When di/flucloxacillin is administered orally for the treatment of conditions such as osteomyelitis, plasma levels should be checked if poor absorption is suspected. Where absorption is normal, the peak plasma level of di/flucloxacillin 1 hour after a 1 g oral dose is usually 20 to 40 mg/L (total drug, approximately 95% protein bound). The addition of probenecid 500 mg (child >2 years: 10 mg/kg up to 500 mg) orally 12-hourly, may be necessary to achieve adequate plasma levels. If di/flucloxacillin results in nausea and/or vomiting, the dose may be reduced from 1 g (child: 25 mg/kg up to 1 g) orally 6-hourly to 500 mg (child: 12.5 mg/kg up to 500 mg) orally 6-hourly plus probenecid (as above), provided that adequate plasma levels are attained.

Continuous-infusion flucloxacillin (adult dose 8 to 12 g/day) usually achieves serum concentrations that are likely to be active against methicillin-susceptible Staphylococcus aureus. Measurement of serum flucloxacillin concentrations may be considered in some situations, such as S. aureus endocarditis and in patients with renal impairment.

There is less clinical experience with continuous-infusion benzylpenicillin therapy, and monitoring of serum benzylpenicillin concentrations is recommended in these patients.