Role of Tris-CaEDTA as an adjuvant with nebulised tobramycin in cystic fibrosis patients with Pseudomonas aeruginosa lung infections: A randomised controlled trial

Puvvadi, Ramaa; Mikkelsen, Helga; McCahon, Lucy; Grogan, Samantha; Ditcham, William; Reid, David; Lamont, Iain L.; Stick, Stephen M.; Clements, Barry

doi:10.1016/j.jcf.2020.12.004

Cited by 4 publications

(2 citation statements)

References 23 publications

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“…CaEDTA is a chelating agent with antimicrobial properties; it binds to a variety of divalent cations including iron, zinc, and magnesium, rendering them unavailable for use by microorganisms. This phenomenon, referred to as “nutritional immunity,” has been successfully studied in vitro and in vivo in animals with chronic PA associated otitis, sinusitis, and endometriosis, and it weakens bacterial defense mechanisms, consequently increasing the bactericidal activity by the concomitant antibiotic [ 52 ]. Additionally, CaEDTA has been shown to disrupt the lipopolysaccharide layer in the outer membrane of PA, thus increasing the cell wall permeability and improving antibiotic penetration of the bacteria cell [ 52 ].…”

Section: Antimicrobial Therapiesmentioning

confidence: 99%

Advances in the Cystic Fibrosis Drug Development Pipeline

Esposito,

Kamper,

Trentacoste

et al. 2023

Life

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Cystic fibrosis is a genetic disease that results in progressive multi-organ manifestations with predominance in the respiratory and gastrointestinal systems. The significant morbidity and mortality seen in the CF population has been the driving force urging the CF research community to further advance treatments to slow disease progression and, in turn, prolong life expectancy. Enormous strides in medical advancements have translated to improvement in quality of life, symptom burden, and survival; however, there is still no cure. This review discusses the most current mainstay treatments and anticipated therapeutics in the CF drug development pipeline within the mechanisms of mucociliary clearance, anti-inflammatory and anti-infective therapies, restoration of the cystic fibrosis transmembrane conductance regulator (CFTR) protein (also known as highly effective modulator therapy (HEMT)), and genetic therapies. Ribonucleic acid (RNA) therapy, gene transfer, and gene editing are being explored in the hopes of developing a treatment and potential cure for people with CF, particularly for those not responsive to HEMT.

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Section: Antimicrobial Therapiesmentioning

confidence: 99%

Advances in the Cystic Fibrosis Drug Development Pipeline

Esposito,

Kamper,

Trentacoste

et al. 2023

Life

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“…In multiple clinical studies, CF patients with P. aeruginosa infection received nebulisation of EDTA and a concomitant antibiotic. In these studies, inhaled EDTA resulted in no harmful effects or adverse events [ 82 , 83 ]. However, assessments of EGTA toxicity performed in mice have noted inflammatory effects in the lungs [ 74 ].…”

Section: Airway Surface Preparation Techniquesmentioning

confidence: 99%

Effective viral-mediated lung gene therapy: is airway surface preparation necessary?

et al. 2022

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Gene-based therapeutics are actively being pursued for the treatment of lung diseases. While promising advances have been made over the last decades, the absence of clinically available lung-directed genetic therapies highlights the difficulties associated with this effort. Largely, progress has been hindered by the presence of inherent physical and physiological airway barriers that significantly reduce the efficacy of gene transfer. These barriers include surface mucus, mucociliary action, cell-to-cell tight junctions, and the basolateral cell membrane location of viral receptors for many commonly used gene vectors. Accordingly, airway surface preparation methods have been developed to disrupt these barriers, creating a more conducive environment for gene uptake into the target airway cells. The two major approaches have been chemical and physical methods. Both have proven effective for increasing viral-mediated gene transfer pre-clinically, although with variable effect depending on the specific strategy employed. While such methods have been explored extensively in experimental settings, they have not been used clinically. This review covers the airway surface preparation strategies reported in the literature, the advantages and disadvantages of each method, as well as a discussion about applying this concept in the clinic.

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