Pediatric Pulmonology State of the Art Optimization of Anti-pseudomonal Antibiotics for Cystic Fibrosis Pulmonary Exacerbations: I. Aztreonam and Carbapenems Jeffery T. Zobell, PharmD, 1,2 * David C. Young, PharmD, 3,4 C. Dustin Waters, PharmD, BCPS, 4,5 Chris Stockmann, MSc, 6,7 Krow Ampofo, MD, 6 Catherine M.T. Sherwin, PhD, 7 and Michael G. Spigarelli, MD, PhD 7 Summary. Acute pulmonary exacerbations (APE) in cystic fibrosis (CF) are associated with loss of lung function that may require aggressive management with intravenous antibiotics. The aim of this review is to provide an evidence-based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing aztreonam and anti-pseudomonal carbape- nems (i.e., doripenem, imipenem–cilastatin, and meropenem) in the treatment of an APE, and to identify areas where further study is warranted. The current dosing recommendations in the United States and Europe for aztreonam are lower than the literature supported dosing range of 200–300 mg/kg/day divided every 6 hr, maximum 8–12 g/day. Invitro, PK/PD, and tolerability studies show the potential of doripenem 90 mg/kg/day divided every 8 hr, infused over 4 hr, maximum 6 g/day in the treatment of APE. Imipenem-cilastatin 100 mg/kg/day divided every 6 hr, maximum 4 g/day and meropenem 120 mg/kg/day divided every 8 hr, maximum 6 g/day have been shown to be tolerable and effective in the treatment of APE. With availability issues of new anti-pseudomonal agents and a large percentage of CF patients will not regain their lung function following an APE, we suggest the need to determine optimization of aztreonam and meropenem dosing in CF, as well as to determine the clinical efficacy of doripenem in the treatment of APE. The usefulness of imipenem-cilastatin may be limited due to the rapid devel- opment of resistance. Pediatr Pulmonol. ß 2012 Wiley Periodicals, Inc. Key words: beta-lactams; Pseudomonas aeruginosa; pharmacokinetics; pharmaco- dynamics. Funding source: none reported. 1 Pharmacy, Intermountain Primary Children’s Medical Center, Salt Lake City, Utah. 2 Intermountain Cystic Fibrosis Pediatric Center, Salt Lake City, Utah. 3 University of Utah College of Pharmacy, Salt Lake City, Utah. 4 Intermountain Cystic Fibrosis Adult Center, Salt Lake City, Utah. 5 Pharmacy, Intermountain McKay-Dee Hospital Center, Ogden, Utah. 6 Division of Pediatric Infectious Disease, University of Utah, Salt Lake City, Utah. 7 Division of Clinical Pharmacology and Clinical Trials Office, Depart- ment of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah. Conflict of interest: None A systematic review was conducted using Medline. MeSH and free text terms included: ‘‘Cystic fibrosis,’’ ‘‘antibiotics,’’ ‘‘pharmacokinetics,’’ ‘‘pharmacodynamics,’’ ‘‘aztreonam,’’ ‘‘doripenem,’’ ‘‘imipenem-cilasta- tin,’’ ‘‘meropenem’’. Search results were restricted to the English language without an age limit. Also, reference lists and conference proceedings were reviewed. *Correspondence to: Jeffery T. Zobell, PharmD, Department of Pharma- cy, Intermountain Primary Children’s Medical Center, 100 North Mario Capecchi Drive, Salt Lake City, UT 84113. E-mail: jeffery.zobell@imail.org Received 15 April 2012; Accepted 17 May 2012. DOI 10.1002/ppul.22655 Published online in Wiley Online Library (wileyonlinelibrary.com). ß 2012 Wiley Periodicals, Inc.