In a typical adult with secondary peritonitis and no significant allergies or renal impairment, what is the recommended broad‑spectrum intravenous antibiotic regimen and duration of therapy?

Secondary Peritonitis: Antibiotic Regimen and Duration

For typical adults with secondary peritonitis, initiate empiric broad-spectrum intravenous therapy with piperacillin-tazobactam 3.375 g every 6 hours or cefotaxime 2 g every 6–8 hours plus metronidazole, and treat for a fixed duration of 4–5 days after adequate source control. 1, 2

Empiric Antibiotic Selection

The choice of initial regimen depends on whether the infection is community-acquired or healthcare-associated:

Community-Acquired Secondary Peritonitis

• Piperacillin-tazobactam 3.375 g IV every 6 hours is the preferred single-agent regimen, providing comprehensive coverage against E. coli, Klebsiella spp., Bacteroides fragilis, and other common colonic flora 1, 2
• Alternative regimen: Cefotaxime 2 g IV every 6–8 hours combined with metronidazole for anaerobic coverage 1, 2
• Both regimens target the polymicrobial nature of secondary peritonitis, which typically involves 2–3 aerobic species and 1–2 anaerobic species 3

Healthcare-Associated or High-Risk Patients

• In critically ill patients with septic shock requiring vasopressor support, consider broad-spectrum carbapenems to ensure adequate coverage 2
• However, carbapenem-sparing strategies should be prioritized in settings with high carbapenem-resistant K. pneumoniae prevalence 2
• For ESBL-producing organisms, piperacillin-tazobactam retains activity against many strains and is preferred over carbapenems when susceptibility allows 2

Special Pathogen Considerations

• Add clindamycin 600–900 mg IV every 8 hours if Clostridium perfringens is suspected or isolated, due to its essential anti-toxin properties that reduce morbidity and mortality 3
• For perforated peptic ulcer specifically, the same broad-spectrum regimens apply, with empiric therapy started as soon as possible after peritoneal fluid collection 1

Duration of Antibiotic Therapy

A fixed 4-day course after adequate source control is as effective as longer, symptom-driven courses and is strongly recommended. 2

• The STOP-IT trial demonstrated that fixed 4-day courses yield outcomes comparable to prolonged treatment when source control is adequate 2
• For perforated peptic ulcer, guidelines suggest 3–5 days or until inflammatory markers normalize 1
• Short-course therapy (5 days) is as effective as 10-day courses in adequately drained infections 1, 2
• Prolonging antibiotics beyond 10 days increases the risk of colonization by resistant strains, including enterococci 3

Criteria for Discontinuation

Antibiotics may be stopped when all three of the following are met: 2

1. No systemic inflammatory signs (afebrile, normal white blood cell count)
2. No clinical evidence of ongoing peritonitis
3. Resolution of physiologic abnormalities (normalized vital signs and laboratory parameters)

Culture-Guided Adjustments

• Obtain peritoneal fluid cultures before initiating antibiotics whenever possible, using bedside inoculation of blood culture bottles to increase sensitivity >90% 2
• Once culture and susceptibility results are available, tailor the antimicrobial regimen to identified pathogens and their resistance patterns 1, 2
• If inflammatory markers do not improve, rule out extra-abdominal sources of infection or different pathogens rather than simply prolonging antibiotics 1

Monitoring and Re-evaluation

• Perform abdominal CT 5–7 days post-operatively to rule out residual peritonitis, abscess formation, or need for re-intervention 2
• Clinical improvement should be evident within 3–5 days after starting antibiotics and adequate source control 1
• If no improvement occurs, re-evaluation and repeat imaging are indicated to determine whether source control was adequate 1

Critical Pitfalls to Avoid

• Failing to achieve adequate source control: Antibiotic therapy cannot compensate for inadequate surgical drainage or debridement 3
• Ignoring local resistance patterns: Empirical regimens must be tailored to institutional antibiograms 2
• Prolonged empiric broad-spectrum therapy without reassessment: This promotes selection of highly resistant bacteria and may lead to tertiary peritonitis 4
• Inadequate initial therapy is strongly associated with higher mortality (42% vs 17.7%), emphasizing the importance of appropriate empiric coverage 3

Secondary vs. Spontaneous Bacterial Peritonitis

In cirrhotic patients with ascites, distinguish secondary peritonitis from spontaneous bacterial peritonitis (SBP): 1

• Secondary peritonitis typically shows PMN count >1,000/mm³, multiple organisms on culture, and at least two of: total protein ≥1 g/dL, LDH above normal serum limits, glucose ≤50 mg/dL
• Secondary peritonitis requires anaerobic coverage (add metronidazole to third-generation cephalosporin) and surgical intervention 1
• SBP alone is treated with cefotaxime 2 g IV every 8 hours for 5–10 days without surgery 1