Stability of ceftolozane and tazobactam in different peritoneal dialysis solutions

Background: Peritonitis is a common and serious complication of peritoneal dialysis (PD). PD-associated peritonitis(PDAP) caused by Pseudomonas is usually resistant to most antibiotics, resulting in high failure rates. Ceftolozane/tazobactam (C/T) has been shown to be effective in treating urinary tract and intra-abdominal infections caused by beta-lactamresistant Pseudomonas and other gram-negative bacteria. Given its favourable adverse effects profile, it has a potential rolein the treatment of PDAP caused by Pseudomonas species resistant to other antibiotics. Intraperitoneal administration ofantibiotics admixed with PD solutions for the treatment of PDAP is associated with superior outcomes. However, there isa lack of published data on the stability of C/T in PD solutions. Therefore, this study investigated the physical and chemicalstability of C/T in commonly used PD solutions at different temperatures.Methods: A total of 27 PD bags (3 PD bags for each type of PD solution including Dianeal®, Extraneal®, Balance® andPhysioneal® PD bags) containing C/T were prepared and stored at 25C for 6 h, followed by 4C for 168 h and then37C for 12 h. An aliquot from each PD bag was withdrawn, and the concentration of C/T before (0 h) and afterpredefined time points was determined using a stability-indicating high-performance liquid chromatography assay.Samples were also assessed for pH, colour change and particulate matter immediately after preparation and on each dayof analysis.Results: C/T retained more than 97% of their initial concentration when stored at 25C for 6 h followed by storage at4C for 168 h and then at 37C for 12 h. Particle formation was not detected at any time under the tested storageconditions. The pH and colour remained essentially unchanged throughout the study.Conclusions: These results provide a platform for clinical studies to determine the safety and therapeutic efficacy ofintraperitoneal C/T for the treatment of PDAP caused by resistant Pseudomonas species