Diverticulitis: Amoxicillin-Clavulanate vs Metronidazole-with-Fluoroquinolone

Investigators examined the effectiveness of amoxicillin-clavulanate vs metronidazole-with-fluoroquinolone in outpatient diverticulitis treatment.

Outpatient treatment of diverticulitis with amoxicillin-clavulanate may reduce the risk of fluoroquinolone-related effects without adversely affecting diverticulitis-specific outcomes, according to study results in the Annals of Internal Medicine.

Investigators sought to determine the risks and effectiveness of treatment with amoxicillin-clavulanate vs metronidazole-with-fluoroquinolone in immunocompetent adults with diverticulitis in the outpatient setting. The researchers conducted separate cohort studies using 2 data sources: the IBM MarketScan Commercial Claims and Encounters Database, which included longitudinal data on patients aged 18 to 64 years enrolled in private, employer-sponsored health insurance from 2000 to 2018, and a 20% random sample of Medicare claims that included longitudinal data on fee-for-service beneficiaries (aged ≥65 years, with a disability, or with end-stage renal disease) from 2007 to 2015.

Outcomes were 1-year risks for inpatient admission, urgent surgery, Clostridioides difficile infection (CDI) and 3-year risk for elective surgery.

In the MarketScan cohort, the study authors identified13,160 new users of amoxicillin-clavulanate and 106,361 new users of metronidazole-with-fluoroquinolone. Patients’ median age was 52 years, and 47.2% were women. No differences were found in the 1-year admission risk (risk difference, 0.1 [95% CI, −0.3 to 0.6] percentage points), 1-year urgent surgery risk (risk difference, 0 [95% CI, −0.1 to 0.1] percentage points), 3-year elective surgery risk (risk difference, 0.2 [95% CI, −0.3 to 0.7] percentage points), or 1-year CDI risk (risk difference, 0  [95% CI, −0.1 to 0.1] percentage points) between the treatment groups.

In the Medicare cohort, the investigators identified 2709 new users of amoxicillin–clavulanate and 17,639 new users of metronidazole-with-fluoroquinolone. Patients’ median age was 73 years, 67.9% were women, and 91.1% were White. No differences were found in the 1-year hospital admission risk (risk difference, 0.1 [95% CI, −0.7 to 0.9] percentage points), 1-year urgent surgery risk (risk difference, −0.2 [95% CI, −0.6 to 0.1] percentage points), or 3-year elective surgery risk (risk difference, −0.3 [95% CI, −1.1 to 0.4] percentage points) between treatment groups. The 1-year CDI risk was higher for metronidazole-with-fluoroquinolone users compared with amoxicillin–clavulanate users (risk difference, 0.6 [95% CI, 0.2-1] percentage points).

“In 2 large nationwide cohorts of immunocompetent adults with outpatient diverticulitis, the 1-year risk for hospital admission or urgent surgery was low, and there was no difference between antibiotic groups,” stated the researchers. “There was also no difference in long-term risk for elective surgery for diverticulitis.”

Among several study limitations, the investigators noted that the MarketScan and Medicare claims data do not reflect antibiotic prescribing or use. Thus, exposure assessment was based on insurance-reimbursed dispensing of prescription antibiotics. Additionally, the study did not assess all important safety outcomes, including drug-induced liver injury.

“We have shown that outpatient diverticulitis treatment with amoxicillin–clavulanate was as effective as treatment with metronidazole-with-fluoroquinolone,” the study authors commented. “There were negligible differences between groups in risk for diverticulitis admissions, visits to the emergency department or outpatient clinics, 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.”

Disclosures: Some of the authors reported affiliations with pharmaceutical companies. Please see the original reference for a full list of disclosures.


Gaber CE, Kinlaw AC, Edwards JK, et al. Comparative effectiveness and harms of antibiotics for outpatient diverticulitis: two nationwide cohort studies. Ann Intern Med. Published online February 23, 2021. doi: 10.7326/M20-6315