Flucloxacillin (Blood)

Diagnostic Use

Beta-lactam antibiotics such as penicillin, amoxycillin, flucloxacillin and cephalosporins have a wide therapeutic index and therapeutic drug monitoring is not normally required. However, when using continuous infusion regimens or if there are concerns about the adherence to treatment then the measuring of antibiotic levels can be useful. In some situations it may be useful to measure the concentration of antibiotic in body fluids other than serum, for example, cerebrospinal fluid.

The efficacy of beta-lactam antibiotics is related to the time for which the serum concentration of the drug exceeds the minimum inhibitory concentration (MIC) of the drug for a particular pathogen. Higher peak levels do not improve the efficacy.

For serious infections such as septicaemia or endocarditis serum concentrations exceeding the MIC by a factor of 10 are associated with better outcomes.

Flucloxacillin is highly protein bound (approx 95%) and clearance is by glomerular filtration and active tubular secretion.

Interpretation

Adults : Continuous infusions of flucloxacillin at doses of 8 and 12 g/day, respectively, have been associated with serum levels of 8 to >40 mg/L (median 29 mg/L) and 11.5 to >40 mg/L (median 27 mg/L), respectively. A single oral dose of 750 mg of flucloxacillin in adults achieves a level of about 34 mg/L.

Children, infants and neonates have been less well studied. In neonates and infants the clearance of flucloxacillin may be reduced and the half life increased. Following a bolus intravenous dose of 30mg/kg-1 of flucloxacillin levels in the range of 70-80 mg/kg were seen; a level well above the MIC.

In the context where the clinical team is considering flucloxacillin therapeutic monitoring, it is sensible to first contact the antimicrobial stewardship pharmacist and/or infectious diseases team for advice.

Reference Intervals

Flucloxacillin levels in the range of 20 – 50 mg/L should be adequate to treat most staphylococcal infections.