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Penetration of meropenem into heart valve tissue
S W Newsom1, J Palsingh, F C Wells
1Papworth Hospital, Cambridge, UK.
Abstract:
Thirty-three patients requiring cardiac valve surgery were administered meropenem 1000 mg by a 5 to 10 min iv injection. Samples of blood, cardiac valve and atrial muscle tissue were removed at valvectomy and analysed for meropenem by high performance liquid chromatography (HPLC) with UV detection. The plasma concentrations observed in the samples from these patients were higher than those reported when meropenem 1000 mg was administered to healthy volunteers by 5 min iv injection. No clinical adverse events attributable to meropenem were reported and the single 1000 mg dose was well tolerated. The penetration of meropenem into cardiac muscle and valve tissue was rapid and in excess of that expected solely on the basis of distribution into extracellular fluid. The concentrations achieved in the tissues were in excess of the MICs of the pathogens commonly causing endocarditis.
Insights
Meropenem (a broad-spectrum antibiotic) concentrations in cardiac surgery patients were higher than in healthy volunteers. This single meropenem dose was well-tolerated and achieved effective tissue levels against common endocarditis pathogens.
Area of Science:
- Pharmacology
- Infectious Diseases
- Cardiovascular Surgery
Background:
- Cardiac valve surgery patients often require antibiotic prophylaxis.
- Meropenem is a broad-spectrum carbapenem antibiotic used for serious bacterial infections.
- Understanding meropenem tissue penetration is crucial for optimizing treatment efficacy.
Purpose of the Study:
- To evaluate meropenem plasma and tissue concentrations in patients undergoing cardiac valve surgery.
- To assess the safety and tolerability of a single 1000 mg meropenem dose in this patient population.
- To compare tissue penetration with previously reported data in healthy volunteers.
Main Methods:
- Thirty-three patients received a 1000 mg intravenous meropenem dose.
- Blood, cardiac valve, and atrial muscle samples were collected during valvectomy.
- Meropenem concentrations were quantified using high-performance liquid chromatography (HPLC) with UV detection.
Main Results:
- Plasma meropenem concentrations were higher in surgical patients compared to healthy volunteers.
- Meropenem demonstrated rapid and extensive penetration into cardiac muscle and valve tissue.
- Achieved tissue concentrations exceeded the minimum inhibitory concentrations (MICs) for common endocarditis-causing pathogens.
Conclusions:
- A single 1000 mg intravenous dose of meropenem is well-tolerated in cardiac valve surgery patients.
- Meropenem exhibits favorable pharmacokinetic properties, with significant tissue penetration in the cardiac environment.
- The achieved tissue concentrations support the use of meropenem for treating or preventing endocarditis in this surgical context.