Training a Drug to Do New Tricks: Insights on Stability of Meropenem Administered as a Continuous Infusion. (October 2018)

• Record Type: Journal Article
• Authors: Venugopalan, Veena; Manigaba, Kayihura; Borgert, Samuel J; Cope, Jessica; Peloquin, Charles A; Klinker, Kenneth P
• Is Part Of: Microbiology insights. Volume 11(2018)
• Publication Date: 2018-10
• Subjects: Drug stability -- meropenem -- continuous infusion -- therapeutic drug monitoring -- antibiotic exposure; Microbiology -- Periodicals; Biology -- Periodicals; Microbiological Phenomena; Biological Phenomena; Biology; Microbiology; Electronic journals; Periodicals; Fulltext; Internet Resources; Periodicals; Periodicals; 616.9041
• DOI: 10.1177/1178636118804549
• Languages: English
• ISSNs: 1178-6361

Abstract

Background: The antibiotic armamentarium used to combat multi-drug resistant organisms (MDROs) include carbapenems. Continuous infusion (CI) dosing is frequently employed to maximize beta-lactam efficacy; however, use of meropenem CI has been limited due to concerns with product instability. Objective: The primary objective of this study was to quantify meropenem serum concentrations to reflect drug stability when administered as CI over 8- or 12-h exchanges. In addition, a stability experiment was performed to further establish meropenem integrity over 12 h. The secondary objectives were to assess the ability of meropenem to achieve target pharmacokinetic/pharmacodynamic (PK/PD) exposures relative to the minimum inhibitory concentration (MIC) of the pathogen, and to determine clinical cure. Methods: This was a retrospective, observational study on use of CI meropenem (infused either over 8- or 12- h) at a 1% concentration. The stability experiment was conducted on 1% meropenem at room temperature. Results: In 22 patients, a median meropenem daily dose of 6 g/day (range 2-6 g/day) resulted in a median serum concentration of 17.8 mg/L (interquartile range, 9.3-27.8 mg/L). In 95% of cases, meropenem delivered as CI resulted in free drug concentrations at or above the MIC of the pathogen for the entire dosing interval. Clinical cure was achieved in 80% of patients included in this review. The stability experiment revealed negligible drug degradation at the end of the 12-h dosing interval. Conclusions: The data from this study provides compelling evidence for the use of meropenem as CI utilizing either a 12- or 8-h exchange process.