Hello all,
The first journal club of the academic year will be coming up on Thursday, the 18th. We are going to be trying some different times this year to see if we can boost attendance, so this month we will have journal club from 4:00 PM to 6:30 PM. Please make every effort to attend. We will be discussing whether or not antibiotics are necessary for the treatment of uncomplicated diverticulitis. Please note that the PGY-1, PGY-3, and PGY-4 articles will be appraised using the Therapy form, while the PGY-2 article will be appraised using the Meta-analysis form.
Vignette
You are halfway through an average weekday shift in EM-2 when you encounter a very pleasant 50-year-old gentleman with abdominal pain. He reports the pain began three days ago and has progressively worsened. It is a dull, moderate pain located in the left lower quadrant with no radiation. He denies fevers or chills, endorses some nausea but no vomiting. He has had some loose stools, but no hematochezia or melena. His past medical history includes hypertension, for which he takes Lisinopril. He has had no previous abdominal surgeries and has no allergies.
His vitals are: T 37.0 BP 135/80, HR 86, RR 16, SpO2 99%. His exam is remarkable for LLQ tenderness with no rebound or guarding. He is comfortable, well-appearing, and nontoxic.
Suspecting diverticulitis as the likely cause of his symptoms, you check basic labs and order a CT scan of the abdomen and pelvis with IV contrast. His WBC is 14K and his CT reveals uncomplicated sigmoid diverticulitis without perforation or abscess formation.
As you are ordering antibiotics, you remember seeing a recent article in ACEPNow suggesting that antibiotics may not actually be necessary to treat diverticulitis. You had previously scoffed at the suggestion and tossed the magazine in the trash, but now wonder if the assertion was based on real science. Aware that evidence has disproven previous dogma regarding the universal need for antibiotics in a variety of conditions (including simple abscesses and acute sinusitis), you open PubMed and begin looking up articles…
PICO Question
Population: Adult patients with acute uncomplicated diverticulitis, without
perforation, abscess, or signs of sepsis
Intervention: Conservative management without the use of antibiotics, either at
home or inpatient
Comparison: Management with oral or IV antibiotics
Outcome: Mortality, complication rate, duration of symptoms, recurrence of disease,
need for surgical intervention, cost, quality of life
Search Strategy
MEDLINE was searched via PubMed using the Mesh terms (“Diverticulitis,
Colonic”[Mesh] AND “Diverticulitis”[Mesh]) AND “Anti-Bacterial Agents”[Mesh],
limited to clinical trials and meta-analyses, to identify 34 articles (https://tinyurl.com/
bectufnt). These were searched and three randomized controlled trials and Cochrane
systematic review were identified.
Article 1: Chabok A, På hlman 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. [Answer Key].
Article 2: Dichman ML, Rosenstock SJ, Shabanzadeh DM. Antibiotics for
uncomplicated diverticulitis. Cochrane Database Syst Rev. 2022 Jun
22;6(6):CD009092. [Answer Key].
Article 3: Mora-Ló pez 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. [Answer Key].
Article 4: van Dijk ST, Daniels L, Ü nlü 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.
[Answer Key].
Bottom Line
The management of acute, uncomplicated diverticulitis has long involved the administration of broad-spectrum antibiotics to theoretically battle the bacteria that have invaded the occluded diverticuli and adjacent colonic wall. This practice is, however, based on no direct evidence. Recent research has challenged the notion that all such patients require antibiotics, and has even led to some guidelines and expert consensus statements suggesting that antibiotics be used selectively, rather than routinely.
One of the earlier studies on this subject was conducted in Sweden in Iceland between 2003 and 2010 (Chabok 2012). In this randomized controlled trial, 309 patients were randomized to not receive antibiotics, while 314 were randomized to receive antibiotics. The risk of an early complication (bowel perforation, abscess formation, or fistula formation) was not statistically different between the two groups (relative risk [RR] of 2.0, 95% CI 0.51-8.0). Slightly more patients in the no antibiotics group required surgery during follow-up compared to the antibiotics group, but this also did not achieve statistical significance (RR 3.0, 95% CI 0.61-15). There was no difference in hospital length of stay or the recurrence of diverticulitis.
More recently, two large non-inferiority trials (DINAMO and DIABOLO, conducted in Spain and The Netherlands, respectively), sought to strengthen these findings. Both were large, multi-center trials enrolling 480 and 528 patients. The DINAMO trial found no significant difference in the primary outcome of risk of ED revisit resulting in hospital admission (2.58% difference; 95% CI 6.32 to -1.17); the upper bound of the 95% CI was less than the prespecified non-inferiority limit of 7%. There was also no significant difference in ED revisit rates or rates of good clinical evolution at 30 days.
Similarly, the DIABOLO trial found no significant difference in median time to recovery (14 days for the observational and 12 days for the antibiotic group; hazard ratio for recovery 0·91 with a lower limit of the 1-sided 95 per cent CI of 0·78). There was also no significant difference in the 6-month risk of complicated diverticulitis, ongoing diverticulitis, recurrent diverticulitis, need for sigmoid resection, readmission, adverse events, or mortality. Hospital stay was significantly shorter in the observation group (2 versus 3 days). A subsequently published comparison of long-term outcomes from the DIABOLO trial demonstrated no significant difference in the proportion of patients with one or more episodes of recurrent diverticulitis within 2 years (15.4% in the observation group vs. 14.9% in the antibiotic group; RR 1.03, 95% CI 0.67 to 1.58), the proportion of patients who developed complicated diverticulitis (RR 1.03; 95% CI 0.67 to 1.58), or the proportion of patients undergoing sigmoid resection.
A recently updated Cochrane systematic review and meta-analysis on the subject identified seven relevant articles, of which two were reports of long-term outcomes from two of the five randomized controlled trials (including the DIABOLO trial). Pooling the results of the studies demonstrated no difference in the risk of complications within 30 days (RR 0.89; 95% CI 0.30 to 2.62). Risk of need for emergency surgery within 30 days occurred infrequently in both groups and less frequently in the no-antibiotic group, although this did not achieve statistical significance (0.5% vs. 1.0%, RR 0.47; 95% CI 0.13 to 1.7). There was also no difference in risk of recurrence, complications, emergency surgery, elective colonic resections, or mortality beyond 30 days. There was a non-statistically significant reduction in adverse events in the no antibiotic group (RR 0.14; 95% CI 0.02 to 1.13; I2= 0%).
The risks of unnecessary antibiotic use are well-documented, including increased antimicrobial resistance, allergic reactions, antibiotic-associated diarrhea, and Clostridium difficile infection. Despite these risks, and in the face of mounting evidence against the routine need for antibiotics for patients with uncomplicated diverticulitis, antibiotics remain the mainstay of treatment in the US. There are multiple potential barriers to practice change, including patient expectation, primary care physician expectation, lack of access to follow-up. It should be noted that none of the studies reviewed (and none included in the Cochrane review) was conducted in the US, where differences in healthcare preclude early follow-up for many patients discharged from the emergency department. Overcoming these barriers to change will be daunting, but, in light of the evidence, physicians should consider withholding antibiotics for select, immunocompetent patients with uncomplicated diverticulitis.