Stability of Tobramycin and Ceftazidime in Icodextrin Peritoneal Dialysis Solution

Abstract

Purpose The data describing the compatibility of tobramycin and ceftazidime in icodextrin-based peritoneal dialysis (PD) solution is limited. The objective of this study was to assess the chemical stability of tobramycin and ceftazidime in icodextrin PD solution in polyvinyl chloride containers. Methods Commercially available 2-L bags of icodextrin 7.5% PD solution were used for each sample. Nine tobramycin study samples were prepared by adding 80 mg tobramycin HCl to each bag. Nine ceftazidime samples were prepared by adding 1000 mg ceftazidime to each bag. Three bags of tobramycin–icodextrin solution were stored under each of the following conditions: refrigeration (4°C), room temperature (25°C), and body temperature (37°C). Three bags of ceftazidime–icodextrin solution were also stored at each of the respective temperatures. Samples were withdrawn from each bag immediately after preparation and at predetermined intervals (1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, and 336 hours after preparation). Solutions were visually inspected for precipitation, cloudiness, and discoloration at each sampling interval. All samples were immediately frozen (–80°C) after collection and stored prior to assay. Total concentrations of tobramycin and ceftazidime in dialysate fluid were determined by high-performance liquid chromatography. The last time point when tobramycin or ceftazidime concentration was >90% from baseline was used to denote stability. Results All solutions were clear in appearance and no color change or precipitation was observed during the study. For tobramycin, under refrigeration, a mean of 94.6% ± 2.3% of the initial concentration remained at 336 hours (14 days); at room temperature, 90.5% ± 4.3% remained at 168 hours (7 days); at body temperature, 90.0% ± 8.1% remained at 24 hours. For ceftazidime, under refrigeration, a mean of 98.0% ± 0.3% of the initial concentration remained at 168 hours (7 days); at room temperature, 91.6% ± 2.0% remained at 48 hours; at body temperature, 93.9% ± 1.1% remained at 8 hours. Stability was not assessed beyond these respective time points. Conclusion Premixed tobramycin–icodextrin PD solution remains stable for 336 hours (14 days) when refrigerated (4°C) and for 168 hours (7 days) at room temperature (25°C). Ceftazidime–icodextrin PD solution is stable for 168 hours and 48 hours, respectively, when stored at 4°C and 25°C. It is recommended that the bags be kept refrigerated whenever possible. Tobramycin–icodextrin solution stored at body temperature was stable up to 24 hours, and ceftazidime–icodextrin solutions up to 8 hours, permitting the practice of pre-warming solutions prior to administration.

Stability of Ceftazidime and Heparin in Four Different Types of Peritoneal Dialysis Solutions

“…In CAPD, the dwell time can be between 4 and 8 hours during the day and normally between 8 and 10 hours during the night (1) and ceftazidime can therefore remain in the peritoneal cavity for 4 to 10 hours. Based on the previously reported findings (24), if the ceftazidime-icodextrin admixture is administered intraperitoneally after its storage for 48 hours at room temperature, then the admixture would have lost more than 8% of its initial ceftazidime concentration by the time it is administered. Depending on the dwell time, the admixture would further lose ceftazidime concentration at body temperature.…”

“…Ceftazidime is recommended as the antibiotic of choice for treatment of PDAP caused by Pseudomonas and can be used to treat PDAP from other susceptible gram-negative bacteria (1). Stability of ceftazidime alone in 1.5% of dextrose- and 7.5% icodextrin-based PD solutions at doses used for peritonitis in adults has been reported (12,24), but this has not been tested in other types of PD solutions. Moreover, these studies used the traditional approach of preparing separate PD bags for testing at different temperature ranges, an approach that is not consistent with real-life practice, where the same PD bag with the antibiotic is exposed to different temperatures before administration.…”

Influence of Different Peritoneal Dialysis Fluids on theIn VitroActivity of Cefepime, Ciprofloxacin, Ertapenem, Meropenem and Tobramycin againstEscherichia Coli

“…Unfortunately, for cefepime and ertapenem, no data on stability and biocompatibility with PDFs at body temperature are available, highlighting the need for further research in this area (3). Tobramycin, however, was shown to be stable at 37°C for at least 8 hours in glucose-containing PDFs, for 24 hours in icodextrin-containing PDFs, and for 4 hours in amino acid-containing PDFs (19)(20)(21). Ciprofloxacin was shown to be stable at body temperature for several weeks in a glucose-based PDF, but no stability data are available for icodextrin-or amino acid-containing PDFs (22).…”

Pyridine levels in ceftazidime – peritoneal dialysis admixtures stored at body temperature

“…storage conditions), types of PD solutions or packaging materials. [23][24][25] Since many PD units may prepare ceftazidime-PD admixtures in advance for their administration at a later time, that is, for administration in the long exchange at night-time in patients on CAPD or the long day exchange in patients on continuous cycling PD, the admixture may be first refrigerated for a variable time period before it is prewarmed to 37 C and then administered. In patients on intermittent dosing, the admixture would undergo a dwell time of a minimum recommended period of 6 h or up to 10 h for ensuring adequate absorption of the antibiotic.…”