Current Trends in the Treatment of Acute Uncomplicated Diverticulitis

Introduction

Diverticulitis is defined as localized inflammation of colonic diverticula and constitutes a significant burden of disease in the US.^1,2 It typically presents with fever, abdominal pain, and leukocytosis with image findings of bowel wall thickening and fat stranding. ³ The pathogenesis is thought to be related to obstruction of colonic diverticulum, which can subsequently lead to stasis, ischemia, micro perforation, and infection. ⁴ More recent studies, however, suggest that the gut microbiome and genetic predisposition may play a role in the development of diverticulitis, leading to a more nuanced understanding of the pathophysiology of the disease.^5,6 Traditionally, the treatment of acute, uncomplicated diverticulitis included antibiotics in addition to supportive measures. However, there has been a paradigm shift in this treatment practice over the past decade with new data suggesting acute uncomplicated diverticulitis can be treated safely without antibiotics.

Current Trends

The current antibiotic regimen recommended for use when treating mild diverticulitis is trimethoprim/sulfamethoxazole, double-strength, twice daily or ciprofloxacin, 500 mg twice daily with metronidazole 500 mg every 6 hours. Alternatively, amoxicillin/clavulanate 500 mg/125 mg three times a day may also be used.^7,8 The duration for either antibiotic combination is typically 7–10 days. Antibiotic treatment is usually coupled with conservative management to include varying levels of bowel rest with or without admission for intravenous hydrating depending on the severity of the patient’s symptoms. ²

Review of the Literature

There have been several randomized control trials (RCTs) assessing outcomes in the treatment of acute, uncomplicated diverticulitis both with and without antibiotics. The AVOD Study (Antibiotics in Uncomplicated Diverticulitis) was the first to look at the treatment of uncomplicated diverticulitis both with and without antibiotics. ⁹ In this multicenter, RCT in Sweden, patients with uncomplicated diverticulitis confirmed by CT imaging were admitted and randomized to either an antibiotic group or IV fluids alone. Authors found that there was no difference in time to recovery, complication rates, or recurrence between the two groups, demonstrating non-inferiority of non-antibiotic management.

The DIABLO trial (Diverticulitis: Antibiotics or Close Observation) was another RCT in the Netherlands. ¹⁰ This trial included patients with their first episode of uncomplicated diverticulitis and randomized them into two groups—admission to the hospital without antibiotics and admission with antibiotics. In their study, they found that there was no difference in median time to recovery, complication, recurrence, surgical resection, readmission, adverse events, or total mortality between the two groups. Moreover, they demonstrated that length of hospital stay was significantly shorter in the observation group compared with the antibiotic treatment group.

The most recent study assessing the use of antibiotics in uncomplicated diverticulitis is the DINAMO-study. This study was a multicenter RCT assessing the efficacy and safety of non-antibiotic treatment of uncomplicated diverticulitis in the outpatient setting. ¹¹ In this multicenter RCT, patients were randomized into either a control group with PO antibiotic treatment or an experimental group without antibiotics in the outpatient setting. Authors found that there was no difference in hospitalization rates, revisits, or inadequate pain control at the 90-day follow-up period.

While these three trials have looked at conservative management as an alternative to antibiotics in the treatment of diverticulitis, the STAND study (Selective Treatment with Antibiotics for Non-Complicated Diverticulitis) has been the only RCT in the literature that assesses non-inferiority with a placebo arm. ¹² In this double-blinded, RCT, authors randomized patients with uncomplicated diverticulitis into a placebo group and an antibiotic group. Patients with CT proven uncomplicated diverticulitis were randomized into two groups and admitted to the hospital for either antibiotic treatment or a placebo including standard supportive measures. At the 30-day end-point, authors found no significant difference in median time of hospital stay, adverse events, or readmission to the hospital. These findings again demonstrate that in select patients, antibiotics may safely be omitted.

These RCTs have been reviewed in several meta-analyses with the general consensus that treatment of uncomplicated acute diverticulitis without antibiotics is safe and effective in immunocompetent patients.^13–18 However, the critique of the literature is that many of these RCTs have either a low quality of evidence or are subject to bias.^14,15 While there is data to suggest that complicated diverticulitis may be more aggressive in immunosuppressed patients, presenting more frequently as complicated diverticulitis and is associated with an increased need for operative intervention, there is little data looking at the effect of antibiotic’s versus non-antibiotic treatment of uncomplicated diverticulitis in this patient population.^19–21 Additionally, these studies included only immunocompetent patients. When retrospectively assessing for risk factors of treatment failure, studies have found that an elevated CRP level is associated with non-antibiotic treatment failure. ²² It is unclear if this association reflects an underlying inflammatory state predisposing the patient to antibiotic failure, or if it is more reflective of a more inflammatory presentation of diverticulitis that then would explain failure of non-antibiotic management. Regardless, most guidelines still recommend the treatment of acute uncomplicated diverticulitis with antibiotics in immunocompromised patients. ²³

Current Practice Guidelines and Society Recommendations

Recent research has led to changes in societal recommendations pertaining to the treatment of uncomplicated diverticulitis. Presently, the American Society of Colon and Rectal Surgeons, European Society of Coloproctology, Surgical Infection Society, American Academy of Family Physicians, and World Society of Emergency Surgery all strongly recommend the avoidance of antibiotics for the routine treatment of acute uncomplicated diverticulitis in immunocompetent patients.^24–28 The American College of Physicians also recommends no antibiotics for the initial management of patients with acute uncomplicated diverticulitis; however, their recommendation is only conditional based on review of evidence. ²⁹

Despite these consensus guidelines, there is still significant variation in clinical practice when treating diverticulitis. In 2019, the European Association of Endoscopic Surgery (EAES) and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) had a consensus conference updating clinicians on current evidence and provided a set of recommendations to guide clinical acute diverticulitis management. Subsequent surveys revealed significant disagreement in the responses. Combined, the two groups reported that non-antibiotic management was the current clinical practice of 26.5% of members, with only 23% of members agreeing that the current evidence and society recommendations would change their clinical practice. ³⁰ Repeat surveys at the SAGES annual conference then revealed that 62% of their members agreed with current recommendations for no antibiotic treatment and 46% of members endorsed it would change practice. EAES responses revealed every high accordance with 71% of members agreeing with both recommendations and reporting an influence in their clinical practice.

Conclusion

The general treatment algorithm for acute, uncomplicated diverticulitis has changed significantly in the past several decades. These changes are the product of several RCTs as well as further research on the pathophysiology of diverticulitis. The literature has demonstrated, however, that acute uncomplicated diverticulitis may be treated effectively without antibiotics in immunocompetent patients. Many society guidelines have thus changed treatment recommendations based on this data. However, some controversy remains in clinical practice.