Antibiotics are not needed in uncomplicated diverticulitis

In a lecture series entitled “Get off the fence”, in which I discuss practice changing evidence based medicine, I have discussed the role of antibiotics in diverticulitis multiple times this year. Although I have discussed the topic previously on First10EM, I wanted to provide a quick summary of the most important publications as a quick reference for people considering practice change.

The RCTs

The DINAMO study: Mora-López L, Ruiz-Edo N, Estrada-Ferrer O, Piñana-Campón ML, Labró-Ciurans M, Escuder-Perez J, Sales-Mallafré R, Rebasa-Cladera P, Navarro-Soto S, Serra-Aracil X; 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. doi: 10.1097/SLA.0000000000005031. PMID: 34183510

Methods: An open-label, non-inferiority RCT comparing symptomatic treatment (ibuprofen and acetaminophen) to antibiotics (amoxicillin-clavulanate 875/125 mg PO BID) plus symptomatic treatment in patients with uncomplicated diverticulitis, no significant comorbidities, no immunosuppression, and no signs of sepsis.

Results: They include a total of 480 patients. Their primary outcome was return visit with hospital admission, and occurred in 3.3% of the no antibiotic group and 5.8% of the antibiotic group (ARR 2.58%, 95% CI 6.32 to -1.17) allowing for the statistical conclusion of non-inferiority. There were also no differences in ED return visits, pain control, or complications. (No one in either group needed emergency surgery.)

Comments: I am always cautious about open-label trials, but I actually would have expected that to bias in favour of antibiotics. The trial demonstrates non-inferiority, but almost all the point estimates look worse in the antibiotic groups, and it is possible a large trial would have actually demonstrated harm from antibiotics.

The STAND trial: Jaung R, Nisbet S, Gosselink MP, Di Re A, Keane C, Lin A, Milne T, Su’a B, Rajaratnam S, Ctercteko G, Hsee L, Rowbotham D, Hill A, Bissett I. 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. doi: 10.1016/j.cgh.2020.03.049. PMID: 32240832

Methods: A double blind placebo controlled multicentre RCT comparing antibiotics (either IV cefuroxime plus oral metronidazole OR oral amoxicillin- clavulanate) to placebo in adult patients with Hinchley 1a (no evidence of perforation, abscess, or peritonitis) uncomplicated acute diverticulitis, and excluding patients with immunocompromise or 2 or more SIRS criteria.

Results: They included 180 patients, and there was no statistical difference in the primary outcome of hospital length of stay (40 vs 46 hours). There were also no differences in any of the secondary outcomes. 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. Readmission within 1 week occurred in 6% of the antibiotic group as compared to 1% of the placebo group.

Comments: Trial too small to make definitive conclusions, but once again the outcomes all look worse in the antibiotics group. The trial only looked at admitted patients, when most patients with uncomplicated diverticulitis can be treated as outpatients. Clearly under powered for rare but serious adverse events (whether infectious or from the antibiotics).

The DIABLO study: Daniels L, Ünlü Ç, de Korte N, van Dieren S, Stockmann HB, Vrouenraets BC, Consten EC, van der Hoeven JA, Eijsbouts QA, Faneyte IF, Bemelman WA, Dijkgraaf MG, Boermeester MA; 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. doi: 10.1002/bjs.10309. Epub 2016 Sep 30. PMID: 27686365

Methods: An open label multicentre pragmatic non-inferiority trial that compared antibiotics (amoxicillin-clavulanate 2 days IV then oral for 8 days) to symptomatic management in adult patients with a first episode of uncomplicated diverticulitis. They included patients with abscesses up to 5 cm in size. Patients were excluded for sepsis and immunocompromise.

Results: They included 570 patients, and there was no difference in their primary outcomes of time to recovery (14 days with no antibiotics vs 12 days with antibiotics). Hospital admission was shorted in the no antibiotic group (2 vs 3 days). Emergency department revisits were higher in the no antibiotics group (13% vs 0.4%)

Comments: Early discharge from the hospital is probably directly tied to the revisit rate, as you are more likely to be symptomatic and have complications in the first few days. Recurrence rates and emergency surgical rates were identical, so these revisits were probably more matters of convenience than long term health. 10% of the observation group had an abscess at the original visits, as compared to 6% of the antibiotic group. 

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. PMID: 22290281

Methods: An open label, multicentre, RCT that compared broad spectrum antibiotics (an intravenous combination of a second- or third generation cephalosporin (cefuroxime or cefotaxime) and metronidazole, or with carbapenem antibiotics (ertapenem, meropenem or imipenem) or piperacillin–tazobactam to just IV fluids in adult patients with CT confirmed uncomplicated diverticulitis, excluding immunosuppression, peritonitis, and sepsis. 

Results: They included 623 patients. There was 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 exactly the same. 

Comments: Basically the same limitations as above. Too small to eliminate rare harms, and open label so high risk of bias.

Observational data

Isacson D, Thorisson A, Andreasson K, Nikberg M, Smedh K, Chabok A. Outpatient, non-antibiotic management in acute uncomplicated diverticulitis: a prospective study. International journal of colorectal disease. 30(9):1229-34. 2015. PMID: 25989930

This is a small observational study of 155 adult patients with CT confirmed uncomplicated diverticulitis, all of whom were treated without antibiotics. 97.4% were treated successfully as outpatients without antibiotics, admissions, or complications. Of the 4 that had complications, 2 were perforations, 1 was an abscess, and the last was admitted but had a normal repeat CT. All 4 were treated with antibiotics but no surgery. 

Guidelines

American Gastroenterological Association Institute (2015)

• “The AGA suggests that antibiotics should be used selectively, rather than routinely, in patients with acute uncomplicated diverticulitis.”
• This was in 2015, before 3 of the 4 RCTs
• https://pubmed.ncbi.nlm.nih.gov/26453777/

World Society of Emergency Surgery (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).”
• https://wjes.biomedcentral.com/articles/10.1186/s13017-020-00313-4

The American Society of Colon and Rectal Surgeons (2020)

• “Selected patients with uncomplicated diverticulitis can be treated without antibiotics.” Grade of Recommendation: Strong recommendation based on high-quality evidence, 1A.”
• https://journals.lww.com/dcrjournal/fulltext/2020/06000/the_american_society_of_colon_and_rectal_surgeons.6.aspx

The 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).”
• https://www.acpjournals.org/doi/10.7326/m21-2710

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 Italian Society 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).”
• https://wjes.biomedcentral.com/articles/10.1186/s13017-022-00408-0

Bottom line

It is now very clear that uncomplicated diverticulitis does not require antibiotic therapy. It is time to change practice. 

In my mind, the easiest way to change practice for most patients is to stop before you even make the diagnosis of diverticulitis. If the only reason you are ordering CT is to look for diverticulitis, just skip the CT (for now at least). Give the patient a few days of symptomatic management before irradiating them, because that is probably the correct approach whether the CT is positive or negative for diverticulitis.

If you do have CT proven diverticulitis, it is clear that the vast majority of patients don’t need antibiotics, but clinical judgment is still important. I am not rushing to apply this evidence to immunosuppressed cancer patients. Finally, shared decision making is always essential in medicine. Reducing unnecessary antibiotic usage is important, but the harms of a single prescription are pretty low. Talk to your patients and help them make the best decision. If they really want antibiotics, consider a delayed prescription to be used only if they aren’t improving in three days time.

Other FOAMed

Diverticulitis and antibiotics: time to change practice?

FOAMcast: Management of Acute, Uncomplicated Diverticulitis