BACKGROUND: Patients with severe methicillin-sensitive Staphylococcus aureus infections are effectively treated with initial continuous intravenous (iv) flucloxacillin followed by oral maintenance therapy. As the absorption of oral flucloxacillin is variable, an oral absorption test (OAT) is used to ensure efficacious therapy. The classical OAT (test A) requires overnight fasting, interruption of iv therapy, and is laborious. We designed a simplified OAT (test B) in which iv therapy is continued and oral dosing is performed after a 1-hour fast. METHODS: In 43 hospitalized patients on iv flucloxacillin, either test A or test B was performed. In each variant, 1 g of oral flucloxacillin was given, and blood samples were taken before and at 1 and 2 hours after dosing. Flucloxacillin concentration was determined by high-performance liquid chromatography. Adequate absorption was defined as a ≥ 10 mg/L increase in flucloxacillin concentration at 1 or 2 hours after dosing. RESULTS: In a population of 43 patients (18F/25M), test A was done in 19 patients and test B in 24 patients. The groups had similar baseline characteristics such as age, renal function, gender, diagnoses, or comedication. All the patients tolerated the test without problems. The absorption was highly variable between patients. The average (SD; range) maximal increase for test A was 22.3 (11.6; 7-50) mg/L and 26.5 (12.6; 8-53) mg/L for test B. There was no significant difference between the 2 tests (P = 0.23), and 10% of the patients were poor absorbers (increase <10 mg/L). There was no influence of serum creatinine, age, or pretest flucloxacillin concentration. No clinical condition or drug use that may have impaired flucloxacillin absorption could be identified. CONCLUSIONS: We designed a simplified OAT that performs well and can be implemented easily. This test may be helpful to rationally and effectively treat patients with severe methicillin-sensitive S. aureus infections with an orally administered small-spectrum antibiotic.
BACKGROUND:Patients with severe methicillin-sensitive Staphylococcus aureus infections are effectively treated with initial continuous intravenous (iv) flucloxacillin followed by oral maintenance therapy. As the absorption of oral flucloxacillin is variable, an oral absorption test (OAT) is used to ensure efficacious therapy. The classical OAT (test A) requires overnight fasting, interruption of iv therapy, and is laborious. We designed a simplified OAT (test B) in which iv therapy is continued and oral dosing is performed after a 1-hour fast. METHODS: In 43 hospitalized patients on iv flucloxacillin, either test A or test B was performed. In each variant, 1 g of oral flucloxacillin was given, and blood samples were taken before and at 1 and 2 hours after dosing. Flucloxacillin concentration was determined by high-performance liquid chromatography. Adequate absorption was defined as a ≥ 10 mg/L increase in flucloxacillin concentration at 1 or 2 hours after dosing. RESULTS: In a population of 43 patients (18F/25M), test A was done in 19 patients and test B in 24 patients. The groups had similar baseline characteristics such as age, renal function, gender, diagnoses, or comedication. All the patients tolerated the test without problems. The absorption was highly variable between patients. The average (SD; range) maximal increase for test A was 22.3 (11.6; 7-50) mg/L and 26.5 (12.6; 8-53) mg/L for test B. There was no significant difference between the 2 tests (P = 0.23), and 10% of the patients were poor absorbers (increase <10 mg/L). There was no influence of serum creatinine, age, or pretest flucloxacillin concentration. No clinical condition or drug use that may have impaired flucloxacillin absorption could be identified. CONCLUSIONS: We designed a simplified OAT that performs well and can be implemented easily. This test may be helpful to rationally and effectively treat patients with severe methicillin-sensitive S. aureus infections with an orally administered small-spectrum antibiotic.
Authors: Anneke C Dijkmans; Dinemarie M Kweekel; Jaap T van Dissel; Michiel J van Esdonk; Ingrid M C Kamerling; Jacobus Burggraaf Journal: Antibiotics (Basel) Date: 2019-08-15