International Journal of Cardiology 113 (2006) 239 – 241 www.elsevier.com/locate/ijcard
Letter to the Editor
Ciprofloxacin-induced torsade de pointes M. Casey Flanagan, Eric S. Mitchell, Mark C.P. Haigney * Departments of Internal Medicine and Cardiology, National Naval Medical Center, Bethesda, MD, and Division of Cardiology, Uniformed Services University of the Health Sciences, A3060, USUHS, 4301 Jones Bridge Road, Bethesda, MD 20814, USA Received 12 August 2005; accepted 20 August 2005 Available online 28 December 2005
Abstract We report a rare case of torsade de pointes, a polymorphic ventricular tachycardia associated with QT interval prolongation, caused by intravenous ciprofloxacin given for pneumonia in a 22-year-old healthy Marine. Although the risk for quinolone-associated torsade de pointes appears to be low, caution is still warranted when given in the presence of pre-existing QT prolongation. Published by Elsevier Ireland Ltd. Keywords: Ciprofloxacin; Torsade de pointes; QT interval
1. Case A 22-year-old active duty Marine without significant past medical history was admitted for multilobar, communityacquired pneumonia and severe respiratory distress. An ECG showed normal sinus rhythm at 91 bpm, inverted T waves in leads II, III, aVf, V3 –V5, and a mildly prolonged QT interval (QT/QTc of 374/460 ms; Fig. 1). His serum magnesium was 1.9 mg/dL and serum potassium was 4.3 mmol/L. The patient was started on intravenous doxycycline, ciprofloxacin, and piperacillin/tazobactam, and endotracheally intubated. The night of the second hospital day the patient manifested significant ventricular ectopy. An ECG on hospital day #3 showed a lengthening of the QT interval (QT/QTc: 640/695) from baseline (Fig. 2). At this time the ciprofloxacin was discontinued because of concerns regarding drug-induced QT prolongation. Ten hours following the last dose of ciprofloxacin the patient had an episode of torsade de pointes (Tdp; Fig. 3) that responded to defibrillation. The patient’s electrolytes were checked and found to be in the normal range (K: 4.0, Mg: 2.5). Nonetheless, the patient was started on a magnesium drip
* Corresponding author. Tel.: +1 301 295 3826; fax: +1 301 295 3557. E-mail address:
[email protected] (M.C.P. Haigney). 0167-5273/$ - see front matter. Published by Elsevier Ireland Ltd. doi:10.1016/j.ijcard.2005.08.048
to prevent recurrent Tdp. Four hours after the first arrhythmia, the patient had a second episode of Tdp, and again responded to defibrillation. He manifested progressive shortening of the QT over the next 5 days, but continued to have deeply inverted T waves in the anterior leads. An MRI of the brain ruled out intracranial pathology. He completed a total antibiotic course of 14 days with ceftriaxone, vancomycin, and doxycyline. A focused history revealed that the patient did admit to experiencing several nearsyncopal episodes, usually during exertion, consistent with an underlying arrhythmic propensity. On hospital day 20 a dual chamber ICD was placed for prevention of future events due to an apparently congenital prolongation of his QT interval. Tdp is a polymorphic form of ventricular tachycardia recognized by a ‘‘twisting’’ of the QRS axis around an isoelectric point [1]. The characteristic oscillation of the axis is preceded by an elongation of the QT interval, the electrocardiographic interval that represents ventricular repolarization. The interval is considered prolonged if it is greater than 450 ms in men or 460 ms in women [1]. Although the rhythm is often self-limiting, it does have the potential to progress to ventricular fibrillation, as it did in our patient, or sudden cardiac death. Many drugs have been associated with a prolonged QT, ranging from antiarrythmics (quinidine, procainamide, sotalol), to antipsychotics (haloperidol or phenothiazones) to
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Fig. 1. Admission electrocardiogram with minimally prolonged QTc.
antibiotics (macrolides and quinolones) [2]. Although the incidence of Tdp associated with these agents is low, there is increased risk in the administration of QT prolonging agents to a patient with underlying risk factors for the development
of Tdp, namely electrolyte abnormalities (hypomagnesaemia and hypokalemia), female sex, heart failure, advanced age, myocardial ischemia, or an unrecognized congenital propensity to QT prolongation as manifested in the present case [1].
Fig. 2. Electrocardiogram after initiation of intravenous ciprafloxicin showing severe QTc prolongation.
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Fig. 3. Episode of polymorphic ventricular tachycardia occurring spontaneously in this subject associated with marked QTc prolongation.
While prolongation of the QT appears to be a class effect of quinolones, the magnitude of prolongation, and thus the likelihood of provoking Tdp, varies between individual agents [3]. The quinolones associated with the most potent effects were grepafloxacin and sparfloxacin, a distinction that resulted in their removal from the market [4]. Among the commonly used quinolones (ciprofloxacin, levofloxacin, gatifloxacin, and moxifloxacin) 25 cases of Tdp were reported in the United States between the dates 1/1/96 and 12/31/00 [3]. Of the 25 U.S. cases ciprofloxacin was associated with only two events. The rarity of ciprofloxacin-associated events is made more apparent when one considers an estimated 66 million prescriptions for ciprofloxacin were written during this 5-year interval, compared to 24 million prescriptions for levofloxacin [3]. Among quinolones, ciprofloxacin is widely regarded as the least likely to prolong the QT and induce Tdp. However, Tdp is listed as a possible adverse effect in the intravenous ciprofloxacin package insert [5]. Interestingly, a similar warning does not exist for the tablet form of ciprofloxacin, despite similar bioavailability [6]. There have been a few case reports of quinolone induced Tdp, but most of these cases occur in patients at high risk for acquired QT syndrome [7]. Furthermore, the majority of these cases lack electrocardiographic evidence of Tdp, instead using clinical symptoms, like syncope, to extrapolate from documented QT prolongation. Our case has
documented changes in the QT interval after ciprofloxacin administration and recorded Tdp. This case demonstrates the unpredictable nature of Tdp and underscores the need to avoid agents associated with even mild QT prolongation when borderline QTc prolongation is present.
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