Continuous vs Thrice-Daily Ceftazidime for Electiv Intravenous Antipseudomonal Therapy in Cystic Fibrosis J. Riethmueller, S. Junge,T.W.Schroeter, K. Kuemmerer, P.Franke,M. Ballmann,A.Claass, S. Broemme, R.Jeschke,A. Hebestreit, D.Staab,K. Koetz,G.Doering,M. Stern Abstract Background/aim: We hypothesized that a continuous 24-h infusion of 100 mg/kg per day ceftazidime (treatment C) would result in equivalent or even superior anti-infectious efficacy in chronic Pseudomonus aeruginosa (PA) infection in patients with cystic fibrosis (CF) in comparison to the usual application of 200 mg/kg per day ceftazidime in three doses (treatment T). Methods:This was a randomized crossover study comparing outcome after 14 days and 35 days. Tobramycin adminis- tered once daily (10 mg/kg per day) was administered con- comitantly in both groups. The primary end-point was a decrease in the leukocyte count, and the secondary end- points were clinical and lung function parameters, Pseudo- monas quantification in sputum, and inflammation markers (immunogloblulin [Ig] G, C-reactive protein [CRP]) in serum. All patients received antibiotics electively as 14-day courses on a regular basis, not for acute exacerbations. Results:Fifty-six patients (29 females, mean patient age 14.4 years, age range 5–37) initially received treatments C or T, followed by the alternative treatment after a mean interval of 37 (± 21) weeks. After 2 weeks of antibiotic treatment, the overall study group showed significant improvements compared to baseline for body weight, leukocyte counts, CRP, forced expi- ratory volume in 1 s (FEV 1 ), FVC (forced vital capacity), and bacterial load in the airways, with no significant differences between treatment groups. Both regimens were well tolerated. Three weeks after cessation of antimicrobial therapy, leukocytes and PA density had returned to pre-treatment values. Conclusion: We conclude that continuous or thrice-daily dosing of intravenous ceftazidime, both combined with once-daily tobramycin, are equally effective application regimens for elective antipseudomonal therapy in clinically stable patients with CF. Infection 2009; 37: 418–423 DOI 10.1007/s15010-009-8116-5 Introduction Chronic Pseudomonas aeruginosa (PA) infection is one of the major factors contributing to the known progressive deterioration oflung function in patients with cystic fibrosis (CF) [1–4].Intravenous antipseudomonal treat- ment is usually performed with a combination ofan aminoglycoside, such as tobramycin, and a beta-lactam, usually ceftazidime. Ceftazidime has the disadvantage of rapid renalelimination, with 65% of the drug recovered within 2 h afteriv administration [5,6]; consequently, continuous 24-h infusions of ceftazidime have been pro- posed a the means to extend the duration of exposure in serum. Although from a pharmacological perspective, the continuous infusion of ceftazidime has several advantages, i.e., lower costs and less vascular irritation, over single doses, data on treatment efficacy in CF are scarce. Clinical trials in this area have shown that continuous ceftazidime has the appropriate efficacy, but these have either had no controlgroup [7],have not administered an aminoglyco- side as concomitant treatment [7], or have administered amikacin instead of tobramycin once daily [8]. We hypothesized that a continuous ceftazidime infu- sion would have an anti-infectious efficacy equivalent to that of the commonly performed application of three doses.We presenthere the resultsof a multicenter crossover study which was designed to compare the clin- ical and laboratory outcome as well as safety and toler- J. Riethmueller (corresponding author), P. Franke, M. Stern University Children’s Hospital, Hoppe-Seyler-Str. 1,72076 Tübingen, Germany; Phone: (+49/7071) 22-81391, Fax: -4450, e-mail:joachim.riethmueller@med.uni-tuebingen.de S. Junge, M. Ballmann Pediatric Department, University of Hannover, Hannover, Germany T.W. Schroeter, A. Claass University Children’s Hospital Kiel,Kiel,Germany K. Kuemmerer University of Freiburg, Freiburg,Germany S. Broemme University Children’s Hospital Halle,Halle,Germany R. Jeschke, A. Hebestreit University Children’s Hospital Würzburg,Würzburg,Germany D. Staab, K. Koetz University Children’s Hospital Berlin-Zehlendorf, Berlin,Germany G. Doering Hygiene-Institut, University of Tübingen, Tübingen,Germany Received: March 20, 2008 Æ Revision accepted: January 8, 2009 Published online: September 5, 2009 Infection Clinical and Epidemiological Study 418 Infection 37 Æ 2009 ÆNo.5 U RBAN& VOGEL