Mol Genet Genomic Med. 2022 Aug 13:e2033. doi: 10.1002/mgg3.2033. Online ahead of print.

NO ABSTRACT

PMID:35962622 | DOI:10.1002/mgg3.2033

Pediatr Pulmonol. 2022 Aug 12. doi: 10.1002/ppul.26114. Online ahead of print.

ABSTRACT

BACKGROUND: Our aim was to determine whether early chronic methicillin-susceptible Staphylococcus aureus (MSSA) colonization in children with cystic fibrosis (CF) is associated at 8 years of age with poorer lung function, poorer nutritional status and increased exacerbation frequency.

METHODS: In this retrospective cohort study, a total of 52 children with chronic MSSA colonization were included. Of them, 26 were chronically colonized with MSSA before the age of 4 years (early-onset), and 26 were chronically colonized from 4 years to 6 years of age (late-onset). At the age of 8 years, lung function, body mass index (BMI) as an indicator of nutritional status and frequency of pulmonary exacerbations were compared between two groups.

RESULTS: At 8 years of age, BMI was similar between the early-onset and late-onset groups [15.0 (min-max: 12.9-26.8) vs 15.7 (min-max: 13.0-24.9), p=0.327]. Percentage of forced expiratory volume in 1 second (FEV1) and forced expiratory flow between 25% and 75% of vital capacity (FEF25-75) in 8-year-old children were significantly lower in the early-onset group compared to the late-onset group [98 (min-max: 44-139) vs 106.5 (min-max: 82-131), p=0.047; 84.9 ± 25.5 vs -102.3 ± 26.3, respectively; p=0.019], although the percentage of forced vital capacity did not differ significantly between two groups [93.5 (min-max: 45-131) vs 103 (min-max: 84-119), respectively; p=0.092]. Exacerbation frequency between the ages of 6 and 8 years in the early-onset group was higher compared to the late-onset group according to the Poisson regression model [1 (min-max:0-10) vs 0 (min-max:0-4), respectively; p=0.044].

CONCLUSIONS: Early chronic MSSA colonization is associated with poorer lung function and frequent exacerbations in children with CF. However, further studies are needed to reveal the cause-and-effect relationship between early chronic MSSA colonization and pulmonary outcome. This article is protected by copyright. All rights reserved.

PMID:35962540 | DOI:10.1002/ppul.26114

Pediatr Pulmonol. 2022 Aug 12. doi: 10.1002/ppul.26116. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) represents a lifelong, chronic disease that requires intensive, regimented care for the entire duration of a patient's life This article is protected by copyright. All rights reserved.

PMID:35962539 | DOI:10.1002/ppul.26116

J Cyst Fibros. 2022 Aug 9:S1569-1993(22)00602-6. doi: 10.1016/j.jcf.2022.07.003. Online ahead of print.

ABSTRACT

QUESTION: In diseases such as asthma and cystic fibrosis (CF), the immune response is dysregulated and the lung is chronically inflamed. Orai1 activation is required for the initiation and persistence of inflammation. However, Orai1 expression in the lung is poorly understood. We therefore tested the hypothesis that Orai1 expression was upregulated in asthmatic and CF lungs.

MATERIALS AND METHODS: We used LungMAP to analyze single-cell RNAseq data of Orai1 and stromal interaction molecule 1 (STIM1) expression in normal human lungs. We then performed RNAscope analysis and immunostaining on lung sections from normal, asthma, and CF donors. We imaged sections by confocal and super resolution microscopy, and analyzed Orai1 and STIM1 expression in different pulmonary cell types.

RESULTS: Orai1 was broadly-expressed, but expression was greatest in immune cells. At mRNA and protein levels, there were no consistent trends in expression levels between the three phenotypes. Orai1 must interact with STIM1 in order to activate and conduct Ca2+. We therefore used STIM1/Orai1 co-localization as a marker of Orai1 activity. Using this approach, we found significantly increased co-localization between these proteins in epithelia, interstitial and luminal immune cells, but not alveoli, from asthma and CF lungs. Orai1 also aggregates as part of its activation process. Using super resolution microscopy, we also found significantly increased Orai1 aggregation in immune cells from asthmatic and CF lungs.

CONCLUSION: We found evidence that Orai1 was more active in asthma and CF than normal lungs. These data suggest that Orai1 is a relevant target for reducing pulmonary inflammation.

PMID:35961837 | DOI:10.1016/j.jcf.2022.07.003

Ther Adv Chronic Dis. 2022 Aug 5;13:20406223221108627. doi: 10.1177/20406223221108627. eCollection 2022.

ABSTRACT

Cystic fibrosis (CF) is caused by two mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. In the last years, drugs targeting the underlying protein defect like lumacaftor/ivacaftor (LUM/IVA) or tezacaftor/ivacaftor (TEZ/IVA) and more recently elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) were admitted. Outcome parameters evaluating therapy response like forced expiratory pressure in 1 s (FEV1), body mass index (BMI) or the efficacy of CFTR function in sweat glands showed improvement in several cases. Other, CFTR biomarkers were analysed rarely. This prospective observational study was aimed at evaluating CFTR function in patients treated with different CFTR modulators together with common valid clinical outcome parameters at standardized appointments (day 0, week 2, 4, 16). We followed four patients with the same mutation (F508del-CFTR), sex, age and disease severity. Monitoring focused on lung function, gastrointestinal aspects and CFTR function of sweat glands, nasal and intestinal epithelium. Sweat tests were performed by pilocarpine iontophoresis. Nasal potential difference (NPD) measured transepithelial voltage in vivo and potential increased when CFTR function improved. Rectal biopsies were obtained for intestinal current measurements (ICM) ex vivo. Intestinal CFTR function was assessed by stimulating chloride secretion with different reagents. Response to CFTR modulators regarding clinical outcome parameters was rather variable. A sweat chloride reduction of 35.3 mmol/L, nasal CFTR rescue of 4.4% and fivefold higher CFTR function in the intestine was seen at week 16 post-LUM/IVA. Due to our monitoring, we identified a non-responder to LUM/IVA and TEZ/IVA. In case of ELX/TEZ/IVA, clinical parameters and CFTR bioassays improved and were concordant. Although our cohort is small, results emphasize that non-responders exist and conclusions could not be drawn if patients were not monitored. Data on CFTR function can confirm or disprove ongoing CFTR dysfunction and might be helpful selectively. Non-responders need other alternative therapy options as demonstrated with ELX/TEZ/IVA.

PMID:35959505 | PMC:PMC9358561 | DOI:10.1177/20406223221108627

Open Forum Infect Dis. 2022 Jul 26;9(8):ofac375. doi: 10.1093/ofid/ofac375. eCollection 2022 Aug.

ABSTRACT

Coinfections are more common in patients with cystic fibrosis and bronchiectasis. Infiltrates on imaging studies are seen more commonly in patients with coinfections, but coinfections did not affect treatment outcomes of pulmonary Mycobacterium avium complex.

PMID:35959208 | PMC:PMC9361173 | DOI:10.1093/ofid/ofac375

Front Pediatr. 2022 Jul 25;10:954608. doi: 10.3389/fped.2022.954608. eCollection 2022.

ABSTRACT

Bronchiectasis (BE) is a chronic condition affecting the bronchial tree. It is characterized by the dilatation of large and medium-sized airways, secondary to damage of the underlying bronchial wall structural elements and accompanied by the clinical picture of recurrent or persistent cough. Despite an increased awareness of childhood BE, there is still a paucity of data on the epidemiology, pathophysiological phenotypes, diagnosis, management, and outcomes in Africa where the prevalence is mostly unmeasured, and likely to be higher than high-income countries. Diagnostic pathways and management principles have largely been extrapolated from approaches in adults and children in high-income countries or from data in children with cystic fibrosis. Here we provide an overview of pediatric BE in Africa, highlighting risk factors, diagnostic and management challenges, need for a global approach to addressing key research gaps, and recommendations for practitioners working in Africa.

PMID:35958169 | PMC:PMC9357921 | DOI:10.3389/fped.2022.954608

Nutrients. 2022 Jul 30;14(15):3160. doi: 10.3390/nu14153160.

ABSTRACT

In the last 20 years, gut microbiota in patients with cystic fibrosis (CF) has become an object of interest. It was shown that these patients had gut dysbiosis and this could explain not only the intestinal manifestations of the disease but also part of those involving the respiratory tract. The acquisition of previously unknown information about the importance of some bacteria, i.e., those partially or totally disappeared in the gut of CF patients, in the regulation of the activity and function of the gut and the lung was the base to suggest the use of probiotics in CF patients. The main aim of this paper is to discuss the biological basis for probiotic administration to CF patients and which results could be expected. Literature analysis showed that CF intestinal dysbiosis depends on the same genetic mutations that condition the clinical picture of the diseases and is aggravated by a series of therapeutic interventions, such as dietary modifications, the use of antibiotics, and the administration of antacids. All this translates into a significant worsening of the structure and function of organs, including the lung and intestine, already deeply penalized by the genetic alterations of CF. Probiotics can intervene on dysbiosis, reducing the negative effects derived from it. However, the available data cannot be considered sufficient to indicate that these bacteria are essential elements of CF therapy. Further studies that take into account the still unsolved aspects on how to use probiotics are absolutely necessary.

PMID:35956335 | DOI:10.3390/nu14153160

Int J Mol Sci. 2022 Aug 8;23(15):8831. doi: 10.3390/ijms23158831.

ABSTRACT

Smoltification (parr-smolt transformation) is a complex developmental process consisting of developmental changes that lead to remodeling of the Atlantic salmon gill. Here, the expression changes of miRNAs and mRNAs were studied by small-RNA sequencing and microarray analysis, respectively, to identify miRNAs and their predicted targets associated with smoltification and subsequent sea water adaptation (SWA). In total, 18 guide miRNAs were identified as differentially expressed (gDE miRNAs). Hierarchical clustering analysis of expression changes divided these into one cluster of 13 gDE miRNAs with decreasing expression during smoltification and SWA that included the miRNA-146, miRNA-30 and miRNA-7132 families. Another smaller cluster that showed increasing expression consisted of miR-101a-3p, miR-193b-5p, miR-499a-5p, miR-727a-3p and miR-8159-5p. The gDE miRNAs were predicted to target 747 of the genes (DE mRNAs), showing expression changes in the microarray analysis. The predicted targets included genes encoding NKA-subunits, aquaporin-subunits, cystic fibrosis transmembrane conductance regulator and the solute carrier family. Furthermore, the predicted target genes were enriched in biological processes associated with smoltification and SWA (e.g., immune system, reactive oxygen species, stress response and extracellular matrix organization). Collectively, the results indicate that remodeling of the gill involves the post-transcriptional regulation of gene expression by the characterized gDE miRNAs.

PMID:35955964 | DOI:10.3390/ijms23158831

Int J Mol Sci. 2022 Jul 29;23(15):8427. doi: 10.3390/ijms23158427.

ABSTRACT

Pseudomonas aeruginosa (P.a) is a pathogen causing significant morbidity and mortality, particularly in hospital patients undergoing ventilation and in individuals with cystic fibrosis. Although we and others have investigated mechanisms used by P.a to subvert innate immunity, relatively less is known about the potential strategies used by this bacterium to fight the adaptive immune system and, in particular, T cells. Here, using RAG KO (devoid of 'classical' αβ and γδ TCR T lymphocytes) and double RAG γC KO mice (devoid of T, NK and ILC cells), we demonstrate that the lymphocytic compartment is important to combat P.a (PAO1 strain). Indeed, we show that PAO1 load was increased in double RAG γC KO mice. In addition, we show that PAO1 down-regulates IL-23 and IL-22 protein accumulation in the lungs of infected mice while up-regulating their RNA production, thereby pointing towards a specific post-transcriptional regulatory mechanism not affecting other inflammatory mediators. Finally, we demonstrate that an adenovirus-mediated over-expression of IL-1, IL-23 and IL-7 induced lung neutrophil and lymphocytic influx and rescued mice against P.a-induced lethality in all WT, RAG γC KO and RAG γC KO RAG-deficient mice, suggesting that this regimen might be of value in 'locally immunosuppressed' individuals such as cystic fibrosis patients.

PMID:35955566 | DOI:10.3390/ijms23158427

Cells. 2022 Aug 4;11(15):2411. doi: 10.3390/cells11152411.

ABSTRACT

Mucociliary clearance is a primary defence mechanism of the airways consisting of two components, ciliary beating and transepithelial ion transport (ISC). Specialised chemosensory cholinergic epithelial cells, named brush cells (BC), are involved in regulating various physiological and immunological processes. However, it remains unclear if BC influence ISC. In murine tracheae, denatonium, a taste receptor agonist, reduced basal ISC in a concentration-dependent manner (EC50 397 µM). The inhibition of bitter taste signalling components with gallein (Gβγ subunits), U73122 (phospholipase C), 2-APB (IP3-receptors) or with TPPO (Trpm5, transient receptor potential-melastatin 5 channel) reduced the denatonium effect. Supportively, the ISC was also diminished in Trpm5-/- mice. Mecamylamine (nicotinic acetylcholine receptor, nAChR, inhibitor) and amiloride (epithelial sodium channel, ENaC, antagonist) decreased the denatonium effect. Additionally, the inhibition of Gα subunits (pertussis toxin) reduced the denatonium effect, while an inhibition of phosphodiesterase (IBMX) increased and of adenylate cyclase (forskolin) reversed the denatonium effect. The cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor CFTRinh172 and the KCNQ1 potassium channel antagonist chromanol 293B both reduced the denatonium effect. Thus, denatonium reduces ISC via the canonical bitter taste signalling cascade leading to the Trpm5-dependent nAChR-mediated inhibition of ENaC as well as Gα signalling leading to a reduction in cAMP-dependent ISC. Therefore, BC activation contributes to the regulation of fluid homeostasis.

PMID:35954259 | DOI:10.3390/cells11152411

Cells. 2022 Jul 31;11(15):2358. doi: 10.3390/cells11152358.

ABSTRACT

In clinical routine, the diagnosis of cystic fibrosis (CF) is still challenging regardless of international consensus on diagnosis guidelines and tests. For decades, the classical Gibson and Cooke test measuring sweat chloride concentration has been a keystone, yet, it may provide normal or equivocal results. As of now, despite the combination of sweat testing, CFTR genotyping, and CFTR functional testing, a small fraction (1-2%) of inconclusive diagnoses are reported and justifies the search for new CF biomarkers. More importantly, in the context of precision medicine, with a view to early diagnosis, better prognosis, appropriate clinical follow-up, and new therapeutic development, discovering companion biomarkers of CF severity and phenotypic rescue are of utmost interest. To date, previous sweat proteomic studies have already documented disease-specific variations of sweat proteins (e.g., in schizophrenia and tuberculosis). In the current study, sweat samples from 28 healthy control subjects and 14 patients with CF were analyzed by nanoUHPLC-Q-Orbitrap-based shotgun proteomics, to look for CF-associated changes in sweat protein composition and abundance. A total of 1057 proteins were identified and quantified at an individual level, by a shotgun label-free approach. Notwithstanding similar proteome composition, enrichment, and functional annotations, control and CF samples featured distinct quantitative proteome profiles significantly correlated with CF, accounting for the respective inter-individual variabilities of control and CF sweat. All in all: (i) 402 sweat proteins were differentially abundant between controls and patients with CF, (ii) 68 proteins varied in abundance between F508del homozygous patients and patients with another genotype, (iii) 71 proteins were differentially abundant according to the pancreatic function, and iv) 54 proteins changed in abundance depending on the lung function. The functional annotation of pathophysiological biomarkers highlighted eccrine gland cell perturbations in: (i) protein biosynthesis and trafficking, (ii) CFTR proteostasis and membrane stability, and (iii) cell-cell adherence, membrane integrity, and cytoskeleton crosstalk. Cytoskeleton-related biomarkers were of utmost interest because of the consistency between variations observed here in CF sweat and variations previously documented in other CF tissues. From a clinical stance, nine candidate biomarkers of CF diagnosis (CUTA, ARG1, EZR, AGA, FLNA, MAN1A1, MIA3, LFNG, SIAE) and seven candidate biomarkers of CF severity (ARG1, GPT, MDH2, EML4 (F508del homozygous), MGAT1 (pancreatic insufficiency), IGJ, TOLLIP (lung function impairment)) were deemed suitable for further verification.

PMID:35954202 | DOI:10.3390/cells11152358

Pharmaceut Med. 2022 Aug 12. doi: 10.1007/s40290-022-00442-y. Online ahead of print.

ABSTRACT

Life science research and development (R&D) companies are all too aware of the importance of patient perspectives but also of the barriers to engaging directly with patients, not least compliance, complex technical and regulatory issues, and the need to meet multifaceted expectations. Medical research charities (MRCs), highly technical and professional organisations, work directly with patients; they represent an expert resource for the science of their field, for disease-related patient advocacy issues and to advise and assist R&D companies in devising meaningful trials. The Pistoia Alliance, a non-profit organisation facilitating life sciences R&D, gathered a number of UK MRCs focused on complex lifelong conditions. The group used workshops and an opinion questionnaire for a snapshot of how the charities believe their knowledge and patient experiences could contribute insights and efficiencies to commercial R&D. MRCs argued that for chronic conditions, the patient perspective is vital in facilitating and de-risking trials, promoting patient motivation, compliance and study viability. MRCs and the patients they represent want to see successful trials, and it is in everyone's interest that well considered studies can proceed. Today, with remote assessments, consumer wearables and digital health technologies, MRCs and patients are already collating substantial data sets that are relevant to quality-of-life benefits, regulatory and value assessments, all of great interest to biopharmaceutical companies. In turn, MRCs would benefit from the experience of biopharma in generating clinical data and implementing novel technologies.

PMID:35953655 | DOI:10.1007/s40290-022-00442-y

Br J Biomed Sci. 2022 Jun 8;79:10468. doi: 10.3389/bjbs.2022.10468. eCollection 2022.

ABSTRACT

Introduction: There is a paucity of reports on non-aeruginosa Pseudomonas (NAPs) in cystic fibrosis, hence this study wished 1). to examine the diversity/frequency of NAPs in an adult CF population, 2) to compare/contrast the microbiology and genomics of NAPs to P. aeruginosa and 3) to propose clinical and laboratory criteria to help determine their clinical significance in CF lung pathology. Materials and Methods: Microbiological data was examined from 100 adult patients with cystic fibrosis from birth to present (31/12/2021), equating to 2455 patient years. 16S rDNA phylogenetic relatedness of NAPs was determined, as well as bioinformatical comparison of whole genomes of P. aeruginosa against P. fluorescens. Results: Ten species were isolated from this patient cohort during this time period, with three species, i.e., P. fluorescens, P. putida and P. stutzeri, accounting for the majority (87.5%) of non-aeruginosa reports. This is the first report of the isolation of P. fragi, P. nitroreducens, P. oryzihabitans and P. veronii in patients with cystic fibrosis. The mean time to first detection of any non-aeruginosa species was 183 months (15.25 years) [median = 229 months (19.1 years)], with a range from 11 months to 338 months (28.2 years). Several of the NAPs were closely related to P. aeruginosa. Discussion: NAPs were isolated infrequently and were transient colonisers of the CF airways, in those patients with CF in which they were isolated. A set of ten clinical and laboratory criteria are proposed to provide key indicators, as to the clinical importance of the non-aeruginosa species isolated.

PMID:35951661 | PMC:PMC9302546 | DOI:10.3389/bjbs.2022.10468

Mikrochim Acta. 2022 Aug 11;189(9):327. doi: 10.1007/s00604-022-05431-1.

ABSTRACT

A silver-manganese nanocomposite was successfully prepared by the urea hydrolysis method and used to detect chloride ions in sweat electrochemically. The synthesis involves the reaction of manganese sulphate, silver nitrate, and urea at 100 °C for 24 h. The crystalline nature of the particle was studied by diffraction analysis and found to be mixed-phase oxides of manganese alongside the oxides of silver. Morphological studies revealed the presence of quasi-prism-like structures, which is characteristic of β-MnO2. A disposable sensor was fabricated by screen-printing the catalyst and used for the electrochemical detection of chloride ions in sweat. The sensor exhibited good selectivity, a sensitivity of 22.93 ± 0.64 µA mM-1 cm-2 in solution and 3010 ± 60 µA (log mM) -1 cm-2 for the fabricated sensor strip with a detection range from 5 mM up to 200 mM. The detection limit is 207 ± 7 µM (S/N = 3) in solution and 17 ± 6 µM for the fabricated sensor strip. The relative standard deviation (RSD) of sensor response is 2.38%. A prototype of the biosensor strip was fabricated and validated using real samples. This brings the possibility of developing a real-time biosensor strip for cystic fibrosis in point-of-care testing applications.

PMID:35951246 | DOI:10.1007/s00604-022-05431-1

Clin Case Rep. 2022 Aug 5;10(8):e05869. doi: 10.1002/ccr3.5869. eCollection 2022 Aug.

ABSTRACT

We present a case report of a fetal diagnosis of cystic fibrosis after ultrasound abnormalities. After delivery, a type 3A intestinal atresia was diagnosed. Segmental enterectomy with end-to-end anastomosis was performed. This case report highlights the diagnosis complexity of a fetal intestinal atresia associated with cystic fibrosis.

PMID:35949411 | PMC:PMC9353861 | DOI:10.1002/ccr3.5869

Ann Palliat Med. 2022 Aug 10:apm-22-290. doi: 10.21037/apm-22-290. Online ahead of print.

ABSTRACT

BACKGROUND: There is a lack of effective platforms that can rapidly screen drugs, for patients to achieve precision treatment. Since an organoid simulates the tissue or organ structure and function in vitro, it can be applied to predict the response to therapy, personalized medicine, and drug screening in clinical practice. However, the rapid development of this field meets several challenges. This study aimed to evaluate the current state of the organoid and prioritize future research areas using bibliometric analysis.

METHODS: We selected articles and reviewers from the Web of Science database, using the search strategy syntax including "organoid" or "organoids", for the years 2011 to 2020. We conducted a general analysis and a thematic evolution analysis using the bibliometrix R package. Networks connecting productive countries/ regions/institutions/authors were generated using VOSviewer. We performed a co-occurrence analysis using VOSviewer, burstness analysis using Citespace, and co-word biclustering analysis and landform map using BICOMB and gCLUTO to identify possible current and future directions and hotspots.

RESULTS: We selected 3,168 publications for our analysis. We found that the number of publications in this field has increased sharply. The greatest contributions to organoid research have been made by the United States (among countries) and the University of Michigan (among institutions), and Hans Clevers is the most influential author. The journals with the highest number of selected articles and citations are Cancer Research and Nature. We observed the possibility of keyword classification into five clusters. Their trend changed from "methods to build organoids" (e.g., "lgr5+ stem cell" and "3D culture") to "practical applications of organoids" (e.g., "cystic fibrosis" and "Zika virus").

CONCLUSIONS: Our study used bibliometric analysis to provide an in-depth understanding of the trends and hotspots of organoid research. The primarily important subject matters are drug screening, disease modeling, personalized medicine, regenerative medicine, and developmental biology. However, this field still faces limitations in the form of lack of reproducibility, low levels of maturity and function, and the absence of appropriate readouts. Therefore, these five significant topics, and possible solutions to limitations (involving bioengineering strategies), might be noteworthy in the future.

PMID:35948469 | DOI:10.21037/apm-22-290

Eur Respir J. 2022 Aug 10;60(2):2200898. doi: 10.1183/13993003.00898-2022. Print 2022 Aug.

NO ABSTRACT

PMID:35948348 | DOI:10.1183/13993003.00898-2022

Am J Respir Crit Care Med. 2022 Aug 10. doi: 10.1164/rccm.202208-1507ED. Online ahead of print.

NO ABSTRACT

PMID:35947636 | DOI:10.1164/rccm.202208-1507ED

J Cyst Fibros. 2022 Aug 6:S1569-1993(22)00638-5. doi: 10.1016/j.jcf.2022.08.001. Online ahead of print.

ABSTRACT

BACKGROUND: Limited data exist to inform antibiotic selection among people with cystic fibrosis (CF) with airway infection by multiple CF-related microorganisms. This study aimed to determine among children with CF co-infected with methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (Pa) if the addition of anti-MRSA antibiotics to antipseudomonal antibiotic treatment for pulmonary exacerbations (PEx) would be associated with improved clinical outcomes compared with antipseudomonal antibiotics alone.

METHODS: Retrospective cohort study using data from the CF Foundation Patient Registry-Pediatric Health Information System linked dataset. The odds of returning to baseline lung function and having a subsequent PEx requiring intravenous antibiotics were compared between PEx treated with anti-MRSA and antipseudomonal antibiotics and those treated with antipseudomonal antibiotics alone, adjusting for confounding by indication using inverse probability of treatment weighting.

RESULTS: 943 children with CF co-infected with MRSA and Pa contributed 2,989 PEx for analysis. Of these, 2,331 (78%) PEx were treated with both anti-MRSA and antipseudomonal antibiotics and 658 (22%) PEx were treated with antipseudomonal antibiotics alone. Compared with PEx treated with antipseudomonal antibiotics alone, the addition of anti-MRSA antibiotics to antipseudomonal antibiotic therapy was not associated with a higher odds of returning to ≥90% or ≥100% of baseline lung function or a lower odds of future PEx requiring intravenous antibiotics.

CONCLUSIONS: Children with CF co-infected with MRSA and Pa may not benefit from the addition of anti-MRSA antibiotics for PEx treatment. Prospective studies evaluating optimal antibiotic selection strategies for PEx treatment are needed to optimize clinical outcomes following PEx treatment.

PMID:35945130 | DOI:10.1016/j.jcf.2022.08.001