Continuous Infusions of Meropenem in Ambulatory Care: Clinical Efficacy, Safety and Stability

Abstract

ObjectivesConcerns 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.MethodsWe 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.ResultsForty-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.ConclusionsMeropenem 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.

Pharmacokinetics and Pharmacodynamics of Continuous Infusion Meropenem in Overweight, Obese, and Morbidly Obese Patients with Stable and Unstable Kidney Function: A Step Toward Dose Optimization for the Treatment of Severe Gram-Negative Bacterial Infections

“…The underlying rationale for this change in infusion rate has been to optimize the T [ MIC profile of meropenem, which is not achieved by short intermittent infusion in some settings [9,10,25], especially when treating critically ill patients [26]. Furthermore, the concerns regarding insufficient chemical stability to permit such optimization have been alleviated by data from several groups [13][14][15]. These stability data have also been extended beyond the reference-listed drug to encompass generic formulations of meropenem [13][14][15].…”

“…Furthermore, the concerns regarding insufficient chemical stability to permit such optimization have been alleviated by data from several groups [13][14][15]. These stability data have also been extended beyond the reference-listed drug to encompass generic formulations of meropenem [13][14][15]. Given that the primary route of meropenem elimination is through the kidneys, nomograms to define meropenem daily doses have been developed based on CL CR estimated using the Cockcroft-Gault equation [7].…”

“…However, early concerns about the chemical stability of meropenem intravenous solutions at room temperature hindered the adoption of this continuous infusion dosing modality [8,13]. Recent work from research groups including ours demonstrate that meropenem is sufficiently stable for 6-8 h at 25-35°C, which permits continuous infusion administration by replacing the intravenous bag three to four times a day [13][14][15]. Our group has defined and validated a dosing nomogram for the administration of meropenem by continuous infusion in patients with severe Gram-negative infection based on CL CR [7].…”

Chemical Stability of Ceftolozane/Tazobactam in Polyvinylchloride Bags and Elastomeric Pumps

“…Continuous or prolonged infusion is also of interest for β-lactams, such as ceftolozane/tazobactam, to ensure the attainment of pharmacokinetic/pharmacodynamic targets (the time that drug concentrations are maintained across the dosing interval at a level above the minimum inhibitory concentration) in certain clinical settings. However, effective infusion with the elastomeric pump requires that the drug remain stable in solution throughout the duration of the infusion[5], [6] to ensure adequate delivery of active drug while avoiding patient exposure to toxic degradation products 7 …”

Optimizing beta-lactam antibiotic dosing in critically ill patients: Prolonged infusion versus intermittent bolus administration

“…Patients receiving RRT are therefore less likely to benefit from altered dosing approaches such as CI administration. Based on these inconsistent findings and other relevant retrospective clinical data [272][273][274][275][276], we await the outcome of future clinical trials that use a more rigorous and stringent methodology to demonstrate the clinical outcome differences between CI and IB, if they do exist. e A priori analysis.…”