Training a Drug to Do New Tricks: Insights on Stability of Meropenem Administered as a Continuous Infusion

Area of Science:

• Pharmacology
• Infectious Diseases
• Clinical Pharmacy

Background:

• Carbapenems are crucial for combating multi-drug resistant organisms (MDROs).
• Continuous infusion (CI) of beta-lactams maximizes efficacy, but meropenem CI has faced limitations due to stability concerns.
• Optimizing meropenem dosing is essential for effective MDRO treatment.

Purpose of the Study:

• To evaluate meropenem serum concentrations and drug stability during continuous infusion (CI) over 8- or 12-hour intervals.
• To assess meropenem's pharmacokinetic/pharmacodynamic (PK/PD) target attainment against pathogen minimum inhibitory concentrations (MICs).
• To determine the clinical cure rate associated with meropenem CI therapy.

Main Methods:

• Retrospective observational study of patients receiving meropenem CI at a 1% concentration (8- or 12-hour exchanges).
• A dedicated stability experiment assessed 1% meropenem integrity at room temperature over 12 hours.
• Serum meropenem concentrations were quantified, and PK/PD targets were analyzed relative to MICs.

Main Results:

• Meropenem CI, at a median dose of 6 g/day, achieved a median serum concentration of 17.8 mg/L.
• In 95% of cases, meropenem CI maintained concentrations above the pathogen's MIC for the entire dosing interval.
• The stability experiment showed negligible meropenem degradation over 12 hours, and 80% of patients achieved clinical cure.

Conclusions:

• Meropenem demonstrates excellent stability when administered via continuous infusion (CI) using 8- or 12-hour exchange protocols.
• CI meropenem effectively achieves therapeutic drug concentrations and high clinical cure rates in patients with MDRO infections.
• This study supports the expanded use of meropenem CI for managing challenging bacterial infections.