Optimization of anti-pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: II. cephalosporins and penicillins

Acute pulmonary exacerbations (APE) are well-described complications of cystic fibrosis (CF) and are associated with progressive morbidity and mortality. Despite aggressive management with two or more intravenous anti-pseudomonal agents, approximately 25% of exacerbations will result in a loss of lung function. The aim of this review is to provide an evidence-based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing anti-pseudomonal cephalosporins (i.e., ceftazidime and cefepime) and penicillins (i.e., piperacillintazobactam and ticarcillinclavulanate) in the treatment of APE and to identify areas where further study is warranted. The ceftazidime and cefepime dosing ranges from the literature are 200400?mg/kg/day divided every 68?hr, maximum 812?g/day, and 150200?mg/kg/day divided every 68?hr, up to 68?g/day, respectively. The literature supported dosing ranges for piperacillin and ticarcillin are 350600?mg/kg/day divided every 4?hr, maximum 1824?g/day of piperacillin component, and 400750?mg/kg/day divided every 6?hr, up to 2430?g/day of ticarcillin component, respectively. As a large portion of CF patients will not regain their lung function following an APE, we suggest the need to optimize antibiotic dosing and dosing regimens used to treat an APE in efforts to improve outcomes for CF patients infected with Pseudomonas aeruginosa. Future studies are needed to determine the clinical efficacy of higher than FDA-approved doses of ceftazidime, cefepime, and ticarcillinclavulanate in APE. The usefulness of high dose piperacillin (>600?mg/kg/day) may be limited due to treatment-related adverse effects. Further understanding of these adverse effects in CF patients is needed. Pediatr Pulmonol. 2013; 48:107122. (c) 2012 Wiley Periodicals, Inc.