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Steering Away from Current Amoxicillin Dose Reductions in Hospitalized Patients with Impaired Kidney Function to
Cornelis Smit1,2, Swapnoleena Sen1,3,4, Elodie von Dach5
1Pediatric Pharmacology and Pharmacometrics Research Center, University of Basel Children's Hospital (UKBB), 4056 Basel, Switzerland.
Abstract:
Current dose reductions recommended for amoxicillin in patients with impaired kidney function could lead to suboptimal treatments. In a prospective, observational study in hospitalized adults with varying kidney function treated with an IV or oral dose of amoxicillin, amoxicillin concentrations were measured in 1−2 samples on the second day of treatment. Pharmacometric modelling and simulations were performed to evaluate the probability of target attainment (PTA) for 40% of the time above MIC following standard (1000 mg q6h), reduced or increased IV dosing strategies. A total of 210 amoxicillin samples was collected from 155 patients with kidney function based on a CKD-EPI of between 12 and 165 mL/min/1.73 m2. Amoxicillin clearance could be well predicted with body weight and CKD-EPI. Recommended dose adjustments resulted in a clinically relevant reduction in the PTA for the nonspecies-related PK/PD breakpoint MIC of 8 mg/L (92%, 62% and 38% with a CKD-EPI of 10, 20 and 30 mL/min/1.73 m2, respectively, versus 100% for the standard dose). For MICs ≤ 2 mg/L, PTA > 90% was reached in these patients following both reduced and standard dose regimens. Our study showed that for amoxicillin, recommended dose reductions with impaired kidney function could lead to subtherapeutic amoxicillin concentrations in hospitalized patients, especially when targeting less susceptible pathogens.
Insights
Current amoxicillin dose reductions for impaired kidney function may cause suboptimal treatment. This study found that reduced doses can lead to subtherapeutic amoxicillin concentrations, especially for less susceptible bacteria.
Area of Science:
- Pharmacology
- Nephrology
- Infectious Diseases
Background:
- Current amoxicillin dosing guidelines for patients with impaired kidney function may not ensure optimal therapeutic outcomes.
- Suboptimal drug concentrations can lead to treatment failure and the development of antimicrobial resistance.
Purpose of the Study:
- To evaluate the impact of current amoxicillin dose reduction recommendations on achieving therapeutic drug concentrations in hospitalized patients with varying kidney function.
- To assess the probability of target attainment (PTA) for amoxicillin using different dosing strategies.
Main Methods:
- Prospective, observational study involving hospitalized adults with impaired kidney function.
- Measurement of amoxicillin concentrations in blood samples.
- Pharmacometric modeling and simulation to determine PTA for various dosing regimens and estimated Glomerular Filtration Rates (eGFR) using CKD-EPI.
Main Results:
- Amoxicillin clearance was predictable using body weight and CKD-EPI.
- Recommended dose reductions significantly decreased PTA, particularly for higher minimum inhibitory concentrations (MICs).
- For MICs of 8 mg/L, PTA decreased from 100% with standard dosing to 38% with reduced dosing in patients with CKD-EPI of 30 mL/min/1.73 m2.
Conclusions:
- Current amoxicillin dose reduction recommendations for impaired kidney function may result in subtherapeutic concentrations.
- Dosing adjustments should be carefully considered to ensure adequate amoxicillin exposure, especially when treating less susceptible pathogens.
- Further research into optimized dosing strategies for amoxicillin in renal impairment is warranted.
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