Effect of macrolide and fluoroquinolone antibacterials on the risk of ventricular arrhythmia and cardiac arrest: An observational study in Italy using case-control, case-crossover and case-time-control designs

Objective: To compare the effect of macrolide and fluoroquinolone antibacterials on the onset of ventricular arrhythmia and cardiac arrest using three different observational designs. Methods: A population-based case-control study was performed by linking automated databases from the Varese Province of Italy. Cases were all subjects who experienced ventricular arrhythmia or cardiac arrest from July 1998 to December 2003. For each case, up to ten controls were randomly selected after matching for sex, age, practitioner and date of arrhythmia onset. The use of macrolides and fluoroquinolones during two time windows denoted as recent and referent intervals was ascertained. Odds ratios were estimated using case-control, case-crossover and case-time-control approaches. Results: 1275 cases and 9189 controls met the inclusion criteria. Adjusted odds ratios (and corresponding 95% CIs) associated with recent exposure to macrolides were 2.13 (1.34, 3.39), 1.70 (0.88, 3.26) and 1.62 (0.78, 3.34) by using case-control, case-crossover and case-time-control designs, respectively. The corresponding estimates for fluoroquinolones were 3.58 (2.51, 5.12), 1.98 (1.19, 3.29) and 1.59 (0.88, 2.87), respectively. Conclusions: Three observational study designs each using entirely different sets of controls consistently showed that recent use of macrolide and fluoroquinolone antibacterials may be associated with increased risk of ventricular arrhythmia and cardiac arrest.