Related Experiment Video
Updated: Jun 4, 2025
Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
Amoxicillin Blood Concentration in High-Dose Intravenous Discontinuous Amoxicillin: Look Beyond Numbers. Max-Amox
Mélissa Clément1, Florence Anglade2, Lucie Gibold3
1Department of Internal Medicine, CH Henri Mondor, Aurillac, France; Department of Internal Medicine, CHU Clermont-Ferrand, Clermont-Ferrand, France.
Purpose:
High doses of amoxicillin are recommended to treat severe infections such as endocarditis. Amoxicillin causes dose-dependent toxicities, in particular crystal nephropathy. Toxicity could be avoided by monitoring of amoxicillin trough plasma concentrations (ATPC). However, the relevance of ATPC testing in routine medical practice remains poorly studied.
Methods:
We conducted a prospective clinical trial in adults treated with high doses of discontinuous intravenous amoxicillin in a French university hospital. The primary outcome was the distribution of ATPCs over three days during the first week of treatment. Urine tests for amoxicillin crystalluria (AC), pH, and density were also performed.
Findings:
Seventy patients were included. Overall intra-class correlation (ICC) was 0.35 IC95% [0.21; 0.53] with the following pairwise concordances: D1-D4 (n= 55) 0.23 IC95% [-0.02; 0.47], D1-D7 (n= 47) 0.41 IC95% [0.19; 0.63], and D4-D7 (n= 50) 0.17 IC95% [-0.10; 0.43]. Inter-individual variability was also significant, with coefficients of variation being 0.87 at D1, 1.20 at D4, and 1.35 at D7. AC occurred in 32 patients (47.8%). Risk of AC increased when pH was below or equal to 6 (P = 0.002). ATPCs were higher in patients with AC and/or acute kidney injury.
Implications:
Variability in ATPC was high and ATPC cannot be considered as the only monitoring tool to adjust amoxicillin dosage. High ATPC, low urinary pH, and presence of AC can alert physicians to a potential iatrogenic effect and lead to the decision to hydrate the patient, alkalinize urine and decrease the dosage of amoxicillin.
Insights
Monitoring amoxicillin trough plasma concentrations (ATPC) showed high variability and is not sufficient alone for dose adjustment. High ATPC, low urinary pH, and amoxicillin crystalluria (AC) indicate potential toxicity.
Area of Science:
- Pharmacology
- Nephrology
- Infectious Diseases
Background:
- High-dose amoxicillin is crucial for severe infections like endocarditis.
- Amoxicillin can cause dose-dependent toxicities, notably crystal nephropathy.
- Monitoring amoxicillin trough plasma concentrations (ATPC) may prevent toxicity, but its routine use is understudied.
Purpose of the Study:
- To evaluate the distribution and variability of ATPC in patients receiving high-dose amoxicillin.
- To assess the clinical relevance of ATPC monitoring in routine practice.
Main Methods:
- Prospective clinical trial in adults receiving high-dose intravenous amoxicillin.
- Primary outcome: distribution of ATPCs over three days during the first week of treatment.
- Secondary outcomes: urine tests for amoxicillin crystalluria (AC), pH, and density.
Main Results:
- Seventy patients were included; high inter-individual variability in ATPC was observed.
- Amoxicillin crystalluria (AC) occurred in 47.8% of patients, increasing with urinary pH ≤ 6.
- Higher ATPCs were associated with AC and/or acute kidney injury.
Conclusions:
- High variability in ATPC suggests it's insufficient as a sole monitoring tool for amoxicillin dosage.
- Elevated ATPC, low urinary pH, and AC presence are indicators of potential iatrogenic effects.
- These findings may guide interventions like hydration, urine alkalinization, and dosage reduction.
More Related Videos
09:17A Robust Pneumonia Model in Immunocompetent Rodents to Evaluate Antibacterial Efficacy against S. pneumoniae, H. influenzae, K. pneumoniae, P. aeruginosa or A. baumannii
Published on: January 2, 2017
06:18A Novel Method to Determine the Longitudinal Antibacterial Activity of Drug-Eluting Materials
Published on: March 3, 2023
Related Concept Videos
01:23Drug Concentrations: Measurements
Plasma...
01:15Drug Concentration Versus Time Correlation
Two pivotal parameters are the minimum effective concentration (MEC) and the minimum toxic concentration (MTC). The MEC is the...
01:24Rational Dosage Regimen: Maintenance Dose and Loading Dose
In most cases, drugs are administered repetitively or infused continuously to maintain a steady-state concentration in the body. At a steady...
01:05Steady State Concentration
Most drugs are administered in repeated doses at fixed intervals or through continuous...
00:59Nonlinear Pharmacokinetics: Drug Elimination for IV Bolus Injection
Following the administration of a single intravenous (IV) bolus injection, we can determine the concentration of the drug in the plasma at any given time. This calculation is achieved using a specific equation that integrates the values of Vmax and KM.
We can also...
01:14Time Course of Drug Effect