What is the recommended treatment for a patient with a fracture-related Methicillin-Sensitive Staphylococcus aureus (MSSA) infection?

Treatment of Fracture-Related MSSA Infection

For MSSA fracture-related infections, use an antistaphylococcal penicillin (nafcillin or oxacillin 2g IV every 6 hours) or cefazolin (1-2g IV every 8 hours) as first-line therapy, combined with rifampin (if implant is retained) after thorough surgical debridement. 1, 2

Surgical Management: The Critical First Step

Surgical debridement is the cornerstone of treatment and must be performed before optimizing antibiotic therapy. 1

Decision Algorithm for Implant Management

Implant retention (DAIR procedure) is appropriate if: 1

• Infection manifests within 3 weeks of fracture fixation (success rates >90%)
• Osteosynthetic construct is stable
• Soft tissue envelope is viable
• Proper debridement is technically feasible based on implant type

Implant exchange or removal is indicated if: 1

• Infection manifests >10 weeks after fixation (DAIR success drops to 51-67%)
• Fracture has healed completely
• Intramedullary nail is present (cannot adequately debride the canal)
• Implant is unstable

Common pitfall: Success rates decline continuously as time elapses post-fixation due to maturing biofilm—there is no absolute cutoff, but the biological reality of biofilm maturation must guide decision-making. 1

Antibiotic Therapy for MSSA

Initial Empiric Coverage

• Start broad-spectrum coverage including anti-MRSA agents (vancomycin 15 mg/kg IV every 12 hours) plus gram-negative coverage until culture results confirm MSSA 1

Definitive MSSA Treatment

First-line agents (once MSSA confirmed): 1, 2

• Nafcillin or oxacillin 2g IV every 6 hours
• Cefazolin 1-2g IV every 8 hours

Alternative agents: 1, 3

• Cephalexin 500 mg PO every 6 hours (for oral step-down therapy)
• Dicloxacillin 250-500 mg PO every 6 hours (taken 1 hour before or 2 hours after meals) 4

Critical point: Antistaphylococcal penicillins (nafcillin, oxacillin) and first-generation cephalosporins remain the gold standard for serious MSSA infections, demonstrating superior outcomes compared to vancomycin. 1, 3, 2

Rifampin Combination Therapy (For Implant Retention)

Rifampin is essential for biofilm eradication when implants are retained: 1

• Must be combined with a companion antibiotic—never use as monotherapy due to rapid resistance emergence 1
• Start rifampin only after thorough debridement and when wounds are dry to prevent resistant organism superinfection 1
• First-choice companion: fluoroquinolone (ciprofloxacin or levofloxacin) 1
• Alternative companions: cotrimoxazole, minocycline, or fusidic acid (less studied) 1

Common pitfall: Starting rifampin before adequate debridement or with high bacterial burden leads to rapid resistance development. 1

Duration of Therapy

With Implant Retention (DAIR)

• Total duration: 12 weeks of antimicrobial therapy 1
• IV therapy for 1-2 weeks until patient is stable and cultures are known 1
• Transition to oral therapy based on OVIVA trial data showing non-inferiority 1
• Regimen: Rifampin + fluoroquinolone (or alternative companion) for remainder of treatment 1

After Implant Removal

• Total duration: 6 weeks of antimicrobial therapy 1
• Standard osteomyelitis treatment duration 1

Suppressive Therapy

• Consider long-term oral suppression if implant cannot be removed and fracture not yet healed 1
• Continue until implant removal is possible 1

Transition to Oral Therapy

Criteria for oral step-down: 1

• Patient clinically stable (afebrile, improving soft tissue condition)
• Culture results available confirming MSSA
• Wounds are dry
• Typically after 1-2 weeks of IV therapy

Oral options for MSSA: 1, 4, 3

• Dicloxacillin 250-500 mg every 6 hours (must take on empty stomach with ≥4 oz water) 4
• Cephalexin 500 mg every 6 hours 1
• Combined with rifampin if implant retained 1

Pediatric Considerations

For children with MSSA fracture-related infections: 1

• Nafcillin or oxacillin for serious infections
• Cefazolin as alternative
• Clindamycin 10-13 mg/kg/dose IV every 6-8 hours if local resistance <10% 1
• Minimum 4-6 week course for osteomyelitis 1
• Can transition to oral therapy once clinically stable 1

Monitoring and Follow-Up

Essential monitoring parameters: 1, 4

• Clinical response assessment within 48-72 hours
• Blood cultures if bacteremia present
• Inflammatory markers (CRP, ESR) trending
• Renal and hepatic function during prolonged therapy 4
• Minimum 12-month follow-up after treatment cessation 1

Critical Pitfalls to Avoid

1. Using vancomycin for MSSA when β-lactams are available—vancomycin has inferior outcomes for MSSA with 2-fold higher recurrence rates 1, 2

2. Starting rifampin too early or as monotherapy—leads to rapid resistance 1

3. Inadequate surgical debridement—antibiotics cannot eradicate mature biofilm regardless of duration 1

4. Retaining implants in late-onset infections (>10 weeks)—success rates drop significantly 1

5. Failing to remove infected devices after fracture healing—source control is critical for cure 1, 2

6. Insufficient treatment duration—premature cessation leads to relapse, especially with retained hardware 1