emDOCs Podcast – Episode 89: Antibiotics for Uncomplicated Diverticulitis

Episode 89: Antibiotics for Uncomplicated Diverticulitis

Background:

• Previously antibiotics were utilized for all patients with diverticulitis.
• Recent evidence suggests antibiotics may not be necessary for all patients with uncomplicated diverticulitis.
• Antibiotics are recommended for those with complicated diverticulitis, as well as surgical specialist consult if necessary (e.g., perforation).

Randomized Controlled Trials:

The AVOD trial: Chabok A, Påhlman L, Hjern F, Haapaniemi S, Smedh K; AVOD Study Group. Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis. Br J Surg. 2012 Apr;99(4):532-9.

• Open label, multicenter, RCT.
• Included patients had confirmed uncomplicated diverticulitis but no immunosuppression, peritonitis, sepsis.
• Compared broad spectrum antibiotics (IV combination of a second- or third generation cephalosporin (cefuroxime or cefotaxime) and metronidazole, or with carbapenem antibiotics (ertapenem, meropenem or imipenem) or piperacillin–tazobactam versus IV fluids.
• 623 patients included.
• No difference in their primary outcome of complications and need for emergency surgery (1.9% vs 1.0%). 10 patients (3.2%) who started without antibiotics were eventually given antibiotics. The recurrence rate and length of hospital stay were the same.

The DIABLO trial: Daniels L, Ünlü Ç, de Korte N, et al; Dutch Diverticular Disease (3D) Collaborative Study Group. Randomized clinical trial of observational versus antibiotic treatment for a first episode of CT-proven uncomplicated acute diverticulitis. Br J Surg. 2017 Jan;104(1):52-61.

• Open label multicenter pragmatic non-inferiority trial including patients with CT-confirmed, primary, left-sided, uncomplicated, acute diverticulitis at 22 clinical sites in the Netherlands. They included patients with abscess up to 5 cm in size. Patients with sepsis and immunocompromise were not included.
• Authors compared antibiotics (amoxicillin-clavulanate 2 days IV then oral for 8 days) to symptomatic management.
• 528 patients included.
• Median time to recovery was 14 (i.q.r. 6-35) days for the observational and 12 (7-30) days for the antibiotic treatment strategy, with a hazard ratio for recovery of 0.91. No significant differences between the observation and antibiotic treatment groups were found for secondary endpoints: complicated diverticulitis (3.8 versus 2.6%), ongoing diverticulitis (7·.3 vs. 4.1%), recurrent diverticulitis (3.4% vs. 3%), sigmoid resection (3.8% vs. 2.3%), readmission (17.6% vs. 12%), adverse events (48.5 vs. 54.5%), and mortality (1.1% vs. 0.4%). Hospital stay was significantly shorter in the observation group (2 versus 3 days; P = 0·006).

van Dijk ST, Daniels L, Ünlü Ç, et al; Dutch Diverticular Disease (3D) Collaborative Study Group. Long-Term Effects of Omitting Antibiotics in Uncomplicated Acute Diverticulitis. Am J Gastroenterol. 2018 Jul;113(7):1045-1052.

• Long term follow-up of the DIABLO study.
• 528 patients with CT-proven, primary, left-sided, uncomplicated acute diverticulitis were randomized to either an observational or an antibiotic treatment strategy. Outcome measures were complicated diverticulitis, recurrent diverticulitis and sigmoid resection at 24 months’ follow up.
• No difference in rates of recurrent diverticulitis (15.4% in the observational group versus 14.9% in the antibiotic group; p = 0.885), complicated diverticulitis (4.8% versus 3.3%; p = 0.403) and sigmoid resection (9.0% versus. 5.0%; p = 0.085).

Isacson D, Smedh K, Nikberg M, Chabok A. Long-term follow-up of the AVOD randomized trial of antibiotic avoidance in uncomplicated diverticulitis. Br J Surg. 2019 Oct;106(11):1542-1548.

• Follow up of AVOD trial.
• 556 of the 623 patients (89.2%) were followed up for a median of 11 years.
• No differences between the no-antibiotic and antibiotic group in recurrences (both 31.3%), complications (4.4 vs. 5%), surgery for diverticulitis (6.2 vs. 7.1%) or colorectal cancer (0.4% vs. 2.1%).

The STAND trial: Jaung R, Nisbet S, Gosselink MP, et al. Antibiotics Do Not Reduce Length of Hospital Stay for Uncomplicated Diverticulitis in a Pragmatic Double-Blind Randomized Trial. Clin Gastroenterol Hepatol. 2020 Mar 30:S1542-3565(20)30426-2.

• Double blind placebo controlled multicenter RCT including adult patients with Hinchley 1a (no evidence of perforation, abscess, or peritonitis) uncomplicated acute diverticulitis. They excluded patients with immunocompromise or 2 or more SIRS criteria.
• Authors compared antibiotics (either IV cefuroxime plus oral metronidazole OR oral amoxicillin- clavulanate) to placebo.
• Included 180 patients.
• No statistical difference in the primary outcome of hospital length of stay (40 vs 46 hours).
• No significant differences between groups in adverse events (12% for both groups; P = 1.0), readmission to the hospital within 1 week (1% for the placebo group vs 6% for the antibiotic group; P = 0.1), and readmission to the hospital within 30 days (11% for the placebo group vs 6% for the antibiotic group; P = 0.3).
• 2 patients needed procedural interventions in the antibiotic group, as compared to 0 in the placebo group. 1 patient in the antibiotic group died as compared to 0 in the placebo group.

The DINAMO trial: Mora-López L, Ruiz-Edo N, Estrada-Ferrer O, et al; DINAMO-study Group. Efficacy and Safety of Nonantibiotic Outpatient Treatment in Mild Acute Diverticulitis (DINAMO-study): A Multicentre, Randomised, Open-label, Noninferiority Trial. Ann Surg. 2021 Nov 1;274(5):e435-e442.

• Open-label, non-inferiority RCT including patients with uncomplicated diverticulitis, no significant comorbidities, no immunosuppression, and no signs of sepsis.
• Authors compared symptomatic treatment (ibuprofen and acetaminophen) to antibiotics (amoxicillin-clavulanate 875/125 mg PO BID) plus symptomatic treatment.
• Patients initially received symptomatic therapy and if symptoms controlled, were randomized to intervention versus control and discharged.
• Included 480 patients, with primary outcome return visit with hospital admission.
• 3% of the no antibiotic group and 5.8% of the antibiotic group returned to the ED and were admitted.
• There were no significant differences in ED return visits, pain control, or complications between groups.

RCT summary:

• These studies suggest that in the appropriately selected patient, symptomatic treatment and no antibiotics is safe. There does not appear to be increased need for surgical interventions or complications.

Guidelines:

• World Society of Emergency Surgery guidelines (2020)
  • “In immunocompetent patients with uncomplicated diverticulitis without signs of systemic inflammation, we recommend to not prescribe antibiotic therapy(strong recommendation based on high-quality evidence, 1A).”
  • “In patients requiring antibiotic therapy, we recommend oral administration whenever possible, primarily, because an early switch from intravenous to oral therapy may facilitate a shorter inpatient length of stay (strong recommendation based on moderate-quality evidence, 1B).”
• The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines (2020)
  • “Selected patients with uncomplicated diverticulitis can be treated without antibiotics.” Grade of Recommendation: Strong recommendation based on high-quality evidence, 1A.”
• American Gastroenterological Association (2021)
  • Best Practice Advice 6: Antibiotic treatment can be used selectively, rather than routinely, in immunocompetent patients with mild uncomplicated diverticulitis
  • Best Practice Advice 7: Antibiotic treatment is advised in patients with uncomplicated diverticulitis who have comorbidities or are frail, who present with refractory symptoms or vomiting, or who have a C- reactive protein >140 mg/L or baseline white blood cell count > 15 3 10⁹ cells/L. Antibiotic treatment is advised in patients with complicated diverticulitis or uncomplicated diverticulitis with a fluid collection or longer segment of inflammation on CT scan.
• American College of Physicians (2022)
  • “ACP suggests that clinicians manage most patients with acute uncomplicated left-sided colonic diverticulitis in an outpatient setting (conditional recommendation; low-certainty evidence).”
  • “ACP suggests that clinicians initially manage select patients with acute uncomplicated left-sided colonic diverticulitis without antibiotics (conditional recommendation; low-certainty evidence).”
• World Society of Emergency Surgery (WSES), the Italian Society of Geriatric Surgery (SICG), the Italian Hospital Surgeons Association (ACOI), the Italian Emergency Surgery and Trauma Association (SICUT), the Academy of Emergency Medicine and Care (AcEMC) and the ItalianSociety of Surgical Pathophysiology (SIFIPAC) (2022)
  • “We suggest that antibiotic therapy should be avoided in immunocompetent elderly patients with uncomplicated left colonic diverticulitis (WSES stage 0) without sepsis-related organ failures [Conditional recommendation, very low-quality of evidence]”
  • “We suggest antibiotic therapy administration for elderly patients with localized complicated left colonic diverticulitis with pericolic air bubbles or little pericolic fluid without abscess (WSES stage 1a).”

Summary:

• Based on the literature and guidelines, antibiotics are not necessary in all patients with uncomplicated diverticulitis. In the right patient, forgoing antibiotics is safe, with no increased risk of complications like perforation or recurrence.
• Criteria for symptomatic therapy with no antibiotics:
  • No perforation, abscess, or fistula.
  • No evidence of sepsis.
  • No major comorbidities (liver disease, ESRD, uncontrolled diabetes)
  • No immunocompromise.
  • Patient can follow up.
• If the patient meets these criteria, discharge with symptomatic therapy and provide return precautions.
• If they don’t meet these criteria, they are septic, or they have complicated diverticulitis, antibiotics are recommended.

References:

1. Chabok A, Påhlman L, Hjern F, et al; AVOD Study Group. Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis. Br J Surg. 2012 Apr;99(4):532-9.
2. Daniels L, Ünlü Ç, de Korte N, et al; Dutch Diverticular Disease (3D) Collaborative Study Group. Randomized clinical trial of observational versus antibiotic treatment for a first episode of CT-proven uncomplicated acute diverticulitis. Br J Surg. 2017 Jan;104(1):52-61.
3. van Dijk ST, Daniels L, Ünlü Ç, et al; Dutch Diverticular Disease (3D) Collaborative Study Group. Long-Term Effects of Omitting Antibiotics in Uncomplicated Acute Diverticulitis. Am J Gastroenterol. 2018 Jul;113(7):1045-1052.
4. Isacson D, Smedh K, Nikberg M, Chabok A. Long-term follow-up of the AVOD randomized trial of antibiotic avoidance in uncomplicated diverticulitis. Br J Surg. 2019 Oct;106(11):1542-1548.
5. Jaung R, Nisbet S, Gosselink MP, et al. Antibiotics Do Not Reduce Length of Hospital Stay for Uncomplicated Diverticulitis in a Pragmatic Double-Blind Randomized Trial. Clin Gastroenterol Hepatol. 2020 Mar 30:S1542-3565(20)30426-2.
6. Mora-López L, Ruiz-Edo N, Estrada-Ferrer O, et al; DINAMO-study Group. Efficacy and Safety of Nonantibiotic Outpatient Treatment in Mild Acute Diverticulitis (DINAMO-study): A Multicentre, Randomised, Open-label, Noninferiority Trial. Ann Surg. 2021 Nov 1;274(5):e435-e442.
7. Sartelli M, Weber DG, Kluger Y, et al. 2020 update of the WSES guidelines for the management of acute colonic diverticulitis in the emergency setting. World J Emerg Surg. 2020 May 7;15(1):32.
8. Hall J, Hardiman K, Lee S, et al; Prepared on behalf of the Clinical Practice Guidelines Committee of the American Society of Colon and Rectal Surgeons. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Treatment of Left-Sided Colonic Diverticulitis. Dis Colon Rectum. 2020 Jun;63(6):728-747.
9. Qaseem A, Etxeandia-Ikobaltzeta I, Lin JS, et al; Clinical Guidelines Committee of the American College of Physicians. Diagnosis and Management of Acute Left-Sided Colonic Diverticulitis: A Clinical Guideline From the American College of Physicians. Ann Intern Med. 2022 Mar;175(3):399-415. doi: 10.7326/M21-2710. Epub 2022 Jan 18. Erratum in: Ann Intern Med. 2023 Apr;176(4):584.
10. Peery AF, Shaukat A, Strate LL. AGA Clinical Practice Update on Medical Management of Colonic Diverticulitis: Expert Review. Gastroenterology. 2021 Feb;160(3):906-911.e1.
11. Fugazzola P, Ceresoli M, Coccolini F, et al. The WSES/SICG/ACOI/SICUT/AcEMC/SIFIPAC guidelines for diagnosis and treatment of acute left colonic diverticulitis in the elderly. World J Emerg Surg. 2022 Jan 21;17(1):5.