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"Amoxicillin and clavulanic acid are suitable for administration via continuous infusion when prepared, stored, and administered in separate containers" Fawaz et al (2021).
Y-site antibiotic administration

Abstract:

Rationale: With the discovery of new antibiotics diminishing, optimising the administration of existing antibiotics such as amoxicillin-clavulanic acid has become a necessity. At present, the optimal approach for enhancing the effectiveness of time-dependent antibiotics involves extending the time at which antibiotic concentrations are maintained above the minimal inhibitory concentration by prolonging the infusion time. This pharmacodynamic rationale cannot be applied to co-amoxiclav because of poor stability at room temperature. The aim of this study was to establish the shelf-life of amoxicillin and clavulanic acid prepared in separate containers to determine the feasibility of 24-hr continuous infusion therapy.

Methods: A previously developed and validated stability-indicating HPLC method was used to establish the shelf-life of reconstituted amoxicillin and clavulanic acid when prepared in separate containers. Stability at clinical concentration was evaluated at three temperatures. To establish whether there were significant differences at the level of both active ingredients and temperature, results were analysed using analysis of covariance (ANCOVA) to assess differences between the attained slopes of regression.

Results: Data obtained indicated amoxicillin and clavulanic acid stability superior to that previously proposed making it suitable for continuous infusion therapy. Analysis of regression slopes via ANCOVA showed that temperature significantly affected amoxicillin and clavulanic acid stability. Amoxicillin retained 90% of its initial concentration for 80.3 hrs when stored at 4°C, 24.8 hrs at 25°C and 9 hrs when incubated at 37°C. Clavulanic acid retained 90% of its initial concentration for 152 hrs when stored at 4°C, 26 hrs at 25°C and 6.4 hrs when incubated at 37°C.

Conclusion: Amoxicillin and clavulanic acid are suitable for administration via continuous infusion when prepared, stored, and administered in separate containers. Results obtained from this study aid in ameliorating current dosing regimens to optimise antibiotic efficacy; however, more in-depth amoxicillin and clavulanic acid y-site compatibility studies are warranted.

Reference:

Fawaz S, Merzouk M, Barton S, Nabhani-Gebara S. Stability of Amoxicillin and Clavulanic Acid in Separate Containers for Administration via a Y-Site. Drug Des Devel Ther. 2021 Sep 21;15:3979-3984. doi: 10.2147/DDDT.S310418. PMID: 34584403; PMCID: PMC8464313.