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Stability of Meropenem and Piperacillin/Tazobactam with Heparin in Various Peritoneal Dialysis Solutions.
Perit Dial Int 2018 Nov-Dec; 38(6):430-440PD

Abstract

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 The same bags were stored at 25°C for 3 hours followed by 10 hours at 37°C. An aliquot withdrawn before storage and at defined time points was analyzed for the concentration of meropenem, PIP, TZB, and heparin using high-performance liquid chromatography.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.

Authors+Show Affiliations

Pharmacy, School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.Pharmacy, School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.Pharmacy, School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.Pharmacy, School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.Pharmacy, School of Medicine, University of Tasmania, Hobart, Tasmania, Australia. Department of Pharmacy, Royal Hobart Hospital, Hobart, Tasmania, Australia.Pharmacy, School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.Pharmacy, School of Medicine, University of Tasmania, Hobart, Tasmania, Australia. School of Pharmacy, KPJ Healthcare University College, Nilai, Negeri Sembilan, Malaysia.Pharmacy, School of Medicine, University of Tasmania, Hobart, Tasmania, Australia. School of Nursing, Peritoneal Dialysis Unit, Blacktown Hospital, Blacktown, New South Wales, Australia. Regional Dialysis Centre, Blacktown Hospital, Blacktown, New South Wales, Australia.Regional Dialysis Centre, Blacktown Hospital, Blacktown, New South Wales, Australia. Department of Renal Medicine, Nepean Hospital and Nepean Clinical School, The University of Sydney, Kingswood, New South Wales, Australia.Pharmacy, School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.Pharmacy, School of Medicine, University of Tasmania, Hobart, Tasmania, Australia Rahul.Patel@utas.edu.au.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29991562

Citation

Mendes, Karryl, et al. "Stability of Meropenem and Piperacillin/Tazobactam With Heparin in Various Peritoneal Dialysis Solutions." Peritoneal Dialysis International : Journal of the International Society for Peritoneal Dialysis, vol. 38, no. 6, 2018, pp. 430-440.
Mendes K, Harmanjeet H, Sedeeq M, et al. Stability of Meropenem and Piperacillin/Tazobactam with Heparin in Various Peritoneal Dialysis Solutions. Perit Dial Int. 2018;38(6):430-440.
Mendes, K., Harmanjeet, H., Sedeeq, M., Modi, A., Wanandy, T., Zaidi, S. T. R., ... Patel, R. P. (2018). Stability of Meropenem and Piperacillin/Tazobactam with Heparin in Various Peritoneal Dialysis Solutions. Peritoneal Dialysis International : Journal of the International Society for Peritoneal Dialysis, 38(6), pp. 430-440. doi:10.3747/pdi.2017.00274.
Mendes K, et al. Stability of Meropenem and Piperacillin/Tazobactam With Heparin in Various Peritoneal Dialysis Solutions. Perit Dial Int. 2018;38(6):430-440. PubMed PMID: 29991562.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stability of Meropenem and Piperacillin/Tazobactam with Heparin in Various Peritoneal Dialysis Solutions. AU - Mendes,Karryl, AU - Harmanjeet,Harmanjeet, AU - Sedeeq,Mohammed, AU - Modi,Ankit, AU - Wanandy,Troy, AU - Zaidi,Syed Tabish R, AU - Ming,Long C, AU - Castelino,Ronald L, AU - Sud,Kamal, AU - Peterson,Gregory M, AU - Patel,Rahul P, Y1 - 2018/07/10/ PY - 2017/12/05/received PY - 2018/03/17/accepted PY - 2018/7/12/pubmed PY - 2019/3/16/medline PY - 2018/7/12/entrez KW - Antibiotics KW - anticoagulant KW - high performance liquid chromatography KW - storage SP - 430 EP - 440 JF - Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis JO - Perit Dial Int VL - 38 IS - 6 N2 - 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. SN - 1718-4304 UR - https://www.unboundmedicine.com/medline/citation/29991562/Stability_of_Meropenem_and_Piperacillin/Tazobactam_with_Heparin_in_Various_Peritoneal_Dialysis_Solutions_ L2 - http://www.pdiconnect.com/cgi/pmidlookup?view=long&pmid=29991562 DB - PRIME DP - Unbound Medicine ER -