Is ceftriaxone monotherapy appropriate for surgical prophylaxis in an uncomplicated appendectomy in a healthy adult without allergies?

Ceftriaxone Monotherapy for Uncomplicated Appendectomy

No, ceftriaxone monotherapy is not optimal for surgical prophylaxis in appendectomy—you should add metronidazole or use an alternative agent with better anaerobic coverage. While ceftriaxone provides excellent gram-negative and some gram-positive coverage, it has inadequate activity against anaerobes like Bacteroides fragilis, which are critical pathogens in appendiceal infections 1.

Recommended Prophylaxis Regimens

First-Line Options for Uncomplicated Appendicitis

• Single-dose cefoxitin or cefotetan (second-generation cephalosporins with anaerobic coverage) are preferred as monotherapy 1
• Ceftriaxone PLUS metronidazole is an acceptable combination if you prefer a third-generation cephalosporin 1
• Alternative combinations: cefazolin, cefuroxime, or cefotaxime, each combined with metronidazole 1

Timing and Duration

• Administer a single preoperative dose 0-60 minutes before surgical incision 1
• No postoperative antibiotics are needed for uncomplicated appendicitis after adequate source control 1
• This single-dose approach effectively reduces wound infections and intra-abdominal abscesses regardless of appendiceal inflammation degree 1

Why Ceftriaxone Alone Is Insufficient

Spectrum Gap

• Ceftriaxone lacks adequate anaerobic coverage, particularly against Bacteroides fragilis and Peptostreptococcus species 1, 2
• Appendiceal infections require coverage for enteric gram-negative organisms AND anaerobes 1
• Research directly comparing ceftriaxone to ampicillin-metronidazole found deep wound infections were more frequent with ceftriaxone monotherapy, though it performed better for superficial incisional infections 3

Clinical Evidence

• A randomized trial of 240 appendectomy patients showed ceftriaxone monotherapy had wound infection rates of 6.1-11.1% in acute appendicitis cases 4
• Single-dose cefotetan achieved 0% wound infection rates versus 11.1% with single-dose cefoxitin in one comparative study, highlighting the importance of anaerobic coverage 5

Practical Algorithm

For uncomplicated appendicitis in healthy adults:

1. Preferred: Single dose of cefoxitin 2g IV or cefotetan 2g IV at induction 1, 5

2. Alternative: Ceftriaxone 1-2g IV PLUS metronidazole 500mg IV at induction 1

3. Timing: Administer 30-60 minutes before incision 1, 2

4. Postoperative: No additional antibiotics needed if appendix is non-perforated and source control is adequate 1

For complicated appendicitis (perforation, abscess, gangrene):

• Continue postoperative antibiotics for 3-5 days maximum with adequate source control 1
• Use broader coverage: piperacillin-tazobactam, or ceftriaxone-metronidazole combination 1

Critical Pitfalls to Avoid

• Don't use ceftriaxone alone for intra-abdominal infections—the FDA label specifically lists intra-abdominal infections as an indication but notes activity against anaerobes like Bacteroides fragilis 2, yet clinical data shows monotherapy increases deep infection risk 3
• Don't confuse ceftriaxone with oral cephalosporins—ceftriaxone has no oral formulation and must be given IV or IM 6, 7
• Don't extend prophylaxis beyond 24 hours for uncomplicated cases—this increases costs and hospital stay without benefit 1
• Don't use extended-spectrum agents unnecessarily—narrower-spectrum antibiotics like cefoxitin are equally effective and promote better antimicrobial stewardship 1