Treating outpatient diverticulitis with amoxicillin plus clavulanate may reduce the risk of fluoroquinolone-related harms with no adverse impact on diverticulitis-specific outcomes, two nationwide cohort studies suggested.
Amoxicillin-clavulanate was found to be as effective as metronidazole-with-fluoroquinolone, with only negligible differences between regimen groups in the risk of diverticulitis admissions, emergency department and outpatient clinic visits, and urgent or elective surgery, reported Anne F. Peery, MD, MSCR, of the University of North Carolina School of Medicine at Chapel Hill, and colleagues.
Notably, among Medicare beneficiaries age 65 and older, treatment with metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate was associated with an increased risk of Clostridioides difficile infection (CDI), the team wrote in Annals of Internal Medicine. “Remarkably, metronidazole-with-fluoroquinolone therapy was seven to eight times as common as amoxicillin–clavulanate for outpatient diverticulitis treatment.”
The FDA has recommended reserving fluoroquinolones for conditions lacking alternative treatment options, Peery and co-authors noted.
To compare the two regimens, the investigators drew on nationwide population-based claims data for U.S. residents in two groups and time frames: those ages 18 to 64 with private employer-sponsored health insurance (years 2000 to 2018) and those 65 and older with Medicare coverage (2006 to 2015).
Eligible participants were immunocompetent patients treated for diverticulitis in the ambulatory setting.
MarketScan (IBM Watson Health) data identified 106,361 new privately insured younger users of metronidazole-with-fluoroquinolone and 13,160 new users of amoxicillin-clavulanate.
No differences in risk were observed between treatment groups for the following study endpoints:
- 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, 95% CI -0.1 to 0.1)
- 3-year elective surgery risk (risk difference 0.2 percentage points, 95% CI -0.3 to 0.7)
- 1 -year CDI risk (risk difference 0.0 percentage points, 95% CI -0.1 to 0.1)
In the age 65 and older Medicare cohort, there were 17,639 newly prescribed users of metronidazole-with-fluoroquinolone and 2,709 new users of amoxicillin-clavulanate. The higher 1-year CDI risk for metronidazole-with-fluoroquinolone was reflected in a risk difference of 0.6 percentage points (95% CI 0.2-1.0).
Again, no differences between treatment groups emerged in this cohort for:
- 1-year admission risk (difference 0.1 percentage points, 95% CI 0.7 to 0.9)
- 1-year urgent surgery risk (difference 0.2 percentage points, 95% CI -0.6 to 0.1)
- 3-year elective surgery risk (difference 0.3 percentage points, 95% CI -1.1 to 0.4)
“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 researchers concluded.
Peery told MedPage Today that the two regimens are comparable in cost, so that is not a factor in prescribing.
Until lately, treating outpatient diverticulitis with antibiotics has been done without good evidence, the authors noted, and recent studies have challenged the benefit of treating acute uncomplicated diverticulitis with antibiotics.
For example, a systematic review and meta-analysis, of nine studies involving 2,505 patients with acute uncomplicated diverticulitis found no difference in clinical outcomes between those treated with or without antibiotics.
The American Gastroenterological Association recently updated its guidance on the treatment of colonic diverticulitis, including antibiotic use. Current guidelines recommend selective antibiotic use for acute uncomplicated diverticulitis. In the outpatient setting, antibiotics are recommended for patients with acute uncomplicated diverticulitis who are immunosuppressed or who have comorbidities as well as for patients with refractory or more severe symptoms.
To date, however, there has been little evidence on which antibiotic regimen is appropriate for these populations, the authors noted.
With the new data, however, “providers may now be able to give equally effective treatment while potentially preventing fluoroquinolone-related harms,” said Christine Lee, MD, a gastroenterologist at the Cleveland Clinic, who was not involved in the research.
Study limitations, the investigators said, included the possibility of residual confounding and an inability to assess all harms associated with these antibiotics, most notably drug-induced liver injury. In addition, since MarketScan and Medicare claims data do not specifically reflect antibiotic prescribing patterns and use, exposure assessment was based on initial insurance-reimbursed dispensing of antibiotics. It was also not known how much of a prescription was consumed as prescribed or if some patients perhaps stopped treatment early, increased their dosage, or switched to other drugs, thereby leaving the analysis open to misclassification bias, the team added.
Last Updated February 22, 2021
The study’s primary funding source was the National Institutes of Health.
The authors reported no competing interests.
Lee disclosed no competing interests with regard to her comments.