Pharmacodynamic target attainment with high-dose extended-interval tobramycin therapy in patients with cystic fibrosis

Abstract

Utilization of high-dose extended-interval aminoglycoside therapy (HEAT) in patients with cystic fibrosis (CF) is supported by primary literature and national guidelines. We sought to evaluate the effectiveness of a local aminoglycoside guideline to achieve pharmacodynamic goals in patients with CF that received ≧3 doses of HEAT from 2005 to 2011. Patients with renal dysfunction at baseline, status-post-lung transplant, or receiving inhaled tobramycin were excluded. In the 282 patient admissions, the average initial tobramycin dose was 10·3 mg/kg with an average initial peak of 21·5 mg/l. At least one dose titration was seen in 39% of patients. Patients who achieved the pharmacodynamic goal received a higher dose (10·4 mg/kg versus 9·7 mg/kg; P<0·001). A mean starting dose of tobramycin at 10·3 mg/kg every 24 hours achieved an average peak above goal. Higher initial dosing resulted in a higher likelihood of achieving the pharmacodynamic goal.

Keywords:

• Aminoglycosides
• Cystic fibrosis
• Tobramycin
• Pharmacodynamics

Acknowledgements

The authors would like to acknowledge Dr Kiki Patel and Dr Sarah Karam for their contribution to this analysis.