Stability, compatibility and microbiological activity studies of meropenem-clavulanate potassium

J Antibiot (Tokyo). 2015 Jan;68(1):35-9. doi: 10.1038/ja.2014.92. Epub 2014 Jul 30.

Abstract

Meropenem (MEM) and clavulanate potassium have been reported to demonstrate highly effective activity against Mycobacterium tuberculosis. There have been no reports on research into the complex of these chemotherapeutics concerning their mutually dependent stability or microbiological action on other microorganisms. Stability and compatibility studies of MEM/clavulanate potassium were conducted by using an HPLC-DAD method. The antibacterial activity of MEM/clavulanate potassium was tested in vitro against a selection of indicator bacteria strains by determining the MIC as well as analyzing the kinetics of changes in the concentrations of Pseudomonas aeruginosa, Staphylococcus aureus and Listeria monocytogenes caused by the action of MEM/clavulanate potassium. The stability and compatibility of MEM/clavulanate potassium were examined in aqua pro iniectione, 0.9% NaCl and 5% glucose at room temperature and at 5 °C. The degradation rates of MEM/clavulanate potassium depended on the type of infusion solvent used. Although in aqueous solutions of MEM/clavulanate potassium neither compound showed any mutual impact on the rate of degradation, clavulanate potassium was more labile than MEM. The synergy between these two resulted in a significantly lower value of MIC as compared to the values observed for the individual activity of either compound. The infusion solvent in which compatibility is observed between the components of the mixture MEM/clavulanate potassium is aqua pro iniectione. The complex MEM/clavulanate potassium demonstrates synergic antibacterial activity against P. aeruginosa, S. aureus and L. monocytogenes.

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Chromatography, High Pressure Liquid / methods
  • Clavulanic Acid / administration & dosage
  • Clavulanic Acid / chemistry
  • Clavulanic Acid / pharmacology*
  • Drug Combinations
  • Drug Incompatibility
  • Drug Synergism
  • Listeria monocytogenes / drug effects*
  • Meropenem
  • Microbial Sensitivity Tests
  • Pseudomonas aeruginosa / drug effects*
  • Solvents / chemistry
  • Staphylococcus aureus / drug effects*
  • Temperature
  • Thienamycins / administration & dosage
  • Thienamycins / chemistry
  • Thienamycins / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Drug Combinations
  • Solvents
  • Thienamycins
  • Clavulanic Acid
  • Meropenem