Fighting Inertia: Why Are We Continuing to Treat Acute Uncomplicated Diverticulitis with Antibiotics?

“An object at rest remains at rest, and an object in motion remains in motion at constant speed and in a straight line unless acted on by an unbalanced force.”

-Newton’s First Law of Motion

If you are one of the over 360,000 people in the United States who present to the emergency department (ED) each year with left lower quadrant pain and are diagnosed with uncomplicated diverticulitis,¹ chances are very good that you will be placed on antibiotics. Based on what used to be taught in medical school, the reasoning for this is sound- a diverticulum gets obstructed, this leads to mucosal abrasions, micro-perforation and translocation of bacteria outside of the gut.² Antibiotics kill bacteria. You end up feeling better after a few days. But our understanding of this disease process has evolved. Diverticulitis is now believed to be as much an inflammatory process as an infectious one.³ And this shift in insight into pathogenesis should come with a change in the way we treat this disease.. Antibiotics cost money and can have serious side effects, including allergic reactions, C. diff infections, and antibiotic-resistant infection. It stands to reason that they may be avoided in acute uncomplicated diverticulitis

Evidence of this paradigm shift comes via a study by Mora-Lopez et al. in this month’s edition of Annals of Surgery. [PLEASE INSERT CITATION OF DINAMO PAPER HERE] The “DINAMO” study was a prospective multicenter, open-label, non-inferiority randomized controlled trial that enrolled patients who presented to the ED with acute uncomplicated diverticulitis (defined as Neff stage 0 or 1a).⁴ Once patients achieved sufficient symptom control in the emergency department, they were randomized to either seven days of ibuprofen/acetaminophen or amoxicillin/clavulanic acid along with symptomatic treatment. The primary outcome was subsequent hospital admission within 90 days. The authors also collected subsequent ED visits, pain control and need for emergency surgery. After randomizing 480 patients, they observed hospitalization rates of 3.3% in the non-antibiotic group and 5.8% in the antibiotic group (mean difference 2.58%, 95% CI 6.32 to −1.17). This did not approach the previously specified non-inferiority margin of 7%. Similar findings were seen in repeat ED visits and pain control. None of the patients in either group required emergency surgery. Limitations to the study design include lack of blinding of treatment to the patient and the large number of patients excluded, but do not significantly threaten the conclusions of the trial.

This study joins two other large, randomized controlled trials that demonstrate that an antibiotic-free approach to the treatment of uncomplicated diverticular disease is appropriate in selected patients. The AVOD trail, published in 2012, randomized 623 total patients with CT diagnosed uncomplicated left-sided diverticular disease into two arms. The standard therapy arm received antibiotics and IV fluids whereas the second arm received only IV fluids. No significant difference was observed between the treatment groups in time to recovery, recurrence or treatment complications.⁵ At a mean follow-up of 11 years, there remained no difference in the two treatment groups in disease recurrence, complications, need for surgery due to diverticular disease, or reported quality of life.⁶ A more recent randomized control trial from the Dutch Diverticular Disease Collaborative also focuses on omitting antibiotic therapy in uncomplicated diverticulitis. This group compared the treatment of first episode of CT confirmed uncomplicated sigmoid diverticular disease with antibiotics versus observation.⁷ Patients were randomized to a 10-day (48 hours IV treatment followed by oral therapy) course of amoxicillin/clavulanic acid or observation with the primary outcome being time to recovery defined as discharge from hospital, normal diet, temperature less than 38°C, VAS pain score below 4 (with no use of daily pain medication), and resumption of working activities as assessed by a daily patient diary. There was no significant difference in time to recovery in the two groups (12 versus 14 days, p = 0.15). No differences in adverse events were found amongst the treatment groups. Upon 24-month follow up, there remained no difference in the groups in recurrent complicated or uncomplicated diverticular disease, readmission or need for surgical resection.⁸ The DINAMO study expands the body of evidence that uncomplicated diverticulitis can be safely treated without antibiotics by extending this concept to the outpatient setting

With mounting evidence that uncomplicated diverticulitis can be safely treated without antibiotics, why are we still using them in North America? The answer is multifactorial and parallels previous struggles to invert widely held medical beliefs on antibiotics. To begin, not all practitioners may be aware of the growing body of literature. Dissemination of medical knowledge to the practice setting is notoriously slow and require a multi-pronged approach to reach all stakeholders.⁹ Perhaps the greatest barrier is that patients have come to expect to have diverticulitis treated with antibiotics.¹⁰ With time crunched appointments, it is often easier to maintain the status quo with a prescription for ciprofloxacin and metronidazole than spent time walking a patient though current best practice. Physicians may also be concerned about the medicolegal ramifications of “observing” a patient with acute diverticulitis. Finally, North American readers may be skeptical of European trials, citing known differences in patient populations, health care systems and expectations.

For clinical practice to catch up with new understanding in both pathophysiology and management, several steps need to happen. Societies need to update their guidelines on management of diverticulitis by including this new data. The American Society of Colon and Rectal Surgeons recently released guidelines state with strong recommendation from high-quality evidence that “selected patients with uncomplicated diverticulitis can be treated without antibiotics.”¹¹ Other societies, both surgical and medical, should highlight this new data as they update their guidelines. Federal agencies, such as the Centers for Disease Control and Prevention, can also issue guidance and work to promote limiting antibiotics in diverticulitis similar to educational campaigns for sinus infections and acute bronchitis.¹² Funding needs to be put forward to determine and implement best dissemination strategies. Finally, there is the question of whether evidence from a North American trial needs to be added to the literature. In a recent Delph Consensus Process of North American patients and physicians, nearly all Delphi participants believed that a North American RCT on the use of antibiotics in acute uncomplicated diverticulitis is still required, and the majority reported the absence of a North American RCT as a major hindrance to adopting a nonantibiotic strategy.¹⁰

Diverticulitis remains a highly prevalent, but poorly understood disease. This study by Mora-Lopez and colleagues adds to the growing literature that we do not need antibiotics to treat acute uncomplicated diverticulitis. But changing the evidence and changing clinical practice are two very different undertakings. The hard work may be yet to come.