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Stability of Meropenem and Piperacillin/Tazobactam with Heparin in Various Peritoneal Dialysis Solutions
Karryl Mendes1, Harmanjeet Harmanjeet1, Mohammed Sedeeq1
1Pharmacy, School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.
Background:
Infections caused by ceftazidime-resistant Pseudomonas and extended-spectrum beta-lactamase (ESBL)-producing gram-negative bacteria are increasing worldwide. Meropenem and piperacillin/tazobactam (PIP/TZB) are recommended for the treatment of peritoneal dialysis-associated peritonitis (PDAP) caused by ceftazidime-resistant Pseudomonas and other resistant gram-negative bacteria. Patients may also receive intraperitoneal heparin to prevent occlusion of their catheters. However, the stability of meropenem or PIP/TZB, in combination with heparin, in different types of peritoneal dialysis (PD) solutions used in clinical practice is currently unknown. Therefore, we investigated the stability of meropenem and PIP/TZB, each in combination with heparin, in different PD solutions.
Methods:
A total of 15 PD bags (3 bags for each type of PD solution) containing meropenem and heparin and 24 PD bags (3 bags for each type of PD solution) containing PIP/TZB and heparin were prepared and stored at 4°C for 168 hours. The same bags were stored at 25°C for 3 hours followed by 10 hours at 37°C. An aliquot withdrawn before storage and at defined time points was analyzed for the concentration of meropenem, PIP, TZB, and heparin using high-performance liquid chromatography. Samples were also analysed for particle content, pH and color change, and the anticoagulant activity of heparin.
Results:
Meropenem and heparin retained more than 90% of their initial concentration in 4 out of 5 types of PD solutions when stored at 4°C for 168 hours, followed by storage at 25°C for 3 hours and then at 37°C for 10 hours. Piperacillin/tazobactam and heparin were found to be stable in all 8 types of PD solutions when stored under the same conditions. Heparin retained more than 98% of its initial anticoagulant activity throughout the study period. No evidence of particle formation, color change, or pH change was observed at any time under the storage conditions employed in the study.
Conclusions:
This study provides clinically important information on the stability of meropenem and PIP/TZB, each in combination with heparin, in different PD solutions. The use of meropenem-heparin admixed in pH-neutral PD solutions for the treatment of PDAP should be avoided, given the observed suboptimal stability of meropenem.
Insights
Piperacillin/tazobactam and heparin are stable in all tested peritoneal dialysis solutions. Meropenem and heparin stability was suboptimal in pH-neutral solutions, advising against their use in such cases for treating PDAP.
Area of Science:
- Nephrology
- Infectious Diseases
- Pharmacology
Background:
- Rising global incidence of infections caused by ceftazidime-resistant Pseudomonas and ESBL-producing gram-negative bacteria.
- Meropenem and piperacillin/tazobactam (PIP/TZB) are recommended treatments for peritoneal dialysis-associated peritonitis (PDAP).
- Intraperitoneal heparin is often used with these antibiotics to prevent catheter occlusion, but its stability with PD solutions is unknown.
Purpose of the Study:
- To investigate the stability of meropenem and PIP/TZB when combined with heparin in various clinical peritoneal dialysis (PD) solutions.
- To assess the impact of different PD solutions on the stability of antibiotic-heparin admixtures.
- To provide data guiding the clinical use of these antibiotic-heparin combinations in PD.
Main Methods:
- Prepared PD bags with meropenem-heparin and PIP/TZB-heparin admixtures in different PD solutions.
- Stored samples at 4°C for 168 hours, followed by 25°C for 3 hours and 37°C for 10 hours.
- Analyzed drug and heparin concentrations, anticoagulant activity, particle content, pH, and color using HPLC and other methods.
Main Results:
- Meropenem and heparin maintained >90% concentration in 4/5 PD solutions under tested conditions.
- Piperacillin/tazobactam and heparin remained stable in all 8 PD solutions tested.
- Heparin retained >98% anticoagulant activity; no significant changes in pH, color, or particle formation were observed.
Conclusions:
- Piperacillin/tazobactam-heparin admixtures demonstrate good stability across various PD solutions.
- Meropenem-heparin stability was suboptimal in pH-neutral PD solutions, suggesting caution or avoidance in such formulations.
- Findings offer crucial data for optimizing PDAP treatment regimens involving antibiotic-heparin combinations.
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