School of Medicine and Health Sciences Poster Presentations

Title

Preliminary Analysis of the Impact of Pharmacokinetics and Pharmacodynamics on Improvement in Pulmonary Function in Children with Cystic Fibrosis.

Poster Number

280

Document Type

Poster

Status

Medical Student

Abstract Category

Immunology/Infectious Diseases

Keywords

cystic fibrosis, pulmonary function, antibiotics, pharmacokinetics, pharmacodynamics

Publication Date

Spring 2018

Abstract

Cystic Fibrosis (CF) is an autosomal recessive pulmonary disease that causes recurrent and chronic infections. Broad spectrum antibiotics are commonly used to treat acute lung infections, also known as acute pulmonary exacerbations. Dosing of the antibiotics is an important area of concern because sub-therapeutic doses may promote bacterial resistance instead of pathogen killing. Pharmacokinetic modeling can be used to predict pharmacodynamics indices to optimize bacterial killing and guide antibiotic therapy. We sought to determine whether sub-therapeutic antibiotic exposure impacted recovery of pulmonary function for treatment of acute pulmonary exacerbations. This is a prospective study of 25 patients with CF who are 18 years of age or younger admitted for treatment of IV antibiotics. Clinical data collected for the first 15 study patients included patient demographics, symptoms at the onset of the exacerbation, respiratory culture results, and results of pulmonary function tests (PFTs). Plasma drug concentrations of IV β-lactam antibiotics were obtained during the treatment course to model the subjects’ antimicrobial exposure. At exacerbation onset, 53% of patients had a decrease of at least 10% in their FEF25-75, while 47% had at least a 10% decrease in their FEV1. Of the 13 patients who had PFTs performed, there was a significant improvement following antibiotic treatment (FVC 92.9% vs 100%, p<0.05 and FEF25-75 69.7% vs 92.9%, p<0.05). We also evaluated for differences between those who had therapeutic (n=4) and sub-therapeutic (n=9) beta-lactam antibiotic courses. FVC %predicted was significantly higher in the therapeutic group at the onset of exacerbation than the sub-therapeutic group (106% vs 87%, p=0.03). When comparing the improvement at the end of antibiotic treatment from onset of exacerbation, there was no significant difference between groups. Further analysis of the full cohort will be important to identify whether antibiotic pharmacokinetics and pharmacodynamics are important determinants in improvement of pulmonary function.

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Preliminary Analysis of the Impact of Pharmacokinetics and Pharmacodynamics on Improvement in Pulmonary Function in Children with Cystic Fibrosis.

Cystic Fibrosis (CF) is an autosomal recessive pulmonary disease that causes recurrent and chronic infections. Broad spectrum antibiotics are commonly used to treat acute lung infections, also known as acute pulmonary exacerbations. Dosing of the antibiotics is an important area of concern because sub-therapeutic doses may promote bacterial resistance instead of pathogen killing. Pharmacokinetic modeling can be used to predict pharmacodynamics indices to optimize bacterial killing and guide antibiotic therapy. We sought to determine whether sub-therapeutic antibiotic exposure impacted recovery of pulmonary function for treatment of acute pulmonary exacerbations. This is a prospective study of 25 patients with CF who are 18 years of age or younger admitted for treatment of IV antibiotics. Clinical data collected for the first 15 study patients included patient demographics, symptoms at the onset of the exacerbation, respiratory culture results, and results of pulmonary function tests (PFTs). Plasma drug concentrations of IV β-lactam antibiotics were obtained during the treatment course to model the subjects’ antimicrobial exposure. At exacerbation onset, 53% of patients had a decrease of at least 10% in their FEF25-75, while 47% had at least a 10% decrease in their FEV1. Of the 13 patients who had PFTs performed, there was a significant improvement following antibiotic treatment (FVC 92.9% vs 100%, p<0.05 and FEF25-75 69.7% vs 92.9%, p<0.05). We also evaluated for differences between those who had therapeutic (n=4) and sub-therapeutic (n=9) beta-lactam antibiotic courses. FVC %predicted was significantly higher in the therapeutic group at the onset of exacerbation than the sub-therapeutic group (106% vs 87%, p=0.03). When comparing the improvement at the end of antibiotic treatment from onset of exacerbation, there was no significant difference between groups. Further analysis of the full cohort will be important to identify whether antibiotic pharmacokinetics and pharmacodynamics are important determinants in improvement of pulmonary function.