<p>Suitability of Amoxicillin–Clavulanic Acid for Administration via Prolonged Infusion</p>

Abstract

Rationale: Previously, we have been able to outpace bacterial mutation by replacing increasingly ineffective antibiotics with new agents. However, with the discovery of new antibiotics diminishing, optimising the administration of existing broad-spectrum antibiotics such as co-amoxiclav has become a necessity. Methods: A stability indicating HPLC method was developed and validated in compliance with International Council for Harmonisation (ICH) guidelines. Stability of co-amoxiclav at clinical concentration was evaluated at three temperatures (4°C, ambient (23-25°C) and 37°C) in three diluents (water for injection (WFI), 0.9% w/v NaCl and Ringer's solution). To establish whether there were significant differences at the level of both diluent and temperature, results were analysed using analysis of covariance (ANCOVA) to assess differences between the attained slopes of regression. Results: Data obtained indicated co-amoxiclav stability superior to that previously proposed making it suitable for extended infusion therapy. The degradation of amoxicillin appeared to follow a linear trend, with the rate of degradation elevated at higher temperatures, demonstrated by the magnitude of the regression slopes in these conditions. Analysis of regression slopes via ANCOVA demonstrated that diluent and temperature both significantly affected co-amoxiclav stability. Amoxicillin retained 90% of its initial concentration for 7.8 to 10 hrs when stored at 4°C, 5.9 to 8.8 hrs at ambient and 3.5 to 4.5 hrs when incubated at 37°C. Conclusion: Co-amoxiclav is suitable for administration via prolonged infusion. Findings from this study aid in ameliorating current dosing regimens to optimise antibiotic efficacy. Other valuable applications conferred from these findings include the ability to pre-prepare solutions for use in bolus administration, minimising preparation time and workload.

Stability of Amoxicillin and Clavulanic Acid in Separate Containers for Administration via a Y-Site

“…Amoxicillin and clavulanic acid solutions retained more of their initial concentration for longer than reported in previously published results where they were prepared in combination. 11 The slopes of the regression lines for both active pharmaceutical ingredients (APIs) at the three temperatures studied showed significant deviation from zero at the 99% level of confidence, indicating amoxicillin and clavulanic acid exhibit degradation with time ( Table 1 ). Similarly, to previously published data, 11 ANCOVA showed that solutions stored at lower temperatures remained stable for significantly longer than solutions at higher temperatures ( Table 2 ).…”

“… 11 The slopes of the regression lines for both active pharmaceutical ingredients (APIs) at the three temperatures studied showed significant deviation from zero at the 99% level of confidence, indicating amoxicillin and clavulanic acid exhibit degradation with time ( Table 1 ). Similarly, to previously published data, 11 ANCOVA showed that solutions stored at lower temperatures remained stable for significantly longer than solutions at higher temperatures ( Table 2 ). The influence of temperature of both APIs is displayed in Figure 2 .…”

“…Results obtained are in alignment with those recently published, suggesting that storage temperature significantly influences the stability of amoxicillin and clavulanic acid ( Tables 1 – 3 ). 11 …”

“…A previously developed and validated method (in accordance with ICH guidelines) was utilised. 11 Separation was conducted using Phenomenex Spherisorb 5µm, 100×4.6 mm column with a binary mobile phase composition consisting of Ammonium Acetate (5mM) pH4 and acetonitrile (50:50 v/v). Analysis was performed at detection wavelength 215nm.…”

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.…”