Among patients receiving early outpatient treatment for diverticulitis, the antibiotic combination of amoxicillin and clavulanate proved to be an effective alternative to metronidazole plus a fluoroquinolone in cohort studies involving two large nationwide cohorts.
The two cohorts were comprised of immunocompetent adults with previously untreated diverticulitis; negligible difference was observed at one year between the two antibiotic treatment groups with regard to hospital admission, need for urgent surgery, or long-term risk for elective surgery related to diverticulitis. But risk for Clostridioides difficile infection (CDI) was greater in older patient (≥65 years) treated with metronidazole-with-fluoroquinolone (risk difference o.6 percentage points, 95% CI, 0.2-1.0).
Findings from the study, which involved nationwide claims data of adults age 64 and younger and data from a separate database involving Medicare recipients, were published online Feb. 22 in Annals of Internal Medicine.
“Remarkably, metronidazole-with-fluoroquinolone therapy was 7 to 8 times as common as amoxicillin-clavulanate for outpatient diverticulitis treatment,” wrote researcher Anne Peery, MD, of the University of North Carolina School of Medicine, Chapel Hill, and colleagues.
In the treatment of acute diverticulitis, antibiotics are commonly prescribed to reduce the risk of progression to obstruction, abscess, or perforation. The two most commonly prescribed antibiotic regimens are metronidazole with a fluoroquinolone and amoxicillin-clavulanate, the researchers noted.
“Despite these antibiotics being commonly prescribed for diverticulitis, their effectiveness and harms remain unknown,” they wrote. “This is a critical gap because the U.S. Food and Drug Administration [FDA] has recommended that fluoroquinolones be reserved for use in conditions with no alternative treatment options because of the risk for potentially permanent and disabling fluoroquinolone-related adverse effects.” The FDA has issued several warnings regarding the risks of fluoroquinolone use over the years, with updated safety communications detailing risk of aortic aneurysm (Dec. 2018), drops in blood sugar and mental health side effects (July 2018), disabling side effects in tendons, muscles, joints, nerves, and central nervous system (July 2016), uncomplicated infections (May 2016), peripheral neuropathy (August 2013), and tendonitis and tendon rupture (July 2008).
Peery and colleagues compared the efficacy of treating outpatients with newly identified diverticulitis with the different antibiotic regimens with data from two administrative health care claims databases — IBM MarketScan Commercial Claims and Encounters Database and samples of Medicare claims.
Their analysis utilized an active-comparator, new-user retrospective cohort study design.
Study outcomes included one-year risk for inpatient admission, urgent surgery, and C. difficile infection due to diverticulitis. The researchers also assessed risk for elective surgery at three years following the diagnosis of diverticulitis.
Urgent surgery was defined using inpatients claims for open or laparoscopic colectomy with diverticulitis in a top five diagnostic code position, with and emergency department visit within seven days prior to surgery.
In the younger cohort (MarketScan, IBM Watson Health) a total of 106,361 new users of metronidazole-with-fluoroquinolone were identified, along with 13,160 new users of amoxicillin-clavulanate. The Medicare cohort included 17,639 new users of metronidazole-with-fluoroquinolone and 2,709 new users of amoxicillin-clavulanate.
Among the main findings:
- In the younger cohort, no differences in one-year admission risk (risk difference, 0.1 percentage points [95% CI, −0.3 to 0.6]), one-year urgent surgery risk (risk difference, 0.0 percentage points [95% CI, −0.1 to 0.1]), three-year elective surgery risk (risk difference, 0.2 percentage points [95% CI, −0.3 to 0.7]), or one-year CDI risk (risk difference, 0.0 percentage points [95% CI, −0.1 to 0.1]) between groups.
- In the Medicare group, there were no differences in one-year admission risk (risk difference, 0.1 percentage points [95% CI, −0.7 to 0.9]), one-year urgent surgery risk (risk difference, −0.2 percentage points [95% CI, −0.6 to 0.1]), or three-year elective surgery risk (risk difference, −0.3 percentage points [95% CI, −1.1 to 0.4]) between groups.
- The one-year CDI risk was higher for metronidazole-with-fluoroquinolone than for amoxicillin–clavulanate in the Medicare group (risk difference, 0.6 percentage points [95% CI, 0.2-1.0]).
A notable study limitation cited by the researchers was the possibility of residual confounding. They were also unable to assess all potential antibiotic-associated harms, including drug-induced liver injury. The researchers concluded that treating diverticulitis in the outpatient setting with amoxicillin-clavulanate may reduce the risk for fluoroquinolone-related harm with similar efficacy to the more commonly prescribed regimen of metronidazole with a fluoroquinolone.
“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,” they wrote.
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Among patients receiving early outpatient treatment for diverticulitis, the antibiotic combination of amoxicillin and clavulanate proved to be an effective alternative to metronidazole and a fluoroquinolone.
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Negligible difference was observed at one year between the two antibiotic treatment groups with regard to hospital admission, need for urgent surgery or long-term risk for elective surgery related to diverticulitis.
Salynn Boyles, Contributing Writer, BreakingMED™
This research was funded by the National Institutes of Health.
Corresponding researcher Anne Peery reported no relevant relationships with industry related to this study.
Cat ID: 111
Topic ID: 77,111,282,494,730,111,192,925
