QT Prolongation and Torsade de Pointes Induced by Fluoroquinolones: Infrequent Side Effects from Commonly Used Medications

Abstract

Although very useful agents, fluoroquinolones are associated with a number of adverse events, some with considerable clinical significance. Prolongation of the QT interval, for example, is an adverse effect associated with the use of fluoroquinolones. Fluoroquinolones prolong the QT interval by blocking voltage-gated potassium channels, especially the rapid component of the delayed rectifier potassium current I_Kr, expressed by HERG (the human ether-a-go-go-related gene). According to the available case reports and clinical studies, moxifloxacin carries the greatest risk of QT prolongation from all available quinolones in clinical practice and it should be used with caution in patients with predisposing factors for Torsades de pointes (TdP). Although gemifloxacin, levofloxacin, and ofloxacin are associated with a lower risk of QT prolongation compared with moxifloxacin, they should also be used with caution in patients at risk for QT prolongation. Ciprofloxacin appears to be associated with the lowest risk for QT prolongation and the lowest TdP rate. The overall risk of TdP is small with the use of fluoroquinolones. Clinicians can minimize that risk by avoiding prescriptions of multiple medications associated with QT-interval prolongation, especially in high-risk patients.

Antibiotic Utilization for Acute Respiratory Tract Infections in U.S. Emergency Departments

“…In addition, antibiotic use and the risk of Clostridium difficile infection have become important concerns (5,6). Quinolone antibiotics in particular have been shown to cause significant collateral damage and toxicity (i.e., QT prolongation [prolongation of time between the start of the Q wave and the end of the T wave in the heart's electrical cycle], drug interactions, and blood glucose fluctuation) (28,29). For these reasons, it is important that actions are taken to reduce inappropriate use in the ED and prevent unnecessary morbidity resulting from exposure to antibiotics.…”

The Use of Systemic and Topical Fluoroquinolones

“…Ciprofloxacin appears to confer the lowest risk. 33 No cases of cardiotoxicity or torsades de pointes in children associated with fluoroquinolones have been reported to date. 34 …”

How can we ensure effective antibiotic dosing in critically ill patients receiving different types of renal replacement therapy?

“…For ciprofloxacin, 0.4-0.8 g/day sufficiently achieved the desired PK/PD target for pathogens with a MIC ≤0.5 mg/L) (Malone et al, 2001b;Spooner et al, 2011). Frequent clinical (electrocardiogram (ECG) monitoring) or therapeutic drug monitoring should be considered where possible to minimize the advent of any unwanted adverse events such as prolongation of QT interval (Ball, 2003;Briasoulis et al, 2011) that could be caused by high quinolone concentrations.…”