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

Kandel, Surendra; Zaidi, Syed Tabish Razi; Wanandy, Stephanus T.; Ming, Long Chiau; Castelino, Ronald L.; Sud, Kamal; Patel, Rahul P.

doi:10.3747/pdi.2017.00115

Cited by 9 publications

(7 citation statements)

References 33 publications

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“…Although previously reported stability studies of ceftazidime in various PD solutions did not determine the amount of generated pyridine, the chemical stability of 125 mg/L of ceftazidime in Physioneal and Dianeal PD solutions presented here is consistent with the findings reported by Deslandes et al and Kandel et al 11,12 The stability results obtained in the current study for 500 mg/L of ceftazidime in Dianeal and Physioneal solutions cannot be compared with the results reported by previous studies due to the differences in either methodological approaches (e.g. storage conditions), types of PD solutions or packaging materials.…”

Section: Discussionsupporting

confidence: 91%

“…9,10 The stability of ceftazidime in PD solutions with different compositions and packaging materials has been investigated before. 11,12 However, none of the previous studies investigated whether the levels of pyridine generated due to the hydrolysis of ceftazidime in PD solutions exceed the maximum permitted daily exposure limit of 2 mg. Therefore, the current study aimed to investigate the levels of pyridine generated due to the degradation of ceftazidime in various PD bags kept at 37 C.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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Background: For the treatment of peritoneal dialysis-associated peritonitis (PDAP), ceftazidime is routinely admixed with peritoneal dialysis (PD) solutions before its intraperitoneal administration. One of the major degradation products of ceftazidime is pyridine, a potentially toxic compound. Depending on the type of PD solution, ceftazidime is exposed to an environment with acidic or basic pH, and depending on the type of dosing and individual unit practices related to preparation and storage, ceftazidime can be at body temperature for 4–10 h, resulting in potentially varying rates of degradation to pyridine by-product. No study has investigated whether the amount of generated pyridine exceeds the maximum daily exposure limit of 2 mg when ceftazidime-PD admixtures are kept at body temperature. Therefore, the current study aimed to determine the levels of pyridine generated in PD-ceftazidime admixtures kept at 37°C for various time points. Methods: Ceftazidime was admixed with 2 L Dianeal (1.5%, 2.5% and 4.25% dextrose) and 2 L Physioneal (1.36%, 2.27% and 3.86% glucose) PD solutions to obtain a concentration of 125 mg/L (continuous dosing model) or 500 mg/L (intermittent dosing model). A total of 36 PD admixtures (3 bags for each type of PD solution and 3 bags for each type of dosing) were prepared and stored at 37°C for 10 h. An aliquot was withdrawn at time 0 (baseline) and after 2, 6, 8 and 10 h of storage. The withdrawn samples were then analysed to determine the concentrations of ceftazidime and pyridine using high-performance liquid chromatography. Results: With the intermittent dosing model (500 mg/L), ceftazidime was found to be stable for only 2 and 6 h when admixed with 3.86% and 2.27% glucose Physioneal PD solutions, respectively. While ceftazidime (500 mg/L) retained more than 90% of its initial concentration in the three types of Dianeal and 1.36% dextrose Physioneal solutions for 10 and 8 h, respectively, the generated amount of pyridine ranged between approximately 290% and 371% more than the daily recommended limit. With the continuous dosing model (125 mg/L), ceftazidime was found to be stable for 6 h in all three types of Physioneal PD solutions, but the total amount of generated pyridine with four daily exchanges (6 h each) was estimated to be 170–360% over the daily recommended limit. Ceftazidime (125 mg/L) was chemically stable when admixed with three types of Dianeal PD solutions and stored at 37°C for 10 h, and the levels of pyridine were estimated to be less than the maximum recommended daily limit. Conclusions: Until the outcomes of this in vitro study are confirmed by appropriate in vivo studies, continuous dosing of ceftzadime–Dianeal admixtures for the treatment of PDAP may be preferred over continuous dosing of ceftazidime–Physioneal admixtures, and intermittent dosing of ceftazidime–Physioneal and ceftazidime–Dianeal admixtures, as ceftazidime remains stable and the generated levels of pyridine are below the maximum recommended daily exposure.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…23 The stability data of antimicrobial combination agents or antimicrobial agents mixed with heparin are listed in Table 3. 11,14,16,19,[29][30][31] Drug combinations did not cause All studied PD solutions were contained in a polyvinyl chloride bag except Balance which is contained in a polyolefin bag. For PD solutions with two compartments such as Balance and Physioneal, it is denoted if the drug stability was evaluated in the mixed or the unmixed PD solution if the information is reported.…”

Section: Resultsmentioning

confidence: 99%

“…A total of 21 studies were included in this review. 11 –31 The stability of 20 single and 8 combination antimicrobial agents was investigated in various drug concentrations and PD solutions. Notably, most included studies of drug stability in newer PD solutions with non-dextrose-based osmotic agents (e.g.…”

Section: Resultsmentioning

confidence: 99%

Stability and compatibility of intraperitoneal antimicrobials in peritoneal dialysate solutions

Lewis,

Alves,

Ratnam

et al. 2023

Perit Dial Int

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To optimise antimicrobial administration in patients with peritoneal dialysis (PD)-related peritonitis, healthcare providers need literature-based information to develop patient-centred pharmacotherapeutic plans. Traditional PD solutions promote osmosis using dextrose or icodextrin with a lactate buffer. Newer PD solutions have modified the osmotic vehicle and buffer. Knowledge of antimicrobial compatibility and stability with newer PD solutions will assist with determining the route of antimicrobial administration as compatible and stable solutions could be delivered directly to the peritoneum using intraperitoneal administration. This review updates the compatibility and stability of antimicrobial additives in newer PD solutions for PD-related peritonitis.

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“…Particle content analysis was performed using a previously described light microscopy method. 14 Samples withdrawn from each PD bag was placed onto a clean glass slide (75 × 25 mm 2 ; Dako Pty Ltd, NSW, Australia), covered with a coverslip (24 × 50 mm 2 ) and observed using light microscopy (Nikon microscope, NSW, Australia) at 5× and 10× optical zoom using NIS Elements software, version 4.5. Particles were counted using the ImageJ software (NIH, Baltimore, Maryland, USA).…”

Section: Methodsmentioning

confidence: 99%

Stability of ceftolozane and tazobactam in different peritoneal dialysis solutions

et al. 2020

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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-lactam resistant Pseudomonas and other gram-negative bacteria. Given its favourable adverse effects profile, it has a potential role in the treatment of PDAP caused by Pseudomonas species resistant to other antibiotics. Intraperitoneal administration of antibiotics admixed with PD solutions for the treatment of PDAP is associated with superior outcomes. However, there is a lack of published data on the stability of C/T in PD solutions. Therefore, this study investigated the physical and chemical stability 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® and Physioneal® PD bags) containing C/T were prepared and stored at 25°C for 6 h, followed by 4°C for 168 h and then 37°C for 12 h. An aliquot from each PD bag was withdrawn, and the concentration of C/T before (0 h) and after predefined 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 day of analysis. Results: C/T retained more than 97% of their initial concentration when stored at 25°C for 6 h followed by storage at 4°C for 168 h and then at 37°C for 12 h. Particle formation was not detected at any time under the tested storage conditions. 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 of intraperitoneal C/T for the treatment of PDAP caused by resistant Pseudomonas species.

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

Abstract: Ceftazidime-heparin admixture retains its stability over long periods of storage at different temperatures, allowing its potential use for PDAP treatment in outpatient and remote settings.

Cited by 9 publications

References 33 publications

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

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

Stability and compatibility of intraperitoneal antimicrobials in peritoneal dialysate solutions

Stability of ceftolozane and tazobactam in different peritoneal dialysis solutions

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