1. The metronidazole-with-fluoroquinolone group had a significantly greater risk of Clostridioides difficile infection compared to the amoxicillin-clavulanate group.
2. The two treatment groups had similar rates of hospital admission risk, surgery risk, and overall burden of recurrent health care visits.
Evidence Rating Level: 2 (Good)
Study Rundown: Acute diverticulitis most commonly manifests without abscess or perforation; therefore, it can be managed on an outpatient basis. Currently, the two most popular regimens are amoxicillin-clavulanate or a combination of metronidazole and fluoroquinolone, but there has yet to be a direct comparison of efficacy and safety between the two alternatives. As such, this study assessed whether either treatment option resulted in any benefits or harms beyond the other. The treatment groups in both cohorts were similar with regard to 1-year diverticulitis-specific hospital admission risk, 1-year urgent surgery risk, 3-year elective surgery risk, and cumulative diverticulitis-related health care use. The 1-year infection risk was significantly greater among those who received metronidazole-with-fluoroquinolone compared to those who received amoxicillin-clavulanate. The study was limited by not investigating the safety outcomes, such as drug-induced liver injury. Overall, these findings suggest that treatment with amoxicillin-clavulanate may reduce the risk for fluoroquinolone-related harms without sacrificing efficacy.
In-Depth [retrospective cohort]: This active-comparator study utilized two separate cohorts, each drawing patient information from U.S. databases. Patients were eligible for inclusion if their first diagnostic code for outpatient diverticulitis occurred during 2000-2018 and the last prescription fill for the study antibiotics occurred at least six months before the new diagnosis. Patients were excluded if they were immunocompromised or had a prior diverticulitis-related diagnostic code, a percutaneous drain, or a colectomy for any indication. In one cohort, 106,361 (89.0%) patients filled prescriptions of metronidazole-with-fluoroquinolone and 13,160 (11.0%) filled prescriptions of amoxicillin-clavulanate. No between-group differences were observed in diverticulitis-specific 1-year hospital admission risk, 1-year urgent surgery risk, 3-year elective surgery risk, or 1-year risk for CDI. In the second cohort, 17,639 (86.7%) patients filled prescriptions of metronidazole-with-fluoroquinolone, and 2,709 (13.3%) filled prescriptions of amoxicillin-clavulanate. The two treatment groups had similar 1-year hospital admission risk and 3-year elective surgery risk, but the 1-year risk for CDI was significantly higher among those who received metronidazole-with-fluoroquinolone (1.2%) compared to those who received amoxicillin-clavulanate (0.6%) (95% confidence interval, 0.2 to 1.0 percentage points). Taken together, amoxicillin-clavulanate treatment reduced the risk of Clostridioides difficile infection compared to metronidazole-with-fluoroquinolone treatment.
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