Chapel Hill, NC—New studies on antibiotics for treating diverticulitis in the outpatient setting make a strong case for one of the commonly prescribed combination therapies compared with the other in order to avoid adverse effects.

The report in Annals of Internal Medicine suggests the antibiotic combination amoxicillin-clavulanate might reduce the risk for fluoroquinolone-related harms without adversely influencing diverticulitis-specific outcomes.

Based on that, the authors of two nationwide cohort studies make a strong recommendation that amoxicillin-clavulanate be prescribed preferentially to metronidazole-with-fluoroquinolone for patients with a first occurrence of diverticulitis.

Background information in the study describes how uncomplicated diverticulitis is often managed with antibiotics in the outpatient setting, both to expedite recovery from the acute episode and to reduce the risk for obstruction, abscess, or perforation. Little research has been done comparing the two most commonly prescribed antibiotic regimens used in this situation—a combination of metronidazole and a fluoroquinolone, or amoxicillin-clavulanate only. The FDA, meanwhile, has recommended that fluoroquinolones be reserved for use in conditions with no alternative treatment options because of the risk of potentially permanent and disabling adverse effects.

Using nationwide claims databases, researchers from the University of North Carolina School of Medicine sought to determine the effectiveness and harms of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for outpatient diverticulitis in two active-comparator, new-user, retrospective cohort studies.

The population-based claims data included U.S. adults up to age 64 years with private employer-sponsored insurance from 2000 to 2018 and those aged 65 years or older with Medicare from 2006 to 2015. The studies focused on immunocompetent adults with diverticulitis in the outpatient setting.

Participants all received either metronidazole-with-fluoroquinolone—prescribed to 106,361 commercial insurance patients—or amoxicillin-clavulanate—prescribed to 13,160 commercial insurance patients. Among Medicare beneficiaries, 17,639 got metronidazole-with-fluoroquinolone and 2,709 got amoxicillin-clavulanate.

Researchers tracked the following:
• 1-year risks for inpatient admission
• Urgent surgery
Clostridioides difficile infection (CDI)
• 3-year risk for elective surgery

In terms of the adults younger than age 65 years, no differences were detected in 1-year admission risk (risk difference, 0.1 percentage points [95% CI, −0.3-0.6]), 1-year urgent surgery risk (risk difference, 0.0 percentage points [CI, −0.1-0.1]), 3-year elective surgery risk (risk difference, 0.2 percentage points [CI, −0.3-0.7]), or 1-year CDI risk (risk difference, 0.0 percentage points [CI, −0.1-0.1]) between groups.

For Medicare beneficiaries, meanwhile, no differences in 1-year admission risk (risk difference, 0.1 percentage points [CI, −0.7-0.9]), 1-year urgent surgery risk (risk difference, −0.2 percentage points [CI, −0.6-0.1]), or 3-year elective surgery risk (risk difference, −0.3 percentage points [CI, −1.1-0.4]) were documented between groups. On the other hand, the 1-year CDI risk was higher for metronidazole-with-fluoroquinolone than for amoxicillin–clavulanate (risk difference, 0.6 percentage points [CI, 0.2-1.0]).

The authors caution that residual confounding is possible in their study, and that “Not all harms associated with these antibiotics, most notably drug-induced liver injury, could be assessed.”

They advise, however, that amoxicillin-clavulanate might be prescribed instead of metronidazole-with-fluoroquinolone to reduce the risk for serious harms associated with fluoroquinolone use, including CDI.

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