• Charles E Gaber, Alan C Kinlaw, Jessie K Edwards, Jennifer L Lund, Til Stürmer, Peacock HintonSharonSSchool of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (J.K.E., J.L.L., S.P.H., V.P.)., Virginia Pate, Luther A Bartelt, Robert S Sandler, and Anne F Peery.
• Center for Gastrointestinal Biology and Disease, University of North Carolina School of Medicine, and School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (C.E.G.).
• Ann. Intern. Med. 2021 Jun 1; 174 (6): 737-746.

BackgroundOutpatient 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.ObjectiveTo determine the effectiveness and harms of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for outpatient diverticulitis.DesignActive-comparator, new-user, retrospective cohort studies.SettingNationwide 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).ParticipantsImmunocompetent adults with diverticulitis in the outpatient setting.InterventionMetronidazole-with-fluoroquinolone or amoxicillin-clavulanate.Measurements1-year risks for inpatient admission, urgent surgery, and Clostridioides difficile infection (CDI) and 3-year risk for elective surgery.ResultsIn 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]).LimitationResidual confounding is possible, and not all harms associated with these antibiotics, most notably drug-induced liver injury, could be assessed.ConclusionTreating diverticulitis in the outpatient setting with amoxicillin-clavulanate may reduce the risk for fluoroquinolone-related harms without adversely affecting diverticulitis-specific outcomes.Primary Funding SourceNational Institutes of Health.

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