Steady-state Pharmacokinetics of Ceftazidime/Avibactam in Cystic Fibrosis

The purpose of this research study is to characterize the pharmacokinetics of intravenous ceftazidime/avibactam in patients with Cystic Fibrosis.

Cystic fibrosis is a genetic disorder characterized by a chronic cycle of airway infection, obstruction, and inflammation leading to progressive loss of lung function and eventual respiratory failure. The principal pathogen is Pseudomonas aeruginosa which is present in the airways of 70% of adult patients with CF. Of particular concern is the increasing resistance observed to existing agents. While ceftazidime has been the mainstay of treatment for many years, its efficacy is limited by reduced susceptibility. Ceftazidime/avibactam offers a potential advancement in the management of infections involving P. aeruginosa in CF due to its excellent activity, penetration into pulmonary secretions, and reduced potential for development of resistance.

Inclusion Criteria: Diagnosis of CF based on positive sweat chloride or know CF mutation Age > 17 years Able to spontaneously expectorate sputum Exclusion Criteria: Any clinically significant laboratory abnormality Presence of an ongoing acute pulmonary exacerbation Pregnancy Serious past allergy to a beta-lactam antibiotic

Bensman TJ, Wang J, Jayne J, Fukushima L, Rao AP, D'Argenio DZ, Beringer PM. Pharmacokinetic-Pharmacodynamic Target Attainment Analyses To Determine Optimal Dosing of Ceftazidime-Avibactam for the Treatment of Acute Pulmonary Exacerbations in Patients with Cystic Fibrosis. Antimicrob Agents Chemother. 2017 Sep 22;61(10):e00988-17. doi: 10.1128/AAC.00988-17. Print 2017 Oct.