Nebuliser systems for drug delivery in cystic fibrosis

Daniels, T.; Mills, Nicola; Whitaker, Paul

doi:10.1002/14651858.cd007639.pub2

Cited by 42 publications

(44 citation statements)

References 49 publications

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“…Several factors can influence the delivery of aerosolized antibiotics to the lungs, although aerosol particle size seems to be the most important factor [30]. Currently available nebulizers include jet, ultrasonic and vibrating mesh devices whose antibiotic delivery efficiency to the lung parenchyma ranges from 15 to 60% across this continuum of devices [31]. To date, the efficacy and safety of aerosolized antibiotics for VAP has been examined in heterogeneous studies and meta-analyses yielding conflicting results [24, 25, 32].…”

Section: New Antibiotics and Antibiotic Deliverymentioning

confidence: 99%

The intensive care medicine research agenda on multidrug-resistant bacteria, antibiotics, and stewardship

et al. 2017

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Purpose: To concisely describe the current standards of care, major recent advances, common beliefs that have been contradicted by recent trials, areas of uncertainty, and clinical studies that need to be performed over the next decade and their expected outcomes with regard to the management of multidrug-resistant (MDR) bacteria, antibiotic use, and antimicrobial stewardship in the intensive care unit (ICU) setting. Methods: Narrative review based on a systematic analysis of the medical literature, national and international guidelines, and expert opinion. Results: The prevalence of infection of critically ill patients by MDR bacteria is rapidly evolving. Clinical studies aimed at improving understanding of the changing patterns of these infections in ICUs are urgently needed. Ideal antibiotic utilization is another area of uncertainty requiring additional investigations aimed at better understanding of dose optimization, duration of therapy, use of combination treatment, aerosolized antibiotics, and the integration of rapid diagnostics as a guide for treatment. Moreover, there is an imperative need to develop non-antibiotic approaches for the prevention and treatment of MDR infections in the ICU. Finally, clinical research aimed at demonstrating the beneficial impact of antimicrobial stewardship in the ICU setting is essential. Conclusions: These and other fundamental questions need to be addressed over the next decade in order to better understand how to prevent, diagnose, and treat MDR bacterial infections. Clinical studies described in this research agenda provide a template and set priorities for investigations that should be performed in this field.

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Section: New Antibiotics and Antibiotic Deliverymentioning

confidence: 99%

The intensive care medicine research agenda on multidrug-resistant bacteria, antibiotics, and stewardship

et al. 2017

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“…In fact, local drug delivery may allow maximum pharmacological targeting, and thus therapeutic efficacy. As a consequence, researchers continue applied efforts to develop new inhalation devices and advanced drug delivery [41]. CFTR-mRNA aerosol administration to airways of CF patients could be delivered as it was previously showed [42].…”

Section: Different Delivery Methodsmentioning

confidence: 99%

Optimization of CFTR-mRNA transfection in human nasal epithelial cells

et al. 2016

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Background: Cystic fibrosis (CF) is the most common life-threatening inherited disease in the Caucasian population. It is caused by genetic defects in the cystic fibrosis transmembrane conductance regulator gene (CFTR), a cAMP regulated chloride-bicarbonate channel mainly located in the apical membrane of polarized epithelial cells. CFTR is proposed to regulate other proteins, including the epithelial sodium channel (ENaC). Recently, we successfully restored chloride current in CFTR deficient human airway epithelial cells using wtCFTR-mRNA transfection compared to non-CF cells showing similar values. The present study aimed to optimize the wtCFTR-mRNA transfection procedures in primary cultured human nasal epithelial (HNE) cells. Methods: Dose and time dependence experiments were performed. In addition, we investigated the possible impact of the wtCFTR-mRNA transfection on ENaC function in transepithelial measurements. We reduced the wtCFTR-mRNA dose stepwise and determined the minimal concentration of 0.6 μg/cm

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“…The need for a power source and long treatment times, the required setup and cleaning, significant variations in performance between manufacturers, and the loss of expensive drug in considerably high residual volumes are significant drawbacks to jet nebulizers (72)(73)(74)(75). In vitro data have demonstrated that drug delivery from a jet nebulizer can be optimized via operation with a nitrogen-oxygen mixture with particles entrained in a helium-oxygen operating circuit (76).…”

Section: Delivery Devicesmentioning

confidence: 99%

Inhaled Antibiotics for Gram-Negative Respiratory Infections

et al. 2016

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SUMMARYGram-negative organisms comprise a large portion of the pathogens responsible for lower respiratory tract infections, especially those that are nosocomially acquired, and the rate of antibiotic resistance among these organisms continues to rise. Systemically administered antibiotics used to treat these infections often have poor penetration into the lung parenchyma and narrow therapeutic windows between efficacy and toxicity. The use of inhaled antibiotics allows for maximization of target site concentrations and optimization of pharmacokinetic/pharmacodynamic indices while minimizing systemic exposure and toxicity. This review is a comprehensive discussion of formulation and drug delivery aspects,in vitroand microbiological considerations, pharmacokinetics, and clinical outcomes with inhaled antibiotics as they apply to disease states other than cystic fibrosis. In reviewing the literature surrounding the use of inhaled antibiotics, we also highlight the complexities related to this route of administration and the shortcomings in the available evidence. The lack of novel anti-Gram-negative antibiotics in the developmental pipeline will encourage the innovative use of our existing agents, and the inhaled route is one that deserves to be further studied and adopted in the clinical arena.

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Nebuliser systems for drug delivery in cystic fibrosis

Cited by 42 publications

References 49 publications

The intensive care medicine research agenda on multidrug-resistant bacteria, antibiotics, and stewardship

The intensive care medicine research agenda on multidrug-resistant bacteria, antibiotics, and stewardship

Optimization of CFTR-mRNA transfection in human nasal epithelial cells

Inhaled Antibiotics for Gram-Negative Respiratory Infections

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