How should I manage a patient with a fracture who has been on oral cephalexin for six days but still shows signs of infection?

Management of Persistent Infection After Cephalexin in Fracture Patient

This patient requires immediate escalation to intravenous antibiotics, surgical debridement, and culture-guided therapy—oral cephalexin alone is insufficient for established fracture-related infection (FRI). 1

Immediate Actions Required

Surgical Intervention

• Perform urgent surgical debridement to obtain deep tissue cultures (minimum 3-5 samples) and reduce bacterial load before optimizing antibiotic therapy 1
• Debridement must be thorough enough to achieve stable soft tissue and dry wounds before transitioning to oral antibiotics 1
• The presence of persistent infection after 6 days indicates established biofilm formation on any implanted hardware, which cannot be eradicated by antibiotics alone 1

Antibiotic Management

Initial Empirical IV Therapy (start immediately after obtaining cultures):

• Initiate a lipoglycopeptide (vancomycin 30mg/kg/day divided) PLUS an agent covering gram-negative bacteria (such as ceftriaxone 2g daily or piperacillin-tazobactam) 1
• This broad coverage addresses the polymicrobial nature of FRI (20-35% of cases) and covers both Staphylococcus aureus and gram-negative organisms 1

Duration of IV Therapy:

• Continue IV antibiotics for 1-2 weeks until soft tissue is stable, wounds are dry, and culture results return 1
• The OVIVA trial demonstrated non-inferiority of oral antibiotics after initial IV therapy, but only after surgical stabilization 1

Culture-Directed Therapy

For Staphylococcal Infections (Most Common)

• Add rifampicin ONLY after debridement and when wounds are completely dry to avoid selecting resistant organisms 1
• Rifampicin must always be combined with a companion antibiotic (never monotherapy): first choice is a fluoroquinolone (ciprofloxacin or levofloxacin) 1
• Alternative companions include cotrimoxazole, minocycline, or fusidic acid if fluoroquinolones are contraindicated 1
• For MRSA, use vancomycin or teicoplanin for initial IV therapy 1

For Gram-Negative Infections

• Fluoroquinolones have excellent biofilm activity but should only start after debridement and dry wounds 1
• For Pseudomonas aeruginosa: use beta-lactams (piperacillin-tazobactam, cefepime, ceftazidime, or carbapenem) initially, consider adding aminoglycoside for 2-5 days 1

For Streptococcal/Enterococcal Infections

• Streptococcal: IV benzyl penicillin 1-2 weeks, then oral amoxicillin 1
• Enterococcal: IV ampicillin 1-2 weeks, then oral amoxicillin (or vancomycin/daptomycin if ampicillin-resistant) 1

Total Treatment Duration

With implant retention: 12 weeks total antibiotic therapy 1

With implant removal: 6 weeks total antibiotic therapy 1

Critical Pitfalls to Avoid

• Never continue oral cephalexin monotherapy for established FRI—it lacks biofilm penetration and adequate coverage 1
• Never start rifampicin or fluoroquinolones before adequate debridement—this rapidly selects resistant organisms when bacterial load is high 1
• Never use fluoroquinolone or rifampicin monotherapy for staphylococci—resistance emerges rapidly with treatment failure rates up to 80% 1
• Never assume negative intraoperative cultures mean infection is cleared—this does not improve long-term outcome or decrease persistent infection risk 1

Why Cephalexin Failed

Oral cephalexin is appropriate only for prophylaxis in closed fractures (not treatment of established infection) 1, 2, and while historical data showed some efficacy in chronic osteomyelitis when combined with IV cephalosporins 3, it lacks the biofilm penetration and spectrum needed for established FRI 1. The persistence of infection after 6 days indicates biofilm maturation has occurred, requiring the surgical-antimicrobial combination approach outlined above 1.