QT INTERVAL PROLONGATION AND RISK OF LIFE-THREATENING ARRHYTHMIAS DURING TOXOPLASMOSIS PROPHYLAXIS WITH SPIRAMYCIN IN NEONATES

We recently reported two cases of QT interval prolongation and cardiac arrest in newborns receiving antibiotic therapy with spiramycin, a ma crolide agent extensively used for toxoplasmosis prophylaxis. In this study we assessed the effects of this drug on ventricular repolarizati on and on the potential risk of lethal arrhythmias in eight newborn in fants in whom toxoplasmosis prophylaxis after birth was necessary. Ele ctrocardiograms (ECGs) and echocardiograms were recorded during spiram ycin therapy (350,000 IU/kg/day) and after its withdrawal. In a contro l group of eight healthy newborns matched for age and sex, no differen ces were found between two ECGs analogously recorded. The QT interval corrected for heart rate (QTc) was longer during spiramycin therapy th an after drug withdrawal (448 +/- 32 msec vs 412 +/- 10 msec, +9%, p = 0.021). QTc dispersion, expressed as the difference between the longe st and the shortest value in 12 different leads (QTc(max - min)), was also higher during spiramycin therapy (60 +/- 32 msec vs 34 +/- 8 msec , +76%, p 0.021), mainly because of a major lengthening of the longest QTc (QTc(max)). QTc and QTc dispersion were markedly increased in the two newborns who experienced cardiac arrest after beginning treatment compared with the six neonates who had no drug-induced symptoms. Duri ng therapy seven of eight newborns had a rare abnormality in the thick ening of the left ventricular posterior wall similar to that observed in patients with congenital long QT syndrome. This abnormality disappe ared after drug withdrawal. Thus antibiotic therapy with spiramycin in the neonatal period may induce QT interval prolongation and increase QT dispersion. When this effect on ventricular repolarization is more marked, it may favor the occurrence of torsades des pointes and lead t o cardiac arrest.