In my “Get Off the Fence” series about my practice of changing evidence-based medicine, I’ve discussed the role of antibiotics in diverticulitis several times this year. Although I’ve discussed the topic before on First10EM, I wanted to provide a quick summary of the most important publications for those looking at practice change.
of RCTs
DINAMO study: Mora-López L, Ruiz-Edo N, Estrada-Ferrer O, Piñana-Campon ML, Labro-Siuranes M, Escuder-Perez J, Sales-Malafrère R, Rebasa-Cladera P, Navarro-Soto S, Serra-Aracil X. ; Dynamo-Study Group. Efficacy and safety of non-antibiotic outpatient treatment in mild acute diverticulitis (DINAMO-study): a multicentre, randomized, open-label, non-inferiority trial. Ann’s wedding. 2021 November 1; 274(5):e435-e442. doi: 10.1097/SLA.000000000005031. PMID: 34183510
Methods: An open-label, non-inferiority RCT comparing symptomatic therapy (ibuprofen and acetaminophen) with antibiotics (amoxicillin-clavulanate 875/125 mg PO BID) in patients with uncomplicated diverticulitis, no significant comorbidities, immunosuppression, and no symptoms. Cesis
Results: They included a total of 480 patients. Their main outcome was a return visit with hospital admission, which allowed a statistical conclusion of non-inferiority 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). There were also no differences in ED return visits, pain relief, or complications. (None in either group required emergency surgery.)
Comments: I’m always wary of open-label trials, but I certainly expected this to bias antibiotics. The trial shows non-inferiority, but all point estimates seem to be worse in the antibiotic groups, and a large trial may actually harm the antibiotics.
STAND Test: 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 in 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 and oral metronidazole or oral amoxicillin-clavulanate) versus placebo in patients with Hinchley 1A (no evidence of perforation, abscess or peritonitis) uncomplicated acute diverticulitis and immunosuppressive disease. Excluding or 2 or more SIRS requirements.
Results: They included 180 patients and there was no statistical difference in the primary outcome of hospital stay (40 vs 46 hours). In addition, there were no differences in any of the secondary outcomes. 2 patients required procedural steps in the antibiotic group compared to 0 in the placebo group. 1 patient in the antibiotic group died compared to 0 in the placebo group. Readmission at 1 week occurred in 6% of the antibiotic group compared to 1% of the placebo group.
Comments: Too little testing to make definitive conclusions, but again the results all seem to be worse in the group of antibiotics. The trial looked only at admitted patients, many patients with uncomplicated diverticulitis can be treated as outpatients. It is clearly underpowered for rare but serious adverse events (either infectious or from 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. First randomized clinical trial of surveillance and antibiotic therapy in 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, multicenter noninferiority trial comparing antibiotics (amoxicillin-clavulanate 2 days IV then orally for 8 days) in adult patients with first-episode uncomplicated diverticulitis. They include patients with abdominal tumors up to 5 cm. Patients were excluded for sepsis and immunosuppression.
Results: They included 570 patients, and there was no difference in the time to recovery (14 days without antibiotics versus 12 days with antibiotics). Hospital admission was shorter in the no antibiotic group (2 vs 3 days). Emergency department re-visits were higher in the no antibiotic group (13% vs 0.4%).
Comments: Early discharge from the hospital is directly related to the rate of re-visits, as symptoms are more likely to appear in the first few days. Recurrence rates and emergency surgery rates were similar, so these revisits were more matters of convenience than long-term health. 10% of the subjects had constipation at the first visit, compared with 6% of the antibiotic group.
AVOD test: Chabok A, Påhlman L, Hjern F, Haapaniemi S, Smedh K; AVOD Study Group A randomized clinical trial of antibiotics in acute uncomplicated diverticulitis. Br J Surg. 2012 April; 99 (4): 532-9. PMID: 22290281
Methods: An open-label, multicenter, RCT comparing broad-spectrum antibiotics (second- or third-generation cephalosporins (cefuroxime or cefotaxime) and intravenous metronidazole in combination with carbapenem antibiotics (ertapenem, meropenem, or imipenem) or IV piperacillin-tazobactam in adults with uncomplicated effusion by CT) They confirmed diverticulitis, excluding immunosuppression, peritonitis and sepsis.
Results: They included 623 patients. There was no difference in the primary outcome of complications and the need for emergency surgery (1.9% vs 1.0%). 10 patients (3.2%) who started without antibiotics were finally given antibiotics. Recurrence rates and length of hospital stay were similar.
Comments: Basically the same restrictions as mentioned above. Too small to rule out rare injuries, and high risk of bias.
observation data
Isakson D, Thorrison A, Andreasen K, Nikberg M, Smedh K, Chabock A. Outpatient, nonantibiotic management of acute uncomplicated diverticulitis: a prospective study.. International Journal of Colorectal Disease. 30(9):1229-34. 2015. PMID: 25989930
This is a small follow-up study of 155 adult patients with CT-diagnosed uncomplicated diverticulitis, all of whom were treated without antibiotics. 97.4% were successfully treated as outpatients without antibiotics, admissions and complications. Of the 4 complications, 2 were perforations, 1 was an abscess, and the last was admitted but had a normal CT. All 4 were treated with antibiotics but did not undergo surgery.
Instructions
Institute of American Gastroenterological Association (2015)
- “AGA suggests that antibiotics should be used selectively rather than routinely in patients with acute uncomplicated diverticulitis.”
- This was in 2015, before 3 of 4 RCTs
- https://pubmed.ncbi.nlm.nih.gov/26453777/
World Association of Emergency Surgery (2020)
- “Uncomplicated diverticulitis without signs of systemic inflammation in immunocompromised patients.” We recommend not to prescribe antibiotic treatment (Strong recommendation based on high-quality evidence, 1A).”
- “In patients requiring antibiotic therapy, we recommend oral administration whenever possible, as early conversion from intravenous to oral therapy may facilitate a shorter patient length of stay (strong recommendation based on moderate-quality data, 1B).”
- https://wjes.biomedcentral.com/articles/10.1186/s13017-020-00313-4
American Association of Colon and Rectal Surgeons (2020)
American College of Physicians (2022)
- “ACP recommends that clinicians manage most patients with acute uncomplicated left-sided colonic diverticulitis in the outpatient setting (conditional recommendation, low-certainty evidence).”
- “ACP recommends that clinicians initially manage selected patients with acute uncomplicated left-sided intestinal diverticulitis without antibiotics (conditional opinion; low-certainty evidence).”
- https://www.acpjournals.org/doi/10.7326/m21-2710
The World Society of Emergency Surgery (WSES), the Italian Society of Geriatric Surgery (SICG), the Italian Association of Hospital Surgeons (ACOI), the Italian Society of Emergency Surgery and Trauma (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 immunocompromised elderly patients with uncomplicated left colonic diverticulitis (WSES grade 0) with sepsis-related organ failure. [Conditional recommendation, very low-quality of evidence]”
- “We recommend antibiotic therapy for elderly patients with complicated left colonic diverticulitis (pericolic air bubbles) or small pericolic effusions without fistulas (WSES grade 1a).
- https://wjes.biomedcentral.com/articles/10.1186/s13017-022-00408-0
at last
It is now clear that uncomplicated diverticulitis does not require antibiotic treatment. It is time to change the practice.
In my opinion, the easiest way to change the practice for most patients is to stop before the diagnosis of diverticulitis. If the only reason you’re ordering a CT is to look for diverticulitis, just skip the CT (at least for now). Give symptomatic treatment for a few days before explaining to the patient, because this is probably the most accurate way to tell if the CT is positive or negative for diverticulitis.
If you have CT-confirmed diverticulitis, most patients obviously don’t need antibiotics, but clinical judgment is still important. I would not rush to apply this evidence to immunocompromised cancer patients. Finally, shared decision-making is always important in medicine. It is important to reduce the unnecessary use of antibiotics, but the harm of one prescription is very low. Talk to your patients and help them make the best decisions. If you really need antibiotics, consider a delayed-release prescription that is only used if you don’t see improvement within three days.
Another FOAMed
Diverticulitis and antibiotics: time to change practice?
FOAMcast: management of acute, uncomplicated diverticulitis
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