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Comparative Effectiveness and Harms of Antibiotics for Outpatient Diverticulitis

Year: 2021

Type: article

Abstract: Background: Outpatient diverticulitis is commonly treated with either a combination of metronidazole and a fluoroquinolone (metronidazole-with-fluoroquinolone) or amoxicillin–clavulanate alone. The U.S. Food and Drug Administration advised that fluoroquinolones be reserved for conditions with no alternative treatment options. The comparative effectiveness of metronidazole-with-fluoroquinolone versus amoxicillin–clavulanate for diverticulitis is uncertain. Objective: To determine the effectiveness and harms of metronidazole-with-fluoroquinolone versus amoxicillin–clavulanate for outpatient diverticulitis. Design: Active-comparator, new-user, retrospective cohort studies. Setting: Nationwide population-based claims data on U.S. residents aged 18 to 64 years with private employer-sponsored insurance (2000 to 2018) or those aged 65 years or older with Medicare (2006 to 2015). Participants: Immunocompetent adults with diverticulitis in the outpatient setting. Intervention: Metronidazole-with-fluoroquinolone or amoxicillin–clavulanate. Measurements: 1-year risks for inpatient admission, urgent surgery, and Clostridioides difficile infection (CDI) and 3-year risk for elective surgery. Results: In MarketScan (IBM Watson Health), new users of metronidazole-with-fluoroquinolone (n = 106 361) and amoxicillin–clavulanate (n = 13 160) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [95% CI, −0.3 to 0.6]), 1-year urgent surgery risk (risk difference, 0.0 percentage points [CI, −0.1 to 0.1]), 3-year elective surgery risk (risk difference, 0.2 percentage points [CI, −0.3 to 0.7]), or 1-year CDI risk (risk difference, 0.0 percentage points [CI, −0.1 to 0.1]) between groups. In Medicare, new users of metronidazole-with-fluoroquinolone (n = 17 639) and amoxicillin–clavulanate (n = 2709) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [CI, −0.7 to 0.9]), 1-year urgent surgery risk (risk difference, −0.2 percentage points [CI, −0.6 to 0.1]), or 3-year elective surgery risk (risk difference, −0.3 percentage points [CI, −1.1 to 0.4]) between groups. The 1-year CDI risk was higher for metronidazole-with-fluoroquinolone than for amoxicillin–clavulanate (risk difference, 0.6 percentage points [CI, 0.2 to 1.0]). Limitation: Residual confounding is possible, and not all harms associated with these antibiotics, most notably drug-induced liver injury, could be assessed. Conclusion: Treating diverticulitis in the outpatient setting with amoxicillin–clavulanate may reduce the risk for fluoroquinolone-related harms without adversely affecting diverticulitis-specific outcomes. Primary Funding Source: National Institutes of Health.

Source: Annals of Internal Medicine

DOI: 10.7326/m20-6315