Importance Respiratory fluoroquinolone antibiotics are some of the most common medications with QT interval–prolonging potential prescribed to patients with hemodialysis-dependent kidney failure—individuals who have a very high risk of sudden cardiac death (SCD). To date, there have been no large-scale, population-specific studies evaluating the cardiac safety of respiratory fluoroquinolones in the hemodialysis population.

Objective To investigate the cardiac safety of respiratory fluoroquinolones among individuals with hemodialysis-dependent kidney failure.

Design, Setting, and Participants A retrospective cohort study examining safety using an active comparator new-user design was conducted using administrative claims data from a US-wide kidney failure registry from January 1, 2007, to December 31, 2016, including 264 968 Medicare beneficiaries receiving in-center maintenance hemodialysis. Data analysis was performed from January 4 to August 16, 2021.

Exposures Respiratory fluoroquinolone (levofloxacin or moxifloxacin) vs amoxicillin-based (amoxicillin or amoxicillin with clavulanic acid) antibiotic treatment.

Main Outcomes and Measures Sudden cardiac death within 5 days of outpatient initiation of a study antibiotic. Inverse probability of treatment-weighted survival models to estimate hazard ratios (HRs), risk differences (RDs), and corresponding 95% CIs. Death due to a cause other than SCD was treated as a competing event. Fracture was considered as a negative control outcome.

Results The study cohort included 264 968 unique in-center hemodialysis patients and 626 322 study antibiotic treatment episodes: 251 726 respiratory fluoroquinolone treatment episodes (40.2%) and 374 596 amoxicillin-based treatment episodes (59.8%). Of the 264 968 patients, 135 236 (51.0%) were men, and the mean (SD) age was 61 (15) years. Respiratory fluoroquinolone vs amoxicillin-based antibiotic treatment was associated with a higher relative and absolute 5-day risk of SCD (weighted HR, 1.95; 95% CI, 1.57-2.41; and weighted RD per 100 000 treatment episodes, 44.0; 95% CI, 31.0-59.2). Respiratory fluoroquinolone vs amoxicillin-based antibiotic treatment was not associated with the 5-day risk of fracture.

Conclusions and Relevance In this study, compared with amoxicillin-based antibiotic treatment, respiratory fluoroquinolone treatment was associated with a higher short-term risk of SCD among patients with hemodialysis-dependent kidney failure. This finding suggests that decisions between the use of respiratory fluoroquinolones and amoxicillin-based antibiotics should be individualized, with prescribers considering both the clinical benefits and potential cardiac risks.

重要性 呼吸系统氟喹诺酮类抗生素是一些最常见的具有 QT 间期的药物——延长血液透析依赖性肾衰竭患者的潜力——这些患者发生心源性猝死 (SCD) 的风险非常高。迄今为止，尚无大规模、针对人群的研究评估呼吸氟喹诺酮类药物在血液透析人群中的心脏安全性。

目的 探讨呼吸性氟喹诺酮类药物在血液透析依赖性肾功能衰竭患者中的​​心脏安全性。

设计、设置和参与者 一项回顾性队列研究使用主动比较新用户设计检查安全性，该研究使用来自美国范围内的肾衰竭登记处 2007 年 1 月 1 日至 2016 年 12 月 31 日的行政索赔数据，包括 264 968 名医疗保险接受中心内维持性血液透析的受益人。数据分析于 2021 年 1 月 4 日至 8 月 16 日进行。

暴露 呼吸氟喹诺酮（左氧氟沙星或莫西沙星）与基于阿莫西林（阿莫西林或阿莫西林与克拉维酸）抗生素治疗。

主要结果和措施 门诊患者开始研究抗生素后 5 天内心源性猝死。用于估计风险比 (HR)、风险差异 (RD) 和相应 95% CI 的治疗加权生存模型的逆概率。由于 SCD 以外的原因导致的死亡被视为竞争事件。骨折被认为是阴性对照结果。

结果 研究队列包括 264 968 名独特的中心血液透析患者和 626 322 次研究抗生素治疗事件：251 726 次呼吸氟喹诺酮治疗事件（40.2%）和 374 596 次基于阿莫西林的治疗事件（59.8%）。在 264 968 名患者中，135 236 名 (51.0%) 为男性，平均 (SD) 年龄为 61 (15) 岁。呼吸性氟喹诺酮类药物与基于阿莫西林的抗生素治疗与更高的 5 天 SCD 相对和绝对风险相关（加权 HR，1.95；95% CI，1.57-2.41；每 100 000 次治疗发作的加权 RD，44.0；95% CI , 31.0-59.2)。呼吸性氟喹诺酮与基于阿莫西林的抗生素治疗与 5 天骨折风险无关。

结论和相关性 在本研究中，与以阿莫西林为基础的抗生素治疗相比，呼吸性氟喹诺酮治疗与血液透析依赖型肾衰竭患者的 SCD 短期风险较高相关。这一发现表明，在使用呼吸性氟喹诺酮类药物和以阿莫西林为基础的抗生素之间的决定应因人而异，处方者应同时考虑临床益处和潜在的心脏风险。