Methicillin-resistant (MRSA) has become a significant acute and chronic respiratory pathogen. While vancomycin is effective against MRSA, its relatively poor penetration into lung secretions and dose-limiting renal toxicity make it less effective in the respiratory setting. As inhaled administration of vancomycin would overcome these limitations, we developed a dry powder formulation suitable for inhalation (AeroVanc). Here, we report a phase I, single-dose, dose-escalating study aimed at demonstrating safety and tolerability of AeroVanc. In part I, 18 healthy subjects received a single dose of 16 mg, 32 mg, or 80 mg of AeroVanc. Two subjects also received a 250-mg dose of intravenous vancomycin. In part 2 of the study, 32 mg and 80 mg AeroVanc were administered to subjects with cystic fibrosis as single doses. There were no serious side effects. A small drop in forced expiratory volume in 1 s (FEV) was observed in 3 subjects with cystic fibrosis, one of whom required salbutamol. Vancomycin was rapidly absorbed after inhalation. Peak and mean plasma concentrations of vancomycin were dose proportional. The average minimum concentration of vancomycin in sputum remained above the usual MIC values for MRSA for up to 24 h (minimum sputum concentration [], 32-mg dose = 3.05 μg/ml, 80-mg dose = 8.0 μg/ml). In conclusion, AeroVanc was well tolerated and achieved high levels in sputum with a mean systemic absorption of 49%, making it a potential therapeutic strategy for respiratory infection with MRSA.
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http://dx.doi.org/10.1128/AAC.01776-19 | DOI Listing |
ACS Nano
January 2025
Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Québec H2X 0A9, Canada.
The abnormally viscous and thick mucus is a hallmark of cystic fibrosis (CF). How the mutated CF gene causes abnormal mucus remains an unanswered question of paramount interest. Mucus is produced by the hydration of gel-forming mucin macromolecules that are stored in intracellular granules prior to release.
View Article and Find Full Text PDFHum Mol Genet
January 2025
Laboratory Medicine and Pathology, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA.
Background: Individuals with cystic fibrosis (CF; a recessive disorder) have an increased risk of colorectal cancer (CRC). Evidence suggests individuals with a single CFTR variant may also have increased CRC risk.
Methods: Using population-based studies (GECCO, CORECT, CCFR, and ARIC; 53 785 CRC cases and 58 010 controls), we tested for an association between the most common CFTR variant (Phe508del) and CRC risk.
Adv Exp Med Biol
January 2025
Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
Despite advances in healthcare, bacterial pathogens remain a severe global health threat, exacerbated by rising antibiotic resistance. Lower respiratory tract infections, with their high death toll, are of particular concern. Accurately replicating host-pathogen interactions in laboratory models is crucial for understanding these diseases and evaluating new therapies.
View Article and Find Full Text PDFClinical trials demonstrate the short-term efficacy of dual CFTR modulators, but long-term real-world data is limited. We aimed to investigate the effects of 24-month lumacaftor/ivacaftor (LUM/IVA) therapy in pediatric CF patients (pwCF). This observational study included pwCF homozygous for F508del mutation treated between 2021 and 2023.
View Article and Find Full Text PDFSci Rep
January 2025
Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, The Netherlands.
Pseudomonas aeruginosa is a Gram-negative bacterium that is notorious for airway infections in cystic fibrosis (CF) subjects. Bacterial quorum sensing (QS) coordinates virulence factor expression and biofilm formation at population level. Better understanding of QS in the bacterium-host interaction is required.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!