Prevention of Arrhythmia Device Infection Trial: The PADIT Trial

Background: Infection of implanted medical devices has catastrophic consequences. For cardiac rhythm devices, pre-procedural cefazolin is standard prophylaxis but does not protect against methicillin-resistant gram-positive organisms, which are common pathogens in device infections. Objective: This study tested the clinical effectiveness of incremental perioperative antibiotics to reduce device infection. Methods: The authors performed a cluster randomized crossover trial with 4 randomly assigned 6-month periods, during which centers used either conventional or incremental periprocedural antibiotics for all cardiac implantable electronic device procedures as standard procedure. Conventional treatment was pre-procedural cefazolin infusion. Incremental treatment was pre-procedural cefazolin plus vancomycin, intraprocedural bacitracin pocket wash, and 2-day post-procedural oral cephalexin. The primary outcome was 1-year hospitalization for device infection in the high-risk group, analyzed by hierarchical logistic regression modeling, adjusting for random cluster and cluster-period effects. Results: Device procedures were performed in 28 centers in 19,603 patients, of whom 12,842 were high risk. Infection occurred in 99 patients (1.03%) receiving conventional treatment, and in 78 (0.78%) receiving incremental treatment (odds ratio: 0.77; 95% confidence interval: 0.56 to 1.05; p = 0.10). In high-risk patients, hospitalization for infection occurred in 77 patients (1.23%) receiving conventional antibiotics and in 66 (1.01%) receiving incremental antibiotics (odds ratio: 0.82; 95% confidence interval: 0.59 to 1.15; p = 0.26). Subgroup analysis did not identify relevant patient or site characteristics with significant benefit from incremental therapy. Conclusions: The cluster crossover design efficiently tested clinical effectiveness of incremental antibiotics to reduce device infection. Device infection rates were low. The observed difference in infection rates was not statistically significant.