Surgical Site Infection Antibiotic Prophylaxis
Cefazolin is the first-choice antibiotic for prophylaxis across most surgical procedures, administered as a single 2g IV dose within 60 minutes before incision. 1, 2
Standard First-Line Prophylaxis
Cefazolin alone is recommended as the universal first-line agent for surgical prophylaxis across all procedure types, based on its optimal spectrum against Staphylococcus aureus, streptococci, and common gram-negative organisms. 1, 2 This represents a shift toward parsimony, with guidelines now favoring standardized recommendations rather than procedure-specific regimens. 1
Dosing and Timing
- Administer 2g IV cefazolin within 60 minutes before surgical incision to ensure optimal tissue concentrations at the time of bacterial contamination. 2, 3
- For patients weighing >100 kg, increase the dose to 3-4g to maintain adequate pharmacokinetic targets. 1
- Re-dose cefazolin intraoperatively if the procedure exceeds 4 hours (two half-lives of the drug) or if there is significant blood loss. 1, 2
Duration of Prophylaxis
Discontinue prophylactic antibiotics within 24 hours after surgery—there is no evidence supporting postoperative continuation for standard procedures. 1, 4 The only exceptions are open-heart surgery and prosthetic arthroplasty, where prophylaxis may extend to 3-5 days given the devastating consequences of infection. 3
Procedure-Specific Modifications
Colorectal and Contaminated Surgery
Add metronidazole 500mg IV to cefazolin when the procedure involves the colorectal tract, appendix, or any contaminated field requiring anaerobic coverage. 1 Alternatively, amoxicillin-clavulanic acid can be used as single-agent therapy. 1
Urological Procedures
Use gentamicin 5mg/kg IV or cefazolin alone for most urological surgeries, except transrectal prostate biopsy where fluoroquinolones (ciprofloxacin or ofloxacin) remain appropriate. 1
Cesarean Section
Administer cefazolin 2g IV 30 minutes before incision, not after umbilical cord clamping, as preoperative dosing reduces SSI risk by 50%. 1
Second-Line and Alternative Agents
When cefazolin is unavailable or contraindicated, the hierarchy of alternatives is: 1
- Cefuroxime (1.5g IV single dose, re-dose if procedure >2 hours)
- Amoxicillin-clavulanic acid (2g IV)
- Gentamicin (5mg/kg IV based on actual weight)
Beta-Lactam Allergy
For true penicillin allergy, use clindamycin 600-900mg IV plus gentamicin 5mg/kg IV to cover both gram-positive and gram-negative organisms. 1, 2 Note that using second-line agents increases SSI risk by 50% compared to cefazolin. 2
MRSA Colonization
Add vancomycin 15mg/kg IV (maximum 2g) to cefazolin for patients with documented MRSA colonization or in high-prevalence settings, ensuring the vancomycin infusion completes 30 minutes before incision. 1, 2 Do not use vancomycin monotherapy, as it lacks adequate gram-negative coverage. 1
Critical Pitfalls to Avoid
- Never extend prophylaxis beyond 24 hours for routine procedures—this promotes resistance without reducing SSI rates. 1, 4
- Never administer prophylaxis after the surgical incision has been made—timing is critical for efficacy. 1, 2
- Never use fluoroquinolones for routine surgical prophylaxis (except prostate biopsy)—reserve these for treatment, not prevention. 1
- Never underdose cefazolin in obese patients—inadequate dosing (1g instead of 2-4g) significantly increases SSI risk. 5
- Never use broad-spectrum agents (carbapenems, piperacillin-tazobactam) for prophylaxis—these should be reserved for treatment of established infections. 1, 4
Evidence Quality and Consensus
The recommendation for cefazolin as first-line prophylaxis is supported by multiple high-quality guidelines including the 2024 WHO Essential Medicines recommendations 1, the American College of Surgeons 2, and the 2018 French Society of Anesthesia 1. The evidence base is robust, with consistent recommendations across international societies favoring cefazolin's safety profile, spectrum of activity, and pharmacokinetics for surgical prophylaxis. 2, 6