How To Minimize Toxic Exposure to Pyridine during Continuous Infusion of Ceftazidime in Patients with Cystic Fibrosis?

• Published in: Antimicrobial agents and chemotherapy 2014-05, Vol.58 (5), p.2849-2855
• Main Authors: BOURGET, P, AMIN, A, PANZO, R, VIDAL, F, VOGE, F, HUBERT, D, DUPONT, C, ABELY, M, DESMAZES-DUFEU, N, DUBUS, J. C, JOUANI, B.-L, MERLETTE, C, NOVE-JOSSERAND, R, PAGES, J
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - chemistry; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Ceftazidime; Ceftazidime - administration & dosage; Ceftazidime - chemistry; Clinical Therapeutics; Cystic Fibrosis; Cystic Fibrosis - metabolism; Errors of metabolism; Humans; Infusions, Intravenous; Kinetics; Medical sciences; Metabolic diseases; Miscellaneous hereditary metabolic disorders; Pharmacology. Drug treatments; Pseudomonas aeruginosa; Pyridines; Pyridines - chemistry; Pyridines - toxicity
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.02637-13

Ceftazidime is particularly efficient against Pseudomonas aeruginosa in cystic fibrosis patients. Thus, the spontaneous production of pyridine, which is a toxic product, raises some concern. Our aim was to examine the kinetics of degradation of ceftazidime in portable infusion pumps either at 4°C, 22°C, or 33°C and to propose some recommendations in order to reduce the pyridine exposure. Two administration models were studied in vitro. In model 1, we administered 12 g of ceftazidime infused over 23 h (once-daily infusion) compared to 6 g infused over 11.5 h in model 2 (twice-daily regimen). Samples were collected at 0 h and then every 4 and 2 h after the shaping of portable infusion pumps in models 1 and 2, respectively. Both ceftazidime and pyridine were analyzed using an ultraviolet high-performance liquid chromatograph. Production of pyridine is highly depending on the temperature. The in situ production of pyridine per day of treatment decreases at a ratio close to 1/6 and 1/3 between 33°C and 4°C in models 1 and 2, respectively. Regardless of the conditions, the production of pyridine is significantly lower in model 2, whereas the total delivery amount of ceftazidime is significantly higher at 4°C and 33°C compared to that in model 1. According to a the precautionary principle, these findings lead to three major recommendations: (i) exposing a solution of ceftazidime to over 22°C should be strictly avoided, (ii) a divided dose of 6 g over 11.5 h instead of a once-daily administration is preferred, and (iii) infusion should be administered immediately after reconstitution.