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.