Can oxacillin be administered orally (PO)?

Can Oxacillin Be Given Orally?

Yes, oxacillin can be administered orally, but it has poor oral bioavailability and should not be used as initial therapy in serious, life-threatening infections. 1

Oral Formulation Availability and Bioavailability

• Oxacillin sodium salt is available for oral administration, along with other penicillinase-resistant penicillins like cloxacillin, dicloxacillin, and nafcillin 1
• However, oxacillin has significantly inferior oral bioavailability compared to other oral penicillinase-resistant penicillins 2
• Research demonstrates that oral oxacillin absorption varies substantially depending on the formulation (capsules vs. tablets), with capsules showing 3 times better absorption than tablets 2

Clinical Use Restrictions

• Oral penicillinase-resistant penicillins should NOT be used as initial therapy in serious, life-threatening infections 1
• Oral therapy with oxacillin may be used as follow-up after parenteral therapy once the clinical condition warrants the transition 1
• The drug should be administered on an empty stomach, at least 1 hour before or 2 hours after meals, with at least 4 fluid ounces (120 mL) of water 1
• Patients should not take oxacillin in the supine position or immediately before going to bed 1

Preferred Alternatives for Oral Therapy

When oral therapy for methicillin-susceptible staphylococcal infections is appropriate, dicloxacillin or flucloxacillin are strongly preferred over oxacillin due to superior oral bioavailability:

• Dicloxacillin is the oral agent of choice for methicillin-susceptible strains in adults, dosed at 125-250 mg every 6 hours for mild to moderate infections, or 250 mg every 6 hours for severe infections 3, 1
• For children weighing less than 40 kg, dicloxacillin is dosed at 12.5-25 mg/kg/day divided every 6 hours 3, 1
• Flucloxacillin (or dicloxacillin) is recommended at 12 g/day IV in 4-6 doses for serious infections like endocarditis, but oral formulations exist for less severe cases 3

Clinical Context from Guidelines

Multiple major guidelines reference oxacillin exclusively for intravenous administration in serious infections:

• For native valve endocarditis due to methicillin-susceptible staphylococci, oxacillin is dosed at 12 g/day IV in 4-6 doses for 4-6 weeks 3
• For prosthetic valve endocarditis, oxacillin is given at 12 g/day IV for ≥6 weeks 3
• For vertebral osteomyelitis due to MSSA, nafcillin or oxacillin is dosed at 1.5-2 g IV every 4-6 hours 4
• Pediatric dosing for serious infections is 100-300 mg/kg/day IV in 4-6 equally divided doses 3

Common Pitfall to Avoid

The critical pitfall is attempting to use oral oxacillin for initial treatment of serious staphylococcal infections. This approach risks treatment failure due to inadequate drug levels. If oral therapy is needed for methicillin-susceptible staphylococcal infections, switch to dicloxacillin or flucloxacillin, which have superior and more predictable oral absorption 3, 1. Alternatively, consider oral agents with excellent bioavailability such as clindamycin (300-450 mg four times daily) or first-generation cephalosporins like cephalexin (500 mg three to four times daily) for step-down therapy after clinical improvement 3.