February 22, 2021
Outpatient treatment of diverticulitis with amoxicillin-clavulanate is as effective as treatment with metronidazole plus a fluoroquinolone, according to a study published online February 22 February 22 in Annals of Internal Medicine.
This less commonly used treatment "has the potential to reduce the risk for fluoroquinolone-related harms, including Clostridioides difficile infection [CDI], without adversely affecting diverticulitis outcomes," study author Anne F. Peery, MD, MSCR, told Medscape Medical News.
The results indicate that amoxicillin-clavulanate "should be the new standard" for patients with uncomplicated diverticulitis who need antibiotics and are not allergic to any of the drug's components, commented David A. Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia School of Medicine, Norfolk, Virginia.
The US Food and Drug Administration (FDA) has recommended limiting exposure to fluoroquinolones when alternatives are available. "Here we have a good alternative," said Johnson, who was not involved in the study.
To compare the antibiotic regimens, Peery, who is with the Center for Gastrointestinal Biology and Disease at the University of North Carolina School of Medicine in Chapel Hill, and colleagues analyzed data from the IBM MarketScan Commercial Claims and Encounters Database for the period 2000 to 2018 and a sample of Medicare claims data from 2007 to 2015.
From MarketScan, they identified adults who were aged 18 to 64 years at the time they were assigned their first outpatient diagnostic code for diverticulitis. From the Medicare database, the investigators identified adults aged 65 years and older at the time they were diagnosed with diverticulitis. The investigators excluded patients whose diagnostic codes or prescription claims were associated with being immunocompromised or immunosuppressed.
In the MarketScan cohort, 106,361 (89%) patients received metronidazole with fluoroquinolone, and 13,160 (11%) patients received amoxicillin-clavulanate. Among the Medicare cohort, 17,639 (86.7%) patients received metronidazole with fluoroquinolone, and 2709 (13.3%) received amoxicillin-clavulanate.
In both cohorts, factors such as age, sex, comorbidities, concomitant medication use, and healthcare use were similar between the treatment groups.
"There were negligible differences between groups in risk for diverticulitis admissions, visits to the ED [emergency department] or outpatient clinics, urgent surgery, and elective surgery," the researchers report.
In the Medicare cohort, however, metronidazole-with-fluoroquinolone treatment was associated with increased risk for CDI, compared with amoxicillin-clavulanate (1.2% vs 0.6%). The increased risk corresponds to a number needed to treat to harm of 167.
Patient outcomes were very similar between the treatment groups in both populations.
Among patients in the MarketScan group, those treated with metronidazole with fluoroquinolone and those treated with amoxicillin-clavulanate were at similar risk for diverticulitis-specific, 1-year hospital admission (cumulative incidence, <4%; risk ratio, 1.04; risk difference [RD], 0.1 percentage points). Risks for 1-year urgent surgery (RD, 0 percentage points) and 3-year elective surgery (RD, 0.2 percentage points) were also similar. For both groups, the 1-year risk for CDI was 0.3% (RD, 0 percentage points).
Among those in the Medicare population, 1-year risk for hospital admission (RD, 0.1 percentage points) and 3-year risk for elective surgery (RD, -0.3 percentage points) were similar between groups. The cumulative incidence of urgent surgery at 1 year was less than 1%, and this risk "was lower in the metronidazole-with-fluoroquinolone group, but this estimate was imprecise," the researchers report (RD, -0.2 percentage points).
Better Safety Profile
The FDA has indicated that potential risks associated with fluoroquinolone use include hypoglycemia, mental health adverse effects, peripheral neuropathy, aortic aneurysm, and tendinitis.
Despite the warnings, "metronidazole-with-fluoroquinolone therapy was 7 to 8 times as common as amoxicillin-clavulanate for outpatient diverticulitis treatment," the researchers note.
Antibiotics traditionally have been overused for the treatment of diverticulitis, Johnson said. Recent guidelines, such as those from the American Gastroenterological Association, indicate that they can be "used selectively rather than routinely in immunocompetent patients that have mild uncomplicated diverticulitis," he said.
However, antibiotics are needed for patients with complicated disease, such as those with systemic inflammation or perforation, he emphasized.
"Physicians should consider treating outpatient diverticulitis with amoxicillin-clavulanate, instead of metronidazole with a fluoroquinolone," Peery said. "I am using more amoxicillin-clavulanate to treat outpatient diverticulitis and less metronidazole with a fluoroquinolone. I expect other clinicians will also take a more fluoroquinolone-sparing approach to treating outpatient diverticulitis."
The research was supported by grants from the National Institutes of Health (NIH). Peery has received grant support from the NIH. Coauthors have received grants from the NIH, the FDA, the Crohns and Colitis Foundation of America, AbbVie, and Novo Nordisk and have other ties to pharmaceutical companies. Johnson is a regular contributor to Medscape. He has disclosed no relevant financial relationships.