and is used for the treatment of patients with cystic fibrosis. This review summarizes the currently available published data about DNases, their activity as a potential biomarker and methods used for their assessment. An overview of the experiments with systemic administration of DNase is also included. Whether low-plasma DNase activity is involved in the etiopathogenesis of diseases remains unknown and needs to be elucidated.

PMID: 32664541 [PubMed - in process]

Role of Tobramycin in the Induction and Maintenance of Viable but Non-Culturable Pseudomonas aeruginosa in an In Vitro Biofilm Model.

Antibiotics (Basel). 2020 Jul 10;9(7):

Authors: Mangiaterra G, Cedraro N, Vaiasicca S, Citterio B, Galeazzi R, Laudadio E, Mobbili G, Minnelli C, Bizzaro D, Biavasco F

Abstract
The recurrence of Pseudomonas aeruginosa (PA) biofilm infections is a major issue in cystic fibrosis (CF) patients. A pivotal role is played by the presence of antibiotic-unresponsive persisters and/or viable but non-culturable (VBNC) forms, whose development might be favored by subinhibitory antibiotic concentrations. The involvement of tobramycin and ciprofloxacin, widely used to treat CF PA lung infections, in the abundance of VBNC cells was investigated in PA biofilms models. In vitro biofilms of the laboratory strain PAO1-N and the clinical strain C24 were developed and starved by subculture for 170 days in a non-nutrient (NN) broth, unsupplemented or supplemented with one-quarter minimal inhibitory concentration (MIC) of tobramycin or ciprofloxacin. VBNC cells abundance, estimated as the difference between total live (detected by qPCR and flow cytometry) and colony forming unit (CFU) counts, showed a strain- and drug-specific pattern. A greater and earlier abundance of VBNC PAO1-N cells was detected in all conditions. Exposure of the C24 strain to NN and NN + ciprofloxacin induced only a transient VBNC subpopulation, which was more abundant and stable until the end of the experiment in tobramycin-exposed biofilms. The same response to tobramycin was observed in the PAO1-N strain. These findings suggest that low tobramycin concentrations might contribute to PA infection recurrence by favoring the development of VBNC forms.

PMID: 32664334 [PubMed]

Restoring Pulmonary and Sleep Services as the COVID-19 Pandemic Lessens: From an Association of Pulmonary, Critical Care, and Sleep Division Directors and American Thoracic Society-coordinated Task Force.

Ann Am Thorac Soc. 2020 Jul 14;:

Authors: Wilson KC, Kaminsky DA, Michaud G, Sharma S, Nici L, Folz RJ, Barjaktarevic I, Bhakta NR, Cheng G, Chupp GL, Cole A, Dixon AE, Finigan JH, Graham B, Hallstrand TS, Haynes J, Hankinson J, MacIntyre N, Mandel J, McCarthy K, McCormack M, Patil SP, Rosenfeld M, Senitko M, Sethi S, Swenson ER, Stanojevic S, Teodorescu M, Weiner DJ, Wiener RS, Powell CA

Abstract
BACKGROUND: In March 2020, the United States Centers for Disease Control and Prevention recommended cancelation of elective medical services in response to the COVID-19 pandemic. The daily case rate is now declining in many states and there is a need for guidance about the resumption of elective clinical services for patients with lung disease or sleep conditions.
METHODS: Volunteers were solicited from the Association of Pulmonary, Critical Care, and Sleep Division Directors (APCCSDD) and American Thoracic Society (ATS). Working groups developed plans by discussion and consensus for resuming elective services in pulmonary and sleep medicine clinics, pulmonary function testing laboratories, bronchoscopy and procedural suites, polysomnography laboratories, and pulmonary rehabilitation facilities.
RESULTS: The community new case rate should be consistently low or have a downward trajectory for at least 14 days before resuming elective clinical services. In addition, institutions should have an operational strategy that consists of patient prioritization, screening, diagnostic testing, physical distancing, infection control, and follow-up surveillance. The goals are to protect patients and staff from exposure to the virus, account for limitations in staff, equipment, and space that are essential for the care of COVID-19 patients, and provide access to care for patients with acute and chronic conditions.
CONCLUSIONS: Transmission of SARS-CoV-2 is a dynamic process and, therefore, it is likely that the prevalence of COVID-19 in the community will wax and wane. This will impact an institution's mitigation needs. Operating procedures should be frequently reassessed and modified as needed. The suggestions provided are those of the authors and do not represent official positions of the APCCSDD or the ATS.

PMID: 32663071 [PubMed - as supplied by publisher]

Combining bacteriophages with cefiderocol and meropenem/vaborbactam to treat a pan-drug resistant Achromobacter species infection in a pediatric cystic fibrosis patient.

Pediatr Pulmonol. 2020 Jul 14;:

Authors: Gainey AB, Burch AK, Brownstein MJ, Brown DE, Fackler J, Horne B, Biswas B, Bivens BN, Malagon F, Daniels R

Abstract
Cystic fibrosis (CF) is associated with significant morbidity and early mortality due to recurrent acute and chronic lung infections. The chronic use of multiple antibiotics without pathogen eradication increases the possibility of extensive drug resistance (XDR) or even pan-drug resistance (PDR). It is imperative that new or alternative treatment options be explored. We present a clinical case of a 10-year-old female cystic fibrosis patient, infected with a PDR Achromobacter spp. She was treated with cefiderocol, meropenem/vaborbactam, and bacteriophage therapy (Ax2CJ45Φ2) during two separate admissions in an attempt to clear her infection and restore baseline pulmonary function. The Centers for Disease Control and Prevention (CDC) confirmed antibiotic susceptibilities, which showed resistance to both cefiderocol and meropenem/vaborbactam. However, after using all three agents concomitantly during the second treatment course, our patient's pulmonary function improved dramatically and the Achromobacter spp. could not be isolated from sputum samples obtained eight weeks and 16 weeks after completion of therapy. Overall, the treatment regimen consisting of cefiderocol, meropenem/vaborbactam, and bacteriophage was safe and well tolerated in our patient. This article is protected by copyright. All rights reserved.

PMID: 32662948 [PubMed - as supplied by publisher]

Genetic Variants in Children with Chronic Respiratory Diseases.

Pediatr Pulmonol. 2020 Jul 14;:

Authors: Alsamri MT, Alabdouli A, Alkalbani AM, Iram D, Antony P, Vijayan R, Souid AK

Abstract
Founder mutations and autosomal recessive disorders are common in the Arabian Peninsula due to frequent consanguineous marriages. As a result, the pulmonary service at Tawam Hospital (Al Ain, UAE) routinely requests genetic testing for children with persistent (unexplained) respiratory problems. The main purpose of this report was to underscore the usefulness of these tests. Ten children with severe respiratory diseases due to complex genetic findings are described here. Forty-one variants (six novel) were detected, averaging four per patient (range, one to nine). Seven (17%) variants were homozygous and 34 (83%) heterozygous; some variants were known to show monoallelic expression. Using binomial probability distribution, the fetal-risk for having autosomal recessive disorder(s) as a function of the number of shared variants by a couple ranged from 0.25 (having one shared variant) to 0.9249 (having nine shared variants). In cultures where increased size of homozygous genomic segments is common, children often have multiple variants that could cause complex clinical phenotypes. Identifying pathogenic variants assists in clinical care, family counseling, and disease prevention through genetic screening. This article is protected by copyright. All rights reserved.

PMID: 32662942 [PubMed - as supplied by publisher]

Association between habitual physical activity (HPA) and sleep quality in patients with cystic fibrosis.

Sleep Breath. 2020 Jul 14;:

Authors: Dietz-Terjung S, Gruber W, Sutharsan S, Taube C, Olivier M, Mellies U, Koerner-Rettberg C, Dillenhöfer S, Stehling F, Welsner M

Abstract
PURPOSE: Sleep disturbances and poor sleep quality are known to be present in patients with CF. Regular physical activity plays an important role in the treatment of CF patients due to its positive influence on progression of disease and quality of life. The aim of this work is to create a home-based sleep and activity profile and to investigate the influence of habitual physical activity (HPA) on sleep quality in children, adolescents, and adults with CF.
METHODS: A total of 109 CF patients (64 male, mean age 22.7 ± 12.0 years; mean ppFEV1 63.0 ± 26.7) were equipped with an actigraph for a home-based collection of data on sleep and activity over 4 weeks.
RESULTS: Age, FEV1, and BMI affect sleep and activity in CF patients. Especially younger age and higher FEV1 show a great influence on certain aspects of sleep (SE, TST, TIB, WASO, # of awakenings) and activity and its different intensities. General HPA does not affect sleep, but there is a strong correlation between times spent in vigorous to very vigorous intensities and better sleep quality.
CONCLUSION: Besides younger age and higher FEV1, daily activity in higher intensities influences sleeping behavior of CF patients in a positive way. Patients with poor sleep quality and sleep disturbances possibly benefit from an intensification of physical activity in the home environment. TRAIL REGISTRATION: number: 14-6117-BO (University Duisburg-Essen) and NCT03518697 (clinical trials).

PMID: 32661789 [PubMed - as supplied by publisher]

Xenogeneic cross-circulation for extracorporeal recovery of injured human lungs.

Nat Med. 2020 Jul;26(7):1102-1113

Authors: Hozain AE, O'Neill JD, Pinezich MR, Tipograf Y, Donocoff R, Cunningham KM, Tumen A, Fung K, Ukita R, Simpson MT, Reimer JA, Ruiz EC, Queen D, Stokes JW, Cardwell NL, Talackine J, Kim J, Snoeck HW, Chen YW, Romanov A, Marboe CC, Griesemer AD, Guenthart BA, Bacchetta M, Vunjak-Novakovic G

Abstract
Patients awaiting lung transplantation face high wait-list mortality, as injury precludes the use of most donor lungs. Although ex vivo lung perfusion (EVLP) is able to recover marginal quality donor lungs, extension of normothermic support beyond 6 h has been challenging. Here we demonstrate that acutely injured human lungs declined for transplantation, including a lung that failed to recover on EVLP, can be recovered by cross-circulation of whole blood between explanted human lungs and a Yorkshire swine. This xenogeneic platform provided explanted human lungs a supportive, physiologic milieu and systemic regulation that resulted in functional and histological recovery after 24 h of normothermic support. Our findings suggest that cross-circulation can serve as a complementary approach to clinical EVLP to recover injured donor lungs that could not otherwise be utilized for transplantation, as well as a translational research platform for immunomodulation and advanced organ bioengineering.

PMID: 32661401 [PubMed - in process]

Author Correction: A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence.

Nat Med. 2020 Jul;26(7):1146

Authors: Menachery VD, Yount BL, Debbink K, Agnihothram S, Gralinski LE, Plante JA, Graham RL, Scobey T, Ge XY, Donaldson EF, Randell SH, Lanzavecchia A, Marasco WA, Shi ZL, Baric RS

Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.

PMID: 32661400 [PubMed - in process]

Setting a new standard in cystic fibrosis newborn screening illustrates controversial issues as new data emerge.

Eur J Hum Genet. 2020 Jul 13;:

Authors: Farrell PM

PMID: 32661329 [PubMed - as supplied by publisher]

Pseudomonas aeruginosa PA14 enhances the efficacy of norfloxacin against Staphylococcus aureus Newman biofilms.

J Bacteriol. 2020 Jul 13;:

Authors: Orazi G, Jean-Pierre F, O'Toole GA

Abstract
The thick mucus within the airways of individuals with cystic fibrosis (CF) promotes frequent respiratory infections that are often polymicrobial. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most prevalent pathogens that cause CF pulmonary infections, and both are among the most common etiologic agents of chronic wound infections. Furthermore, the ability of P. aeruginosa and S. aureus to form biofilms promotes the establishment of chronic infections that are often difficult to eradicate using antimicrobial agents. In this study, we found that multiple LasR-regulated exoproducts of P. aeruginosa, including HQNO, siderophores, phenazines, and rhamnolipids, likely contribute to the ability of P. aeruginosa PA14 to shift S. aureus Newman norfloxacin susceptibility profiles. Here, we observe that exposure to P. aeruginosa exoproducts leads to an increase in intracellular norfloxacin accumulation by S. aureus We previously showed that P. aeruginosa supernatant dissipates the S. aureus membrane potential, and furthermore, depletion of the S. aureus proton-motive force recapitulates the effect of P. aeruginosa PA14 supernatant on shifting norfloxacin sensitivity profiles of biofilm-grown S. aureus Newman. From these results, we hypothesize that exposure to P. aeruginosa PA14 exoproducts leads to increased uptake of the drug and/or an impaired ability of S. aureus Newman to efflux norfloxacin. Surprisingly, the effect observed here of P. aeruginosa PA14 exoproducts on S. aureus Newman susceptibility to norfloxacin seemed to be specific to these strains and this antibiotic. Our results illustrate that microbially-derived products can alter the ability of antimicrobial agents to kill bacterial biofilms.Importance Pseudomonas aeruginosa and Staphylococcus aureus are frequently co-isolated from multiple infection sites, including the lungs of individuals with cystic fibrosis (CF) and non-healing diabetic foot ulcers. Co-infection with P. aeruginosa and S. aureus has been shown to produce worse outcomes compared to infection with either organism alone. Furthermore, the ability of these pathogens to form biofilms enables them to cause persistent infection and withstand antimicrobial therapy. In this study, we found that P. aeruginosa-secreted products dramatically increase the ability of the antibiotic norfloxacin to kill S. aureus biofilms. Understanding how interspecies interactions alter the antibiotic susceptibility of bacterial biofilms may inform treatment decisions and inspire the development of new therapeutic strategies.

PMID: 32661077 [PubMed - as supplied by publisher]

Repeteability of Circulating Eosinophil Measures and Inhaled Corticosteroids Effect in Bronchiectasis. A Post Hoc Analysis of a Randomized Clinical Trial.

Arch Bronconeumol. 2020 Jul 10;:

Authors: Martinez-Garcia MA, Posadas T, Sotgiu G, Blasi F, Saderi L, Aliberti S

PMID: 32660708 [PubMed - as supplied by publisher]

Oil supplementation with a special combination of n-3 and n-6 long-chain polyunsaturated fatty acids does not protect for exercise induced asthma: a double-blind placebo-controlled trial.

Lipids Health Dis. 2020 Jul 13;19(1):167

Authors: Dreßler M, Fussbroich D, Böhler L, Herrmann E, Benker N, Tytyk M, Schulze J, Schubert R, Beermann C, Zielen S

Abstract
BACKGROUND: Many patients suffering from exercise-induced asthma (EIA) have normal lung function at rest and show symptoms and a decline in FEV1 when they do sports or during exercise-challenge. It has been described that long-chain polyunsaturated fatty acids (LCPUFA) could exert a protective effect on EIA.
METHODS: In this study the protective effect of supplementation with a special combination of n-3 and n-6 LCPUFA (sc-LCPUFA) (total 1.19 g/ day) were investigated in an EIA cold air provocation model.
PRIMARY OUTCOME MEASURE: Decrease in FEV1 after exercise challenge and secondary outcome measure: anti-inflammatory effects monitored by exhaled NO (eNO) before and after sc-LCPUFA supplementation versus placebo.
RESULTS: Ninety-nine patients with exercise-induced symptoms aged 10 to 45 were screened by a standardized exercise challenge in a cold air chamber at 4 °C. Seventy-three patients fulfilled the inclusion criteria of a FEV1 decrease > 15% and were treated double-blind placebo-controlled for 4 weeks either with sc-LCPUFA or placebo. Thirty-two patients in each group completed the study. Mean FEV1 decrease after cold air exercise challenge and eNO were unchanged after 4 weeks sc-LCPUFA supplementation.
CONCLUSION: Supplementation with sc-LCPUFA at a dose of 1.19 g/d did not have any broncho-protective and anti-inflammatory effects on EIA.
TRIAL REGISTRATION: Clinical trial registration number: NCT02410096. Registered 7 February 2015 at Clinicaltrial.gov.

PMID: 32660564 [PubMed - in process]

Bacterial Quorum Sensing During Infection.

Annu Rev Microbiol. 2020 Jul 13;:

Authors: Azimi S, Klementiev AD, Whiteley M, Diggle SP

Abstract
Bacteria are highly interactive and possess an extraordinary repertoire of intercellular communication and social behaviors, including quorum sensing (QS). QS has been studied in detail at the molecular level, so mechanistic details are well understood in many species and are often involved in virulence. The use of different animal host models has demonstrated QS-dependent control of virulence determinants and virulence in several human pathogenic bacteria. QS also controls virulence in several plant pathogenic species. Despite the role QS plays in virulence during animal and plant laboratory-engineered infections, QS mutants are frequently isolated from natural infections, demonstrating that the function of QS during infection and its role in pathogenesis remain poorly understood and are fruitful areas for future research. We discuss the role of QS during infection in various organisms and highlight approaches to better understand QS during human infection. This is an important consideration in an era of growing antimicrobial resistance, when we are looking for new ways to target bacterial infections. Expected final online publication date for the Annual Review of Microbiology, Volume 74 is September 8, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID: 32660382 [PubMed - as supplied by publisher]

Non-Tuberculous Mycobacterial Diseases in Children.

Pathogens. 2020 Jul 09;9(7):

Authors: Meoli A, Deolmi M, Iannarella R, Esposito S

Abstract
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.

PMID: 32660053 [PubMed]

Palivizumab Prophylaxis among Infants at Increased Risk of Hospitalization due to Respiratory Syncytial Virus Infection in UAE: A Hospital-Based Study.

Can Respir J. 2019;2019:2986286

Authors: Elhalik M, El-Atawi K, Dash SK, Faquih A, Satyan AD, Gourshettiwar N, Khan A, Varughese S, Ramesh A, Khamis E

Abstract
Background: Respiratory syncytial virus (RSV) represents a significant public health burden and the leading cause of lower respiratory tract infections globally, and it is the major cause of hospitalization during the winter. We aimed to evaluate the effectiveness of palivizumab prophylaxis to reduce the hospitalization in children at high risk of RSV infection.
Methods: We performed a retrospective observational single-arm hospital-based study including five RSV seasons (September to March) from 2012 to 2017. We retrospectively included premature infants born at less than 35 weeks of gestation with chronic lungs disease or hemodynamic significant congenital heart disease for palivizumab prophylaxis against RSV infection according to the criteria presented.
Results: A total of 925 children were enrolled in the study over the five RSV seasons. Of them, 410 (44.3%) infants born at <32 weeks of gestation and 515 (55.6%) infants born at 32-35 weeks of gestation with mean (±SD) birth weight of 1104.8 ± 402.85 and 1842.5 ± 377.5, respectively. The compliance with the course of palivizumab was reported in 841 (90.9%) children. Of them, about 75 (8.9%) hospitalized children were reported, and 17 (2.02%) RSV positive children were detected. Hospitalization due to RSV infection was decreased from 9.23% in the 2012-2013 season to 0.67% in the 2016-2017 season.
Conclusion: This study demonstrated that palivizumab prophylaxis in children at high risk of developing RSV infection was effective in reducing the risk of hospitalization with a high compliance rate over the five RSV seasons.

PMID: 31871513 [PubMed - indexed for MEDLINE]

GCK-MODY in a child with cystic fibrosis: the doubt of the treatment plan.

J Pediatr Endocrinol Metab. 2020 Jul 13;:

Authors: Salzano G, Passanisi S, Lucanto MC, Costa S, Pajno GB, Lombardo F

Abstract
Objectives The diagnosis of cystic fibrosis related diabetes (CFRD) is not often easy as glucose homeostasis may be influenced by various disease-related conditions such as enteral continuous drip feeding, frequent acute illness, use of systemic corticosteroids and other concomitant medications. Other forms of diabetes should be considered in the diagnostic work-up, particularly in the first decade of life. Case presentation We hereby present the case of a cystic fibrosis 6-year-old female child diagnosed with glucokinase-maturity onset of diabetes of the young (GCK-MODY). The choice of treatment plan was doubtful since GCK-MODY does not usually require insulin treatment, but hyperglycemia could pose a threat to the respiratory tract. After intensive glucose monitoring, we decided to defer pharmacological treatment based on acceptable daily glycemic control. To date, no worsening in her respiratory function has been revealed. Conclusions Recognition of non-CFRD forms of diabetes is fundamental to plan the most suitable treatment and follow-up.

PMID: 32658865 [PubMed - as supplied by publisher]

Promoting Emotional Wellness in Children with CF, Part I: Child And Family Resilience.

Pediatr Pulmonol. 2020 Jul 13;:

Authors: Prieur MG, Christon LM, Mueller A, Smith BA, Georgiopoulos AM, Boat TF, Filigno SS

Abstract
Attention should be given to individual and family wellbeing from a child's first interaction with the medical team and continuing throughout development, especially for families who experience chronic illnesses, such as cystic fibrosis (CF). While much attention has been given to the mental health of people with CF 12 years and older, this paper explores various areas for CF teams to assess and provide additional resources during the first 12 years of a child's life to promote child and family wellness. In this paper, we discuss parental mental health, social determinants of health, adherence/self-care, nutrition, attention to family lifestyle factors, engagement with school and peers, and modulator therapy for this age group of people with CF. This is the first of two companion papers which examines emotional wellness of children during the early years. The second paper examines mental health assessment and intervention for children under 12. Both encourage teams to strive to promote optimal child and family emotional health and wellness, emphasizing holistic health promotion and prevention, early identification, and intervention. This article is protected by copyright. All rights reserved.

PMID: 32658376 [PubMed - as supplied by publisher]