Antibiotic Use in Cystic Fibrosis

Kelly, H. William; Lovato, Carol

doi:10.1177/106002808401801001

Cited by 42 publications

(13 citation statements)

References 119 publications

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“…People with CF are often treated with antibiotics, (16, 17), and thus there is a possibility for a beneficial interaction with ivacaftor. We therefore asked whether ivacaftor might display positive interactions with other antibiotics, thereby suggesting additivity or synergy.…”

Section: Resultsmentioning

confidence: 99%

Antibacterial properties of the CFTR potentiator ivacaftor

Reznikov

Alaiwa

Dohrn

et al. 2014

Journal of Cystic Fibrosis

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Background Ivacaftor increases CFTR channel activity and improves pulmonary function for individuals bearing a G551D mutation. Because ivacaftor structurally resembles quinolone antibiotics, we tested the hypothesis that ivacaftor possesses antibacterial properties. Methods Bioluminescence, colony forming unit, and minimal inhibitory concentration assays were used to assess viability of Staphylococcus aureus, Pseudomonas aeruginosa and multiple clinical microbial isolates. Results Ivacaftor induced a dose-dependent reduction in bioluminescence of S. aureus and decreased the number of colony forming units. We observed a similar but less robust effect in P. aeruginosa following outer membrane permeabilization. Ivacaftor inhibited the growth of respiratory isolates of S. aureus and Streptococcus pneumoniae and exhibited positive interactions with antibiotics against lab and respiratory strains of S. aureus and S. pneumoniae. Conclusion These data indicate that ivacaftor exhibits antibacterial properties and raise the intriguing possibility that ivacaftor might have an antibiotic effect in people with CF.

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Section: Resultsmentioning

confidence: 99%

Antibacterial properties of the CFTR potentiator ivacaftor

Reznikov

Alaiwa

Dohrn

et al. 2014

Journal of Cystic Fibrosis

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“…However, culture and disc sensitivity testing has significant limitations in predicting clinical response, and results correlate poorly with clinical response to antibiotics. 3 PA isolates of different colonial morphology are often identified in the same sputum sample; however, only individual colonies of each morphotype are routinely used to determine antibiotic sensitivity and guide antibiotic selection. Considerable variation in antibiotic susceptibility is found within each morphotype, and thus individual sensitivity results may not reflect population susceptibility to antibiotics.…”

Section: Discussionmentioning

confidence: 99%

Clinical application of direct sputum sensitivity testing in a severe infective exacerbation of cystic fibrosis

Serisier

Jones²,

Tuck³

et al. 2003

Pediatric Pulmonology

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A 16-year-old male with cystic fibrosis (CF) was admitted to hospital with a severe infective exacerbation. Despite standard management, including conventionally selected intravenous antibiotics for Pseudomonas aeruginosa, chest physiotherapy, and institution of noninvasive ventilation (NIV) for progressive hypercapneic respiratory failure, he continued to deteriorate. Direct sputum sensitivity testing (DSST) revealed a novel combination of antibiotics that resulted in a rapid and remarkable clinical improvement. DSST is a form of "whole" sputum sensitivity testing that provides information on antibiotic synergy, and may more accurately reflect in vivo antibiotic sensitivity patterns in cystic fibrosis.

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“…tensive chest physiotherapy and repeated courses of potent, broad spectrum antibiotics, are currently recommended for the treatment of pulmonary exacerbations (Hoiby et al 1982;Marks 1981;Thomassen et al 1987;Wood 1979;Wood & Leigh 1987;Wood et al 1976). These pharmacotherapeutic recommendations are, however, confounded by the fact that numerous investigators have described markedly different disposition profIles for a number of drugs in patients with cystic fibrosis compared with unaffected individuals (Blumer et al 1986;de Groot & Smith, 1987;Hoiby et al 1982;Kearns et al 1982;Kelly & Lovato 1984;Levy et al 1984;Marks 1981;Prandota 1987;Thomassen et al 1987). The multiple pathophysiological and biochemical abnormalities, which include exocrine pancreatic insufficiency, hypoalbuminaemia and blood volume differences (Rosenthal et al 1977;Schwartz 1960), hepatic cirrhosis (Park & Grant 1981), cor pulmonale (Moss 1982) and altered bile acid absorption (Fondacaro et al 1982) have all been described in patients with cystic fibrosis and are partly responsible for altered drug disposition (Prandota 1987;Wood 1979;Wood et al 1976).…”

Section: Cystic Fibrosismentioning

confidence: 99%

Clinical Pharmacokinetics in Infants and Children A Reappraisal

Kearns

Reed

1989

Clinical Pharmacokinetics

174

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A significant increase in the knowledge base in paediatric clinical pharmacology has occurred over the past 2 decades and has largely been the result of important scientific and sociological advancements pertaining to paediatric therapeutics. Although the data on drug disposition in infants and children have increased considerably over the past few years, pharmacokinetic-pharmacodynamic interactions, particularly the effect of development on pharmacodynamics, remain poorly understood.The impact of developmental physiology on drug absorption, distribution, metabolism and elimination in infants and children is reviewed and contrasted to the determinants of clinical pharmacokinetics in neonates. The most notable differences in drug disposition between in/ants and children when compared with neonates and young adults centre around alterations in body water and serum protein composition and the affinity/capacity for hepatic biotransformation of xenobiotics.As opposed to examining the effect of age on the disposition of specific compounds, the differences in developmental pharmacology are highlighted by the review of important and/or emerging pharmacokinetic-pharmacodynamic controversies in infants and children. These include the issues of altered drug distribution and metabolism in cysticjibrosis, pharmacokinetic determinants of successful antimicrobial therapy in bacterial meningitis and the pharmacokinetic determinants of immunosuppression treatment with cyclosporin. The pharmacological differences which are characteristic of development in both infants and children are also reviewed by examination of considerations for clinical pharmacokinetic evaluations such as specific routes and techniques for both drug administration and determination of sampling strategies.Clinical pharmacokinetics will continue to function as a bridge between the generation of new information and the practical application of this knowledge. Consequently, pharmacokinetics provides a pharmacological tool for use in research and clinical care. The clinical application of this tool is examined by a review of the pertinent assumptions and limitations, as well as useful mathematical techniques for use in paediatric patients. Additionally, 'non-traditional' uses of clinical pharmacokinetics (forensic application and use to evaluate organ function) in infants and children are discussed as are considerations for research use of clinical pharmacokinetic data.

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Antibiotic Use in Cystic Fibrosis

Cited by 42 publications

References 119 publications

Antibacterial properties of the CFTR potentiator ivacaftor

Antibacterial properties of the CFTR potentiator ivacaftor

Clinical application of direct sputum sensitivity testing in a severe infective exacerbation of cystic fibrosis

Clinical Pharmacokinetics in Infants and Children A Reappraisal

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