Continuous infusions of meropenem in ambulatory care: clinical efficacy, safety and stability

Abstract

Objectives: Concerns regarding the clinical impact of meropenem instability in continuous infusion (CI) devices may contribute to inconsistent uptake of this method of administration across outpatient parenteral antimicrobial therapy (OPAT) services.

Methods: We retrospectively reviewed the clinical efficacy and safety of CIs of meropenem in two Australian tertiary hospitals and assessed its stability under simulated OPAT conditions including in elastomeric infusion devices containing 1% (2.4 g) or 2% (4.8 g) concentrations at either 'room temperature' or 'cooled' conditions. Infusate aliquots were assayed at different time-points over 24 hours.

Results: Forty-one (82%) of 50 patients had clinical improvement or were cured. Adverse patient outcomes including hemato-, hepato- and nephrotoxicity were infrequent. Cooled infusers with 1% meropenem had a mean 24-hour recovery of 90.3%. Recoveries of 1% and 2% meropenem at room temperature and 2% under cooled conditions were 88%, 83% and 87%, respectively. Patients receiving 1% meropenem are likely to receive >95% of the maximum deliverable dose (MDD) over a 24-hour period whilst patients receiving 2% meropenem should receive 93% and 87% of the MDD under cooled and room temperature conditions, respectively.

Conclusions: Meropenem infusers are likely to deliver ∼95% MDD and maintain effective plasma concentrations throughout the dosing period. These data reflect our local favourable clinical experience with meropenem CIs.

Conflict of interest statement

Competing Interests: The elastomeric infusion devices, temperature monitoring strips, meropenem for infusion, ertapenem internal standard and ice bricks were provided free of charge by Baxter Healthcare, Timestrip UK Ltd, Ranbaxy Australia Pty Ltd, Merck & Co., Inc. and Interaction Branding Pty Ltd, respectively. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Meropenem degradation in elastomeric infusion devices at different conditions over a 24-hour period (data points are mean values).

Figure 2. Median and 95% prediction intervals (PI95) of simulated plasma meropenem concentrations incorporating degradation as well as pharmacokinetic variability in 200 simulations of an average, 70 kg male patient receiving meropenem by continuous infusion in a cooled infuser containing 1% meropenem (figure 2A) and ‘room temperature’ infuser containing 2% meropenem (figure 2B).

Susceptibility breakpoints for Pseudomonas aeruginosa (upper grey dashed line) and Enterobacteriaciae (lower grey dashed line) are also shown in each.