The normal endothelium is resistant to infection and thrombus formation unless it is injured by high-pressure gradients and turbulent flow states. Such abnormal hemodynamic states occur commonly in those with preexisting valvular or congenital cardiac defects. In injection drug use, endothelial damage likely occurs by a different mechanism, such as from repetitive bombardment with particulate matter (i.e., talc) present in injected material or from ischemia brought on by vasospasm from the injected drug. Cocaine use is particularly associated with increased rates of endocarditis. The resultant endothelial damage promotes deposition of platelets and fibrin and the formation of sterile vegetations (nonbacterial thrombotic endocarditis).
Nonbacterial thrombotic endocarditis can also arise as a result of hypercoagulable states, such as in patients with malignancy (marantic endocarditis) or systemic lupus erythematosus (Libman-Sacks endocarditis), and in areas surrounding foreign bodies like vascular catheters or prosthetic valves. In the setting of preexistent nonbacterial thrombotic endocarditis, transient bacteremia may result in colonization of vegetations and conversion to infective endocarditis.
Transient bacteremia can occur from trauma to the skin or mucosal surfaces of the oropharynx or GI or GU tracts (all of which are normally laden with endogenous flora). Even in the absence of trauma, spontaneous bacteremia can occur in patients with periodontal disease or other localized infections. In cases of bacteremia, the bacterial load usually does not exceed 10 organisms per milliliter of blood, and the bloodstream is usually sterilized in <30 minutes. In the presence of nonbacterial thrombotic endocarditis, this time interval is sufficient for bacteria to adhere to the vegetation and transform it into an infected lesion.
The coexistence of bacteremia and nonbacterial thrombotic endocarditis does not uniformly result in infective endocarditis. To cause infective endocarditis, the infecting organism must be able to adhere to the nonbacterial thrombus on the endothelium. Different organisms vary in this ability. Furthermore, although nonbacterial thrombotic endocarditis is often present in those who develop infective endocarditis, it not an absolute prerequisite, and highly invasive organisms (e.g., S. aureus) can directly invade the endocardium. Adherent organisms stimulate further deposition of platelets and fibrin, leading to sequestration of organisms into a "protected site" that phagocytic cells cannot easily penetrate. As the disease progresses, the vegetation continuously fragments, shedding surface organisms into the circulation and causing sustained bacteremia.
A wide range of bacteria and fungi, as well as Rickettsia and Chlamydophila species, can cause infective endocarditis. Bacteria are the predominant cause overall, with a small number of species responsible for the majority of cases. Causative microorganisms vary based on the specific conditions (i.e., native vs prosthetic valve) and risk factors (injection drug use or intracardiac devices; Table 155-1). Overall, recent reports from the United States and European countries indicate that Staphylococcus is the single most common cause, followed by streptococci and enterococci.1,3,12,13,14
TABLE 155-1Microbiology of Infective Endocarditis (IE) ||Download (.pdf) TABLE 155-1 Microbiology of Infective Endocarditis (IE)
|Native Valve IE (% of cases) ||Intracardiac Device IE (% cases) |
| ||Nonaddict ||IV Drug Addict || ||Prosthetic Valve IE ||Other Devices* |
|Staphylococcus aureus ||28 ||68 ||S. aureus ||23 ||35 |
|Coagulase-negative Staphylococcus ||9 ||3 ||Coagulase-negative Staphylococcus ||17 ||26 |
|Viridans group streptococci ||21 ||10 ||Viridans group streptococci ||12 ||8 |
|Other streptococci ||14 ||3 ||Streptococcus bovis ||10 ||7 |
|Enterococcus species ||11 ||4 ||Enterococcus species ||12 ||6 |
|HACEK ||2 ||0 ||HACEK ||2 ||1 |
|Fungus ||1 ||1 ||Fungus ||4 ||1 |
|Polymicrobial ||1 ||3 ||Polymicrobial ||1 ||0 |
|Others ||4 ||5 ||Others ||7 ||6 |
|Culture negative ||9 ||3 ||Culture negative ||12 ||10 |
The increase in the number of cases caused by staphylococci is likely linked to the observed increase in healthcare-associated endocarditis and also more frequent intravenous drug use. Staphylococcal endocarditis can cause rapid destruction of valves, multiple distal abscesses, myocardial abscesses, conduction defects, and pericarditis. Staphylococcal endocarditis has an increased risk of in-hospital death.1 In contrast, streptococcal endocarditis tends to be indolent. Patients with enterococcal endocarditis generally have underlying valvular disease and risk factors such as diabetes mellitus or manipulation of the GU or lower GI tract.
Blood cultures are the best initial method for detection but are negative in about 5% of patients; in one third to one half of patients, cultures are negative because of prior antibiotic administration. For those cases associated with negative blood cultures and without prior antibiotic administration, infection is due to fastidious organisms, such as the HACEK group (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella), Bartonella species, or Coxiella burnetii.
Skin flora and contaminated injection devices are the most frequent sources of microorganisms in injection drug use–associated endocarditis. S. aureus accounts for >50% of cases, followed in decreasing frequency by streptococcal species (including enterococci) and coagulase-negative staphylococci. The well-established predilection for S. aureus to infect normal heart valves, particularly tricuspid valves, is seen in injection addicts, although streptococci and enterococci often infect abnormal mitral or aortic valves in these patients.
Microorganisms involved in prosthetic valve endocarditis often reflect contamination during the perioperative period, with Staphylococcus epidermidis being a commonly isolated organism. Aspergillus and Candida albicans account for the majority of cases of mycotic prosthetic valve endocarditis and often have large vegetations and emboli.