How to minimize toxic exposure to pyridine during continuous infusion of ceftazidime in patients with cystic fibrosis?

Ceftazidime is particularly efficient against Pseudomonas aeruginosa inCystic fibrosis patients. Thus, the spontaneous production of pyridine, which is a toxic product, raises someConcern. Our aim was to examine the kinetics of degradation ofCeftazidime in portable infusion pumps either at 4 degrees C, 22 degrees C, or 33 degrees 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 ofCeftazidime infused over 23 h ( once-daily infusion)Compared to 6 g infused over 11.5 h in model 2 ( twice- daily regimen). Samples wereCollected at 0 h and then every 4 and 2 h after the shaping of portable infusion pumps in models 1 and 2, respectively. BothCeftazidime and pyridine were analyzed using an ultraviolet high- performance liquidChromatograph. Production of pyridine is highly depending on the temperature. The in situ production of pyridine per day of treatment decreases at a ratioClose to 1/ 6 and 1/ 3 between 33 degrees C and 4 degrees C in models 1 and 2, respectively. Regardless of theConditions, the production of pyridine is significantly lower in model 2, whereas the total delivery amount ofCeftazidime is significantly higher at 4 degrees C and 33 degrees CCompared to that in model 1. According to a the precautionary principle, these findings lead to three major recommendations: ( i) exposing a solution ofCeftazidime to over 22 degrees 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.