Randomized Noninferiority Study of an Antibacterial Envelope Alone Versus Envelope Plus Intraoperative Antibacterial Irrigant and Postoperative Antibiotics to Prevent Cardiac Implantable Electronic Device Infections in High-Risk Patients

1.0 Background

The number of cardiac implantable electronic devices (CIEDs) implanted each year has grown rapidly over the past two decades, largely due to expanding use of implantable cardioverter-defibrillators (ICDs) and devices capable of delivering cardiac resynchronization therapy (CRT). CIEDs have increasingly been utilized in older patients with multiple medical comorbidities. As a result CIED infections, defined as infections involving the generator implant site (pocket) and/or intravascular leads, have become increasingly prevalent, with the rate of growth in infections outpacing that of CIED procedures. The increase in incidence of CIED infections has outpaced the growth in device implantation, in large part due to the medical complexity of today's CIED patients. These devastating complications are associated with significant cost, morbidity, and mortality. The odds of both short term and long term mortality are at least doubled in patients who suffer CIED infections, and long term survival is particularly poor in women.

Patient-specific risk factors for CIED infections have been examined in multiple registries and case-control studies. For patients with at least two risk factors, the reported incidence of CIED infection is 2-3%. Management of these infections is complex and expensive. The cornerstone of management is the complete removal of all infected hardware whenever possible, which in itself poses significant risks for patients. Therefore prevention of infections is crucial.

Best practices for reducing CIED infections are an active area of research. Since most infections occur as a result of bacterial seeding at the time of device implantation or revision, careful attention to strict sterile technique is mandatory. Optimal skin preparation and perioperative intravenous antibiotics have been associated with a reduced rate of CIED infections in randomized controlled studies. Additionally, several recent retrospective studies have suggested an important role of the minocycline and rifampin impregnated TYRX antibacterial envelope in reducing infections. The device consists of 2 polypropylene mesh sheets joined on 3 sides with a 3mm seam and is available in 2 sizes to accommodate pacemaker and ICD pulse generators. This polypropylene envelope releases minocycline and rifampin from a bioresorbable polyarylate polymer over approximately 7 days, directly into the CIED generator pocket.

Aside from optimal skin preparation and perioperative intravenous antibiotics, other practices to reduce the risk of CIED infections vary widely. Many operators use an antibacterial solution (e.g., polymyxin-B/bacitracin) to irrigate the pocket during device implantation. Additionally, many centers have adopted the routine use of prophylactic postoperative antibiotics to reduce the risk of CIED infections. However, neither of these strategies has been evaluated in randomized clinical studies. Antibacterial irrigation solution is expensive, and oral antibiotics are associated with a small yet clinically important risk of adverse effects, including Clostridium difficile infection. Therefore, prospective randomized studies are needed to evaluate the efficacy, safety, and cost-effectiveness of intraoperative antibacterial rinse and postoperative oral antibiotics.