What is the appropriate use and dosage of Cefazolin (a first-generation cephalosporin antibiotic) for surgical prophylaxis and treatment of bacterial infections?

Cefazolin: Appropriate Use and Dosing

Cefazolin is the first-choice antibiotic for surgical prophylaxis in most procedures, administered as a single 2g IV dose within 60 minutes before incision, with re-dosing every 4 hours if the procedure is prolonged. 1, 2

Surgical Prophylaxis Applications

Primary Indications

• Cefazolin is recommended as the antibiotic of choice for most surgical procedures requiring prophylaxis, including cardiac surgery, vascular surgery, orthopedic procedures (including joint replacements), neurosurgery, thoracic surgery, and clean-contaminated procedures. 1, 2
• The drug provides excellent coverage against Staphylococcus aureus (including beta-lactamase-producing strains), Staphylococcus epidermidis, streptococci, E. coli, and Proteus mirabilis—the primary pathogens in surgical site infections. 2, 3, 4

Procedure-Specific Recommendations

Colorectal Surgery:

• Cefazolin 2g IV must be combined with metronidazole 500mg-1g IV to provide adequate anaerobic coverage, particularly against Bacteroides fragilis. 1, 5
• Alternatively, cefoxitin 2g IV as monotherapy is acceptable but less preferred. 1, 5

Cesarean Section:

• Single-dose first-generation cephalosporin (cefazolin 2g IV) is recommended for all women undergoing cesarean section. 1

Cardiac and Vascular Surgery:

• Cefazolin provides optimal coverage and has demonstrated lower rates of postoperative pneumonia and all-cause mortality compared to antibiotics with only gram-positive activity. 1, 2

Orthopedic Surgery with Prostheses:

• Cefazolin 2g IV is the standard choice, though vancomycin should be added (not substituted) in patients with documented MRSA colonization. 1, 2

Upper GI and Biliary Surgery:

• Cefazolin 2g IV alone is sufficient unless obstruction or paralytic ileus is present, in which case metronidazole should be added. 1, 5

GI Endoscopy:

• Cefazolin is specifically recommended before PEG/PEJ tube placement. 1

Dosing and Administration

Standard Dosing

• 2g IV administered within 60 minutes before surgical incision (infusion should be completed before incision). 1, 2
• Re-dose with 1g IV if the procedure exceeds 4 hours or if there is significant blood loss (>1500 mL). 1, 2

Weight-Based Adjustments

• Patients weighing ≥120 kg may benefit from 3g IV dosing, though evidence remains primarily pharmacokinetic rather than outcome-based. 6
• For bariatric surgery specifically, consider 4g IV dosing. 2

Duration of Prophylaxis

• Prophylaxis should be discontinued within 24 hours after surgery for most procedures. 3, 7
• For procedures where infection would be catastrophic (open-heart surgery, prosthetic arthroplasty), continuation for 3-5 days post-operatively is acceptable. 3
• Single-dose prophylaxis is effective, inexpensive, and does not induce bacterial resistance. 7

Treatment of Established Infections

FDA-Approved Therapeutic Indications

Cefazolin is indicated for treatment of serious infections including:

• Respiratory tract infections due to S. pneumoniae, S. aureus, and S. pyogenes. 3
• Urinary tract infections due to E. coli and P. mirabilis. 3
• Skin and soft tissue infections due to S. aureus and streptococci. 3
• Biliary tract infections, bone and joint infections, septicemia, and endocarditis due to susceptible organisms. 3

Therapeutic Dosing

• For established infections: 1-2g IV every 8 hours (not detailed in prophylaxis guidelines but standard therapeutic dosing). 8

Critical Considerations and Pitfalls

When NOT to Use Cefazolin Alone

• Never use cefazolin monotherapy for colorectal surgery—anaerobic coverage is essential and must be added via metronidazole. 1, 5
• Cefazolin has poor activity against Pseudomonas aeruginosa, Enterobacter species, indole-positive Proteus, and enterococci. 4
• For patients with true penicillin allergies (not just intolerance), use clindamycin 600-900mg IV plus gentamicin 5mg/kg IV instead, as cross-reactivity risk exists. 1, 2

MRSA Considerations

• Routine vancomycin substitution is not recommended even in settings with high MRSA prevalence, as no threshold has been identified where glycopeptides outperform cefazolin for prophylaxis. 1
• In documented MRSA carriers, add vancomycin to cefazolin rather than replacing it. 2

Timing Is Critical

• Administration more than 60 minutes before incision or after incision significantly reduces efficacy. 2
• Cefazolin has excellent pharmacokinetics with adequate tissue penetration when properly timed. 7, 4

Safety Profile

• Minimal pain with intramuscular injection, low risk of thrombophlebitis with IV administration. 4
• No significant renal toxicity or Coombs test positivity in clinical studies. 4
• Superior safety profile compared to broader-spectrum alternatives. 2