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Fluoroquinolones were associated with a modest uptick in sudden cardiac death (SCD) among people getting hemodialysis, though the benefits of these antibiotics may still outweigh their risks in this group, according to a study.

SCD rates within 5 days of outpatient initiation of antibiotic therapy were 105.7 per 100,000 people prescribed levofloxacin or moxifloxacin, compared with 40.0 per 100,000 people prescribed amoxicillin (HR 1.95, 95% CI 1.57-2.41).

The number needed to harm, estimated from nearly 265,000 Medicare beneficiaries receiving in-center maintenance hemodialysis, suggested that one additional SCD would occur for every 2,273 respiratory fluoroquinolone treatment episodes in patients with kidney failure.

Results were consistent when follow-up was extended to 7, 10, and 14 days, reported Jennifer Flythe, MD, MPH, of UNC School of Medicine in Chapel Hill, and colleagues in .

Thus, the study finds the link between fluoroquinolone use with cardiac complications in the general population to be present in a cohort at even higher risk -- kidney patients on hemodialysis are at particularly high risk of SCD and may be particularly susceptible to the QT interval-prolonging effects of respiratory fluoroquinolones, the authors noted.

The fear is that fluoroquinolone use may ultimately result in the life-threatening ventricular tachyarrhythmia torsade de pointes (TdP) in this population. Moreover, users of these antibiotics have been warned of serious musculoskeletal complications, nerve damage, and other serious side effects beyond cardiac risk.

"Our data suggest that curtailing respiratory fluoroquinolone prescribing may be one actionable strategy to mitigate SCD risk in the hemodialysis population. However, the associated absolute risk reduction would be relatively small," Flythe and colleagues said.

"Given that pathogen-directed treatment of respiratory infections is paramount, the risks associated with undertreatment of an infection with an amoxicillin-based antibiotic likely far outweigh the potential cardiac risks from treatment with a respiratory fluoroquinolone. Respiratory fluoroquinolones should still be prescribed to patients receiving hemodialysis when an amoxicillin-based antibiotic would be suboptimal," they urged.

Flythe and colleagues noted that nearly one in five of people getting respiratory fluoroquinolones in the study were using concomitant medications with known TdP risk.

As such, they emphasized "the importance of performing a thorough medication review and considering pharmacodynamic drug interactions before prescribing new drug therapies for any condition."

ECG monitoring before and during antibiotic therapy may also be considered for high-risk patients, the group added.

The retrospective cohort study relied on administrative data from the , a national kidney failure registry.

Included were 264,968 individuals (51.0% men; mean age 61) with Medicare Part D prescription claims for outpatient antibiotic fills in 2007-2016. Each person had a median two treatment episodes during the study period.

Fluoroquinolones accounted for 40.2% of the treatment episodes of interest, and amoxicillin the remaining 59.8%.

Compared with the amoxicillin group, people who got fluoroquinolones tended to be older with a greater prevalence of heart failure and other cardiovascular comorbidities. After inverse probability of treatment weighting, the two groups shared similar baseline characteristics.

Nonetheless, the observational study could still be affected by bias and residual confounding, Flythe's group acknowledged.

Case in point: the finding of increased all-cause mortality with fluoroquinolones versus amoxicillin antibiotic treatment. "Despite accounting for numerous clinical and health care use metrics to minimize confounding from difficult-to-measure factors, it is possible that indication bias may remain, and our results should be interpreted within the context of these limitations," they cautioned.

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