Amoxicillin-clavulanate appears safe, effective for diverticulitis in outpatients

A retrospective cohort study compared amoxicillin-clavulanate with metronidazole-fluoroquinolone and found no differences in outcomes including risks for inpatient admission or surgery, while Clostridioides difficile risk appeared higher in older patients on the latter regimen.


Outpatient treatment with amoxicillin-clavulanate is safe and effective and may reduce risk for fluoroquinolone-related harms, according to a recent study.

Researchers used data from two nationwide U.S. claims databases, one from 2000 to 2018 including patients ages 18 to 64 years with private employer-sponsored insurance and one from 2006 to 2015 including patients ages 65 years or older with Medicare, to compare the effectiveness of combination treatment with metronidazole-fluoroquinolone and amoxicillin-clavulanate for a first occurrence of outpatient diverticulitis. The primary outcome measures were one-year risks for inpatient admission, urgent surgery, and Clostridioides difficile infection (CDI) and three-year risk for elective surgery. The results were published Feb. 23 by Annals of Internal Medicine.

The first database of younger patients included 106,361 (89.0%) new users of metronidazole-fluoroquinolone and 13,160 (11.0%) new users of amoxicillin-clavulanate. The median patient age was 52 years, and 47% were women. No between-group differences were seen in one-year admission risk (risk difference, 0.1 percentage point [95% CI, −0.3 to 0.6 percentage point]), one-year urgent surgery risk (risk difference, 0.0 percentage points [95% CI, −0.1 to 0.1 percentage point]), three-year elective surgery risk (risk difference, 0.2 percentage point [95% CI, −0.3 to 0.7 percentage point]), or one-year CDI risk (risk difference, 0.0 percentage points [95% CI, −0.1 to 0.1 percentage point]).

The second database of Medicare patients included 17,639 (86.7%) new users of metronidazole-fluoroquinolone and 2,709 (13.3%) new users of amoxicillin-clavulanate. The median patient age was 73 years, and 67.9% were women. In this database, no between-group differences were seen for one-year admission risk, one-year urgent surgery risk, or three-year elective surgery risk (risk differences, 0.1 percentage point [95% CI, −0.7 to 0.9 percentage point], −0.2 percentage point [95% CI, −0.6 to 0.1], and −0.3 percentage point [95% CI, −1.1 to 0.4], respectively). One-year risk for CDI infection was higher in those receiving metronidazole-fluoroquinolone than in those receiving amoxicillin-clavulanate (risk difference, 0.6 percentage point [95% CI, 0.2 to 1.0 percentage point]).

The authors noted that their data were based on dispensed antibiotics reimbursed by insurance rather than antibiotic use and that they did not examine all safety outcomes, including drug-induced liver injury, among other limitations. They concluded that amoxicillin-clavulanate is as effective as metronidazole-fluoroquinolone for treatment of outpatient diverticulitis, with negligible between-group differences in risk for diverticulitis admissions, ED or outpatient visits, urgent surgery, and elective surgery. “When selectively treating outpatient diverticulitis with antibiotics, physicians may consider treatment with amoxicillin-clavulanate over metronidazole-with-fluoroquinolone to reduce the risk for serious harms associated with fluoroquinolone use, including CDI,” the authors wrote.