title: How to minimize toxic exposure to pyridine during continuous infusion of ceftazidime in patients with cystic fibrosis?
abstract: 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.
authors.affiliation: University Hospital Necker-Enfants Malades, Clinical Pharmacy Department, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Bourget
authors.forename: A
authors.initials: A
authors.lastname: Amin
authors.forename: C
authors.initials: C
authors.lastname: Dupont
authors.forename: M
authors.initials: M
authors.lastname: Abely
authors.forename: N
authors.initials: N
authors.lastname: Desmazes-Dufeu
authors.forename: J C
authors.initials: JC
authors.lastname: Dubus
authors.forename: B-L
authors.initials: BL
authors.lastname: Jouani
authors.forename: C
authors.initials: C
authors.lastname: Merlette
authors.forename: R
authors.initials: R
authors.lastname: Nové-Josserand
authors.forename: J
authors.initials: J
authors.lastname: Pages
authors.forename: R
authors.initials: R
authors.lastname: Panzo
authors.forename: F
authors.initials: F
authors.lastname: Vidal
authors.forename: F
authors.initials: F
authors.lastname: Voge
authors.forename: D
authors.initials: D
authors.lastname: Hubert
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry*; D002442:Ceftazidime / Q000008:administration & dosage* / Q000737:chemistry; D003550:Cystic Fibrosis / Q000378:metabolism*; D006801:Humans; D007262:Infusions, Intravenous; D007700:Kinetics; D011725:Pyridines / Q000737:chemistry / Q000633:toxicity*
chemical_list: D000900:Anti-Bacterial Agents; D011725:Pyridines; D002442:Ceftazidime; C023666:pyridine