Fluoroquinolone-related adverse events resulting in health service use and costs: A systematic review

Background and objectives
Adverse events (AEs) associated with the use of fluoroquinolone antimicrobials include Clostridium difficile associated diarrhea (CDAD), liver injury and seizures. Yet, the economic impact of these AEs is seldom acknowledged. The aim of this review was to identify health service use and subsequent costs associated with ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin and ofloxacin -related AEs.
Methods
A literature search covering Medline, SCOPUS, Cinahl, Web of Science and Cochrane Library was performed in April 2017. Two independent reviewers systematically extracted the data and assessed the quality of the included studies. All costs were converted to 2016 euro in order to improve comparability.
Results
Of the 5,687 references found in the literature search, 19 observational studies, of which five were case-controlled, fulfilled the inclusion criteria. Hospitalization was an AE-related health service use outcome in 17 studies. Length of hospital stay associated with AEs varied between <5 and 45 days. The estimated cost of an AE episode ranged between 140 and 18,252 €. CDAD was associated with the longest stays in hospital. Ten studies reported AE-related length of stays and five evaluated costs associated with AEs. Due to the lack of published literature, health service use and costs associated with many high-risk FQ-related AEs could not be evaluated.
Conclusions
Because of the wide clinical use of fluoroquinolones, in particular serious fluoroquinolone-related AEs can have substantial economic implications, in addition to imposing potentially devastating health complications for patients. Further measures are required to prevent and reduce health service use and costs associated with fluoroquinolone-related AEs. Equally, better-quality reporting and additional published data on health service use and costs associated with AEs are needed.

背景与研究目的
与氟喹诺酮类抗菌药物（fluoroquinolone antimicrobials）使用相关的不良事件（Adverse Events，AEs）包括艰难梭菌相关性腹泻（Clostridium difficile Associated Diarrhea，CDAD）、肝损伤及癫痫发作。然而，此类不良事件所带来的经济影响尚未得到足够重视。本综述旨在明确与环丙沙星（ciprofloxacin）、左氧氟沙星（levofloxacin）、莫西沙星（moxifloxacin）、诺氟沙星（norfloxacin）及氧氟沙星（ofloxacin）相关的不良事件所对应的医疗服务使用情况及后续成本。

研究方法
本研究于2017年4月针对Medline、SCOPUS、Cinahl、Web of Science及Cochrane Library数据库开展系统性文献检索。由两名独立评审员系统提取研究数据，并对纳入研究的方法学质量进行评估。为提升不同研究间的可比性，所有成本均统一转换为2016年欧元计价。

研究结果
本次文献检索共获取5687条参考文献，其中19项观察性研究（含5项病例对照研究）符合纳入标准。17项研究将住院作为不良事件相关医疗服务使用的核心结局指标。与不良事件相关的住院时长介于不足5天至45天的区间内。单起不良事件对应的估算成本介于140欧元至18252欧元之间。其中，艰难梭菌相关性腹泻对应的住院时长最长。10项研究报告了不良事件相关住院时长，5项研究评估了不良事件相关医疗成本。由于可获取的公开文献较为有限，诸多高危氟喹诺酮类相关不良事件对应的医疗服务使用情况及成本尚未能得到有效评估。

研究结论
鉴于氟喹诺酮类药物在临床中应用广泛，其相关严重不良事件不仅会给患者带来潜在致命性健康并发症，还可造成显著的经济负担。亟需采取进一步措施以预防、减少氟喹诺酮类相关不良事件带来的医疗服务使用及相关成本。同时，还需提升此类研究的报告质量，并补充关于不良事件相关医疗服务使用与成本的公开数据。