What antibiotics are used to treat diverticulitis?

Antibiotic Selection and Management for Diverticulitis

First-Line Oral Antibiotic Regimens

For uncomplicated diverticulitis requiring antibiotics, use oral amoxicillin-clavulanate (Augmentin) 875/125 mg twice daily OR ciprofloxacin 500 mg twice daily plus metronidazole 500 mg three times daily for 4-7 days. 1, 2

When Antibiotics Are Actually Indicated

Most immunocompetent patients with uncomplicated diverticulitis do NOT require antibiotics—observation with supportive care is first-line treatment. 1 However, antibiotics should be prescribed for patients meeting ANY of these criteria:

• Immunocompromised status (chemotherapy, high-dose steroids, organ transplant recipients) 1, 2
• Systemic inflammatory response (persistent fever >101°F, chills, sepsis) 1, 2
• Elevated inflammatory markers: WBC >15 × 10^9 cells/L or CRP >140 mg/L 1
• High-risk clinical features: Age >80 years, pregnancy, ASA score III-IV 1, 2
• Concerning CT findings: Fluid collection, longer segment of inflammation, or pericolic extraluminal air 1
• Prolonged symptoms >5 days or presence of vomiting 1
• Significant comorbidities: Cirrhosis, chronic kidney disease, heart failure, poorly controlled diabetes 2

Specific Antibiotic Regimens by Setting

Outpatient oral therapy (for patients tolerating oral intake):

• Amoxicillin-clavulanate 875/125 mg orally twice daily 1, 2, 3
• Alternative: Ciprofloxacin 500 mg orally twice daily PLUS metronidazole 500 mg orally three times daily 1, 2, 3
• Penicillin allergy: Cefalexin plus metronidazole 2, 3

Inpatient IV therapy (for patients unable to tolerate oral intake or with severe disease):

• Ceftriaxone plus metronidazole 1, 2
• Piperacillin-tazobactam 1, 2
• Cefuroxime plus metronidazole 2
• Ampicillin-sulbactam 2

Duration of Antibiotic Therapy

Standard duration is 4-7 days for immunocompetent patients with uncomplicated diverticulitis. 1, 2 The duration should be stratified as follows:

• Immunocompetent patients: 4-7 days 1, 2, 3, 4
• Immunocompromised patients: 10-14 days (significantly longer due to higher risk of progression) 1, 5
• Complicated diverticulitis with adequate source control: 4 days postoperatively 1, 5
• Critically ill or inadequate source control: Up to 7 days 1

Transition Strategy for Hospitalized Patients

Switch from IV to oral antibiotics as soon as the patient can tolerate oral intake to facilitate earlier discharge. 1 The total antibiotic duration remains 4-7 days regardless of route. 1

For IV-to-oral transition:

• Start with amoxicillin-clavulanate 1200 mg IV four times daily for at least 48 hours 1
• Transition to oral Augmentin 625 mg three times daily once tolerating oral intake 1
• Hospital stays are actually shorter (2 vs 3 days) in observation groups compared to antibiotic-treated patients 1

Complicated Diverticulitis with Perforation

For perforated diverticulitis with diffuse peritonitis, use broad-spectrum IV antibiotics covering gram-positive, gram-negative, and anaerobic bacteria for 4 days after adequate source control. 5

Recommended regimens:

• Piperacillin-tazobactam 5
• Ceftriaxone plus metronidazole 5
• Consider local resistance patterns and epidemiological data when selecting antibiotics 5

The STOP IT trial demonstrated that 4 days of antibiotics after adequate source control produces similar outcomes to longer courses. 5 However, immunocompromised patients require 10-14 days even with source control. 5

Outpatient Management Criteria

Patients are appropriate for outpatient oral antibiotic therapy when they meet ALL of the following:

• Temperature <100.4°F 1
• Pain score <4/10 (controlled with acetaminophen only) 1
• Able to tolerate oral fluids and medications 1, 3
• No significant comorbidities or frailty 1
• Adequate home support and ability for self-care 1, 3

Re-evaluation within 7 days is mandatory, with earlier follow-up if clinical condition deteriorates. 1

Evidence Quality and Recent Findings

A 2024 randomized non-inferiority trial demonstrated that oral antibiotics are equally safe and efficacious as IV antibiotics for uncomplicated diverticulitis, with no significant difference in 30-day unplanned admissions, inflammatory markers, pain resolution, or return to normal function. 6 This supports the shift toward outpatient oral management for appropriate candidates.

Multiple high-quality randomized controlled trials, including the DIABOLO trial with 528 patients, have shown that antibiotics neither accelerate recovery nor prevent complications or recurrence in uncomplicated cases without risk factors. 1

Critical Pitfalls to Avoid

• Do NOT automatically prescribe antibiotics for all diverticulitis cases—observation is first-line for uncomplicated disease in immunocompetent patients 1
• Do NOT extend antibiotics to 10-14 days for all patients—this duration is specifically for immunocompromised patients only 1
• Do NOT continue antibiotics beyond 4 days postoperatively in complicated cases with adequate source control unless the patient is immunocompromised or critically ill 1, 5
• Do NOT stop antibiotics early even if symptoms improve, as this may lead to incomplete treatment and recurrence 1
• Avoid alcohol consumption until at least 48 hours after completing metronidazole to prevent disulfiram-like reactions 1

Special Considerations

Elderly patients (>80 years) should receive antibiotics due to higher likelihood of resistant organisms and increased risk of complications. 5, 2

Patients on corticosteroids are at major risk for perforation and death, requiring lower threshold for antibiotic treatment and surgical consultation. 1

If no clinical improvement occurs within 2-3 days of antibiotic therapy, repeat CT imaging is needed to evaluate for abscess, phlegmon, or fistula requiring percutaneous drainage or surgery. 4