What pre‑operative antibiotic regimen should be given to an adult undergoing appendectomy for acute appendicitis, including dosing, weight‑based adjustments, alternatives for penicillin or cephalosporin allergy, addition of vancomycin for MRSA risk, and considerations for perforated versus non‑perforated disease, pregnancy, and pediatric patients?

Preoperative Antibiotic Prophylaxis for Appendectomy in Adults

For acute non-perforated appendicitis, administer cefazolin 2g IV as a single dose 30-60 minutes before incision; for perforated appendicitis, use ceftriaxone 1-2g IV plus metronidazole 500mg IV preoperatively, then continue postoperatively until clinical improvement. 1, 2

Standard Prophylaxis for Non-Perforated Appendicitis

Primary Regimen:

• Cefazolin 2g IV administered as a slow infusion 30-60 minutes before surgical incision 1
• This is a single-dose prophylaxis that should not extend beyond 24 hours postoperatively 1
• Target organisms include E. coli, other Enterobacteriaceae, S. aureus (methicillin-susceptible), and anaerobic bacteria 1

Alternative Cephalosporin Options:

• Cefuroxime 1.5g IV or cefamandole 1.5g IV as single-dose alternatives 1
• Cefoxitin 2g IV provides broader anaerobic coverage and may be preferred by some surgeons 1

Intraoperative Re-dosing (if needed):

• Cefazolin: Re-inject 1g if surgery exceeds 4 hours 1
• Cefuroxime/cefamandole: Re-inject 0.75g if surgery exceeds 2 hours 1
• Cefoxitin: Re-inject 1g if surgery exceeds 2 hours 1

Perforated Appendicitis: Treatment Antibiotics (Not Just Prophylaxis)

For perforated appendicitis, this becomes therapeutic antibiotic treatment, not prophylaxis, and requires extended postoperative coverage. 2, 3

Preferred Regimen (Based on Recent Quality Improvement Data):

• Ceftriaxone 1-2g IV once daily PLUS metronidazole 500mg IV every 8 hours 2, 3
• This regimen demonstrated superior outcomes in a 2025 quality improvement study, with significantly reduced broad-spectrum antibiotic use (from 62.2% to 25.4%) without increasing surgical site infections 2
• Continue postoperatively until patient is afebrile for 24 hours, tolerating oral intake, and has normalized white blood cell count (typically 3-5 days) 2, 3

Clinical Advantages of Ceftriaxone + Metronidazole:

• Once-daily dosing simplifies administration 3
• Patients defervesce more rapidly compared to traditional triple therapy (mean maximum temperature significantly lower from postoperative day 1 onward, p<0.001) 3
• Reduced length of stay (6.8 vs 7.8 days, p=0.03) 3
• Substantially lower medication costs ($81.32/day vs $318.53/day for traditional regimens) 3
• Comparable abscess rates (8.8% vs 14.2%, p=0.37) 2, 3

Beta-Lactam Allergy Alternatives

For Documented Penicillin/Cephalosporin Allergy:

• Clindamycin 900mg IV slow infusion PLUS gentamicin 5 mg/kg IV as single doses for non-perforated appendicitis 1, 4
• For perforated appendicitis with allergy: Continue clindamycin 900mg IV every 8 hours plus gentamicin 5 mg/kg/day until clinical improvement 1
• If surgery exceeds 4 hours, re-dose clindamycin 600mg 4

Alternative for Severe Beta-Lactam Allergy:

• Metronidazole 1g IV infusion PLUS gentamicin 5 mg/kg IV provides anaerobic and gram-negative coverage 1

MRSA Risk Considerations

Vancomycin addition is NOT routinely indicated for appendicitis. 1

Vancomycin 30 mg/kg IV (infused over 120 minutes, maximum 4g) should be added ONLY if:

• Documented MRSA colonization 1
• Recent hospitalization in a unit with known MRSA ecology 1
• Recent antibiotic therapy predisposing to resistant organisms 1
• The vancomycin infusion must be completed at least 30 minutes before incision 1, 4

Critical Timing Principles

Antibiotic administration timing is crucial for efficacy:

• Administer 30-60 minutes before skin incision to ensure adequate tissue concentrations 1, 5
• If the initial dose is given more than 60 minutes before incision and surgery is delayed beyond one hour, repeat the full prophylactic dose 6, 4
• For patients who received broad-spectrum antibiotics in the emergency department, additional pre-incisional cefazolin does NOT reduce surgical site infections and is unnecessary 5

Duration of Prophylaxis: A Critical Pitfall

Prophylactic antibiotics must be discontinued within 24 hours for non-perforated appendicitis. 1

• Extending prophylaxis beyond 24 hours constitutes treatment, not prophylaxis, and increases antimicrobial resistance risk 1, 6
• The presence of surgical drains does NOT justify extending prophylaxis duration 1, 6
• For perforated appendicitis, therapeutic antibiotics (not prophylaxis) should continue until clinical resolution, typically 3-7 days 2, 3

Weight-Based Dosing Adjustments

Standard doses apply to most adults; adjust for extremes:

• Gentamicin: Always dose at 5 mg/kg based on actual body weight 1
• Vancomycin: 30 mg/kg based on actual body weight (maximum 4g) 1
• Cefazolin, ceftriaxone, metronidazole: Standard doses adequate for most adults; no routine weight adjustment needed unless morbid obesity 1

Pregnancy Considerations

Appendicitis in pregnancy requires careful antibiotic selection:

• Cefazolin 2g IV remains the preferred agent (FDA Pregnancy Category B) 1
• Ceftriaxone plus metronidazole is acceptable for perforated appendicitis in pregnancy 2, 3
• Avoid gentamicin if possible due to ototoxicity risk; if necessary, use lowest effective dose with therapeutic drug monitoring 1
• Fluoroquinolones are contraindicated in pregnancy 1

Pediatric Dosing

For children with appendicitis:

• Non-perforated: Cefazolin 30 mg/kg IV (maximum 2g) as single dose 3
• Perforated: Ceftriaxone 50-75 mg/kg/day IV (maximum 2g) plus metronidazole 30 mg/kg/day IV divided every 8 hours (maximum 4g/day) 3
• The ceftriaxone-metronidazole regimen in pediatric perforated appendicitis shows superior outcomes compared to traditional triple therapy 3

Evidence Strength and Nuances

The 2025 quality improvement study by Surgical Infections represents the most recent high-quality evidence specifically addressing appendicitis antibiotic management 2. This study demonstrated that ceftriaxone plus metronidazole is superior to broad-spectrum agents like piperacillin-tazobactam for perforated appendicitis, with comparable safety and improved efficiency.

The 2019 French Society guidelines provide the foundational framework for surgical prophylaxis principles, emphasizing single-dose prophylaxis for clean-contaminated surgery and the critical importance of timing 1. However, these guidelines do not specifically address appendicitis as a distinct entity.

A critical 2025 study found that patients receiving emergency department antibiotics do not benefit from additional pre-incisional cefazolin 5. This challenges traditional surgical dogma and suggests that broad-spectrum treatment antibiotics given in the ED provide adequate coverage without redundant prophylaxis.

Common Pitfalls to Avoid

1. Do not use piperacillin-tazobactam routinely for appendicitis—it represents unnecessary broad-spectrum coverage that increases resistance without improving outcomes 2

2. Do not continue prophylactic antibiotics beyond 24 hours for non-perforated appendicitis, even with drains present 1, 6

3. Do not give additional pre-incisional antibiotics if the patient already received broad-spectrum treatment antibiotics in the emergency department within the past hour 5

4. Do not use fluoroquinolones for surgical prophylaxis in appendicitis—they have no role in this indication 1

5. Do not add vancomycin routinely—reserve it only for documented MRSA risk factors 1