What are the antibiotics of choice for treating peritonitis?

Antibiotics of Choice for Treating Peritonitis

For community-acquired peritonitis of mild-to-moderate severity, use amoxicillin-clavulanate, cefazolin or cefuroxime plus metronidazole, or ertapenem; for high-severity community-acquired peritonitis, use piperacillin-tazobactam, imipenem-cilastatin, meropenem, or a third/fourth-generation cephalosporin (cefotaxime, ceftriaxone, ceftazidime, cefepime) plus metronidazole. 1

Community-Acquired Peritonitis

Mild-to-Moderate Severity

The choice of antibiotics should prioritize narrower-spectrum agents that are not commonly used for nosocomial infections 1:

• Amoxicillin-clavulanate (ampicillin-sulbactam): First-line option, though local susceptibility profiles should be reviewed due to increasing E. coli resistance 1
• Cefazolin or cefuroxime plus metronidazole: Effective combination therapy 1
• Ertapenem: Single-agent carbapenem option for this severity level 1
• Ciprofloxacin or levofloxacin plus metronidazole: Fluoroquinolone-based regimen, though increasing B. fragilis resistance to quinolones necessitates the addition of metronidazole 1

Important caveat: The World Society of Emergency Surgery recommends amoxicillin-clavulanate or ciprofloxacin plus metronidazole for extra-biliary or biliary acute infections in patients who are not critically ill and have no risk factors for extended-spectrum β-lactamases 1

High-Severity or Immunocompromised Patients

Patients with severe infections (defined by physiologic scoring systems) or immunosuppression require broader-spectrum coverage against gram-negative organisms 1:

• Piperacillin-tazobactam: Broad-spectrum β-lactam/β-lactamase inhibitor 1, 2
• Imipenem-cilastatin or meropenem: Carbapenems with excellent coverage 1, 2, 3
• Third/fourth-generation cephalosporins (cefotaxime, ceftriaxone, ceftizoxime, ceftazidime, cefepime) plus metronidazole: Effective combination 1
• Ciprofloxacin plus metronidazole: Alternative fluoroquinolone-based regimen 1
• Aztreonam plus metronidazole: Monobactam-based option 1

Evidence note: A systematic review found better clinical cure with cephalosporins and β-lactams (OR 3.21,95% CI 1.49-6.92) and with fluoroquinolones combined with an anti-anaerobic agent (OR 1.74,95% CI 1.11-2.73) compared to other comparators 1

Hospital-Acquired (Nosocomial) Peritonitis

Without Critical Illness but Risk of Multidrug-Resistant Organisms

• Piperacillin-tazobactam or tigecycline: Recommended by the World Society of Emergency Surgery 1

Critically Ill Patients

• Piperacillin-tazobactam, tigecycline, or a carbapenem (meropenem, imipenem, or doripenem): Primary options 1
• Consider adding teicoplanin plus an antifungal agent: For severely ill patients 1
• Imipenem plus amikacin: Reference treatment for nosocomial or tertiary peritonitis 4
• Antifungal treatment (fluconazole): Usually necessary until peritoneal fluid culture results are available 4

Critical consideration: Hospital-acquired infections are caused by more resistant flora, including Pseudomonas and extended-spectrum β-lactamase (ESBL)-producing organisms 1

Carbapenem-Sparing Strategies

In settings with high incidence of carbapenem-resistant organisms, consider 1:

• Ceftolozane-tazobactam plus metronidazole: Effective against ESBLs and P. aeruginosa 1
• Ceftazidime-avibactam plus metronidazole: Active against Klebsiella pneumoniae carbapenemases (KPCs) 1

Important warning: Tigecycline was associated with higher mortality (OR 1.33,95% CI 1.03-1.72) and more adverse events compared to other antibiotics in severe infections 1. It should not be first-line in bacteremic patients due to poor plasma concentrations 1

Special Considerations

Enterococcal Coverage

Enterococci are more prevalent in hospital-acquired infections (22.3% in HA-IAIs versus 13.9% in CA-IAIs) 1:

• Empirical enterococcal coverage is NOT recommended for community-acquired infections 1
• Coverage should be considered for postoperative/nosocomial peritonitis 1
• For vancomycin-resistant Enterococcus (VRE): Use linezolid (monomicrobial infection) or tigecycline (polymicrobial infection) 1

Candida Coverage

The presence of Candida in peritoneal samples is a poor prognostic factor 1. Consider antifungal therapy in critically ill patients with hospital-acquired peritonitis 1, 4

Pseudomonas aeruginosa

When treating complicated skin and skin structure infections or peritonitis caused by P. aeruginosa, meropenem 1 gram every 8 hours is recommended 2

Duration of Therapy

Treatment duration varies from 48 hours in less severe forms to 14 days, depending on clinical response and severity 4

Common Pitfalls

• Avoid fluoroquinolone monotherapy without metronidazole due to increasing B. fragilis resistance 1
• Do not use clindamycin, cefotetan, cefoxitin, or quinolones alone in contexts where B. fragilis is likely, as susceptibility profiles show substantial resistance 1
• Extended fluoroquinolone use should be discouraged due to selective pressure for ESBLs and MRSA 1
• Aminoglycosides showed poorer clinical success (OR 0.65,95% CI 0.46-0.92) compared to other antibiotics 1
• Review local susceptibility patterns before using ampicillin-sulbactam due to increasing E. coli resistance 1
• Carbapenem overuse should be avoided to reduce selective pressure for carbapenem-resistant Enterobacteriaceae 1