Cystic Fibrosis

Current clinical opinion on CFTR dysfunction and patient risk of pancreatitis: diagnostic and therapeutic considerations

Fri, 2022-05-27 06:00

Expert Rev Gastroenterol Hepatol. 2022 May 27. doi: 10.1080/17474124.2022.2084072. Online ahead of print.

ABSTRACT

INTRODUCTION: Cystic fibrosis transmembrane conductance regulator (CFTR)-mediated chloride and bicarbonate secretion is integral to the pancreas' ability to produce the alkaline pancreatic juice required for proper activation of enzymes for digestion. Disruption in this process increases the risk for pancreatitis.

AREAS COVERED: Using original basic and clinical research, as well as clinical case reports and recent reviews indexed in PubMed, we discuss why patients with CFTR dysfunction are at risk for pancreatitis. We also discuss diagnostic modalities for assessing CFTR function, as well as new therapeutic advancements and the impact these are having on pancreatic function, pancreatitis in particular.

EXPERT OPINION: CFTR-related pancreatitis occurs in the presence of monallelic or biallelic mutations and/or from toxin-mediated channel disruption. Research-based CFTR diagnostics have been expanded, yet all current methods rely on measuring CFTR chloride transport in non-pancreatic cells/tissue. Newer CFTR-directed therapies ("CFTR modulators") are both improving pancreatitis (pancreatic-sufficient CF patients) and increasing the risk for pancreatitis (previously pancreatic-insufficient CF patients). Our experiences with these drugs are enlightening us on how CFTR modulation can affect pancreatitis risk across a wide spectrum of pancreatic disease, and represents an opportunity for therapeutic relief from pancreatitis in those without CF, but who suffer from CFTR-related pancreatitis.

PMID:35623009 | DOI:10.1080/17474124.2022.2084072

Categories: Literature Watch

Association of Late Preterm Birth and Size for Gestational Age With Cardiometabolic Risk in Childhood

Fri, 2022-05-27 06:00

JAMA Netw Open. 2022 May 2;5(5):e2214379. doi: 10.1001/jamanetworkopen.2022.14379.

ABSTRACT

IMPORTANCE: The long-term cardiometabolic consequences of late preterm birth (34-36 weeks' gestation) are not well understood.

OBJECTIVE: To assess whether late preterm birth and size for gestational age are associated with cardiometabolic risk (CMR) in childhood.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included 1742 children born in Ontario, Canada, between April 1, 2006, and September 30, 2014, and followed up until September 30, 2019. Data from children enrolled in The Applied Research Group for Kids (TARGet Kids!) primary care practice-based research network were linked to administrative health care data at ICES (formerly known as the Institute for Clinical Evaluative Sciences). Participants were excluded if they had conditions affecting growth (eg, failure to thrive or cystic fibrosis), any acute or chronic conditions (other than asthma and high-functioning autism), severe developmental delay, or families who were unable to communicate in English.

EXPOSURES: Late preterm birth, gestational age as a continuous measure, and size for gestational age.

MAIN OUTCOMES AND MEASURES: The primary outcome was composite CMR score (overall age- and sex-standardized z score of CMR components, including waist circumference, log triglyceride level, glucose level, systolic blood pressure, and high-density lipoprotein cholesterol level). Secondary outcomes were the individual CMR components. Multivariable linear regression analysis was used to separately evaluate the associations of late preterm birth, continuous gestational age, and size for gestational age with CMR at ages 3 to 12 years.

RESULTS: Among 2440 eligible children, 1742 (mean [SD] age, 5.6 [2.2] years; 951 boys [54.6%]) were included in the final cohort. Overall, 87 children (5.0%) were born moderately preterm (<34 weeks' gestation), 145 (8.3%) were born late preterm (34-36 weeks' gestation), 455 (26.1%) were born early term (37-38 weeks' gestation), and 1055 (60.6%) were born full term (≥39 weeks' gestation). Compared with children born full term, those born moderately preterm (adjusted β = 0.50; 95% CI, 0.24-0.75) and late preterm (adjusted β = 0.27; 95% CI, 0.06-0.47) had higher CMR scores. Each additional gestational week was associated with a 0.06 U (adjusted β; 95% CI, -0.08 to -0.03 U) decrease in CMR.

CONCLUSIONS AND RELEVANCE: In this study, children born late preterm and moderately preterm had higher CMR. These results suggest that screening and early-life interventions for these children may prevent cardiometabolic outcomes.

PMID:35622362 | DOI:10.1001/jamanetworkopen.2022.14379

Categories: Literature Watch

Antibacterial Activity of Lactobacillus plantarum Supernatant on Non-Fermenting Gram-Negative Bacteria

Fri, 2022-05-27 06:00

Bull Exp Biol Med. 2022 May 27. doi: 10.1007/s10517-022-05493-4. Online ahead of print.

ABSTRACT

We studied the effect of the L. plantarum strain supernatant on the growth of culture and biofilm of non-fermenting bacteria of the genera Pseudomonas, Achromobacter, and Burkholderia. To obtain a supernatant, the culture of L. plantarum was grown for 48 h at 37°C on a Lactic broth nutrient medium with casein peptone, then centrifuged and filtered through a 0.22-μm Millipore filter. Antimicrobial activity was determined by broth microdilution assay. The inhibitory effect of the supernatant on the growth of bacteria of all three genera was demonstrated. The maximum inhibition was observed for P. aeruginosa (by 13 times compared to the control). For bacteria of the Achromobacter and Burkholderia genera, the inhibition was less pronounced: by 7 and 6 times, respectively. The supernatant also inhibited biofilm formation by P. aeruginosa and A. ruhlandii, but did not affect formed biofilm. Thus, the L. plantarum supernatant obtained by us exhibited pronounced antimicrobial activity against non-fermenting bacteria, the causative agents of nosocomial infections, especially in immunocompromised individuals, very often in cystic fibrosis patients.

PMID:35622249 | DOI:10.1007/s10517-022-05493-4

Categories: Literature Watch

Children with cystic fibrosis have elevated levels of fecal chitinase-3-like-1

Fri, 2022-05-27 06:00

J Pediatr Gastroenterol Nutr. 2022 May 27. doi: 10.1097/MPG.0000000000003477. Online ahead of print.

ABSTRACT

Although chitinase-3-like-1 (CHI3L1), predominately produced by epithelial cells and macrophages, is relevant to pulmonary disease in cystic fibrosis (CF), fecal levels have not yet been assessed in children with CF. Fecal CHI3L1 was measured with a commercial immunoassay using fecal samples provided by children with CF and healthy control children (HC). Higher median (IQR) fecal CHI3L1 levels were seen in the 52 children with CF than in the 35 controls: 15.97 (3.34-50.53) ng/g versus 2.93 (2.13-9.27) ng/g (p=0.001). Fecal CHI3LI did not differ according to sex. In the children with CF, fecal CHI3L1 levels did not correlate with growth parameters nor were the levels affected by pancreatic insufficiency. Children with CF had higher fecal CHI3L1 levels, suggesting underlying gut inflammation. Further work is required to confirm the current findings and to ascertain the longer-term significance of elevated CHI3L1.

PMID:35622011 | DOI:10.1097/MPG.0000000000003477

Categories: Literature Watch

Genomic characterization of lytic bacteriophages targeting genetically diverse <em>Pseudomonas aeruginosa</em> clinical isolates

Fri, 2022-05-27 06:00

iScience. 2022 May 10;25(6):104372. doi: 10.1016/j.isci.2022.104372. eCollection 2022 Jun 17.

ABSTRACT

Pseudomonas aeruginosa infections can be difficult to treat and new therapeutics are needed. Bacteriophage therapy is a promising alternative to traditional antibiotics, but large numbers of isolated and characterized phages are lacking. We collected 23 diverse P. aeruginosa isolates from people with cystic fibrosis (CF) and clinical infections, and used them to screen and isolate over a dozen P. aeruginosa-targeting phages from hospital wastewater. Phages were characterized with genome sequencing, comparative genomics, and lytic activity screening against all 23 bacterial host isolates. We evolved bacterial mutants that were resistant to phage infection for four different phages, and used genome sequencing and functional analysis to study them further. We also tested phages for their ability to kill P. aeruginosa grown in biofilms in vitro and ex vivo on CF airway epithelial cells. Overall, this study demonstrates how systematic genomic and phenotypic characterization can be deployed to develop bacteriophages as precision antibiotics.

PMID:35620437 | PMC:PMC9127202 | DOI:10.1016/j.isci.2022.104372

Categories: Literature Watch

New drugs in cystic fibrosis: what has changed in the last decade?

Fri, 2022-05-27 06:00

Ther Adv Chronic Dis. 2022 May 21;13:20406223221098136. doi: 10.1177/20406223221098136. eCollection 2022.

ABSTRACT

Cystic fibrosis (CF), a life-limiting chronic disease caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene, affects more than 90,000 people worldwide. Until recently, the only available treatments were directed to symptom control, but they failed to change the course of the disease. New drugs developed in the last decade have the potential to change the expression, function, and stability of CFTR protein, targeting the basic molecular defect. The authors seek to provide an update on the new drugs, with a special focus on the most promising clinical trials that have been carried out to date. These newly approved drugs that target specific CFTR mutations are mainly divided into two main groups of CFTR modulators: potentiators and correctors. New therapies have opened the door for potentially disease-modifying, personalized treatments for patients with CF.

PMID:35620188 | PMC:PMC9128052 | DOI:10.1177/20406223221098136

Categories: Literature Watch

Antitoxin CrlA of CrlTA Toxin-Antitoxin System in a Clinical Isolate <em>Pseudomonas aeruginosa</em> Inhibits Lytic Phage Infection

Fri, 2022-05-27 06:00

Front Microbiol. 2022 May 10;13:892021. doi: 10.3389/fmicb.2022.892021. eCollection 2022.

ABSTRACT

Pseudomonas aeruginosa is an important opportunistic pathogen in cystic fibrosis patients and immunocompromised individuals, and the toxin-antitoxin (TA) system is involved in bacterial virulence and phage resistance. However, the roles of TA systems in P. aeruginosa are relatively less studied and no phage Cro-like regulators were identified as TA components. Here, we identified and characterized a chromosome-encoded prophage Cro-like antitoxin (CrlA) in the clinical isolate P. aeruginosa WK172. CrlA neutralized the toxicity of the toxin CrlA (CrlT) which cleaves mRNA, and they formed a type II TA system. Specifically, crlA and crlT are co-transcribed and their protein products interact with each other directly. The autorepression of CrlA is abolished by CrlT through the formation of the CrlTA complex. Furthermore, crlTA is induced in the stationary phase, and crlA is expressed at higher levels than crlT. The excess CrlA inhibits the infection of lytic Pseudomonas phages. CrlA is widely distributed among Pseudomonas and in other bacterial strains and may provide antiphage activities.

PMID:35620101 | PMC:PMC9127804 | DOI:10.3389/fmicb.2022.892021

Categories: Literature Watch

A Commensal Streptococcus Dysregulates the <em>Pseudomonas aeruginosa</em> Nitrosative Stress Response

Fri, 2022-05-27 06:00

Front Cell Infect Microbiol. 2022 May 10;12:817336. doi: 10.3389/fcimb.2022.817336. eCollection 2022.

ABSTRACT

Chronic infections in the cystic fibrosis (CF) airway are composed of both pathogenic and commensal bacteria. However, chronic Pseudomonas aeruginosa infections are the leading cause of lung deterioration in individuals with CF. Interestingly, oral commensals can translocate to the CF lung and their presence is associated with improved lung function, presumably due to their ability to antagonize P. aeruginosa. We have previously shown that one commensal, Streptococcus parasanguinis, produces hydrogen peroxide that reacts with nitrite to generate reactive nitrogen intermediates (RNI) which inhibit P. aeruginosa growth. In this study, we sought to understand the global impact of commensal-mediated RNI on the P. aeruginosa transcriptome. RNA sequencing analysis revealed that S. parasanguinis and nitrite-mediated RNI dysregulated expression of denitrification genes in a CF isolate of P. aeruginosa compared to when this isolate was only exposed to S. parasanguinis. Further, loss of a nitric oxide reductase subunit (norB) rendered an acute P. aeruginosa isolate more susceptible to S. parasanguinis-mediated RNI. Additionally, S. parasanguinis-mediated RNI inactivated P. aeruginosa aconitase activity. Lastly, we report that P. aeruginosa isolates recovered from CF individuals are uniquely hypersensitive to S. parasanguinis-mediated RNI compared to acute infection or environmental P. aeruginosa isolates. These findings illustrate that S. parasanguinis hinders the ability of P. aeruginosa to respond to RNI, which potentially prevents P. aeruginosa CF isolates from resisting commensal and host-induced RNI in the CF airway.

PMID:35619650 | PMC:PMC9127344 | DOI:10.3389/fcimb.2022.817336

Categories: Literature Watch

Polymicrobial infections can select against Pseudomonas aeruginosa mutators because of quorum-sensing trade-offs

Thu, 2022-05-26 06:00

Nat Ecol Evol. 2022 May 26. doi: 10.1038/s41559-022-01768-1. Online ahead of print.

ABSTRACT

Bacteria with increased mutation rates (mutators) are common in chronic infections and are associated with poorer clinical outcomes, especially in the case of Pseudomonas aeruginosa infecting cystic fibrosis (CF) patients. There is, however, considerable between-patient variation in both P. aeruginosa mutator frequency and the composition of co-infecting pathogen communities. We investigated whether community context might affect selection of mutators. Using an in vitro CF model community, we show that P. aeruginosa mutators were favoured in the absence of other species but not in their presence. This was because there were trade-offs between adaptation to the biotic and abiotic environments (for example, loss of quorum sensing and associated toxin production was beneficial in the latter but not the former in our in vitro model community) limiting the evolvability advantage of an elevated mutation rate. Consistent with a role of co-infecting pathogens selecting against P. aeruginosa mutators in vivo, we show that the mutation frequency of P. aeruginosa population was negatively correlated with the frequency and diversity of co-infecting bacteria in CF infections. Our results suggest that co-infecting taxa can select against P. aeruginosa mutators, which may have potentially beneficial clinical consequences.

PMID:35618819 | DOI:10.1038/s41559-022-01768-1

Categories: Literature Watch

High Adherence, Microbiological Control and Reduced Exacerbations in Patients With Non-Cystic Fibrosis Bronchiectasis Treated With Nebulised Colistin. A Prospective Observational Study

Thu, 2022-05-26 06:00

Arch Bronconeumol. 2022 Apr 27:S0300-2896(22)00320-9. doi: 10.1016/j.arbres.2022.03.023. Online ahead of print.

NO ABSTRACT

PMID:35618581 | DOI:10.1016/j.arbres.2022.03.023

Categories: Literature Watch

ERS International Congress 2021: highlights from the Respiratory Infections Assembly

Thu, 2022-05-26 06:00

ERJ Open Res. 2022 May 23;8(2):00642-2021. doi: 10.1183/23120541.00642-2021. eCollection 2022 Apr.

ABSTRACT

The European Respiratory Society International Congress 2021 took place virtually for the second year running due to the coronavirus pandemic. The Congress programme featured more than 400 sessions and 3000 abstract presentations, covering the entire field of respiratory science and medicine. In this article, early career members of the Respiratory Infections Assembly summarise a selection of sessions across a broad range of topics, including presentations on bronchiectasis, non-tuberculosis mycobacteria, tuberculosis, cystic fibrosis and COVID-19.

PMID:35615420 | PMC:PMC9124871 | DOI:10.1183/23120541.00642-2021

Categories: Literature Watch

ERS International Congress 2021: highlights from the Paediatric Assembly

Thu, 2022-05-26 06:00

ERJ Open Res. 2022 May 23;8(2):00643-2021. doi: 10.1183/23120541.00643-2021. eCollection 2022 Apr.

ABSTRACT

In this review, Early Career Members of the European Respiratory Society (ERS) and the Chairs of the ERS Assembly 7: Paediatrics present the highlights in paediatric respiratory medicine from the ERS International Congress 2021. The eight scientific Groups of this Assembly cover respiratory physiology and sleep, asthma and allergy, cystic fibrosis (CF), respiratory infection and immunology, neonatology and intensive care, respiratory epidemiology, bronchology, and lung and airway development. We here describe new developments in lung function testing and sleep-disordered breathing diagnosis, early life exposures affecting pulmonary function in children and effect of COVID-19 on sleep and lung function. In paediatric asthma, we present the important role of the exposome in asthma development, and how biologics can provide better outcomes. We discuss new methods to assess distal airways in children with CF, as some details remain blind when using the lung clearance index. Moreover, we summarise the new ERS guidelines for bronchiectasis management in children and adolescents. We present interventions to reduce morbidity and monitor pulmonary function in newborns at risk of bronchopulmonary dysplasia and long-term chronic respiratory morbidity of this disease. In respiratory epidemiology, we characterise primary ciliary dyskinesia, identify early life determinants of respiratory health and describe the effect of COVID-19 preventive measures on respiratory symptoms. Also, we describe the epidemiology of interstitial lung diseases, possible consequences of tracheomalacia and a classification of diffuse alveolar haemorrhage in children. Finally, we highlight that the characterisation of genes and pathways involved in the development of a disease is essential to identify new biomarkers and therapeutic targets.

PMID:35615416 | PMC:PMC9125040 | DOI:10.1183/23120541.00643-2021

Categories: Literature Watch

Non-invasive MR imaging techniques for measuring femoral arterial flow in a pediatric and adolescent cohort

Thu, 2022-05-26 06:00

Physiol Rep. 2022 May;10(10):e15182. doi: 10.14814/phy2.15182.

ABSTRACT

Magnetic Resonance Imaging (MRI) is well-suited for imaging peripheral blood flow due to its non-invasive nature and excellent spatial resolution. Although MRI is routinely used in adults to assess physiological changes in chronic diseases, there are currently no MRI-based data quantifying arterial flow in pediatric or adolescent populations during exercise. Therefore the current research sought to document femoral arterial blood flow at rest and following exercise in a pediatric-adolescent population using phase contrast MRI, and to present test-retest reliability data for this method. Ten healthy children and adolescents (4 male; mean age 14.8 ± 2.4 years) completed bloodwork and resting and exercise MRI. Baseline images consisted of PC-MRI of the femoral artery at rest and following a 5 × 30 s of in-magnet exercise. To evaluate test-retest reliability, five participants returned for repeat testing. All participants successfully completed exercise testing in the MRI. Baseline flow demonstrated excellent reliability (ICC = 0.93, p = 0.006), and peak exercise and delta rest-peak flow demonstrated good reliability (peak exercise ICC = 0.89, p = 0.002, delta rest-peak ICC = 0.87, p = 0.003) between-visits. All three flow measurements demonstrated excellent reliability when assessed with coefficients of variance (CV's) (rest: CV = 6.2%; peak exercise: CV = 7.3%; delta rest-peak: CV = 7.1%). The mean bias was small for femoral arterial flow. There was no significant mean bias between femoral artery flow visits 1 and 2 at peak exercise. There were no correlations between age or height and any of the flow measurements. There were no significant differences between male and female participants for any of the flow measurements. The current study determined that peripheral arterial blood flow in children and adolescents can be evaluated using non-invasive phase contrast MRI. The MRI-based techniques that were used in the current study for measuring arterial flow in pediatric and adolescent patients demonstrated acceptable test-retest reliability both at rest and immediately post-exercise.

PMID:35614568 | DOI:10.14814/phy2.15182

Categories: Literature Watch

VOCAL: An observational study of ivacaftor for people with cystic fibrosis and selected non-G551D-CFTR gating mutations

Wed, 2022-05-25 06:00

J Cyst Fibros. 2022 May 22:S1569-1993(22)00141-2. doi: 10.1016/j.jcf.2022.05.007. Online ahead of print.

ABSTRACT

BACKGROUND: VOCAL was an observational study of the effect of long-term ivacaftor on real-world clinical outcomes and healthcare resource utilization (HCRU) in people with cystic fibrosis (pwCF) in Italy, the Netherlands, and the UK.

METHODS: pwCF aged ≥6 years with non-G551D-CFTR gating mutations were eligible. Prospective data were collected up to 48 months after enrollment; retrospective data were collected to ensure that 12 months of pre-ivacaftor data were available. Endpoints included absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV1) and measures of nutritional status. Pulmonary exacerbation (PEx) rates, HCRU, and respiratory microbiology during ivacaftor treatment were compared with data from the 12-month period before initiation.

RESULTS: Seventy-three eligible pwCF were enrolled and received ivacaftor; 65 (89.0%) completed the study (48 [65.8%] completed ≥48 months of ivacaftor). During the first 6 months of ivacaftor, ppFEV1, body mass index (BMI), and BMI-for-age z-score showed least-squares mean absolute improvements of 10.8 percentage points, 0.79 kg/m2, and 0.54, respectively; improvements were maintained through 48 months. Rates of PEx, antibiotic use due to PEx, and hospitalization decreased by >50% during ivacaftor treatment compared with before ivacaftor. The number of respiratory cultures and sputum was lower post-ivacaftor, as was the percentage of pwCF with positive respiratory cultures for 3 of 9 pathogens evaluated (Pseudomonas aeruginosa, Aspergillus fumigatus, Stenotrophomonas maltophilia). Reported safety results were consistent with CF and ivacaftor's known safety profile.

CONCLUSIONS: These results demonstrate the positive long-term effectiveness of ivacaftor on clinical outcomes and HCRU in pwCF with non-G551D-CFTR gating mutations in real-world settings.

PMID:35613999 | DOI:10.1016/j.jcf.2022.05.007

Categories: Literature Watch

Proceedings of the ISCT scientific signature series symposium, "sdvances in cell and gene therapies for lung diseases and critical illnesses": International society for cell &amp; gene therapies, burlington VT, US, July 16, 2021

Wed, 2022-05-25 06:00

Cytotherapy. 2022 May 22:S1465-3249(22)00002-0. doi: 10.1016/j.jcyt.2021.11.007. Online ahead of print.

ABSTRACT

The ISCT Scientific Signature Series Symposium "Advances in Cell and Gene Therapies for Lung Diseases and Critical Illnesses" was held as an independent symposium in conjunction with the biennial meeting, "Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases," which took place July 12-15, 2021, at the University of Vermont. This is the third Respiratory System-based Signature Series event; the first 2, "Tracheal Bioengineering, the Next Steps" and "Cellular Therapies for Pulmonary Diseases and Critical Illnesses: State of the Art of European Science," took place in 2014 and 2015, respectively. Cell- and gene-based therapies for respiratory diseases and critical illnesses continue to be a source of great promise and opportunity. This reflects ongoing advancements in understanding of the mechanisms by which cell-based therapies, particularly those using mesenchymal stromal cells (MSCs), can mitigate different lung injuries and the increasing sophistication with which preclinical data is translated into clinical investigations. This also reflects continuing evolution in gene transfer vectors, including those designed for in situ gene editing in parallel with those targeting gene or cell replacement. Therefore, this symposium convened global thought leaders in a forum designed to catalyze communication and collaboration to bring the greatest possible innovation and value of cell- and gene-based therapies for patients with respiratory diseases and critical illnesses.

PMID:35613962 | DOI:10.1016/j.jcyt.2021.11.007

Categories: Literature Watch

Antibiotic resistance in chronic respiratory diseases: from susceptibility testing to the resistome

Wed, 2022-05-25 06:00

Eur Respir Rev. 2022 May 25;31(164):210259. doi: 10.1183/16000617.0259-2021. Print 2022 Jun 30.

ABSTRACT

The development of resistome analysis, i.e. the comprehensive analysis of antibiotic-resistance genes (ARGs), is enabling a better understanding of the mechanisms of antibiotic-resistance emergence. The respiratory microbiome is a dynamic and interactive network of bacteria, with a set of ARGs that could influence the response to antibiotics. Viruses such as bacteriophages, potential carriers of ARGs, may also form part of this respiratory resistome. Chronic respiratory diseases (CRDs) such as cystic fibrosis, severe asthma, chronic obstructive pulmonary disease and bronchiectasis, managed with long-term antibiotic therapies, lead to multidrug resistance. Antibiotic susceptibility testing provides a partial view of the bacterial response to antibiotics in the complex lung environment. Assessing the ARG network would allow personalised, targeted therapeutic strategies and suitable antibiotic stewardship in CRDs, depending on individual resistome and microbiome signatures. This review summarises the influence of pulmonary antibiotic protocols on the respiratory microbiome, detailing the variable consequences according to antibiotic class and duration of treatment. The different resistome-profiling methods are explained to clarify their respective place in antibiotic-resistance analysis in the lungs. Finally, this review details current knowledge on the respiratory resistome related to therapeutic strategies and provides insight into the application of resistome analysis to counter the emergence of multidrug-resistant respiratory pathogens.

PMID:35613743 | DOI:10.1183/16000617.0259-2021

Categories: Literature Watch

Characteristics of Stenotrophomonas maltophilia isolates from cystic fibrosis patients in Russia

Wed, 2022-05-25 06:00

Klin Lab Diagn. 2022 May 21;67(5):315-320. doi: 10.51620/0869-2084-2022-67-5-315-320.

ABSTRACT

Stenotrophomonas maltophilia is a common opportunistic microorganism and an important respiratory pathogen in cystic fibrosis (CF). The aim of this study was to determine antimicrobial resistance phenotypes, sequence-types (ST) and genetic determinants of antibiotic resistance in S. maltophilia strains recovered from CF patients in Russia. S. maltophilia isolates recovered from 170 CF patients were analyzed. Minimum inhibitory concentrations of antibacterial agents were determined using Sensititre Gram Negative GNX2F plates and the results were interpreted according to Clinical and Laboratory Standards Institute (CLSI) criteria. Whole-genome sequencing (WGS) was performed on MGISEQ-2000 platform. SPAdes software, Galaxy, ResFinder, Integrall and PubMLST were used for analysis of WGS data. S. maltophilia strains were identified from 24/170 (14%) CF patients. In total, 25 isolates were detected, two strains were isolated from the same patient. The isolates belonged to 17 different STs, including 5 new STs; ST4 was the most prevalent ST. Resistance to ceftazidime was observed in 60% of strains, to ticarcillin-clavulanate - in 32%, to levofloxacin - in 24%, to trimethoprim/sulfamethoxazole - in 12% of strains. All isolates were susceptible to minocycline. All ST4 isolates were resistant or intermediate to ceftazidime and ticarcillin-clavulanate. In two isolates, the sul1 gene was detected. In one isolate, sul1 was part of a class 1 integron. The detected integron also contained the blaGES-7 and aac(6')-Ib-cr genes. The ST4 sequence-type was the most prevalent ST among S. maltophilia strains recovered from CF patients in Russia. Antibiotic resistance genes, including sul1, blaGES-7, aac(6')-Ib-cr, were detected in single strains.

PMID:35613352 | DOI:10.51620/0869-2084-2022-67-5-315-320

Categories: Literature Watch

The Use of Machine Learning Techniques to Predict Diabetes in Patients with Cystic Fibrosis

Wed, 2022-05-25 06:00

Stud Health Technol Inform. 2022 May 25;294:567-568. doi: 10.3233/SHTI220526.

ABSTRACT

The accuracy of the prognosis of diabetes in patients with cystic fibrosis is crucial, as it highly connected with mortality and other complications. The prognosis of diabetes is a time-consuming process. Usually, it is performed by medical staff and can often lead to misdiagnosis. The aim of the study was to analyze and evaluate risk factors of developing diabetes in patients diagnosed with Cystic Fibrosis by using classification machine learning techniques. The ECFS data register was used to train and test the models. Visualization of our results using SHAP values highlights that most important features are age, antibiotic treatment, FEV1 value and lung transplant as risk predictors for diabetes.

PMID:35612147 | DOI:10.3233/SHTI220526

Categories: Literature Watch

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