There is a bit of an axiom that circulates in medical school: “Half of what you’re learning is wrong, but we don’t yet know which half.” This has borne out observationally simply by examining the frequency of reversed medical practices in the major medical journals.¹ There is also an entire school of academic inquiry into the likelihood of research arriving at erroneous conclusions, and it can be statistically demonstrated that most published findings are false.²

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The treatment of diverticulitis seems poised to be the next domino to fall in reversal of dogmatic medical practice. Some patients with diverticulitis progress to perforation, abscess, sepsis, and death, and the advent of antibiotic therapy substantially reduced morbidity and mortality associated with diverticulitis. The classic teaching, then, has required hospitalization and intravenous antibiotic therapy while monitoring for deterioration. However, with better understanding of the disease process, it was proposed that diverticulitis is primarily an inflammatory rather than an infectious state, and only those with a complicated disease course may benefit from antibiotic therapy.³

Given the increasing challenges of antimicrobial resistance paired with the rise of disabling Clostridium difficile infection, such a hypothesis did not go unnoticed. The first bits of evidence testing the disutility of antibiotics in acute, uncomplicated diverticulitis have been trickling out over the past three years. The first, the AVOD randomized trial, was an open, multicenter study in Sweden published in 2012.⁴ In this study, 669 patients with a CT-confirmed diagnosis of acute, uncomplicated diverticulitis were hospitalized and randomized to either intravenous fluids only or intravenous fluids and intravenous antibiotics in combination with fluids. Patients were evaluated daily while hospitalized, then followed for up to six months following enrollment.

The quick results summary: no difference. Patients in each group had nearly identical hospital courses, with similar rates of resolution of pain and fever, and median in-hospital length of stay of fewer than three days. The number of patients progressing to complicated disease was in the single digits in both cohorts. Ten patients randomized to no antibiotics were started on antibiotics due to suspicion of clinical worsening, while three patients on antibiotics terminated therapy due to allergic side effects. Recurrent episodes of diverticulitis during follow-up were likewise identical at six months.

The second, the DIABOLO randomized trial, was performed in a multicenter Dutch population, and the results were presented in 2014.⁵ Similar to AVOD, this trial hospitalized most uncomplicated cases of diverticulitis and randomized them to either intravenous fluids or intravenous antibiotics. This trial enrolled 528 patients, and again, outcomes were not different between cohorts. Patients in the no-antibiotics arm were treated more frequently as outpatients, had fewer in-hospital days, and ultimately had a crossover rate to antibiotics of 5 percent. Most important, similar to AVOD, no patients in the no-antibiotics arm suffered serious complications, either short-term due to progression of disease or in their six-month long-term follow-up window.

The final bit of evidence comes from the same group conducting the AVOD clinical trial.⁶ Based on their findings, these authors initiated practice change at two of the hospitals involved in the prior research and began treating qualifying diverticulitis patients without antibiotics as outpatients. To qualify, patients needed to have clinical symptoms and a CT-confirmed diagnosis of uncomplicated diverticulitis. Patients were then excluded based on being immunocompromised, pregnant, experiencing severe pain or vomiting, or at risk of poor compliance. These authors tracked 155 patients treated in accordance with this strategy, and there were a mere four treatment failures requiring hospitalization and antibiotic therapy. This failure rate, 2.6 percent, was no different than the expected rate of failure with antibiotics of approximately 2 percent. Of the failures, one had progression of a small abscess missed by the radiologist at initial presentation. Contrariwise, there were two patients whose initial CTs showed a missed perforation. Neither of these patients developed complications secondary to observation without antibiotics.

The American Gastroenterological Association published new guidance in December 2015, indicating a “selective” antibiotic strategy for acute, uncomplicated diverticulitis is reasonable.

These data, taken cumulatively, are quite fascinating. However, these data are also quite weak—the GRADE classification of the quality of this evidence is “low.” The AVOD trial suffers from substantial risk of bias, while the DIABOLO trial has been presented only in oral abstract form. The observational evidence is important but also suffers from bias and lack of a control cohort. All this said, however, these data have not gone unnoticed, and many guidelines have changed.

The American Gastroenterological Association (AGA) published new guidance in December 2015, indicating a “selective” antibiotic strategy for acute, uncomplicated diverticulitis is reasonable.⁷ While this might seem premature to many, given the strength of the evidence, the AGA is actually rather late to the party: the Danish Surgical Society, a Dutch guidelines working group, an Italian consensus conference, and a German society of gastroenterology have all gone on record endorsing similar limitations in the use of antibiotics.^7–11 More evidence is certainly needed to strengthen these recommendations, and our lessons regarding medical practice reversal must yet be heeded with any practice change. However, given the benefits associated with avoidance of unnecessary antibiotic use, the growing evidence makes a selective antibiotic strategy appealing.

The limitations of the evidence should be discussed with patients, and appropriate follow-up should be available or arranged. An initial liquid diet seems to be the most appropriate starting point, with progression as tolerated. Patients should expect to have continued, slow resolution of their symptoms over, in general, a week’s duration.

With these guidelines in place, appropriate patients with uncomplicated diverticulitis may be considered for an observation-only strategy. The limitations of the evidence should be discussed with patients, and appropriate follow-up should be available or arranged. An initial liquid diet seems to be the most appropriate starting point, with progression as tolerated. Patients should expect to have continued, slow resolution of their symptoms over, in general, a week’s duration. Treatment failures appear to be infrequent but will occur, and patients should be in a position to seek medical care should their clinical status worsen.

Expect further evidence regarding selective antibiotic treatment strategies for diverticulitis to continue trickling out over the next few months and years. Stay tuned to your favorite early knowledge translation resource to keep up to date with the latest developments.

References

1. Prasad V, Vandross A, Toomey C, et al. A decade of reversal: an analysis of 146 contradicted medical practices. Mayo Clin Proc. 2013;88(8):790-798.
2. Ioannidis JP. Why most published research findings are false. PLoS Med. 2005;2(8):e124.
3. Floch MH. A hypothesis: is diverticulitis a type of inflammatory bowel disease? J Clin Gastroenterol. 2006;40(Suppl 3):S121–S125.
4. Chabok A, Påhlman L, Hjern F, et al. Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis. Br J Surg. 2012;99(4):532-539.
5. Daniels L. Diverticulitis: antibiotics or close observation? Presented at: United European Gastroenterology Global Congress, Oct. 2014; Vienna, Austria.
6. Isacson D, Thorisson A, Andreasson K, et al. Outpatient, non-antibiotic management in acute uncomplicated diverticulitis: a prospective study. Int J Colorectal Dis. 2015;30(9):1229-1234.
7. Stollman N, Smalley W, Hirano I. American Gastroenterological Association Institute guideline on the management of acute diverticulitis. Gastroenterology. 2015;149(7):1944-1949.
8. Andersen JC, Bundgaard L, Elbrond H, et al. Danish national guidelines for treatment of diverticular disease. Dan Med J. 2012;59:C4453.
9. Andeweg CS, Mulder IM, Felt-Bersma RJ, et al. Guidelines of diagnostics and treatment of acute left-sided colonic diverticulitis. Dig Surg. 2013;30:278-292.
10. Cuomo R, Barbara G, Pace F, et al. Italian consensus conference for colonic diverticulosis and diverticular disease. United European Gastroenterol J. 2014;2:413-442.
11. Kruis W, Germer CT, Leifeld L, et al. Diverticular disease: guidelines of the German Society for Gastroenterology, Digestive and Metabolic Diseases and the German Society for General and Visceral Surgery. Digestion 2014;90:190-207.