What is the recommended antibiotic therapy for a patient with peritonitis?

Antibiotic Therapy for Peritonitis

For community-acquired secondary peritonitis, initiate empirical therapy with piperacillin-tazobactam 3.375g IV every 6 hours or cefotaxime 2g IV every 6-8 hours plus metronidazole, with treatment duration of 5-7 days after adequate source control. 1, 2

Initial Empirical Antibiotic Selection

The choice of empirical antibiotics must be stratified by acquisition setting and severity:

Community-Acquired Peritonitis (Mild-Moderate Severity)

• Piperacillin-tazobactam 3.375g IV every 6 hours is the preferred single-agent regimen, providing coverage for E. coli, Bacteroides fragilis group, and other common pathogens 3, 1
• Cefotaxime 2g IV every 6-8 hours combined with metronidazole is an alternative, particularly for spontaneous bacterial peritonitis in cirrhotic patients 1
• Amoxicillin-clavulanate IV followed by oral step-down (625mg TID orally) achieves similar resolution rates to cefotaxime with lower cost 1, 2

Hospital-Acquired or Postoperative Peritonitis

• Broader-spectrum regimens are mandatory due to high risk of multidrug-resistant organisms (MDROs), particularly ESBL-producing Enterobacteriaceae 1
• Imipenem-cilastatin plus amikacin plus vancomycin provides 99% adequacy in postoperative peritonitis with prior antibiotic exposure 4
• Piperacillin-tazobactam 4.5g IV every 6 hours plus amikacin plus vancomycin achieves 94% adequacy as an alternative 4
• Prior broad-spectrum antibiotic use between initial surgery and reoperation increases MDRO risk 5-fold (OR=5.1), necessitating combination therapy 4

Critical Illness with Septic Shock

• Initiate broad-spectrum antibiotics within 1 hour of sepsis recognition, as delayed or inadequate therapy significantly increases mortality (42% vs 17.7%) 1, 5
• Carbapenem-based regimens (imipenem or meropenem) plus aminoglycoside plus vancomycin/linezolid provide optimal coverage 1, 4

Special Pathogen Considerations

ESBL-Producing Enterobacteriaceae

• Carbapenem-sparing strategies should be prioritized in settings with high carbapenem-resistant K. pneumoniae prevalence 1
• Piperacillin-tazobactam retains activity against many ESBL producers and is preferred over carbapenems when susceptibility allows 1, 4
• Ceftazidime-avibactam or ceftolozane-tazobactam (both with metronidazole) are valuable alternatives for ESBL infections, with ceftazidime-avibactam active against KPC producers 1

Clostridium perfringens in Fecal Peritonitis

• Add clindamycin 600-900mg IV every 8 hours to standard regimens for its essential anti-toxin properties that reduce morbidity and mortality 5
• Standard beta-lactam/beta-lactamase inhibitors lack clindamycin's toxin-suppressing effects crucial in C. perfringens infections 5

Enterococcus Coverage

• Routine empirical enterococcal coverage is not necessary for community-acquired peritonitis 1
• Add vancomycin or linezolid only for hospital-acquired peritonitis, postoperative infections, or patients with septic shock 1

Candida Species

• Empirical antifungal therapy (fluconazole) is justified in two situations: patients with septic shock in community-acquired infections, or postoperative/tertiary peritonitis 1, 6
• Candida presence in peritoneal samples indicates poor prognosis 1

Antibiotics to Avoid

Fluoroquinolones

• Extended use should be discouraged due to selective pressure for ESBL-producing Enterobacteriaceae and MRSA 1
• Reserve for beta-lactam allergies only, using ciprofloxacin 500mg IV/PO BID plus metronidazole 500mg TID 1, 2
• Ciprofloxacin monotherapy is inadequate due to moderate anaerobic activity 1

Cephalosporins (Extended Use)

• Limit extended-spectrum cephalosporins to pathogen-directed therapy in settings with high ESBL prevalence to reduce selective pressure 1

Aminoglycosides

• Never use as monotherapy due to lack of anaerobic coverage 1, 6
• Avoid in cirrhotic patients due to nephrotoxicity risk 1

Treatment Duration and De-escalation

Standard Duration

• 5-7 days total therapy (including IV and oral phases) is adequate for uncomplicated peritonitis with complete source control 1, 2
• 5-day courses are as effective as 10-day courses in adequately drained infections 1

Reassessment at 48-72 Hours

• Perform repeat paracentesis if inadequate clinical response to verify neutrophil count decrease to <25% of pre-treatment value 1, 7
• Obtain cultures before initiating antibiotics by inoculating ≥10mL peritoneal fluid into blood culture bottles at bedside 1
• De-escalate or discontinue antibiotics based on culture results and clinical improvement 1

Prolonged Therapy Risks

• Avoid extending beyond 10 days without justification, as this increases colonization by resistant strains including VRE 1, 7, 5

Oral Step-Down Therapy

Spontaneous Bacterial Peritonitis

• Ciprofloxacin 500mg PO BID after initial IV therapy for uncomplicated SBP without renal failure, hepatic encephalopathy, or shock 1, 2
• Oral ofloxacin achieves similar results to IV cefotaxime in uncomplicated cases 1

Secondary Peritonitis

• Amoxicillin-clavulanate 625mg PO TID is first-line for community-acquired peritonitis after clinical improvement 2
• Moxifloxacin 400mg PO daily achieves 80-82% clinical success rates as step-down therapy 2
• Ciprofloxacin 500mg BID plus metronidazole 500mg TID for beta-lactam allergies 2

Contraindications to Oral Therapy

• Do not use oral antibiotics initially for septic shock, organ failure, hospital-acquired/postoperative peritonitis with MDRO risk, or impaired GI absorption 2

Dosing Considerations

Loading Doses

• Administer loading doses in critically ill patients to rapidly achieve therapeutic concentrations 1

Extended Infusions

• Use extended or prolonged infusions for beta-lactams to optimize time-dependent killing 1

Renal Adjustment

• Standard dosing adjustments apply for renal impairment, though specific peritoneal penetration must be considered 1

Common Pitfalls

• Failing to obtain cultures before antibiotics: Bedside inoculation of blood culture bottles increases sensitivity >90% 1
• Using narrow-spectrum agents for hospital-acquired infections: Prior antibiotic exposure mandates broader coverage 1, 4
• Omitting anaerobic coverage: Bacteroides fragilis is a key pathogen requiring metronidazole or beta-lactam/beta-lactamase inhibitor coverage 1, 6
• Ignoring local resistance patterns: Empirical regimens must be tailored to institutional antibiograms 1
• Continuing antibiotics beyond clinical resolution: Fixed 4-day duration after source control shows similar outcomes to prolonged therapy 5