448 results found
Davies J, Matthews J, Dobra R, et al., 2023, Levelling the playing field through the London Network of the UK Clinical Trials Accelerator Platform, Contemporary Clinical Trials Communications, ISSN: 2451-8654
Dobra R, Davies J, Elborn S, et al., 2023, A discrete choice experiment to quantify the influence of trial features on the decision to participate in cystic fibrosis trials, Journal of Cystic Fibrosis, ISSN: 1569-1993
Dobra R, Pinnell S, Jones A, et al., 2023, How representative are clinical trial cohorts of the general CF population? Implications for trial planning., J Cyst Fibros
Understanding the number of patients eligible to participate in research is important to design protocols and define research priorities. We reviewed the records of all patients with CF, age 12+, who receive care at our centre. We assessed their eligibility for trial participation based on common trial inclusion/exclusion criteria. 643 patients were included in the analysis, 31 were modulator ineligible(MI). Only 198(31 %) of the total cohort and 7(23 %) of the MI cohort were eligible for participation based on the hypothetical criteria. The most common reason for ineligibility was ppFEV1 ≥90 % followed by clinical instability, complex comorbidity and anticipated inability to adhere to the protocol. We suggest this would be a useful exercise for centres planning to either participate in, or refer subjects into, upcoming trials to undertake for their own cohort. We also make suggestions for protocol designs that optimise the number of patients who are eligible to participate.
Davies J, Murphy RA, Pizzato J, et al., 2023, Antimicrobial peptide glatiramer acetate targets Pseudomonas aeruginosa lipopolysaccharides to breach membranes without altering lipopolysaccharide modification, Nature Portfolio Journals Antimicrobials and Resistance
McNally P, Lester K, Stone G, et al., 2023, Improvement in Lung Clearance Index and Chest Computed Tomography Scores with Elexacaftor/Tezacaftor/Ivacaftor Treatment in People with Cystic Fibrosis Aged 12 Years and Older - The RECOVER Trial., Am J Respir Crit Care Med, Vol: 208, Pages: 917-929
Rationale: Clinical trials have shown that use of elexacaftor/tezacaftor/ivacaftor (ETI) is associated with improvements in sweat chloride, pulmonary function, nutrition, and quality of life in people with cystic fibrosis (CF). Little is known about the impact of ETI on ventilation inhomogeneity and lung structure. Objectives: RECOVER is a real-world study designed to measure the impact of ETI in people with CF. The primary endpoints were lung clearance (lung clearance index; LCI2.5) and FEV1. Secondary endpoints included spirometry-controlled chest computed tomography (CT) scores. Methods: The study was conducted in seven sites in Ireland and the United Kingdom. Participants ages 12 years and older who were homozygous for the F508del mutation (F508del/F508del) or heterozygous for F508del and a minimum-function mutation (F508del/MF) were recruited before starting ETI and were followed up over 12 months. LCI2.5 was measured using nitrogen multiple breath washout (MBW) at baseline and at 6 and 12 months. Spirometry was performed as per the criteria of the American Thoracic Society and the European Respiratory Society. Spirometry-controlled chest CT scans were performed at baseline and at 12 months. CT scans were scored using the Perth Rotterdam Annotated Grid Morphometric Analysis (PRAGMA) system. Other outcome measures include weight, height, Cystic Fibrosis Quality of Life Questionnaire-Revised (CFQ-R), and sweat chloride. Measurements and Main Results: One hundred seventeen people with CF ages 12 and older were recruited to the study. Significant improvements were seen in LCI scores (-2.5; 95% confidence interval [CI], -3.0, -2.0) and in the percents predicted for FEV1 (8.9; 95% CI, 7.0, 10.9), FVC (6.6; 95% CI, 4.9, 8.3), and forced expiratory flow between 25% and 75% of expired volume (12.4; 95% CI, 7.8, 17.0). Overall PRAGMA-CF scores reflecting airway disease improved significantly (-3.46; 95% CI, -5.23, -1.69). Scores for trapped air, mucus plugging, an
Sole A, Davies JC, Quintana-Gallego E, 2023, Cystic Fibrosis: From Salty Malediction to Possible Cure., Arch Bronconeumol
Southern KW, Burgel P-R, Castellani C, et al., 2023, Standards for the care of people with cystic fibrosis (CF)., J Cyst Fibros
Edmondson C, Westrupp N, Short C, et al., 2023, Unsupervised home spirometry is not equivalent to supervised clinic spirometry in children and young people with cystic fibrosis: results from the CLIMB-CF study, Pediatric Pulmonology, Vol: 58, Pages: 2871-2880, ISSN: 1099-0496
BACKGROUND: Handheld spirometry allows monitoring of lung function at home, of particular importance during the COVID-19 pandemic. Pediatric studies are unclear on whether values are interchangeable with traditional, clinic-based spirometry. We aimed to assess differences between contemporaneous, home (unsupervised) and clinic (supervised) spirometry and the variability of the former. The accuracy of the commercially available spirometer used in the study was also tested. METHODS: Data from participants in the Clinical Monitoring and Biomarkers to stratify severity and predict outcomes in children with cystic fibrosisc (CLIMB-CF) Study aged ≥ 6 years who had paired (±1 day) clinic and home forced expiratory volume in 1 s (FEV1 ) readings were analyzed. Variability during clinical stability over 6-months was assessed. Four devices from Vitalograph were tested using 1 and 3 L calibration syringes. RESULTS: Sixty-seven participants (median [interquartile range] age 10.7 [7.6-13.9] years) provided home and clinic FEV1 data pairs. The mean (SD) FEV1 % bias was 6.5% [±8.2%]) with wide limits of agreement (-9.6% to +22.7%); 76.2% of participants recorded lower results at home. Coefficient of variation of home FEV1 % during stable periods was 9.9%. Data from the testing of the handheld device used in CLIMB-CF showed a potential underread. CONCLUSION: In children and adolescents, home spirometry using hand-held equipment cannot be used interchangeably with clinic spirometry. Home spirometry is moderately variable during clinical stability. New handheld devices underread, particularly at lower volumes of potential clinical significance for smaller patients; this suggests that supervision does not account fully for the discrepancy. Opportunities should be taken to obtain dual device measurements in clinic, so that trend data from home can be utilized more accurately.
Mayer-Hamblett N, Clancy JP, Jain R, et al., 2023, Advancing the pipeline of cystic fibrosis clinical trials: a new roadmap with a global trial network perspective, The Lancet Respiratory Medicine, Vol: 11, Pages: 932-944, ISSN: 2213-2600
The growing use of modulator therapies aimed at restoring cystic fibrosis transmembrane conductance regulator (CFTR) protein function in people with cystic fibrosis has fundamentally altered clinical trial strategies needed to advance new therapeutics across an orphan disease population that is now divided by CFTR modulator eligibility. The development of a robust pipeline of nucleic acid-based therapies (NABTs)-initially directed towards the estimated 10% of the cystic fibrosis population who are genetically ineligible for, or intolerant of, CFTR modulators-is dependent on the optimisation of restricted trial participant resources across multiple development programmes, a challenge that will preclude the use of gold standard placebo-controlled trials. Advancement of a full pipeline of symptomatic therapies across the entire cystic fibrosis population will be challenged by smaller effect sizes and uncertainty regarding their clinical importance in a growing modulator-treated population with more mild and stable pulmonary disease. In this Series paper, we aim to lay the foundation for clinical trial strategy and community partnership that must deviate from established and familiar precedent to advance the future pipeline of cystic fibrosis therapeutics.
Shawcross A, Davies JC, Pabary R, 2023, Variable and evolving degrees of CFTR dysfunction: Implications for diagnosis and clinical management, PAEDIATRIC RESPIRATORY REVIEWS, Vol: 47, Pages: 16-18, ISSN: 1526-0542
Andreou SH, Davies JC, 2023, Cystic fibrosis to CFSPID: burden of care vs need and rational approach to weaning therapies, Paediatric Respiratory Reviews, Vol: 47, Pages: 27-29, ISSN: 1526-0542
We present a case of a 10-year-old boy initially diagnosed with CF based on NBS guidelines. However, as CF genetics knowledge has advanced, he has been reclassified as CFSPID based on normal investigations and excellent general clinical status, in line with updated CFSPID guidelines. This case highlights the significance of reviewing CF diagnoses according to the latest understanding of CFTR mutation phenotypes, as well as the patient's clinical status. In order to identify opportunities to save patients from burdensome CF treatment and management, we review current CFSPID guidelines, emphasizing care tailored to each individual case.
McNally P, Linnane B, Williamson M, et al., 2023, The clinical impact of Lumacaftor-Ivacaftor on structural lung disease and lung function in children aged 6-11 with cystic fibrosis in a real-world setting, Respiratory Research, Vol: 24, Pages: 1-9, ISSN: 1465-9921
BACKGROUND: Data from clinical trials of lumacaftor-ivacaftor (LUM-IVA) demonstrate improvements in lung clearance index (LCI) but not in FEV1 in children with Cystic Fibrosis (CF) aged 6-11 years and homozygous for the Phe508del mutation. It is not known whether LUM/IVA use in children can impact the progression of structural lung disease. We sought to determine the real-world impact of LUM/IVA on lung structure and function in children aged 6-11 years. METHODS: This real-world observational cohort study was conducted across four paediatric sites in Ireland over 24-months using spirometry-controlled CT scores and LCI as primary outcome measures. Children commencing LUM-/IVA as part of routine care were included. CT scans were manually scored with the PRAGMA CF scoring system and analysed using the automated bronchus-artery (BA) method. Secondary outcome measures included rate of change of ppFEV1, nutritional indices and exacerbations requiring hospitalisation. RESULTS: Seventy-one participants were recruited to the study, 31 of whom had spirometry-controlled CT performed at baseline, and after one year and two years of LUM/IVA treatment. At two years there was a reduction from baseline in trapped air scores (0.13 to 0.07, p = 0.016), but an increase from baseline in the % bronchiectasis score (0.84 to 1.23, p = 0.007). There was no change in overall % disease score (2.78 to 2.25, p = 0.138). Airway lumen to pulmonary artery ratios (AlumenA ratio) were abnormal at baseline and worsened over the course of the study. In 28 participants, the mean annual change from baseline LCI2.5 (-0.055 (-0.61 to 0.50), p = 0.85) measurements over two years were not significant. Improvements from baseline in weight (0.10 (0.06 to 0.15, p < 0.0001), height (0.05 (0.02 to 0.09), p = 0.002) and BMI (0.09 (0.03 to 0.15) p = 0.005) z-scores were seen with LUM/IVA treatment. The mean annual
De Wachter E, Davies JC, Simmonds NJ, et al., 2023, Letter to the editor: Risk of false newborn screening after intra-uterine exposure to ETI., J Cyst Fibros
Wainwright C, McColley SA, McNally P, et al., 2023, Long-term safety and efficacy of elexacaftor/tezacaftor/ivacaftor in children aged ⩾6 years with cystic fibrosis and at least one F508del allele: a phase 3, open-label clinical trial., American Journal of Respiratory and Critical Care Medicine, Vol: 208, Pages: 68-78, ISSN: 1073-449X
Rationale: A 24-week, phase 3, open-label study showed elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was safe and efficacious in children aged 6-11 years with cystic fibrosis (CF) and one or more F508del-CFTR alleles. Objectives: To assess long-term safety and efficacy of ELX/TEZ/IVA in children who completed the pivotal 24-week phase 3 trial. Methods: In this phase 3, two-part (part A and part B), open-label extension study, children aged ⩾6 years with CF heterozygous for F508del and a minimal function CFTR mutation (F/MF genotypes) or homozygous for F508del (F/F genotype) who completed the 24-week parent study received ELX/TEZ/IVA based on weight. Children weighing <30 kg received ELX 100 mg once daily/TEZ 50 mg once daily/IVA 75 mg every 12 hours, whereas children weighing ⩾30 kg received ELX 200 mg once daily/TEZ 100 mg once daily/IVA 150 mg every 12 hours (adult dose). The 96-week analysis of part A of this extension study is reported here. Measurements and Main Results: Sixty-four children (F/MF genotypes, n = 36; F/F genotype, n = 28) were enrolled and received one or more doses of ELX/TEZ/IVA. Mean (SD) period of exposure to ELX/TEZ/IVA was 93.9 (11.1) weeks. The primary endpoint was safety and tolerability. Adverse events and serious adverse events were consistent with common manifestations of CF disease. Overall, exposure-adjusted rates of adverse events and serious adverse events (407.74 and 4.72 events per 100 patient-years) were lower than in the parent study (987.04 and 8.68 events per 100 patient-years). One child (1.6%) had an adverse event of aggression that was moderate in severity and resolved after study drug discontinuation. From parent study baseline at Week 96 of this extension study, the mean percent predicted FEV1 increased (11.2 [95% confidence interval (CI), 8.3 to 14.2] percentage points), sweat chloride
Davies J, Southern KW, Barben J, et al., 2023, Raised intracranial pressure in three children with cystic fibrosis receiving elexacaftor-tezacaftor-ivacaftor modulator therapy, American Journal of Respiratory and Critical Care Medicine, Vol: 208, Pages: 103-105, ISSN: 1073-449X
Sandhu D, Redmond JL, Smith NMJ, et al., 2023, Computed cardiopulmonography and the idealized lung clearance index, iLCI2.5, in early-stage cystic fibrosis., Journal of Applied Physiology, Vol: 135, Pages: 205-216, ISSN: 1522-1601
This study explored the use of computed cardiopulmonography (CCP) to assess lung function in early-stage cystic fibrosis (CF). CCP has two components. The first is a particularly accurate technique for measuring gas exchange. The second is a computational cardiopulmonary model where patient-specific parameters can be estimated from the measurements of gas exchange. Twenty-five participants (14 healthy controls, 11 early-stage CF) were studied with CCP. They were also studied with a standard clinical protocol to measure the lung clearance index (LCI2.5). Ventilation inhomogeneity, as quantified through CCP parameter σlnCl, was significantly greater (P < 0.005) in CF than in controls, and anatomical deadspace relative to predicted functional residual capacity (DS/FRCpred) was significantly more variable (P < 0.002). Participant-specific parameters were used with the CCP model to calculate idealized values for LCI2.5 (iLCI2.5) where extrapulmonary influences on the LCI2.5, such as breathing pattern, had all been standardized. Both LCI2.5 and iLCI2.5 distinguished clearly between CF and control participants. LCI2.5 values were mostly higher than iLCI2.5 values in a manner dependent on the participant's respiratory rate (r = 0.46, P < 0.05). The within-participant reproducibility for iLCI2.5 appeared better than for LCI2.5, but this did not reach statistical significance (F ratio = 2.2, P = 0.056). Both a sensitivity analysis on iLCI2.5 and a regression analysis on LCI2.5 revealed that these depended primarily on an interactive term between CCP parameters of the form σlnCL*(DS/FRC). In conclusion, the LCI2.5 (or iLCI2.5) probably reflects an amalgam of different underlying lung changes in early-stage CF that would require a multiparameter approach, such as potentially CCP, to resolve.NEW & NOTEWORTHY Computed cardiopulmonography is a new technique comprising a highly accurate sensor for measuring respiratory gas exchange coupled with a cardiopulm
Andrade EDQ, Bailey B, Davies JCC, et al., 2023, Reply to migration is not the perfect answer: Optimized methodology to assess LCI agreement between corrected legacy multiple breath nitrogen washout data and that directly collected on updated software, PEDIATRIC PULMONOLOGY, Vol: 58, Pages: 1861-1863, ISSN: 8755-6863
Davies J, Dobra R, Wilson G, et al., 2023, A systematic review to identify and collate factors influencing patient journeys through clinical trials, JRSM Open, Vol: 14, Pages: 1-11, ISSN: 2054-2704
Patient-centred trial design and delivery; improves recruitment and retention; increases participant satisfaction; encourages participation by a more representative cohort; and allows researchers to better meet participants’ needs. Research in this area mostly focusses on narrow facets of trial participation. We aimed to systematically identify the breadth of patient-centred factors influencing participation and engagement in trials, and collate them into a framework. Through this we hoped to assist researchers to identify factors that could improve patient-centred trial design and delivery. Robust qualitative and mixed methods systematic reviews are becoming increasingly common in health research. The protocol for this review was prospectively registered on PROSPERO, CRD42020184886. We used the SPIDER (Sample, Phenomenon of Interest, Design, Evaluation, Research Type) framework as a standardised systematic search strategy tool. 3 databases were searched as well as references checking, and thematic synthesis was conducted. Screening agreement was performed and code and theme checking were conducted by 2 independent researchers. Data were drawn from 285 peer-reviewed articles. 300 discrete factors were identified, and sorted into 13 themes and subthemes. The full catalogue of factors is included in the Supplementary Material. A summary framework is included in the body of the article. This paper focusses on outlining common ground that themes share, highlighting critical features, and exploring interesting points from the data. Through this, we hope researchers from multiple specialities may be better able to meet patients’ needs, protect patients’ psychosocial wellbeing, and optimise trial recruitment and retention, with direct positive impact on research time and cost efficiency.
Davies J, Morales S, Alton E, et al., 2023, Lytic bacteriophage is a promising adjunct to common antibiotics across cystic fibrosis clinical strains and culture models of Pseudomonas aeruginosa infection, Antibiotics, Vol: 12, Pages: 1-14, ISSN: 2079-6382
Bacteriophages (phages) are antimicrobials with resurgent interest that are being investigated for the treatment of antibiotic refractory infection, including for Pseudomonas aeruginosa (Pa) lung infection in cystic fibrosis (CF). In vitro work supports the use of this therapy in planktonic and biofilm culture models; however, consistent data are lacking for efficacy across different clinical Pa strains, culture models, and in combination with antibiotics in clinical use. We first examined the efficacy of a 4-phage cocktail as an adjunct to our CF centre’s first-line systemic combination antibiotic therapy (ceftazidime + tobramycin) for 16 different clinical Pa strains and then determined subinhibitory interactions for a subset of these strains with each antibiotic in planktonic and biofilm culture. When a 4-phage cocktail (4 × 108 PFU/mL) was added to a ceftazidime-tobramycin combination (ceftazidime 16 mg/mL + tobramycin 8 mg/mL), we observed a 1.7-fold and 1.3-fold reduction in biofilm biomass and cell viability, respectively. The four most antibiotic resistant strains in biofilm were very susceptible to phage treatment. When subinhibitory concentrations of antibiotics and phages were investigated, we observed additivity/synergy as well as antagonism/inhibition of effect that varied across the clinical strains and culture model. In general, more additivity was seen with the phage-ceftazidime combination than with phage-tobramycin, particularly in biofilm culture, where no instances of additivity were seen when phages were combined with tobramycin. The fact that different bacterial strains were susceptible to phage treatment when compared to standard antibiotics is promising and these results may be relevant to ongoing clinical trials exploring the use of phages, in particular in the selection of subjects for clinical trials.
Davies J, Hughes D, Rosenthal M, et al., 2023, An invisible threat? Aspergillus positive cultures and co-infecting bacteria in airway sample, Journal of Cystic Fibrosis, Vol: 22, Pages: 320-326, ISSN: 1569-1993
BackgroundAspergillus fumigatus (Af) infection is associated with poor lung health in chronic suppurative lung diseases but often goes undetected. We hypothesised that inhibition of Af growth by Pseudomonas aeruginosa (Pa) increases the frequency of false-negative Af culture in co-infected people. Using a substantial group of cystic fibrosis (CF) airway samples, we assessed the relationship between Af and bacterial pathogens, additionally comparing fungal culture with next-generation sequencing.MethodsFrequency of co-culture was assessed for 44,554 sputum/BAL cultures, from 1,367 CF patients between the years 2010–2020. In a subgroup, Internal Transcribed Spacer-2 (ITS2) fungal sequencing was used to determine sequencing-positive, culture-negative (S+/C-) rates.ResultsPa+ samples were nearly 40% less likely (P<0.0001) than Pa- samples to culture Af, an effect that was also seen with some other Gram-negative isolates. This impact varied with Pa density and appeared to be moderated by Staphylococcus aureus co-infection. Sequencing identified Af-S+/C- for 40.1% of tested sputa. Samples with Pa had higher rates of Af-S+/C- (49.3%) than those without (35.7%; RR 1.38 [1.02–1.93], P<0.05). Af-S+/C- rate was not changed by other common bacterial infections. Pa did not affect the S+/C- rates of Candida, Exophiala or Scedosporium.ConclusionsPa/ Af co-positive cultures are less common than expected in CF. Our findings suggest an Af-positive culture is less likely in the presence of Pa. Interpretation of negative cultures should be cautious, particularly in Pa-positive samples, and a companion molecular diagnostic could be useful. Further work investigating mechanisms, alternative detection techniques and other chronic suppurative lung diseases is needed.
Robinson L, Collins A, Murphy R, et al., 2023, Diversity and prevalence of type VI secretion system effectors in clinical Pseudomonas aeruginosa isolates, Frontiers in Microbiology, Vol: 13, ISSN: 1664-302X
Pseudomonas aeruginosa is an opportunistic pathogen and a major driver of morbidity and mortality in people with Cystic Fibrosis (CF). The Type VI secretion system (T6SS) is a molecular nanomachine that translocates effectors across the bacterial membrane into target cells or the extracellular environment enabling intermicrobial interaction. P. aeruginosa encodes three T6SS clusters, the H1-, H2- and H3-T6SS, and numerous orphan islands. Genetic diversity of T6SS-associated effectors in P. aeruginosa has been noted in reference strains but has yet to be explored in clinical isolates. Here, we perform a comprehensive bioinformatic analysis of the pangenome and T6SS effector genes in 52 high-quality clinical P. aeruginosa genomes isolated from CF patients and housed in the Personalised Approach to P. aeruginosa strain repository. We confirm that the clinical CF isolate pangenome is open and principally made up of accessory and unique genes that may provide strain-specific advantages. We observed genetic variability in some effector/immunity encoding genes and show that several well-characterised vgrG and PAAR islands are absent from numerous isolates. Our analysis shows clear evidence of disruption to T6SS genomic loci through transposon, prophage, and mobile genetic element insertions. We identified an orphan vgrG island in P. aeruginosa strain PAK and five clinical isolates using in silico analysis which we denote vgrG7, predicting a gene within this cluster to encode a Tle2 lipase family effector. Close comparison of T6SS loci in clinical isolates compared to reference P. aeruginosa strain PAO1 revealed the presence of genes encoding eight new T6SS effectors with the following putative functions: cytidine deaminase, lipase, metallopeptidase, NADase, and pyocin. Finally, the prevalence of characterised and putative T6SS effectors were assessed in 532 publicly available P. aeruginosa genomes, which suggests the existence of accessory effectors. Our in silico study of
Southern KW, Castellani C, Lammertyn E, et al., 2023, Standards of care for <i>CFTR</i> variant-specific therapy (including modulators) for people with cystic fibrosi, JOURNAL OF CYSTIC FIBROSIS, Vol: 22, Pages: 17-30, ISSN: 1569-1993
Mall MA, Brugha R, Gartner S, et al., 2022, Efficacy and Safety of Elexacaftor/Tezacaftor/Ivacaftor in Children 6 Through 11 Years of Age with Cystic Fibrosis Heterozygous for <i>F508del</i> and a Minimal Function Mutation A Phase 3b, Randomized, Placebo-controlled Study, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 206, Pages: 1361-1369, ISSN: 1073-449X
Gifford AH, Taylor-Cousar JL, Davies JC, et al., 2022, Update on Clinical Outcomes of Highly Effective Modulator Therapy, CLINICS IN CHEST MEDICINE, Vol: 43, Pages: 677-695, ISSN: 0272-5231
Brown D, Davies J, Dobra R, et al., 2022, LEVELLING THE PLAYING FIELD: IMPROVING ACCESS TO CYSTIC FIBROSIS CLINICAL TRIALS FOR A LARGE, REGIONAL POPULATION. LESSONS LEARNED FROM THE LONDON NETWORK OF THE UK CLINICAL TRIALS ACCELERATOR PLATFORM, Winter Meeting of the British-Thoracic-Society (BTS), Publisher: BMJ PUBLISHING GROUP, Pages: A115-A116, ISSN: 0040-6376
King JA, Cunanan A, Aziz S, et al., 2022, PAWS FOR THOUGHT: SNIFFER DOGS FOR INFECTION SURVEILLANCE IN NON-SPUTUM PRODUCING PEOPLE WITH CF, Winter Meeting of the British-Thoracic-Society (BTS), Publisher: BMJ PUBLISHING GROUP, Pages: A21-A21, ISSN: 0040-6376
Dobra RA, Davies JC, Elborn JS, et al., 2022, A DISCRETE CHOICE EXPERIMENT (DCE) TO QUANTIFY THE INFLUENCE OF TRIAL FEATURES ON THE DECISION TO PARTICIPATE IN CYSTIC FIBROSIS (CF) TRIALS, Winter Meeting of the British-Thoracic-Society (BTS), Publisher: BMJ PUBLISHING GROUP, Pages: A114-A115, ISSN: 0040-6376
Drevinek P, Canton R, Johansen HK, et al., 2022, New concepts in antimicrobial resistance in cystic fibrosis respiratory infections, JOURNAL OF CYSTIC FIBROSIS, Vol: 21, Pages: 937-945, ISSN: 1569-1993
Mahenthiralingam E, Weiser R, Floto RA, et al., 2022, Selection of relevant bacterial strains for novel therapeutic testing: a guidance document for priority cystic fibrosis lung pathogens, Current Clinical Microbiology Reports, Vol: 9, Pages: 33-45, ISSN: 2196-5471
Purpose of ReviewPeople with cystic fibrosis (CF) suffer chronic lung infections with a range of antimicrobial-resistant bacterial pathogens. There is an urgent need for researchers to develop novel anti-infectives to treat these problematic infections, but how can we select bacterial strains which are relevant for robust testing and comparative research?Recent FindingsPseudomonas aeruginosa, Burkholderia cepacia complex and Burkholderia gladioli, Mycobacterium abscessus complex, Staphylococcus aureus, Haemophilus influenza, and several multidrug-resistant Gram-negative species were selected as key CF infections that urgently require new therapeutics. Reference isolates and strain panels were identified, and a summary of the known genotypic diversity of each pathogen was provided.SummaryHere, we summarise the current strain resources available for priority CF bacterial pathogens and highlight systematic selection criteria that researchers can use to select strains for use in therapeutic testing.
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