Simulated Y-Site Compatibility of Vancomycin and Piperacillin-Tazobactam

Abstract

Purpose:To evaluate the physical compatibility of vancomycin with piperacillin-tazobactam during simulated Y-site administration. Methods: Vancomycin and piperacillin-tazobactam were tested using 2 different diluents: 0.9% sodium chloride and 5% dextrose for injection. Vancomycin concentrations of 2, 5, and 10 mg/mL were tested using 0.9% sodium chloride and 4 and 8 mg/mL in 5% dextrose. Piperacillin-tazobactam was diluted to 16, 30, 40, 80, and 100 mg/mL, representing common concentrations used clinically in hospitals, and concentrations were tested in both 0.9% sodium chloride and 5% dextrose for injection. Medications were reconstituted under USP <797> aseptic technique. Combinations were tested in duplicate and reverse order with control solutions. Compatibility testing for Y-site included visual inspection, inspection with a high-intensity monodirectional light source (Tyndall beam), turbidimeter for turbidity evaluation, pH, and microscopic viewing. Testing occurred immediately after mixing, 15 minutes, 60 minutes, and 4 hours. If inconsistencies were observed between samples, testing was repeated to confirm results. Solutions were deemed incompatible if any one test failed and compatible if all tests were accepted. Results: When dextrose 5% for injection was used as the diluent, vancomycin 4 mg/mL was Y-site compatible with piperacillin-tazobactam 16, 30, and 40 mg/mL and incompatible with 80 and 100 mg/mL. Vancomycin 8 mg/mL was incompatible with all tested concentrations of piperacillin-tazobactam. When 0.9% sodium chloride was used as the diluents, Y-site compatibility was found with vancomycin 2 and 5 mg/mL and all tested concentrations of piperacillin-tazobactam. Vancomycin 10 mg/mL was incompatible with piperacillin-tazobactam 40, 80, and 100 mg/mL. Incompatibilities formed a white precipitate immediately on mixing. Conclusion: Y-site incompatibility was greater for the tested concentrations of piperacillintazobactam and vancomycin when 5% dextrose was used as the diluent versus 0.9% sodium chloride. Y-site incompatibility was seen immediately in the form of a white precipitate on mixing.

Y-site Incompatibility between Premix Concentrations of Vancomycin and Piperacillin-Tazobactam: Do Current Compatibility Testing Methodologies Tell the Whole Story?

“…This white precipitant was consistent with previous reports of vancomycin and piperacillin-tazobactam incompatibility. 8,9 No evidence of physical incompatibility was noted when standard procedures were used to simulate Y-site infusion. The mechanism of this discrepancy is unclear, but we believe it may likely be secondary to an interaction between the IV tubing and the combined mixture of vancomycin and piperacillin-tazobactam.…”

“…7 Wade and colleagues found that vancomycin 4 mg/mL in D5W was physically compatible with piperacillin-tazobactam 40 mg/ mL in D5W. 8 O'Donnell and colleagues found that vancomycin 4 to 7 mg/mL in D5W or NS was physically compatible with piperacillin-tazobactam 33.75 to 90 mg/mL in D5W or NS. 11 Based on these studies, it would appear that vancomycin and piperacillintazobactam are physically compatible at a variety of concentrations.…”

“…Most compatibility studies mix investigated medications in a 1:1 mixture within a test tube and test physical compatibility using simulated Y-site compatibility methodology including visual inspection, turbidity assessment, and pH evaluation. [7][8][9][10][11] This procedure does not account for physiochemical interactions that may occur during actual administration, such as the interaction between medications and intravenous (IV) tubing. Furthermore, previous literature has suggested that some medications show evidence of physical incompatibility during actual Y-site administration.…”

“…[4][5][6] Vancomycin and piperacillin-tazobactam have historically been considered to be Y-site incompatible at various concentrations. [7][8][9][10] However, recent published data suggest that vancomycin and piperacillintazobactam are physically compatible, particularly at commercially available premix formulation concentrations. 11 Given the logistical advantages of simultaneous administration, some institutions may have considered allowing concurrent Y-site administration for these agents in the clinical setting based on these reports.…”

Prospective Cohort Study of the Tolerability of Prosthetic Joint Infection Empirical Antimicrobial Therapy

“…Our results advocate the first option since a vancomycin plasma overexposure was found in only one-third of patients developing an AKI. In addition, the hypothesis of a physicochemical interaction between the two molecules is supported by the incompatibility observed when the two drugs are administered simultaneously, with a risk of formation of precipitates in the infusion lines (19,20). It can be assumed that these precipitates may form in the renal tubules in certain conditions, leading to renal obstruction.…”