What cefazolin prophylaxis dose should be given to an average‑weight adult (≤120 kg) for a three‑hour clean or clean‑contaminated surgery, and how should the dose be adjusted for patients >120 kg or with a β‑lactam allergy?

Cefazolin Prophylaxis Dosing for Clean/Clean-Contaminated Surgery

Standard Dosing for Average-Weight Adults (≤120 kg)

For a three-hour clean or clean-contaminated surgery in an average-weight adult, administer cefazolin 2 g IV slow as a single preoperative dose, with no intraoperative redosing required since the procedure duration is under 4 hours. 1

Dosing Algorithm by Procedure Duration

• Surgery ≤4 hours: Cefazolin 2 g IV slow as single dose preoperatively (30-60 minutes before incision) 1
• Surgery >4 hours: Initial 2 g dose, then reinject 1 g at the 4-hour mark intraoperatively 1
• Do not extend prophylaxis beyond 24 hours postoperatively under any circumstances, as this constitutes treatment rather than prophylaxis 1, 2

Pharmacokinetic Rationale

The 2 g cefazolin dose achieves peak serum concentrations of approximately 185 mcg/mL and maintains therapeutic levels above the minimum inhibitory concentration for at least 5-6 hours, providing adequate coverage for most surgical procedures without redosing. 3, 4 Cefazolin displays time-dependent killing kinetics, meaning higher concentrations do not enhance bacterial killing once levels exceed the MIC. 4

Dose Adjustment for Patients >120 kg

The evidence does not support routine dose escalation to 3 g in patients >120 kg; maintain the standard 2 g dose. 4, 5

Weight-Based Dosing Controversy

• Current guidelines often recommend 3 g for patients ≥120 kg, but this recommendation lacks robust clinical evidence and is based primarily on flawed pharmacokinetic assumptions 4, 5
• Cefazolin is hydrophilic and does not penetrate adipose tissue regardless of dose; adipose tissue is not a valid target for SSI prophylaxis 4
• A 2019 retrospective study found no statistically significant increase in SSI rates among patients ≥120 kg receiving 2 g versus historical controls, though trends toward increased infection were noted (9.8% vs 5.0%, p=0.17) 5
• Pharmacokinetic studies demonstrate that 2 g cefazolin provides adequate serum/tissue concentrations for procedures <5-6 hours duration regardless of BMI 3, 4

Practical Recommendation

• For patients >120 kg undergoing surgery ≤4 hours: Use standard 2 g dose 4
• For patients >120 kg undergoing surgery >4 hours: Give 2 g initially, then 1 g at 4 hours 1
• Consider 3 g initial dose only in patients >120 kg with additional high-risk factors (e.g., diabetes, immunosuppression, contaminated procedures), though evidence for this approach remains limited 5

β-Lactam Allergy Alternative

For patients with documented β-lactam allergy, substitute vancomycin 30 mg/kg (based on actual body weight) infused over 120 minutes, with the infusion completed before surgical incision. 1, 6

Vancomycin Dosing Protocol

• Dose: 30 mg/kg actual body weight (approximately 2 g for a 68 kg adult) 1, 6
• Infusion time: 120 minutes, ideally finishing 30 minutes before incision 1, 6
• Redosing: Single dose only; no intraoperative redosing for procedures ≤4 hours 1
• Alternative for non-severe allergy: Clindamycin 900 mg IV slow plus gentamicin 5 mg/kg IV as single doses 2

Critical Vancomycin Pitfalls

• Vancomycin provides inferior coverage against methicillin-susceptible S. aureus and streptococci compared to cefazolin; routine use without specific MRSA risk increases SSI odds by approximately 50% 6
• Reserve vancomycin for: documented severe β-lactam allergy, known/suspected MRSA colonization, reoperation in MRSA-endemic units, or recent systemic antibiotic therapy 1, 6
• Administering vancomycin later than the 120-minute infusion window markedly reduces tissue concentrations at bacterial exposure 6

Common Pitfalls to Avoid

• Duration error: Never extend prophylaxis beyond 24 hours; presence of surgical drains does not justify prolonged antibiotics 1, 2, 6
• Timing error: If the initial dose is given >60 minutes before incision and surgery is delayed beyond one hour, repeat the full prophylactic dose 2
• Inappropriate weight-based escalation: Avoid reflexive 3 g dosing in obese patients without clinical evidence of benefit 4, 5
• Vancomycin overuse: Do not use vancomycin as first-line prophylaxis without specific MRSA risk factors 6