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The simplified oral flucloxacillin absorption test: an accurate method to identify patients with inadequate oral
A C Dijkmans1, D M Kweekel, C Balmforth
1Centre for Human Drug Research, Leiden, the Netherlands.
Background:
The preferred treatment for severe methicillin-sensitive Staphylococcus aureus infections is flucloxacillin, a small-spectrum antibiotic administered intravenously (IV) and orally. However, clinicians switch to the less preferred broad-spectrum antibiotics because of the variable absorption after oral administration of flucloxacillin. A classical oral absorption test (OAT) requires overnight fasting and interruption of IV therapy, and is laborious. In the current study, we investigated whether a simplified OAT can be utilized in a clinical setting to guide antibiotic treatment in patients with severe S. aureus infections. For this, OAT IV therapy is continued and oral dosing is performed after a one-hour fast and implemented after a small study.
Methods:
In 196 patients receiving IV flucloxacillin by continuous infusion, a classical OAT (test A) or simplified version of the OAT (test B) was performed. In both tests, 1 g oral flucloxacillin was given and serum samples were taken prior to intake and at one and two hours after administration. Flucloxacillin concentrations were determined by high-performance liquid chromatography. Adequate absorption was defined as an increase of flucloxacillin concentration of at least 10 mg/l after one or two hours compared to baseline.
Results:
In a sample of 196 patients (85 F/111 M), test A was performed in 28 patients, and test B in 168 patients. Age, gender, and baseline values of creatinine and albumin were similar in both groups. The maximal increase of flucloxacillin absorption was highly variable between patients. In 26 (13%) of the 196 patients, the flucloxacillin increase did not reach the value of 10 mg/l. The median (interquartile range, IQR) maximal increase of flucloxacillin absorption was 22.0 (15-31.25) mg/l for test A and 21.5 (13-32.25) mg/l for test B. There was no significant difference in maximal increase of flucloxacillin absorption between test A and B (p = 0.74), nor between males and females (p = 0.95). Age, creatinine, and albumin were not correlated with flucloxacillin levels.
Conclusions:
The simplified version of the OAT is useful to identify patients with adequate oral flucloxacillin absorption, and to ensure the effective continuation of an oral small-spectrum treatment.
Insights
A simplified oral absorption test (OAT) effectively identifies patients who can continue oral flucloxacillin treatment for Staphylococcus aureus infections. This method avoids IV interruption, improving clinical management of antibiotic therapy.
Area of Science:
- Pharmacology
- Infectious Diseases
- Clinical Pharmacy
Background:
- Severe methicillin-sensitive Staphylococcus aureus infections are preferably treated with flucloxacillin.
- Variable oral absorption of flucloxacillin leads clinicians to use broader-spectrum antibiotics.
- Classical oral absorption tests (OAT) are laborious and require IV therapy interruption.
Purpose of the Study:
- To investigate the utility of a simplified OAT in a clinical setting.
- To guide antibiotic treatment decisions for severe S. aureus infections.
- To assess if a simplified OAT can enable continuation of oral flucloxacillin therapy.
Main Methods:
- A simplified OAT (test B) was compared to a classical OAT (test A) in 196 patients receiving IV flucloxacillin.
- 1g oral flucloxacillin was administered after a one-hour fast, with serum samples collected at 0, 1, and 2 hours.
- Flucloxacillin concentrations were measured using high-performance liquid chromatography; adequate absorption was defined as a ≥10 mg/l increase from baseline.
Main Results:
- No significant difference in maximal flucloxacillin absorption increase was observed between the simplified OAT (21.5 mg/l) and classical OAT (22.0 mg/l).
- 13% of patients showed inadequate oral flucloxacillin absorption.
- Absorption levels were not correlated with age, creatinine, or albumin, and showed no gender differences.
Conclusions:
- The simplified OAT is a viable tool for assessing oral flucloxacillin absorption in clinical practice.
- This simplified test facilitates the identification of patients suitable for continued oral small-spectrum antibiotic therapy.
- It supports effective management of severe S. aureus infections by enabling oral flucloxacillin use.
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