Stability of the Combination of Ceftazidime and Cephazolin in Icodextrin or PH Neutral Peritoneal Dialysis Solution

Abstract

♦ Introduction: The objective of this study was to inves ti gate the stability of ceftazidime and cephazolin in a 7.5% icodextrin or pH neutral peritoneal dialysis (PD) solution. ♦ Methods: Ceftazidime and cephazolin were injected into either a 7.5% icodextrin or pH neutral PD bag to obtain the concentration of 125 mg/L of each antibiotic. A total of nine 7.5% icodextrin or pH neutral PD bags containing ceftazidime and cephazolin were prepared and stored at 1 of 3 different temperatures: 4°C in a domestic refrigerator; 25°C at room temperature; or 37°C (body temperature) in an incubator. An aliquot was withdrawn immediately before (0 hour) or after 12, 24, 48, 96, 120, 144, 168 and 336 hours of storage. Each sample was analyzed in duplicate for the concentration of ceftazidime and cephazolin using a stabilityindicating highperformance liquid chromatography technique. Ceftazidime and cephazolin were considered stable if they retained more than 90% of their initial concentration. Samples were also assessed for pH, colour changes and evidence of precipitation immediately after preparation and on each day of analysis. ♦ Results: Ceftazidime and cephazolin in both types of PD solution retained more than 90% of their initial concentration for 168 and 336 hours respectively when stored at 4°C. Both of the antibiotics lost more than 10% of the initial concentration after 24 hours of storage at 25 or 37°C. There was no evidence of precipitation at any time under the tested storage conditions. Change in the pH and color was observed at 25 and 37°C, but not at 4°C. ♦ Conclusion: Premixed ceftazidime and cephazolin in a 7.5% icodextrin or pH neutral PD solution is stable for at least 168 hours when refrigerated. This allows the prepa ration of PD bags in advance, avoiding the necessity for daily preparation. Both the antibiotics are stable for at least 24 hours at 25 and 37°C, permitting storage at room temperature and prewarming of PD bags to body tempera ture prior to its administration.

Stability of Antibiotics for Intraperitoneal Administration in Extraneal 7.5% Icodextrin Peritoneal Dialysis Bags (Stab Study)

“…Lin et al determined stability of cefazolin (500 mg/L) only in icodextrin solution at 4°C and 25°C for 30 days and at 37°C for 24 hours and found cefazolin to be stable for 30 days at 4°C, 7 days at 25°C, and 24 hours at 37°C (11).These studies did not address the stability of combinations of antibiotics in icodextrin solution. Patel et al found that premixed ceftazidime (125 mg/L) and cefazolin (125 mg/L) in 7.5% icodextrin and pH neutral PD solution is stable for at least 7 days when refrigerated (10). The current study has demonstrated that higher doses of these drugs (500 mg/L), the dosages recommended by the ISPD for intermittent dosing, are stable alone or in combination for 14 days when refrigerated.…”

“…Previous studies on the stability of some antibiotics in icodextrin provide only minimal information because they do not fully cover the entire range of temperature storage conditions and likely storage time periods encountered in clinical practice (4)(5)(6)(7)(8)(9). Patel et al examined the stability of the combination of cefazolin and ceftazidime in icodextrin but did not study the combination of either cefazolin and gentamicin, vancomycin and ceftazidime, or gentamicin in icodextrin (10). The aim of this study was to describe the stability of commonly used IP antibiotics in a 7.5% icodextrin solution, at a dosage recommended by ISPD for intermittent dosing (2), a practice followed by many centers, at 3 different temperatures for a period of up to 2 weeks.…”

Practical Considerations When Prescribing Icodextrin: A Narrative Review

“…One showed that combining vancomycin and gentamicin in an icodextrin-based solution did not result in any loss of activity at room temperature in 48 h [63]. The second, more recent study, demonstrated the stability of cefazolin and ceftazidime in icodextrin at 4°C (168 h), 25°C (24 h), and 37°C (24 h) [64]. Third, there are only two studies to our knowledge that evaluated the biocompatibility of icodextrin, antibiotics, and heparin.…”

The new ISPD peritonitis guideline

“…Although the stability of antibiotics in PD solutions has long been a theoretical concern, recent evidence suggests that all first-line IP antibiotics are stable for routine clinical use, including pre-injection by helpers [12,13]. However, when vancomycin and gentamicin are used in combination, they should preferably be injected to different bags of PD solution [13], and vancomycin should not be given into amino-acid based solution [14].…”

“…However, when vancomycin and gentamicin are used in combination, they should preferably be injected to different bags of PD solution [13], and vancomycin should not be given into amino-acid based solution [14]. The latest version of the guideline also provide an exhaustive list of antibiotics suitable for IP administration, together with their recommended dosage and supporting literature [9].…”