ICES Western, Victoria Hospital, London, Ontario, Canada.
Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.
JAMA Netw Open. 2022 Aug 1;5(8):e2224892. doi: 10.1001/jamanetworkopen.2022.24892.
Population-based data are needed to inform the safe prescribing of fluoroquinolone antibiotics to patients with advanced chronic kidney disease (CKD).
To quantify the 14-day risk of a hospital visit with nervous system and/or psychiatric disorders, hypoglycemia, or a collagen-associated event in patients with advanced CKD newly prescribed a fluoroquinolone at a higher vs a lower dose.
DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study in Ontario, Canada (January 1, 2008, to March 17, 2020) used linked health care data to identify new users of fluoroquinolone antibiotics. Participants included adults 66 years or older with advanced CKD (an estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2 but not receiving dialysis). Data analysis was performed from January 1 to April 30, 2021.
A new prescription for a higher-dose fluoroquinolone (ciprofloxacin, 501-1000 mg/d; levofloxacin, 501-750 mg/d; or norfloxacin, 401-800 mg/d) vs a lower-dose fluoroquinolone (ciprofloxacin, 500 mg/d; levofloxacin, 250-500 mg/d; or norfloxacin, 400 mg/d).
The primary outcome was the 14-day risk of a hospital visit with nervous system and/or psychiatric disorders, hypoglycemia, or a collagen-associated event. Secondary outcomes included a hospital visit with sepsis, retinal detachment or other tendinopathies, all-cause hospitalization, all-cause mortality, and sudden cardiac death. Inverse probability of treatment weighting on the propensity score was used to balance comparison groups on baseline health. Weighted risk ratios and risk differences were obtained using modified Poisson regression and binomial regression, respectively.
Of 11 917 patients (median age, 83 years [IQR, 77-89 years]; 7438 women [62.4%]; median eGFR, 25 [IQR, 21-28] mL/min/1.73 m2) included in the analysis, 5482 (46.0%) received a higher-dose and 6435 (54.0%) received a lower-dose fluoroquinolone. After weighting, the primary composite outcome-a hospital visit with nervous system and/or psychiatric disorders, hypoglycemia, or a collagen-associated event-occurred in 68 of 5482 patients (1.2%) treated with a higher-dose fluoroquinolone and in 47 of 5516 (0.9%) treated with a lower-dose fluoroquinolone (weighted risk ratio, 1.45 [95% CI, 1.01-2.08]; weighted risk difference, 0.39% [95% CI, 0.01%-0.76%]). The risk of sepsis, retinal detachment, all-cause hospitalization, all-cause mortality, and sudden cardiac death did not differ significantly between groups.
These findings suggest that older patients with advanced CKD who were prescribed a fluoroquinolone at a higher-than-recommended dose were significantly more likely to experience the composite outcome of a hospital visit with nervous system and/or psychiatric disorders, hypoglycemia, or a collagen-associated event, although the absolute risk of these events was less than 2%.
需要基于人群的数据来为患有晚期慢性肾脏病（CKD）的患者安全开氟喹诺酮类抗生素提供信息。
定量评估新处方较高剂量与较低剂量氟喹诺酮类抗生素的晚期 CKD 患者在 14 天内出现神经系统和/或精神障碍、低血糖或胶原相关事件的医院就诊风险。
设计、地点和参与者：这项在加拿大安大略省进行的基于人群的队列研究（2008 年 1 月 1 日至 2020 年 3 月 17 日）使用了链接的医疗保健数据来识别氟喹诺酮类抗生素的新使用者。参与者包括年龄在 66 岁或以上、患有晚期 CKD（估计肾小球滤过率[eGFR]＜30 mL/min/1.73 m2 但未接受透析）的成年人。数据分析于 2021 年 1 月 1 日至 4 月 30 日进行。
新处方较高剂量氟喹诺酮类药物（环丙沙星，501-1000 mg/d；左氧氟沙星，501-750 mg/d；或诺氟沙星，401-800 mg/d）与较低剂量氟喹诺酮类药物（环丙沙星，500 mg/d；左氧氟沙星，250-500 mg/d；或诺氟沙星，400 mg/d）。
主要结果是在 14 天内因神经系统和/或精神障碍、低血糖或胶原相关事件而住院的风险。次要结果包括因败血症、视网膜脱离或其他腱病、全因住院、全因死亡率和心脏性猝死而住院。使用倾向评分的逆概率治疗加权来平衡基线健康状况的比较组。使用校正泊松回归和二项式回归分别获得加权风险比和风险差异。
在纳入分析的 11917 名患者中（中位年龄，83 岁[四分位距，77-89 岁]；7438 名女性[62.4%]；中位 eGFR，25[四分位距，21-28]mL/min/1.73 m2），5482 名（46.0%）接受了较高剂量，6435 名（54.0%）接受了较低剂量氟喹诺酮类药物。在加权后，主要复合结局（因神经系统和/或精神障碍、低血糖或胶原相关事件而住院）在 5482 名接受较高剂量氟喹诺酮类药物治疗的患者中发生了 68 例（1.2%），在 5516 名接受较低剂量氟喹诺酮类药物治疗的患者中发生了 47 例（0.9%）（加权风险比，1.45[95%CI，1.01-2.08]；加权风险差异，0.39%[95%CI，0.01%-0.76%]）。两组之间败血症、视网膜脱离、全因住院、全因死亡率和心脏性猝死的风险无显著差异。
这些发现表明，接受推荐剂量以上氟喹诺酮类药物治疗的晚期 CKD 老年患者出现神经系统和/或精神障碍、低血糖或胶原相关事件的复合结局的可能性显著增加，尽管这些事件的绝对风险小于 2%。
