Narrow-spectrum penicillins with antistaphylococcal activity: dicloxacillin and flucloxacillin

Dicloxacillin and flucloxacillin are stable to beta-lactamase enzymes produced by staphylococci, including penicillin-resistant, methicillin-susceptible Staphylococcus aureus (MSSA). They are also active against streptococci, so are recommended as first-line treatment for many skin and soft tissue infections.

Food impairs the absorption of dicloxacillin and flucloxacillin. Ideally, they should be dosed at 6-hourly intervals, but for practical purposes (eg in children) four-times-daily dosing, evenly spaced during waking hours, is often used.

Flucloxacillin is usually well tolerated; rarely, it is associated with cholestatic jaundice, particularly in older patients taking prolonged therapy. Hepatotoxicity can occur, particularly during prolonged (more than 6 days) intravenous administration, and up to 6 weeks after stopping treatment. Monitoring for hepatotoxicity is recommended for patients receiving prolonged intravenous therapy (more than 6 days)Tang, 2022. Dicloxacillin appears to cause less irreversible hepatotoxicity, but causes more interstitial nephritis. Dicloxacillin may be preferable to flucloxacillin for patients requiring prolonged oral therapy.