What is the recommended prophylactic antibiotic regimen for open fractures, including dosing and duration for Gustilo‑Anderson type I, II, and III injuries, and how should it be adjusted for β‑lactam allergy or renal impairment?

Open Fracture Antibiotic Prophylaxis

For Type I and II open fractures, administer cefazolin within 3 hours of injury and continue for 24 hours; for Type III fractures, add an aminoglycoside and continue antibiotics for 48-72 hours but no more than 24 hours after wound closure. 1, 2

Antibiotic Selection by Gustilo-Anderson Classification

Type I and II Open Fractures

• First-generation cephalosporin (cefazolin) alone is sufficient for gram-positive coverage (Staphylococcus aureus and streptococci) 3, 1, 4
• The 2022 Surgical Infection Society guidelines specifically recommend against extended-spectrum antibiotic coverage for Type I/II fractures, as it does not decrease infection rates and adds unnecessary cost 2, 4
• Duration: 24 hours after initial injury 3, 1

Type III Open Fractures

• First-generation cephalosporin PLUS aminoglycoside (e.g., cefazolin + gentamicin) for gram-negative coverage 3, 1
• However, the 2022 Surgical Infection Society guidelines recommend against extended antimicrobial coverage beyond gram-positive organisms even for Type III fractures, representing a shift toward narrower spectrum therapy 2
• Duration: 48-72 hours after injury but no more than 24 hours after wound closure 3, 1

Special Contamination Scenarios

• Add penicillin for farm-related injuries, soil contamination, or wounds with ischemic tissue to cover anaerobes, particularly Clostridium species 3, 1

Timing of Administration

• Initiate antibiotics within 3 hours of injury (ideally within 60 minutes) 3, 1
• Delay beyond 3 hours significantly increases infection risk 5
• Start antibiotics as soon as possible after injury, before surgical debridement 3

Dosing Regimens

Standard Dosing

• Cefazolin: 1-2 grams IV every 8 hours (therapeutic dosing, not prophylactic) 3, 1
• Gentamicin: 5-7 mg/kg IV daily (or divided dosing per institutional protocol) 3, 1
• Penicillin G: 2-4 million units IV every 4-6 hours (when indicated for anaerobic coverage) 3

β-Lactam Allergy Alternatives

• Clindamycin 600-900 mg IV every 8 hours for gram-positive coverage 4
• Aztreonam for gram-negative coverage (alternative to aminoglycosides) 3
• Fluoroquinolone (ciprofloxacin) may be considered for gram-negative coverage 6
• Vancomycin for MRSA risk in severe penicillin allergy 1

Renal Impairment Adjustments

• Aminoglycosides: Dose adjust based on creatinine clearance; consider extended-interval dosing with therapeutic drug monitoring 1
• Cefazolin: Reduce frequency to every 12-24 hours for CrCl <50 mL/min 1
• Consider third-generation cephalosporins (ceftriaxone) as alternative to aminoglycosides in renal impairment 3

Local Antibiotic Therapy

• Antibiotic-impregnated PMMA beads should be combined with systemic therapy for Type III fractures 3
• The 2022 Surgical Infection Society recommends local antibiotic therapy in addition to systemic therapy for Type III fractures with bone loss 2

Critical Pitfalls to Avoid

• Do not use initial wound cultures to guide prophylactic antibiotic selection—infecting pathogens do not correlate with organisms initially cultured 1
• Do not extend antibiotics beyond recommended durations: More than 24 hours for Type I/II or more than 72 hours for Type III increases resistance risk without benefit 3, 2
• Do not use prophylactic dosing: These are contaminated wounds requiring therapeutic doses, not surgical prophylaxis doses 5, 6
• Do not forget allergy history: Reconcile medication allergies before administration 1
• Do not overlook exposure history: Farm injuries, water exposure, or soil contamination require anaerobic coverage 1

Evidence Quality Considerations

The most recent high-quality evidence from the 2022 Surgical Infection Society guidelines represents a significant shift toward narrower spectrum antibiotic therapy and shorter durations compared to older recommendations 2. This conflicts with older 2006 AAOS guidelines that recommended broader coverage and longer durations 3. The 2022 guidelines should take precedence, as they reflect modern antibiotic stewardship principles and are based on systematic review of recent evidence showing no benefit to extended-spectrum coverage in most open fractures 2, 4.