What antibiotics are recommended for appendicitis in a patient with a penicillin (PCN) allergy?

Antibiotic Selection for Appendicitis in Penicillin-Allergic Patients

For patients with penicillin allergy and appendicitis, use fluoroquinolone-based regimens (ciprofloxacin 400 mg IV every 8 hours plus metronidazole 500 mg IV every 6 hours) or moxifloxacin 400 mg IV every 24 hours as monotherapy for community-acquired cases. 1

Primary Recommendations for Beta-Lactam Allergic Patients

Community-Acquired Appendicitis (Non-Critically Ill)

Fluoroquinolone-based combinations are the standard alternative:

• Ciprofloxacin 400 mg IV every 8 hours PLUS metronidazole 500 mg IV every 6 hours 1
• Moxifloxacin 400 mg IV every 24 hours as monotherapy (provides both gram-negative and anaerobic coverage) 1

These regimens provide appropriate coverage against enteric gram-negative organisms (E. coli) and anaerobes (Bacteroides spp.) that are the primary pathogens in appendicitis. 2

Alternative Options When Fluoroquinolones Are Contraindicated

If fluoroquinolones cannot be used (e.g., pregnancy, pediatric patients, or local resistance patterns):

• Aminoglycoside-based regimen: Amikacin 15-20 mg/kg IV every 24 hours PLUS metronidazole 500 mg IV every 6 hours 1
• Tigecycline 100 mg IV loading dose, then 50 mg IV every 12 hours (monotherapy with broad coverage including anaerobes and ESBL-producing organisms, but lacks Pseudomonas coverage) 1

Important caveat: Aminoglycosides require monitoring of serum levels and renal function due to nephrotoxicity risk, and they lack anaerobic coverage, necessitating combination with metronidazole. 3

Special Considerations for Complicated Appendicitis

Healthcare-Associated or Critically Ill Patients

For patients with perforated appendicitis, abscess formation, or those who are critically ill with beta-lactam allergy:

• Aminoglycoside combinations with amikacin 15-20 mg/kg IV every 24 hours are recommended in the guideline framework 1
• Consider tigecycline for ESBL-producing organisms, though caution is advised in bacteremia 1

Patients at Risk for ESBL-Producing Organisms

Even with penicillin allergy, if the patient has risk factors for ESBL-producing Enterobacteriaceae (recent antibiotic exposure, healthcare contact):

• Tigecycline 100 mg IV loading dose, then 50 mg IV every 12 hours 1
• Note: Tigecycline lacks activity against Pseudomonas aeruginosa and Proteus mirabilis 1

Cross-Reactivity Considerations

Critical distinction regarding cephalosporin use:

• For patients with non-severe, delayed-type penicillin allergy (e.g., rash occurring >1 hour after administration), cephalosporins may be considered, particularly those without similar side chains 1
• For patients with severe immediate-type reactions (anaphylaxis, angioedema, bronchospasm), all beta-lactams including cephalosporins should be avoided 1
• Aztreonam can be safely used in patients with penicillin allergy (except in those with ceftazidime allergy due to shared side chains) 1

However, given the availability of effective non-beta-lactam alternatives for appendicitis, avoiding all beta-lactams in documented penicillin allergy is the safest approach in acute settings. 1

Treatment Duration

• Uncomplicated appendicitis with adequate source control: 3-5 days postoperatively 1
• Complicated appendicitis (perforation, abscess): Continue until clinical improvement, typically 5-7 days total 1
• Prolonging antibiotics beyond 5 days in adequately source-controlled complicated appendicitis offers no additional benefit 1

Pediatric Considerations

For children with penicillin allergy and appendicitis:

• Ciprofloxacin plus metronidazole remains an option, though fluoroquinolone use in pediatrics requires careful risk-benefit assessment 1
• Gentamicin 7.5 mg/kg/day IV (divided dosing or once daily) plus metronidazole is commonly used 1, 3
• Ceftriaxone plus metronidazole may be considered if the penicillin allergy is non-severe and delayed-type 1, 4

Common Pitfalls to Avoid

Do not use fluoroquinolones as monotherapy without metronidazole (except moxifloxacin, which has anaerobic activity) - ciprofloxacin and levofloxacin lack adequate anaerobic coverage. 1

Avoid tigecycline in suspected bacteremia - it has lower serum concentrations and is associated with increased mortality in bloodstream infections. 1

Do not assume all "penicillin allergies" are true allergies - obtain detailed history about the type and timing of reaction, as this may expand antibiotic options safely. 1

Monitor aminoglycoside levels and renal function if using gentamicin or amikacin, particularly in prolonged courses or elderly patients. 3