Solving the degradation problem of continuous ceftazidime infusions-the Cooltaz study

Ceftazidime is an effective antipseudomonal antibiotic, used commonly in cystic fibrosis. Continuous 24-hour intravenous infusion allows children to receive daily treatment at home. However, the instability of 24-h ceftazidime infusions and production of toxic pyridine has led to recommendations not to use them. We aimed to determine a suitable target temperature to limit degradation of ceftazidime in 24-h infusions and assess effectiveness of simple temperature control. For in vitro experiments, infusers with 6g ceftazidime in 0.9% saline were incubated at 4ºC, 25ºC and 33ºC and sampled over 24h to measure ceftazidime and pyridine concentrations using high-performance liquid chromatography. For carried infuser experiments, to simulate 24-h home infusions, children carried two insulated carry bags containing ceftazidime 2g, 6g or 12g infusers with zero, 1 or 2 ice-packs for 24h. Samples were analysed for ceftazidime and pyridine concentrations. Results for in vitro experiments showed that after 24h, ceftazidime remained stable (>90% original concentration) at 4ºC and 25ºC but not 33ºC (decreased to 84%). Pyridine increased over 24h at 4ºC, 25ºC and 33ºC by 50%, 550% and 1,040% respectively. For carried infuser experiments, at a controlled temperature of 17-25ºC, ceftazidime concentration remained >90% for all infusers except 12g with no ice-pack. Pyridine production in infusers with one or two ice-packs were reduced by 44-57% compared to no ice-pack. In conclusion, adding an ice-pack to a ceftazidime infuser in an insulated carry bag halves the pyridine produced. This indicates that a temperature-controlled daily 24-h continuous intravenous infusion of ceftazidime can replace the recommended twice daily 12-h infusions, allowing patients to receive ceftazidime treatment at home.