PHARMACOKINETICS AND CLINICAL OUTCOMES OF TOBRAMYCIN IN ADULT CYSTIC
FIBROSIS PATIENTS WITH ACUTE PULMONARY EXACERBATION
Background Acute pulmonary exacerbation (APE) in cystic fibrosis
patients is frequent and associated with a decline in pulmonary
function, quality of life and survival. Tobramycin is often used in
regimens requiring activity against Pseudomonas aeruginosa,
however, an important number of centers do not use official dosing
recommendation. The current dosing strategy may be suboptimal.
Methods This retrospective cohort analysis was performed on all
adult cystic fibrosis patients that were admitted at a tertiary care
facility for treatment of APE and with tobramycin between January 2015
and December 2019. The primary objective was to evaluate the predictive
performance of previously published pharmacokinetic (PK) models and,
secondly, to evaluate potential factors that impact clinical outcomes.
Clinical outcomes were only evaluated in a sub-group of patients with
cultures positive for P. aeruginosa. Results A total of
202 APEs from 51 patients were included in the PK analysis. Two
population PK models were assessed and failed to fit our data. In all,
109 APEs from 32 patients were included in the clinical analysis.
Factors that significantly impacted clinical outcome were the number of
prior APE and concomitant antibiotics. Clinical success rate for
regimens containing at least one active agent against P.
aeruginosa according to its susceptibility was 67%. Conclusion
Population PK models evaluated in this study cannot be used to perform
simulations. A new model must be developed for our population. In
patients positive for P. aeruginosa, Ceftazidime in combination
to tobramycin may be a superior regimen. APE history remains predictive
for outcomes in adult CF patients treated for an APE.