An analysis of two separate cohorts of adults who received antibiotics for diverticulitis indicates that amoxicillin-clavulanate is a safe and effective treatment and may reduce the risk of fluoroquinolone-related harms, US researchers reported today in the Annals of Internal Medicine.
Using two large insurance claims databases, researchers from the University of North Carolina at Chapel Hill compared the outcomes for diverticulitis patients treated with the two most commonly prescribed antibiotic regimens for diverticulitis—metronidazole combined with a fluoroquinolone or amoxicillin-clavulanate alone—and found no differences in the 1-year risk of hospital admission or urgent surgery, or the long-term risk of elective surgery. Furthermore, older patients treated with metronidazole-with-fluoroquinolone had an increased risk of Clostridioides difficile infection (CDI).
The study authors say this is the first study to compare the two most common antibiotic treatments for acute diverticulitis, a common inflammatory condition of the colon that is typically treated in outpatient settings.
The findings are noteworthy because the US Food and Drug Administration (FDA) has warned that fluoroquinolones can increase the risk of serious adverse effects in some patients, and should be limited to certain conditions with no alternative treatment options.
Comparative effectiveness of 2 treatments
The active-comparator, retrospective cohort study included nearly 140,000 US adults who received outpatient antibiotics for diverticulitis over a 19-year period (2000 through 2018).
One cohort comprised adults ages 18 to 64 in the IBM MarketScan Commercial Claims and Encounters database; the other was a 20% random sample of adults age 65 and over from the Medicare claims database. All patients were identified at their first diagnosis of diverticulitis, and had a prescription for either metronidazole with oral ciprofloxacin or levofloxacin or oral amoxicillin-clavulanate.
Outcome follow-up on these patients began at 14 days after diagnosis, and the outcomes included 1-year risk for inpatient admission, 1-year risk for urgent surgery, CDI in the year after diagnosis, and the risk for elective surgery within 3 years.
In both cohorts, metronidazole-with-fluoroquinolone therapy was seven to eight times as common as amoxicillin-clavulanate therapy. In the MarketScan cohort, researchers identified 106,361 (89%) metronidazole-plus-fluoroquinolone users and 13,160 (11%) amoxicillin-clavulanate users. In the Medicare cohort, 17,639 (86.7%) patients were treated with metronidazole-plus-fluoroquinolone, compared with 2,709 (13.3%) treated with amoxicillin-clavulanate.
Risk analysis, controlled for different confounding factors, found no difference in outcomes in either cohort. In the MarketScan cohort, there were no differences in the diverticulitis-specific 1-year admission risk (risk difference, 0.1 percentage points; 95% confidence interval [CI], -0.3 to 0.6), 1-year urgent surgery risk (risk difference, 0.0; 95% CI, -0.1 to 0.1), 3-year elective surgery risk (risk difference, 0.2; 95% CI, -0.3 to 0.7), or CDI risk (risk difference, 0.0; 95% CI, -0.1 to 0.1).
Similarly, no differences were observed in the Medicare cohort for 1-year admission risk (risk difference, 0.1; 95% CI, -0.7 to 0.9), 1-year urgent surgery risk (risk difference -0.2; 95% CI, -0.6 to 0.1), or 3-year elective surgery risk (risk difference, -0.3; 95% CI, -1.1 to 0.4). The 1-year risk for CDI, however, was significantly higher for patients treated with metronidazole-with-fluoroquinolone in this group (risk difference, 0.6; 95%, 0.2 to 1.0), a finding the study's authors suggest may be due to the overall high risk of CDI in older adults.
"There was no difference in risk for CDI in the MarketScan population, likely because the risk in this younger population was one quarter the risk in the Medicare cohort, placing a low ceiling on a potential measured effect," they wrote.
Since 2008, the FDA has issues several updates to its black box warning label for fluoroquinolones, which cover a broad spectrum of gram-negative and gram-positive bacteria and are used to treat a variety of common bacterial infections.
In 2016, the FDA's revised black box warning advised that fluoroquinolone use was associated with disabling and potentially permanent side effects involving tendons, muscles, joints, nerves, and the central nervous system, and said that patients who have acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, and uncomplicated urinary tract infections should use fluoroquinolones only if no other options are available.
Other risks associated with fluoroquinolone use include hypoglycemia, peripheral neuropathy, aortic dissection, mental health adverse effects, tendinitis, and tendon rupture.
The authors say a fluoroquinolone-sparing approach to outpatient diverticulitis could help avoid such harms.
"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.