The simplified oral flucloxacillin absorption test: an accurate method to identify patients with inadequate oral flucloxacillin absorption.

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.

A systematic literature review of the human skin microbiome as biomarker for dermatological drug development.

AIMS: To explore the potential of the skin microbiome as biomarker in six dermatological conditions: atopic dermatitis (AD), acne vulgaris (AV), psoriasis vulgaris (PV), hidradenitis suppurativa (HS), seborrhoeic dermatitis/pityriasis capitis (SD/PC) and ulcus cruris (UC). METHODS: A systematic literature review was conducted according to the PRISMA guidelines. Two investigators independently reviewed the included studies and ranked the suitability microbiome implementation for early phase clinical studies in an adapted GRADE method. RESULTS: In total, 841 papers were identified and after screening of titles and abstracts for eligibility we identified 42 manuscripts that could be included in the review. Eleven studies were included for AD, five for AV, 10 for PV, two for HS, four for SD and 10 for UC. For AD and AV, multiple studies report the relationship between the skin microbiome, disease severity and clinical response to treatment. This is currently lacking for the remaining conditions. CONCLUSION: For two indications - AD and AV - there is preliminary evidence to support implementation of the skin microbiome as biomarkers in early phase clinical trials. For PV, UC, SD and HS there is insufficient evidence from the literature. More microbiome-directed prospective studies studying the effect of current treatments on the microbiome with special attention for patient meta-data, sampling methods and analysis methods are needed to draw more substantial conclusions.