Stability of Meropenem After Reconstitution for Administration by Prolonged Infusion

Abstract

Objective: Meropenem is a parenteral carbapenem antibiotic which has a broad spectrum of activity against aerobes and anaerobes. Meropenem's bactericidal activity is determined by the time during which meropenem concentration remains above the minimal inhibition concentration (MIC) during the dosing interval. Thus, prolonged infusion is the optimal way to maximize the time-dependant activity. However, studies to date have shown that carbapenems and in particular, meropenem, are relatively unstable in solution. The aims of this study were therefore (1) to establish the effects of temperature on the concentration of a generic brand reconstituted meropenem solution and (2) to determine whether 24-hour continuous infusion is possible without concentrations dropping below the recommended 90%. Method: Preliminary examination was carried out by the means of nuclear magnetic resonance (NMR) spectroscopy. Meropenem was subsequently assayed using high-performance liquid chromatography (HPLC). The method was developed and validated in compliance with International Council for Harmonisation (ICH) guidelines. Meropenem's stability was examined at two temperatures 22°C and 33°C to mimic average and high temperature in hospital wards. Solutions were prepared aseptically at the clinically relevant concentration. Results: NMR results obtained showed an increase in open ring methyl groups peak intensity, indicating that meropenem begins to degrade upon dissolution (d=1.05 and 1.25). Results obtained from quantitative HPLC confirm that meropenem concentrations dropped to 90% of initial concentration at 7.4 hours and 5.7 hours at 22°C and 33°C, respectively. Conclusion: Although results obtained indicate that meropenem should not be continuously infused over 24 hours, it is possible that meropenem could be continuously infused for at least 7 hours if temperature does not exceed 22°C and for 5 hours if temperature does not exceed 33°C.

Meropenem use and therapeutic drug monitoring in clinical practice: a literature review

“…Optimizing the duration of exposure may help in the adjustment of meropenem concentrations. Studies demonstrated that meropenem stability at room temperature is about 6–8 h. Therefore, it is necessary for a continuous infusion administration scheme to change the infusion bag periodically, avoiding loss of power and possible side effects due to exposure to harmful products that originated in meropenem degradation 41,45 …”

“…Studies demonstrated that meropenem stability at room temperature is about 6-8 h. Therefore, it is necessary for a continuous infusion administration scheme to change the infusion bag periodically, avoiding loss of power and possible side effects due to exposure to harmful products that originated in meropenem degradation. 41,45 Therapeutic drug monitoring is a practical way to assess exposure to antimicrobials in the right dosage, correlating with patients' clinical signs. TDM applies knowledge of PK/PD parameters and profiles, patients' physiology, and MIC of the causative pathogen to help guide therapy, individualize dose regimen and effectively eradicate infection.…”

Combination inhibition activity of chlorhexidine and antibiotics on multidrug-resistant Acinetobacter baumannii in vitro

“…The solution of IMP in normal saline solution was stable 3 to 4 h stored at 25 °C [ 22 ]. MER in 0.9% saline was stable at least 7 h if the temperature does not increase to 22 °C, while MER stability at 5 h when temperature does not exceed 33 °C [ 23 ]. Chlorhexidine combination with MER shown synergistic effects than IMP, and chlorhexidine together with IMP was indifferent in 10% of isolates.…”

Optimizing the role of ambulatory chemotherapy in response to the Covid-19 pandemic

“…Prolonged infusions of antibiotics are already under study and have shown promising results. 13,14 There are, however, some key challenges to address for this scheme to be successfully implemented.…”