Baddour et al Cardiovascular Device Infections 461 exogenously from the hospital inanimate environment or from the hands of hospital workers. In support of endogenous acquisition, an association has been noted between the presence of preaxillary skin flora and the pathogens isolated from pacemaker infection.35 Although low concentrations of methicillin-resistant CoNS have been detected in individuals with no healthcare contact and no recent antibiotic expo- sure,47 a disproportionate frequency of CIED infections due to multidrug-resistant staphylococci26,40 suggests that a healthcare environment is the site of infection acquisition.48,49 Pathogenesis The pocket may become infected at the time of implantation, during subsequent surgical manipulation of the pocket, or if the generator or subcutaneous electrodes erode through the skin. In the latter case, erosion can also occur as a secondary event due to underlying infection. Pocket infection may track along the intravascular portion of the electrode to involve the intracardiac portion of the pacemaker or ICD. Alternatively, the pocket or intracardiac portion of the electrode may become infected as a result of hematogenous seeding during a bout of bacteremia or fungemia secondary to a distant infected focus. Hematogenous seeding of a CIED is unlikely to occur in cases of Gram-negative bacillary bacteremia, as discussed below. Bacteremia due to S aureus can result in device infection, but the prevalence of this occurrence and the differentiation of this mechanism of device infection from intraoperative contamination at the time of device placement or manipulation are difficult to determine. There are no data that examine the likelihood of hematogenous seeding of a device due to other Gram-positive cocci that are more common causes of bloodstream infection or due to fungi, in particular Candida species. Device-related infection is the result of the interaction between the device, the microbe, and the host. 