What is the empiric antibiotic of choice for intra‑abdominal sepsis in an adult patient without known drug allergies or renal impairment?

Empiric Antibiotic of Choice for Intra-Abdominal Sepsis

For community-acquired intra-abdominal sepsis of high severity, piperacillin-tazobactam 3.375–4.5 g IV every 6 hours is the first-line empiric antibiotic, providing comprehensive coverage of gram-negative aerobes, anaerobes, and enterococci in a single agent. 1, 2, 3

Community-Acquired Mild-to-Moderate Severity

For patients without severe physiologic disturbance, advanced age, or immunocompromise:

• Ertapenem 1 g IV every 24 hours is the preferred single-agent option, offering once-daily dosing with excellent coverage of E. coli (71% of isolates) and Bacteroides fragilis (35% of cases). 2

• Alternative single agents: Cefoxitin 2 g IV every 6 hours or moxifloxacin 400 mg IV every 24 hours. 2

• Combination regimens: Metronidazole 500 mg IV every 8 hours plus ceftriaxone 1–2 g IV every 12–24 hours, cefuroxime 1.5 g IV every 8 hours, or levofloxacin 750 mg IV every 24 hours. 1, 2

Critical Agents to Avoid in Community-Acquired Infection

• Ampicillin-sulbactam – E. coli resistance exceeds 20% in most communities. 1, 2
• Cefotetan or clindamycin – rising B. fragilis resistance rates. 1, 2
• Fluoroquinolones – avoid when local E. coli resistance exceeds 10–20% or if the patient received a quinolone within 3 months. 2
• Aminoglycosides – not recommended for routine empiric use due to toxicity when equally effective alternatives exist. 1, 2

Community-Acquired High-Severity Infections

For patients with severe physiologic disturbance, APACHE II ≥15, advanced age, or immunocompromise:

• Piperacillin-tazobactam 3.375–4.5 g IV every 6 hours (for Pseudomonas coverage, increase to 4.5 g every 6 hours). 1, 2, 3

• Carbapenem alternatives: Meropenem 1 g IV every 8 hours, imipenem-cilastatin 500 mg IV every 6 hours, or doripenem 500 mg IV every 8 hours. 1, 2

• Empiric enterococcal coverage is recommended in high-severity infections; piperacillin-tazobactam provides this, or add ampicillin if using other regimens. 2

• Do not add aminoglycosides routinely; reserve for documented resistant organisms. 1, 2

• Antifungal therapy is not indicated unless Candida is isolated from cultures. 1, 2

Health-Care-Associated Intra-Abdominal Infections

Empiric therapy must be driven by local resistance patterns and institutional antibiograms:

• Carbapenems (meropenem, imipenem-cilastatin, doripenem) are first-line when local prevalence of ESBL-producing Enterobacteriaceae, multidrug-resistant Pseudomonas aeruginosa, or Acinetobacter exceeds 20%. 1, 2

• For ESBL-producing organisms: Carbapenem or piperacillin-tazobactam 4.5 g IV every 6 hours plus metronidazole 500 mg IV every 8 hours. 1, 2

• For Pseudomonas with >20% ceftazidime resistance: Add gentamicin 5–7 mg/kg IV every 24 hours (with therapeutic drug monitoring). 1, 2

• For MRSA risk (colonization, prior treatment failure, extensive quinolone exposure): Add vancomycin 15–20 mg/kg IV every 8–12 hours. 1, 2

• Enterococcal coverage is required in postoperative infections, prior cephalosporin use, immunocompromised hosts, or valvular heart disease; use ampicillin or piperacillin-tazobactam. 2

• Antifungal therapy: Fluconazole 400 mg IV daily if Candida is cultured; switch to caspofungin 70 mg loading then 50 mg IV daily for fluconazole-resistant species or critically ill patients. 2

Septic Shock Presentation

• Meropenem 1 g IV every 6 hours by extended infusion is the preferred agent for intra-abdominal sepsis with septic shock, providing the broadest spectrum against resistant organisms. 4

• Alternative agents: Doripenem 500 mg IV every 8 hours by extended infusion, imipenem-cilastatin 500 mg IV every 6 hours by extended infusion, or eravacycline 1 mg/kg IV every 12 hours (for beta-lactam allergy). 4

• Source control through surgical intervention or drainage must occur as soon as possible; antibiotics alone are insufficient. 4

Duration of Therapy

• 4 days total after adequate source control for immunocompetent, non-critically ill patients. 2, 4

• Up to 7 days for immunocompromised or critically ill patients, guided by clinical response and inflammatory markers (WBC, CRP, procalcitonin). 2, 4

• Do not extend beyond 7 days when adequate source control has been achieved; longer courses increase C. difficile risk and antimicrobial resistance without improving outcomes. 2, 4

Culture-Directed Therapy and De-escalation

• Obtain intra-operative or percutaneous drainage cultures before initiating antibiotics to enable de-escalation. 1, 2

• Narrow therapy at 3–5 days based on susceptibility results and clinical response. 2

• Susceptibility testing should be performed for Pseudomonas, Proteus, Acinetobacter, S. aureus, and predominant Enterobacteriaceae (moderate-to-heavy growth), as these are more likely to yield resistant organisms. 1

Common Pitfalls

• Overuse of carbapenems in mild-moderate community infections promotes carbapenem resistance; reserve for high-severity or health-care-associated cases. 1, 2

• Delaying appropriate antimicrobial therapy increases mortality risk, necessity for reoperation, and prolongs hospitalization. 4

• Failure to obtain cultures in high-risk patients impedes appropriate de-escalation and prolongs unnecessary broad-spectrum therapy. 2

• Inadequate source control – antibiotics are adjunctive; surgical or percutaneous drainage is mandatory for treatment success. 4