Hospital Pharmacy Services, Mayo Clinic, Rochester, MN, USA.
Antimicrob Agents Chemother. 2013 Mar;57(3):1121-7. doi: 10.1128/AAC.00958-12. Epub 2012 Dec 10.
QTc prolongation is a risk factor for development of torsades de pointes (TdP). Combination therapy with fluoroquinolones and azoles is used in patients with hematologic malignancies for prophylaxis and treatment of infection. Both drug classes are implicated as risk factors for QTc prolongation. The cumulative effect on and incidence of QTc prolongation for this combination have not been previously described. A retrospective chart review was performed with hospitalized inpatients from 1 September 2008 to 31 January 2010 comparing QTc interval data from electrocardiogram (ECG) assessment at baseline and after the initiation of combination therapy. Ninety-four patients were eligible for inclusion. The majority, 88 patients (93.6%), received quinolone therapy with levofloxacin. Fifty-three patients (56.4%) received voriconazole; 40 (42.6%) received fluconazole. The overall mean QTc change from baseline was 6.1 (95% confidence interval [CI], 0.2 to 11.9) ms. Twenty-one (22.3%) of the studied patients had clinically significant changes in the QTc while receiving combination fluoroquinolone-azole therapy. Statistically significant risk factors for clinically significant changes in QTc were hypokalemia (P = 0.03) and a left-ventricular ejection fraction of <55% (P = 0.02). Low magnesium (P = 0.11), exposure to 2 or more drugs with the potential to prolong the QTc interval (P = 0.17), and female sex (P = 0.21) trended toward significance. Combination therapy with fluoroquinolone and azole antifungals is associated with increased QTc from baseline in hospitalized patients with hematologic malignancies. One in five patients had a clinically significant change in the QTc, warranting close monitoring and risk factor modification to prevent the possibility of further QTc prolongation and risk of TdP.
QTc 延长是尖端扭转型室性心动过速（TdP）发展的一个危险因素。氟喹诺酮类和唑类药物联合治疗用于血液恶性肿瘤患者以预防和治疗感染。这两类药物都被认为是 QTc 延长的危险因素。这种联合用药对 QTc 延长的累积效应和发生率以前没有描述过。对 2008 年 9 月 1 日至 2010 年 1 月 31 日住院患者进行了回顾性图表审查，比较了基线时和联合治疗开始后心电图（ECG）评估的 QTc 间期数据。94 名患者符合纳入标准。大多数患者（88 名患者，93.6%）接受了左氧氟沙星治疗的喹诺酮类药物治疗。53 名患者（56.4%）接受了伏立康唑治疗；40 名患者（42.6%）接受了氟康唑治疗。从基线开始，整体平均 QTc 变化为 6.1（95%置信区间[CI]，0.2 至 11.9）ms。在接受氟喹诺酮类-唑类联合治疗的研究患者中，有 21 名（22.3%）患者的 QTc 发生了临床显著变化。低钾血症（P = 0.03）和左心室射血分数<55%（P = 0.02）是 QTc 发生临床显著变化的统计学显著危险因素。低镁血症（P = 0.11）、暴露于 2 种或更多有潜在延长 QTc 间期的药物（P = 0.17）以及女性（P = 0.21）呈趋势有统计学意义。氟喹诺酮类和唑类抗真菌药物联合治疗与血液恶性肿瘤住院患者的基线 QTc 延长有关。五分之一的患者 QTc 发生了临床显著变化，需要密切监测和调整危险因素，以防止进一步的 QTc 延长和 TdP 风险。
