Antibiotic linked to serious adverse events in older patients with CKD

A study published in JAMA Open Network showed an increased risk of adverse event (AE)-related hospitalization among older patients with chronic kidney disease (CKD) receiving fluoroquinolone at higher than recommended doses.¹

Fluoroquinolone is the most prescribed broad-spectrum antibiotic, even though the FDA has severe black box warnings about its risks. Fluoroquinolones (ciprofloxacin, levofloxacin, or norfloxacin) are typically eliminated by the kidneys, but patients with reduced kidney function excrete the antibiotic at a lower rate.

Population-based studies and meta-analyses already show an association between fluoroquinolone and rare but serious AEs. These AEs include nervous system disorders, psychiatric disorders, hypoglycemia, and collagen-associated AEs.

Researchers analyzed these AEs and whether they were associated with a higher vs lower dose of fluoroquinolone in older patients with advanced CKD. Primary endpoints included hospitalization due to AEs during the first 14 days of taking medication. Secondary outcomes included hospital visits due to sepsis, retinal detachment, all-cause hospitalization, all-cause mortality, or sudden cardiac death.

From January 2008 to March 2020, researchers conducted a new user, population-based cohort study in Ontario, Canada, analyzing 11,917 CKD patients taken from 8 health care databases. Participants were 66 years of age and older, most of whom with an estimated glomerular filtration rate [eGFR] of less than 30 mL/min/1.73 m2.

Researchers gave participants either a single higher dose of oral fluoroquinolone—which includes ciprofloxacin (501 to 1000 mg/d), levofloxacin (501 to 750 mg/d) or norfloxacin (401 to 800 mg/d)—or a low-dose prescription of ciprofloxacin (500 mg/d), levofloxacin (250 to 500 mg/d), or norfloxacin (400 mg/d). The thresholds were determined by current patient guidelines for patients with advanced CKD.

In 2021, the team found that the higher fluoroquinolone dose associated with a higher risk of severe AEs, supporting the primary outcome. Neither the high- nor low-dose groups were associated with any secondary outcomes. Researchers also discovered that 46% of patients with advanced CKD were being prescribed higher than recommended doses.

In the study, participants taking the larger dose of fluoroquinolone also had a significantly higher risk of hospitalization for altered mental status, which was the most common AE.

The study authors further conducted 4 post hoc sensitivity analyses, showing a consistent survival analysis, low confidence of primary outcomes, insignificant risk of heart failure on the antibiotic, and overall consistent results.

In the study, there was only 1 hospitalization for every 256 patients. In total, only 1.2% of high-dose users were hospitalized for AEs.

The authors identified some limitations to the study, specifically being that it is the first of its kind to evaluate this association. Other factors such as age and disease limit the results of this drug, and researchers used multiple types of fluoroquinolones, generalizing the entire antibiotic.

The findings suggest that fluoroquinolones should be prescribed at lower doses to adults with advanced CKD due to their high-risk AEs, the authors concluded.

Reference

1. Muanda, Flory, Sood, Manish, Weir, Matthew, et al. Association of Higher-Dose Fluoroquinolone Therapy With Serious Adverse Events in Older Adults With Advanced Chronic Kidney Disease. JAMA Netw Open. 2022;5(8):e2224892. doi:10.1001/jamanetworkopen.2022.24892.