Dicloxacillin

Dicloxacillin is an oral penicillinase-resistant penicillin used for methicillin-susceptible staphylococcal and streptococcal skin and soft tissue infection, and osteoarticular infection in countries where it is available. Intravenous forms exist in some regions.

Classification. Beta-lactam, isoxazolyl penicillin, closely related to flucloxacillin.

Mechanism. Binds penicillin-binding proteins; resists hydrolysis by staphylococcal beta-lactamase.

Spectrum. MSSA, beta-haemolytic streptococci. Inactive against MRSA, enterococci and Gram-negative bacilli.

Pharmacokinetics. Oral bioavailability about 50 to 70%, reduced by food. Half-life about 40 minutes. Protein binding over 95%. Eliminated by kidneys and bile.

No loading dose. Maximum oral dose 4 g daily in adults.

Mild to moderate skin and soft tissue infection, adults. 250 to 500 mg orally every 6 hours for 5 to 7 days. Severe infection: 500 mg every 6 hours, oral step-down after IV therapy where licensed.

Osteomyelitis or septic arthritis step-down, adults. 1 g orally every 6 hours under specialist direction; total duration 6 weeks for osteomyelitis.

Children under 40 kg. 12.5 to 25 mg/kg/day for mild to moderate infection and 25 to 50 mg/kg/day in severe infection, in four divided doses.

Intravenous (where licensed). 1 g every 6 hours; maximum 8 g daily.

Alternatives. Flucloxacillin, cephalexin, cefadroxil, clindamycin, doxycycline or co-trimoxazole for mild infection; vancomycin or linezolid for MRSA.

Contraindications. Penicillin hypersensitivity; previous dicloxacillin-associated liver injury.

Adverse effects. Nausea, diarrhoea, rash. Serious: cholestatic hepatitis (reported with both agents, more commonly with flucloxacillin), interstitial nephritis, cytopenias, anaphylaxis, Clostridioides difficile infection.

Interactions. Warfarin (INR may fall), methotrexate, oral typhoid vaccine, voriconazole (may lower levels), probenecid.

Common prescribing errors. Taking with food, using it for MRSA, prolonged courses without liver tests.

Special groups. - Pregnancy and breastfeeding: acceptable. - Older adults: monitor liver tests. - Kidney impairment: usual dose; extend interval in creatinine clearance under 10 mL/min. - Liver impairment: avoid in significant disease. - Children: dose by weight. - Region: availability varies in East Africa; flucloxacillin is more common.

Formulations. Capsules 250 mg and 500 mg; oral solution where available.

Administration. Take on an empty stomach, 1 hour before or 2 hours after food, with a full glass of water.

Baseline and monitoring. - Baseline: allergy history, liver tests, creatinine. - Courses over 14 days: liver tests and full blood count weekly. - No therapeutic drug monitoring.

Stop rules. Stop for jaundice, rising liver enzymes over 3 times the upper limit of normal, severe rash or hypersensitivity.

Referral and escalation. Refer for treatment failure at 48 to 72 hours, deep abscess needing drainage, bone or joint infection, and suspected MRSA.