Antimicrobial-Associated QT Interval Prolongation: Pointes of Interest

Until recently, cardiac toxicity manifesting in the form of arrhythmias related to QT interval prolongation was uncommonly appreciated within the antimicrobial class of drugs, but it was well described among antiarrhythmic agents. Antimicrobials that are associated with QT prolongation include the macrolides/ketolides, certain fluoroquinolones and antimalarials, pen-tamidine, and the azole antifungals. Although, in most cases, mild delays in ventricular repolarization caused by these drugs are clinically unnoticable, they may serve to amplify the risk for torsades de pointes (TdP) when prescribed in the setting of other risk factors. Conditions or variables that influence proarrhythmic risk include sex, age, electrolyte derangements, structural heart disease, pharmacokinetic/pharmacodynamic interactions, and genetic predisposition. It is important that clinicians be knowledgable about drugs with QT liability, as well as the risk factors that increase the probability of TdP. Additionally, because TdP remains a difficult-to-measure adverse event, we must rely upon multiple data sources to determine the risk versus the benefit for newly approved drugs. Cardiac toxicity can occur as an unintended consequence of drug therapy and is considered to be an increasingly important, but rare, medication-related adverse event. In the United States alone, between 300,000 and 400,000 people die annually of sudden cardiac death [1]. Torsades de pointes (TdP), a poten