Relationship of Pulmonary Outcomes, Microbiology, and Serum Antibiotic Concentrations in Cystic Fibrosis Patients

J Pediatr Pharmacol Ther. Sep-Oct 2018;23(5):379-389. doi: 10.5863/1551-6776-23.5.379.

Abstract

Objectives: To determine the frequency of subtherapeutic exposure to intravenously administered β-lactam antibiotics in a cohort of cystic fibrosis (CF) patients who were treated for a pulmonary exacerbation, and its impact on pulmonary function.

Methods: Nineteen CF patients between the ages of 5 and 21 years treated at Children's National Health System for a pulmonary exacerbation were followed between March 2015 and August 2016 in a prospective, longitudinal study. Pharmacokinetic modeling and minimum inhibitory concentrations (MICs) of the involved pathogens were used to determine therapeutic or subtherapeutic β-lactam antibiotic exposure based on the time the antibiotic concentration was above the MIC. Clinical outcomes were measured by spirometry values.

Results: The 19 participants were treated with a total of 29 courses of antibiotics. The most common β-lactam antibiotics used in a treatment course were ceftazidime (62%) and meropenem (45%). There was no difference in age, CF genotype, or creatinine clearance between the 9 participants (47%) who reached therapeutic concentrations versus the 10 (53%) who did not. Those who achieved sufficiently high antibiotic exposure had more significant improvement of their pulmonary function tests.

Conclusions: We found that sufficient antibiotic exposure during treatment of CF pulmonary exacerbations was associated with improved pulmonary function. Moreover, it was impossible to predict, solely from the dosing regimen used, which patients were going to reach therapeutic β-lactam antibiotic serum concentrations. This suggests that CF patients may benefit from closer monitoring of their β-lactam exposure and bacterial MIC for optimal clinical outcomes.

Keywords: beta-lactams; cystic fibrosis; pediatrics; pharmacodynamics; pulmonary.