Torsades de Pointes Following Clarithromycin Treatment
Torsades de Pointes Following Clarithromycin Treatment
A 75-year-old woman presenting with pre-syncope, shortness of breath and nausea was admitted to the emergency department following treatment with clarithromycin. Shortly after admission she developed a prolonged QT interval leading to torsades de pointes (TdP) and cardiac arrest. She was successfully cardioverted and clarithromycin was discontinued resulting in restoration of her usual QT interval. This case is an example of acquired long QT syndrome; a disorder that can be precipitated by macrolide antibiotics such as clarithromycin. Additional risk factors present in this case include: female gender, old age, heart disease, hypokalemia and hypomagnesemia. In this manuscript we comprehensively review past cases of clarithromycin-induced long QT syndrome (LQTS) and discuss them within the context of this case.
Acquired long QT syndrome (LQTS) is a disorder of cardiac repolarization characterized by prolongation of the QT interval. It typically occurs in the setting of metabolic disturbances such as hypokalemia and hypomagnesemia, as well as during the use of specific drugs that delay cardiac repolarization. Common causes of drug-induced long QT include antiarrhythmics, promotility medications, antimicrobials and antipsychotics. Additional risk factors for the development of long QT include old age, female gender, genetic predisposition and heart disease. Sufficient prolongation of the QT interval increases the risk of developing torsades de pointes (TdP) and sudden cardiac death.
Clarithromycin, a commonly prescribed macrolide antibiotic, has been identified as an antimicrobial with the potential to prolong the QT interval. This is not surprising, as structurally similar macrolides have also been shown to cause QT interval prolongation. The mechanism by which clarithromycin induces QT prolongation is thought to be through the inhibition of the rapidly activating delayed rectifier potassium current (IKr) in cardiac myocytes. This current plays an important role in cardiac repolarization and its inhibition manifests as an increase in the duration of the QT interval. With increasingly delayed repolarization, cardiac myocytes begin to exhibit early afterdepolarizations; proarrhythmic cellular events that may potentially causing TdP.
Exacerbated transmural heterogeneity of repolarization with IKr blockade may also contribute to a substrate for re-entrant arrhythmia. The high frequency with which macrolide antibiotics are prescribed calls for continued characterization of the risks of QT interval prolongation and TdP with clarithromycin therapy.
In the following report, we describe a new case of clarithromycin-induced long QT interval leading to TdP. We also conducted a systematic review of the literature and discuss it within the context of this case.
Abstract and Introduction
Abstract
A 75-year-old woman presenting with pre-syncope, shortness of breath and nausea was admitted to the emergency department following treatment with clarithromycin. Shortly after admission she developed a prolonged QT interval leading to torsades de pointes (TdP) and cardiac arrest. She was successfully cardioverted and clarithromycin was discontinued resulting in restoration of her usual QT interval. This case is an example of acquired long QT syndrome; a disorder that can be precipitated by macrolide antibiotics such as clarithromycin. Additional risk factors present in this case include: female gender, old age, heart disease, hypokalemia and hypomagnesemia. In this manuscript we comprehensively review past cases of clarithromycin-induced long QT syndrome (LQTS) and discuss them within the context of this case.
Introduction
Acquired long QT syndrome (LQTS) is a disorder of cardiac repolarization characterized by prolongation of the QT interval. It typically occurs in the setting of metabolic disturbances such as hypokalemia and hypomagnesemia, as well as during the use of specific drugs that delay cardiac repolarization. Common causes of drug-induced long QT include antiarrhythmics, promotility medications, antimicrobials and antipsychotics. Additional risk factors for the development of long QT include old age, female gender, genetic predisposition and heart disease. Sufficient prolongation of the QT interval increases the risk of developing torsades de pointes (TdP) and sudden cardiac death.
Clarithromycin, a commonly prescribed macrolide antibiotic, has been identified as an antimicrobial with the potential to prolong the QT interval. This is not surprising, as structurally similar macrolides have also been shown to cause QT interval prolongation. The mechanism by which clarithromycin induces QT prolongation is thought to be through the inhibition of the rapidly activating delayed rectifier potassium current (IKr) in cardiac myocytes. This current plays an important role in cardiac repolarization and its inhibition manifests as an increase in the duration of the QT interval. With increasingly delayed repolarization, cardiac myocytes begin to exhibit early afterdepolarizations; proarrhythmic cellular events that may potentially causing TdP.
Exacerbated transmural heterogeneity of repolarization with IKr blockade may also contribute to a substrate for re-entrant arrhythmia. The high frequency with which macrolide antibiotics are prescribed calls for continued characterization of the risks of QT interval prolongation and TdP with clarithromycin therapy.
In the following report, we describe a new case of clarithromycin-induced long QT interval leading to TdP. We also conducted a systematic review of the literature and discuss it within the context of this case.