What is the recommended dosing frequency of oxacillin (antistaphylococcal penicillin) for a patient with osteomyelitis, a fracture-related hip infection due to methicillin-sensitive Staphylococcus aureus (MSSA), and a bone cement spacer in place?

Oxacillin Dosing for MSSA Osteomyelitis

For osteomyelitis due to methicillin-sensitive Staphylococcus aureus (MSSA), oxacillin should be administered at 1-2 grams every 4 hours intravenously, which translates to 6 doses per day, not every 6 hours. 1, 2

Recommended Dosing Regimen

• Adult dosing: Oxacillin 1-2 grams IV every 4 hours for severe infections including osteomyelitis 1, 2
• This equates to 6 doses per 24-hour period (every 4 hours around the clock) 2
• The FDA label explicitly states "1 gram IM or IV every 4 to 6 hours (severe infections)" with the every 4-hour interval being standard for bone infections 2

Treatment Duration

• Minimum 8 weeks of antibiotic therapy is recommended for MSSA osteomyelitis 3, 4
• The FDA label notes that "treatment of endocarditis and osteomyelitis may require a longer duration of therapy" 2
• Continue therapy for at least 48 hours after the patient becomes afebrile, asymptomatic, and cultures are negative 2

Adjunctive Therapy Considerations

• Addition of rifampin (600 mg daily or 300-450 mg twice daily) should be considered due to excellent bone and biofilm penetration 3, 4
• Rifampin should only be added after bacteremia clearance (if present) to prevent resistance development 3
• Always combine rifampin with another active agent to prevent emergence of resistance 3, 4

Critical Pitfalls to Avoid

• Do not dose every 6 hours for osteomyelitis—this is the dosing for mild to moderate infections, not bone infections 1, 2
• The every 4-hour dosing is critical because oxacillin levels in diseased bone remain above the MIC for only 2 hours after injection, necessitating more frequent dosing 5
• Watch for thrombophlebitis with IV administration, particularly in elderly patients 2

Special Considerations for Your Case

Given the fracture-related hip infection with a bone cement spacer in place:

• Surgical debridement is the cornerstone of therapy and should be performed whenever feasible 3, 4
• The presence of a spacer may require eventual two-stage revision with continued antibiotic therapy 3
• If adequate surgical debridement removes all infected bone, a shorter course (2-14 days) may be sufficient depending on soft tissue status, though this is uncommon with retained hardware 4