What are the best empiric antibiotics for gastric perforation and peritonitis?

Best Empiric Antibiotics for Gastric Perforation and Peritonitis

For gastric perforation and peritonitis, the recommended empiric antibiotic regimen is a broad-spectrum combination that covers gram-negative, gram-positive, and anaerobic bacteria, with piperacillin/tazobactam 4.5g every 6 hours or meropenem 1g every 8 hours being the preferred options for critically ill patients. 1

Initial Antibiotic Selection

For Non-Critically Ill Patients:

• Piperacillin/tazobactam 4.5g every 6 hours is the recommended first-line therapy due to its vigorous activity against gram-positive, gram-negative, and anaerobic bacteria 1
• Treatment should be started as soon as possible after peritoneal fluid collection for culture 1

For Critically Ill Patients:

• Piperacillin/tazobactam 4.5g every 6 hours OR cefepime 2g every 8 hours plus metronidazole 500mg every 6 hours 1
• For patients at risk of infection with ESBL-producing Enterobacteriaceae: meropenem 1g every 8 hours, doripenem 500mg every 8 hours, or imipenem/cilastatin 1g every 8 hours 1, 2
• Meropenem is FDA-approved for complicated intra-abdominal infections caused by viridans group streptococci, E. coli, K. pneumoniae, P. aeruginosa, B. fragilis, B. thetaiotaomicron, and Peptostreptococcus species 2

Special Considerations

Secondary Peritonitis vs. Spontaneous Bacterial Peritonitis

• Gastric perforation causes secondary peritonitis, which requires anaerobic coverage in addition to a third-generation cephalosporin 1
• Secondary peritonitis from perforation typically shows multiple organisms (including fungi and enterococci) on Gram stain and culture 1

Duration of Therapy

• A short course (3-5 days) of antibiotic therapy is recommended if adequate source control is achieved 1
• Continue antibiotics until inflammatory markers normalize 1
• Studies show that outcomes after fixed-duration antibiotic therapy (approximately 4 days) were similar to longer courses when adequate source control was achieved 1

Antifungal Therapy

• Routine antifungal therapy is not recommended for all cases of gastric perforation 1, 3
• Antifungal therapy should be reserved for patients who are critically ill and/or severely immunocompromised 1
• When indicated, fluconazole (loading dose 12 mg/kg up to 800 mg, then 6 mg/kg/day) can be used in critically ill patients with community-acquired Candida peritonitis without prior azole exposure 1
• Echinocandins are recommended as first-line therapy for invasive infections and candidemia in non-neutropenic critically ill patients 1

Risk Factors for Multidrug-Resistant Organisms

• Previous antimicrobial therapy, especially broad-spectrum antibiotics between initial intervention and reoperation 4
• Healthcare-associated infections (particularly ICU patients or those hospitalized for more than 1 week) 1
• Corticosteroid use, organ transplantation, baseline pulmonary or hepatic disease 1
• For patients with these risk factors, combination therapy may be necessary to achieve high adequacy rates 4

Monitoring and Follow-up

• If inflammatory markers do not improve, rule out other extra-abdominal sources of infections or different pathogens 1
• Consider a de-escalation approach once culture results are available to avoid the development of antimicrobial resistance 1
• Modification of the antibiotic regimen should be guided by culture results and clinical status 1

Common Pitfalls

• Delayed initiation of antibiotics can increase mortality - start empiric therapy as soon as possible 1
• Inadequate empiric coverage increases treatment failure rates and hospital length of stay 4
• Unnecessary use of broad-spectrum agents for community-acquired infections may contribute to antimicrobial resistance 1
• Overuse of antifungal therapy does not improve outcomes in patients with lower GI perforations and may be similarly unnecessary for upper GI perforations in non-immunocompromised patients 3