Therapeutic drug monitoring in cystic fibrosis and associations with pulmonary exacerbations and lung function

Abstract

BackgroundCystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy have resulted in longer life expectancies, yet pulmonary exacerbations remain a leading cause of morbidity. Intravenous antibiotics is the mainstay treatment, however achieving adequate concentrations remains challenging. The effect of therapeutic drug monitoring (TDM) of beta-lactams on exacerbations and lung function has not been studied. MethodsPatient demographics, antibiotic regimens, forced expiratory volume 1 s (FEV1), and exacerbation history was obtained from 32 patients with cystic fibrosis admitted for exacerbations. All patients were colonized with Pseudomonas aeruginosa, received CFTR therapy for at least one year, and had 3-month interval follow ups. Plasma concentrations, FEV1, and exacerbation history was obtained before and after therapeutic drug monitoring. This included peak and trough plasma concentrations of piperacillin-tazobactam and cefepime using liquid chromatography with mass spectrometry. T-test and Mann-Whitney U test were used to compare medians/means of FEV1 and pulmonary exacerbations pre and post-TDM as well as free trough-to-minimum inhibitory concentration ratio (fCmin/MIC) ≥1 and ≥ 4. ResultsTDM was associated with decreased exacerbations/year from 1.91 to 1.31 (p = 0.04) and among the cohort with >/ = 2 exacerbations per year, there was a longer exacerbation free interval after TDM (196.2 vs 103.7 days, p = 0.02). The decline in FEV1% predicted after therapeutic drug monitoring to the first exacerbation was −4.9 compared to −9.7 prior (p = 0.03). ConclusionsTDM for cystic fibrosis pulmonary exacerbations results in decreased pulmonary exacerbations, longer intervals to pulmonary exacerbation, and lower decline in FEV1% predicted.