Off‐label use of intravenous antimicrobials for inhalation in patients with cystic fibrosis

McKinzie, Cameron J.; Chen, Lori; Ehlert, Kim; Grisso, Alison G.; Linafelter, Alaina; Lubsch, Lisa; O’Brien, Catherine E.; Pan, Alice; Wright, Brittany A.; Elson, E. Claire

doi:10.1002/ppul.24511

Cited by 12 publications

(7 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, there are no commercially available inhaled antimicrobials that are effective against MRSA, i.e., ciprofloxacin and VAN formulations are in different stages of clinical development, denoting the high potential clinical relevance that local optimized treatments against MRSA could have to increase the survival of patients with CF [ 8 , 9 ]. In this line, the off-label use of inhaled VAN by nebulization of the intravenous formulation has been reported for the treatment of MRSA in the setting of CF, demonstrating a reduction in colonies but not eradication [ 10 ]. Nevertheless, inhaled formulations can present side effects, such as cough, bronchospasm, hoarseness and dysphagia, among others, which are frequently associated with the mucosal deposition of crystalline drug particles with slow dissolution rates [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Novel Dry Hyaluronic Acid–Vancomycin Complex Powder for Inhalation, Useful in Pulmonary Infections Associated with Cystic Fibrosis

Magi,

de Lafuente,

Quarta

et al. 2024

Pharmaceutics

View full text Add to dashboard Cite

Polyelectrolyte–drug complexes are interesting alternatives to improve unfavorable drug properties. Vancomycin (VAN) is an antimicrobial used in the treatment of methicillin-resistant Staphylococcus aureus pulmonary infections in patients with cystic fibrosis. It is generally administered intravenously with a high incidence of adverse side effects, which could be reduced by intrapulmonary administration. Currently, there are no commercially available inhalable formulations containing VAN. Thus, the present work focuses on the preparation and characterization of an ionic complex between hyaluronic acid (HA) and VAN with potential use in inhalable formulations. A particulate–solid HA-VAN25 complex was obtained by spray drying from an aqueous dispersion. FTIR spectroscopy and thermal analysis confirmed the ionic interaction between HA and VAN, while an amorphous diffraction pattern was observed by X-ray. The powder density, geometric size and morphology showed the suitable aerosolization and aerodynamic performance of the powder, indicating its capability of reaching the deep lung. An in vitro extended-release profile of VAN from the complex was obtained, exceeding 24 h. Microbiological assays against methicillin-resistant and -sensitive reference strains of Staphylococcus aureus showed that VAN preserves its antibacterial efficacy. In conclusion, HA-VAN25 exhibited interesting properties for the development of inhalable formulations with potential efficacy and safety advantages over conventional treatment.

show abstract

Section: Introductionmentioning

confidence: 99%

Novel Dry Hyaluronic Acid–Vancomycin Complex Powder for Inhalation, Useful in Pulmonary Infections Associated with Cystic Fibrosis

Magi,

de Lafuente,

Quarta

et al. 2024

Pharmaceutics

View full text Add to dashboard Cite

show abstract

“…Off-label use of intravenous antibiotics such as meropenem, vancomycin and amikacin are also used for inhalation in people with CF. The evidence to support this practice is minimal and beyond the scope of this article [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Role of inhaled antibiotics in the era of highly effective CFTR modulators

et al. 2023

View full text Add to dashboard Cite

Recurrent and chronic bacterial infections are common in people with cystic fibrosis (CF) and contribute to lung function decline. Antibiotics are the mainstay in the treatment of exacerbations and chronic bacterial infection in CF. Inhaled antibiotics are effective in treating chronic respiratory bacterial infections and eradicatingPseudomonas aeruginosafrom the respiratory tract, with limited systemic adverse effects. In the past decade, highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulators have become a new therapy that partially corrects/opens chloride transport in patients with selected CFTR mutations, restoring mucus hydration and improving mucociliary clearance. The recent triple CFTR modulator combination is approved for ∼80–90% of the CF population and significantly reduces pulmonary exacerbations and improves respiratory symptoms and lung function. CFTR modulators have shifted the focus from symptomatic treatment to personalised/precision medicine by targeting genotype-specific CFTR defects. While these are highly effective, they do not fully normalise lung physiology, stop inflammation or resolve chronic lung damage, such as bronchiectasis. The impact of these new drugs on lung health is likely to change the future management of chronic pulmonary infections in people with CF. This article reviews the role of inhaled antibiotics in the era of CFTR modulators.

show abstract

“…About half of adults with CF are infected by P. aeruginosa (UK Cystic Fibrosis Registry 2020 , Cystic Fibrosis Foundation 2021 ). Infections are treated with a range of antibiotics such as ciprofloxacin (a fluoroquinolone), meropenem (a carbapenem), and tobramycin (an aminoglycoside) (Langton and Smyth 2017 , McKinzie et al 2019 , Smith and Rowbotham 2022 ). Antibiotic therapy relieves the symptoms, but once an infection is established, existing treatment regimens usually fail to eradicate these bacteria (Kirkby et al 2009 ).…”

Section: Introductionmentioning

confidence: 99%

Pseudomonas aeruginosa is oxygen-deprived during infection in cystic fibrosis lungs, reducing the effectiveness of antibiotics

Martin

Gray

Brockway

et al. 2023

FEMS Microbiology Letters

View full text Add to dashboard Cite

Pseudomonas aeruginosa infects the lungs of patients with cystic fibrosis. Sputum expectorated from the lungs of patients contains low levels of oxygen indicating that P. aeruginosa may be oxygen-deprived during infection. During in vitro growth under oxygen-limiting conditions a P. aeruginosa reference strain increases expression of a cytochrome oxidase with a high affinity for oxygen, and of nitrate and nitrite reductases that enable it to use nitrate instead of oxygen during respiration. Here, we quantified transcription of the genes encoding these three enzymes in sputum samples from 18 infected patients, and in bacteria isolated from the sputum samples and grown in aerobic and anaerobic culture. In culture, expression of all three genes was increased by averages of 20- to 500-fold in anaerobically grown bacteria compared with those grown aerobically, although expression levels varied greatly between isolates. Expression of the same genes in sputum was similar to that of the corresponding bacteria in anaerobic culture. The isolated bacteria were less susceptible to tobramycin and ciprofloxacin, two widely-used anti-pseudomonal antibiotics, when grown anaerobically than when grown aerobically. Our findings show that P. aeruginosa experiences oxygen starvation during infection in cystic fibrosis, reducing the effectiveness of antibiotic treatment.

show abstract

Off‐label use of intravenous antimicrobials for inhalation in patients with cystic fibrosis

Cited by 12 publications

References 77 publications

Novel Dry Hyaluronic Acid–Vancomycin Complex Powder for Inhalation, Useful in Pulmonary Infections Associated with Cystic Fibrosis

Novel Dry Hyaluronic Acid–Vancomycin Complex Powder for Inhalation, Useful in Pulmonary Infections Associated with Cystic Fibrosis

Role of inhaled antibiotics in the era of highly effective CFTR modulators

Pseudomonas aeruginosa is oxygen-deprived during infection in cystic fibrosis lungs, reducing the effectiveness of antibiotics

Contact Info

Product

Resources

About