■ Homograft after recent implantation ■ Chronic periaortitis (GPA, EGPA) Pyrexia ■ Chronic infections ■ Line infections ■ Pyrexia of unknown origin ■ Bacteremia from different focus APS, Antiphospholipid syndrome; EGPA, eosinophilic granulomatous polyangiitis; GPA, granulomatous polyangiitis; SLE, systemic lupus erythematosus Pathogenesis Intact vascular endothelium is resistant to microbial adhesion in most circumstances In order for IE to develop there are a number of distinct pathophysiologic events that need to occur Vascular endothelial damage with subsequent exposure of the subendothelial matrix can lead to fibrin and platelet deposition and the formation of NBTE This lesion can act as a nidus for microbial (fungal) adhesion and establishment of an infected endovascular lesion Vascular damage can occur via a number of different ways: ■ High velocity, turbulent jets occur with regurgitant and stenotic valves ■ Mechanical friction, or interruption to normal flow resulting in turbulence, can result in endothelial damage when there are either abnormal structures, or due to the presence of foreign indwelling devices ■ Prosthetic material used to repair CHD can act as a substrate for bacterial adhesion and biofilm formation, and this can last up to 6 months post procedure, after which they are relatively protected through endothelialization ■ Children with artificial valves and those with palliative shunts are more at risk because there are residual defects causing flow problems and often incomplete endothelialization Bacteria (or fungi) must either gain access to the circulation or directly infect material for an NBTE or a prosthetic device to become infected The routes by which this can happen, and the various ways to prevent or mitigate against this occurring, are summarized in Table 56.3 Table 56.3 Routes of Entry of Microbial Pathogens Route/Source of Entry Activities of daily living (e.g., tooth brushing, flossing, chewing) Prevention/Procedures to Mitigate Low-level cumulative bacteremia is likely to pose a risk that will be potentially worse when dental health is poor Recommended regular dental review (twice yearly in highrisk patients) with emphasis on dental hygiene Dental procedures: High-risk manipulation of gingival or periapical region or perforation of oral mucosa Low-risk treatment of superficial caries, local anesthetic injection, removal of sutures, orthodontic procedures Bacterial carriage (e.g., Staphylococcus aureus, group A streptococcus) High-risk procedures: Insertion of pacemaker or implantable defibrillator (recommended) Implantation of prosthetic valve, graft (consider) Low- or minimal-risk procedures: Respiratory (bronchoscopy, laryngoscopy) Gastrointestinal/genitourinary (endoscopy, colonoscopy) Bacterial infections/abscesses, empyema, other Indwelling venous catheters Body piercing and tattooing Prophylaxis given only in high-risk procedures in high-risk patient (see Box 56.6) Preoperative screening for S aureus, with eradication offered presurgery Appropriate perioperative antimicrobial prophylaxis recommended (1) or considered (2) Optimal surgical technique, including sterility of devices, instruments, theater air quality No prophylaxis routinely required Antimicrobial only required when procedure is done in the context of infection Prompt drainage of any abscess/and optimal antimicrobial therapy for systemic infections Potential sources of sepsis eliminated ≥2 weeks prior to elective surgery Avoid long-term placement of central venous line in highrisk patients unless medically required Strict indwelling venous catheter care and adherence to protocols to prevent exit and tunnel infections and luminal contamination should be observed Probable increased risk with piercing of the oral mucosa; minimal data exist for skin tattoos done with aseptic technique Risks of potential infection should be explained, as well as the fact that the efficacy of antibiotic prophylaxis has not been studied Aseptic technique for skin piercing and body art should be used Neutrophil extracellular traps are a recently proven mechanism in which the IE pathogen promotes vegetation formation.79 Neutrophil extracellular traps were discovered in 2004 as a protective neutrophil mechanism independent of phagocytosis by forming a network of fibers outside the cell and may promote and expand vegetation formation through enhancing and entrapping bacteria-platelet aggregates on the injured heart valves The suggested possibility of DNAse use to counteract this mechanism has not had any clinical test