Biofilm is defined as a surface-associated community of 1 or more microbial species that are firmly attached to each other and the solid surface and are encased in an extracellular polymeric matrix that holds the biofilm together. Microbes in a biofilm are more resistant to antibiotics and host defenses, perhaps as a result of the dense extracellular matrix that protects the microbes secluded in the interior of the community. When a bacterial cell switches modes from free-floating (planktonic) organisms to biofilm, it undergoes a phenotypic shift in behavior in which large groups of genes are regulated.50 Microbial Persistence Phenotypic variation is also thought to be operative in supporting the persistence of infection due to staphylococci in a biofilm that coats the surface of a CIED. Small colony variants are phenotypes that have caused CIED infec- tions61 63 and harbor several characteristics that are thought to enhance the survival of staphylococci either in a biofilm or in endothelial cells that cover the device, including resistance to certain antibiotics.64 66 Host Factors Host factors associated with increased risk of CIED infection were outlined in a previous section of this document. These include renal failure, corticosteroid use, congestive heart failure, hematoma formation, diabetes mellitus, and antico- agulation use. Diagnosis CIED infection can present as different syndromes. In the majority of cases, local inflammatory changes of the generator-pocket site are present, or cutaneous erosion with percutaneous exposure of the generator and/or leads is seen. These local changes, often accompanied by pain or discom- fort, usually prompt patients to seek medical attention. Fever and other signs of systemic toxicity are frequently absent. Some patients present with vague symptoms that include malaise, fatigue, anorexia, or decreased functional capacity. 