Assessment of Meropenem Stability in Meropenem Admixtures Using 2 g Vials and Normal Saline Prepared Using addEASE ® Connectors

Background: Pharmacokinetic and pharmacodynamic optimization of β-lactams, including meropenem, using extended infusion are recommended by contemporary guidance to overcome elevated MICs and high interpatient pharmacokinetic variability associated with severe illness. Logistical challenges including drug stability must be considered when employing extended infusion meropenem. Although meropenem stability has been determined in a variety of settings to allow for extended infusion, confirmation for use of ready to use dispensing devices would be of interest. The purpose of this study was to assess meropenem concentrations using commercially available 2 g vials when diluted in 100 mL normal saline prepared via addEASE connectors. Methods: Five replicate bags were prepared and sampled at 0, 1, 2, 3, 4, 5, and 6 hours. Samples were stored frozen at ~-70ºC until meropenem concentrations determination using validated HPLC-UV and LC-MS/MS methods. Stability was defined as >90% recovery at the individual time point relative to the 0-hour concentration. Results: Starting concentrations were similar across all five replicates with an average (range) of 21.2 (20.2-21.9) and 19.4 mg/mL (17.7-20.5 mg/mL) for HPLC-UV and LC/MS-MS, respectively. No time point resulted in < 90% meropenem recovery from the starting concentration as determined by either assay method. Conclusion: These data demonstrated meropenem concentrations using 2 g vials diluted in 100 mL normal saline when prepared using addEASE connectors remained >90% of the initial concentration over 6 hours at room temperature. This supports extended infusion administration of meropenem per contemporary guidance when prepared using this methodology. Since this method allows storage of doses in automated dispensing cabinets and bedside preparation, this may streamline pharmacy workflows and potentially reduce time to administration.