What is the recommended first‑line antibiotic regimen (drug choices, doses, route, and duration) for acute appendicitis in an adult patient without known drug allergies, and what alternatives should be used for a serious penicillin allergy?

First-Line Antibiotics for Acute Appendicitis in Adults

For uncomplicated appendicitis, administer a single preoperative dose of cefoxitin, cefotetan, or piperacillin-tazobactam 0-60 minutes before surgical incision, then discontinue antibiotics within 24 hours postoperatively. For complicated (perforated) appendicitis, use piperacillin-tazobactam 3.375g IV every 6 hours or combination therapy with ceftriaxone 2g IV daily plus metronidazole 500mg IV every 6-8 hours, continuing for 4-7 days maximum. 1, 2, 3

Uncomplicated (Non-Perforated) Appendicitis

Preferred Single-Agent Regimens

• Piperacillin-tazobactam 3.375g IV every 6 hours is the preferred single-agent therapy due to its simplicity and broad coverage against both aerobic gram-negatives and anaerobes 2, 3
• Cefoxitin 2g IV or cefotetan 2g IV as a single preoperative dose are acceptable alternatives 2, 4
• Ertapenem 1g IV every 24 hours is another single-agent option 2, 3

Combination Regimens

• Ceftriaxone 2g IV daily plus metronidazole 500mg IV every 6-8 hours provides adequate coverage when single agents are unavailable 2, 3
• Cefazolin, cefuroxime, levofloxacin, or ciprofloxacin combined with metronidazole are acceptable alternatives 2

Duration for Uncomplicated Cases

• Discontinue antibiotics within 24 hours after appendectomy if adequate source control is achieved 1, 2, 3
• Prolonging antibiotics beyond 24 hours provides no additional benefit and increases resistance risk 4, 3

Complicated (Perforated/Abscess) Appendicitis

Preferred Regimens

• Piperacillin-tazobactam 3.375g IV every 6 hours remains first-line for broader coverage 3, 5
• Imipenem-cilastatin 1g IV every 8 hours or meropenem 1g IV every 8 hours for more severe cases 3
• Ceftriaxone 2g IV daily plus metronidazole 500mg IV every 6-8 hours as an alternative combination 2, 3

Duration for Complicated Cases

• Limit therapy to 4-7 days total when adequate source control is achieved 1, 2
• Maximum of 3-5 days postoperatively even without complete source control 2, 3
• Resolution of clinical signs (afebrile, normal WBC, tolerating oral diet) should guide cessation of therapy 1

Regimens to AVOID

High Resistance Rates

• Ampicillin-sulbactam: Avoid due to E. coli resistance rates exceeding 20% 2, 3
• Cefotetan or clindamycin monotherapy: Avoid due to increasing Bacteroides fragilis resistance 2, 3
• Aminoglycosides: Avoid for routine use in adults due to toxicity when equally effective alternatives exist 2, 3

Coverage Considerations

• Do NOT routinely cover Enterococcus in community-acquired appendicitis 2
• Do NOT provide empiric antifungal coverage for Candida 2
• Avoid quinolones unless local E. coli susceptibility is ≥90% 2

Penicillin Allergy Alternatives

For Serious Penicillin Allergy

• Moxifloxacin 400mg IV every 24 hours as monotherapy (if local E. coli susceptibility ≥90%) 2
• Ciprofloxacin 400mg IV every 12 hours plus metronidazole 500mg IV every 6-8 hours 2, 3
• Levofloxacin 750mg IV every 24 hours plus metronidazole 500mg IV every 6-8 hours 2
• Tigecycline 100mg IV loading dose, then 50mg IV every 12 hours 2

Critical Pitfalls to Avoid

Timing and Coverage Errors

• Initiate antibiotics 0-60 minutes before surgical incision—do not delay while awaiting imaging or transfer 2, 3
• Never use ceftriaxone alone—it lacks adequate anaerobic coverage against Bacteroides fragilis and requires metronidazole 2
• Do not continue antibiotics beyond 24 hours for uncomplicated cases—this increases resistance without benefit 2, 4, 3

Duration Errors

• Do not prolong antibiotics beyond 3-5 days postoperatively in complicated cases with adequate source control 1, 2, 3
• For patients with delayed surgery (>24 hours), continue the same antibiotic regimen until operative intervention occurs 3

Non-Operative Management Considerations

When antibiotics are used as primary therapy without surgery, evidence suggests 63-78% success at one year, compared to 97% with immediate appendectomy 6, 7. This approach requires:

• CT-confirmed uncomplicated appendicitis without appendicolith 6
• Minimum 48 hours IV antibiotics followed by oral therapy for total 7-10 days 3, 8
• Appendicolith presence predicts 40-60% failure rate of antibiotic therapy 6
• Recurrence rate at 5 years is 39%—patients must be counseled accordingly 3

The network meta-analysis comparing antibiotic regimens found that carbapenems had fewer treatment-related complications compared to surgery and may be preferred for non-operative management, though surgery still achieved higher 1-year treatment success rates 9.