Introduction
Cystic fibrosis (CF) is the most common fatal genetic disease affecting
children and young adults in North America. Lung infections are common
in patients with CF with and increasing predominance ofPseudomonas aeruginosa as the patient advances in age. Annually,
63% of patients over the age of 18 experience infections and periodic
worsening signs and symptoms of respiratory health, recognized as acute
pulmonary exacerbations (APE) (1). APE are estimated to be responsible
for about half of the long-term decline in ppFEV1(2) and
are associated with a significant decrease in survival(3, 4).
Published guidelines affirm lack of evidence on best treatment practices
(5). Current Cystic Fibrosis Foundation (CFF) guidelines recommend
treating APEs in CF with two antipseudomonal agents, such as a
beta-lactam (BL) and an aminoglycoside (AG) (5). Tobramycin is the most
commonly used AG (6). The CFF and European consensus guidelines
recommend an intravenous (IV) regimen of 10 mg/kg/day to achieve needed
serum concentrations (7). However, an important number of CF centers do
not use the official CFF dosing recommendations(7).
Tobramycin has wide inter- and intraindividual variability in its
pharmacokinetic (PK) behaviour(8). An empiric 10 mg/kg daily dose of
tobramycin in CF patients achieves target serum concentrations of 20-30
mg/L in only 42% of patients (9). This supports a recommendation of a
daily dose of 12 mg/kg. . Further investigations are needed to assess
and confirm the optimal dosing strategy.
The objectives of the study are to establish optimal dosing
recommendations by performing an external validation of previously
published PK models using data from a tertiary care facility, and to
describe clinical outcomes and identify potential risk factors.