INTRODUCTION — The epidemiology, risk factors, and microbiology of native valve infective endocarditis (IE) will be reviewed here. Issues related to the epidemiology of prosthetic valve IE are discussed separately. (See "Prosthetic valve endocarditis: Epidemiology, clinical manifestations, and diagnosis".)
EPIDEMIOLOGY — Infective endocarditis (IE) may be acquired in the community or in the context of health care exposure [1]. Community-associated IE refers to IE that develops in the absence of recent contact with a health care setting, with diagnosis established within 48 hours of hospital admission. Health care-associated IE refers to IE that develops in the context of recent contact with a health care setting, with onset of symptoms ≥48 hours after hospitalization.
Between 2000 and 2011, the incidence of IE in the United States increased from 11 per 100,000 population to 15 per 100,000 population [2,3]. The precise incidence of IE is difficult to ascertain because case definitions have varied over time between authors and between clinical centers [4]. In addition, the incidence of predisposing conditions such as rheumatic heart disease or injection drug use is variable over time and between regions and in low- and high-income countries [5].
For example, the incidence of IE among patients admitted to Philadelphia-area hospitals from 1988 to 1990 was approximately 11.6 cases per 100,000 person-years [6]. In contrast, the incidence of IE in a Minnesota county between 1970 and 2006 was 5.0 to 7.9 cases per 100,000 person-years [7,8]. During this time span, the incidence of IE in men remained stable (8.6 to 12.7 cases/100,000 person-years) while the incidence of IE in women increased (from 1.4 to 6.7 cases/100,000 person-years). Other studies have reported incidence rates for IE ranging from 0.6 to 6.0 cases per 100,000 person-years [4,9-12].
A population-based observational study in France in 2008 noted the annual incidence of IE was 33.8 cases per million [13]. The incidence was highest in men 75 to 79 years and the majority of patients had no known prior heart disease; health care-associated IE accounted for 27 percent of cases. Similarly, an observational study in Spain noted an increase in the incidence of IE between 2003 and 2014, from 2.72 to 3.49 per 100,000 person-years; the rise was higher among older adults [14].
Some observations of changes in the incidence of IE have been associated with changes to guidelines regarding antimicrobial prophylaxis for prevention of IE published in 2007; this issue is discussed further separately. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures", section on 'Effect of guideline changes'.)
RISK FACTORS — A number of factors predispose to the development of infective endocarditis (IE), as outlined in the following sections. Issues related to antimicrobial prophylaxis for prevention of IE are discussed separately. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)
Patient factors
Age >60 years — More than half of all IE cases in the United States and Europe occur in patients over the age of 60; the median age has increased steadily during the past 40 years [12,15-17]. This trend is probably due to two factors: the decline in the incidence and importance of rheumatic heart disease as a risk factor for IE and the increasing proportion of older adult individuals in the general population. Older adults are more likely to develop degenerative valve disease and to require valve replacement, both of which are associated with an increased risk of IE.
Male sex — Men predominate in most case series of IE; male-to-female ratios range from 3:2 to 9:1 [12,18,19].
Injection drug use — Risk factors related to injection drug use include bloodstream seeding with skin flora, oral flora, and/or organisms contaminating the drug or materials used for injection [20]. In addition, some illicit drugs may induce valvular endothelial damage, predisposing to subsequent infection. Issues related to IE and injection drug use are discussed further separately. (See "Right-sided native valve infective endocarditis".)
Poor dentition or dental infection — Poor dentition and/or dental infection are likely to be risk factors for IE due to oral flora [21,22]. Routine dental cleaning is not a risk factor for IE; dental procedures that involve manipulation of gingival tissue or the periapical region of the teeth or perforation of the oral mucosa can increase risk for IE [23,24].
Some studies have suggested that dental hygiene may be associated with risk of IE [22,25,26]. One study including 73 patients with IE due to oral streptococci and 192 patients with IE due to non-oral pathogens noted that patients with IE due to oral streptococci used toothpicks, dental floss, water jets, and/or an interdental brush more frequently than patients with IE due to non-oral streptococci, but were less likely to brush their teeth after meals; findings on dental examination were similar in both groups [26].
Antimicrobial prophylaxis for prevention of IE is appropriate for patients undergoing invasive dental procedures in the setting of underlying structural heart disease or prosthetic heart valve(s); this is discussed further separately. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)
Comorbid conditions
Structural heart disease — Approximately three-fourths of patients with IE have a pre-existing structural cardiac abnormality at the time that endocarditis develops [7,27]. A Danish study including more than 3000 patients with hypertrophic cardiomyopathy, the risk for IE was higher than the population-based controls (hazard ratio [HR] 6.5, 95% CI 2.3-18.5), yet lower than a high-risk population with prosthetic valves (HR 0.13, 95% CI 0.06-0.29) [28]. A Spanish study reported that the proportion of patients without underlying heart conditions increased between 2001 and 2013 (compared with 1987 to 2001) [17]; patients without pre-existing heart disease were more likely to be immunosuppressed and more likely to acquire infection after exposure to health care settings.
Antimicrobial prophylaxis for prevention of IE is appropriate for some patients undergoing invasive procedures in the setting of underlying structural heart disease; this is discussed further separately. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)
Valvular disease — Valvular disease includes rheumatic heart disease, mitral valve prolapse (usually with coexistent mitral regurgitation), aortic valve disease, and other valvular abnormalities.
One report evaluating cases of IE in New York between 1938 and 1967 noted that rheumatic heart disease was a common cardiac abnormality (39 percent of cases) [29]. In contrast, a subsequent series of IE cases between 1980 and 1984 noted the presence of rheumatic heart disease in only 6 percent of patients with IE [27].
Mitral valve disease, such as mitral valve prolapse [30] (usually with coexistent mitral regurgitation) and/or mitral annulus calcification, is a risk factor for IE. Two reports of IE noted mitral valve prolapse was the underlying cardiac lesion in 22 and 29 percent of cases [27,31]. The risk of IE in patients with mitral valve prolapse and associated regurgitation is estimated to be five to eight times higher than that in patients with a normal mitral valve [32,33]. In addition, mitral valve prolapse has been associated with viridans group streptococcal IE [34]. However, mitral valve prolapse without mitral insufficiency is a more common abnormality that is associated with only a small risk of endocarditis.
Aortic valve disease (sclerosis, stenosis, and/or regurgitation) occurs in 12 to 30 percent of IE cases [35]. (See 'Congenital heart disease' below.)
The risk of IE among patients with acquired valvular disorders (ie, aortic stenosis or regurgitation, mitral stenosis or regurgitation, mitral valve prolapse, rheumatic heart disease) compared with age and sex matched population-based controls was evaluated in a Danish registry between 2000 and 2015 [28]. Patients with a valve disorder had a higher risk of IE compared with matched controls (HR 8.7, 95% CI 6.3-12.0) yet lower risk of IE compared with high-risk prosthetic heart valve patients (HR 0.27, 95% CI 0.23-0.33). The results support our understanding of risk for IE in patients with acquired valve disorders and their categorization as 'moderate' risk for acquiring IE.
The risk of IE appears to be low in adults with pulmonary or tricuspid regurgitation due to pulmonary hypertension in the setting of inherently normal pulmonic and tricuspid valves. In one series of 186 such patients who were followed for a mean of nine years, no cases of endocarditis occurred (with the exception of a single intravenous drug abuser) [36].
Congenital heart disease — Congenital heart lesions predisposing to IE include aortic stenosis, bicuspid aortic valve [30], pulmonary stenosis, ventricular septal defect, patent ductus arteriosus, coarctation of the aorta, and tetralogy of Fallot.
In one series including 2401 patients with congenital aortic stenosis, pulmonary stenosis, or a ventricular septal defect, the incidence of endocarditis was 135 cases/100,000 person-years [37]. IE occurred most frequently among patients with aortic stenosis and ventricular septal defects (271 and 145 cases per 100,000 person-years, respectively). Among patients with aortic stenosis, increasing peak gradient across the aortic valve correlated with increasing risk of IE. In another series, the risk of IE with aortic stenosis was approximately twice as high as with aortic regurgitation (73 versus 40 cases per 100,000 person-years) [38].
Pulmonic stenosis appears to confer a relatively low rate of IE among congenital heart lesions; one case was noted among 592 patients with this lesion [37].
History of infective endocarditis — A prior history of endocarditis is an important predisposing cause for subsequent IE. In one large cohort of patients who survived IE, recurrent IE occurred in 4.5 percent of patients [39]. Other studies have reported rates of IE recurrence ranging from 2.5 to 9 percent [40].
Indwelling intravascular device — Bacteremia associated with the presence of an intravenous catheter or an invasive intravascular procedure can be complicated by health care-associated endocarditis [6,41-45]. Among 2781 patients with IE in one cohort, 23 percent of cases were health care associated [46,47]. Less common intravascular devices with risk for IE include peritoneovenous shunts for the control of intractable ascites [48] and ventriculoatrial shunts for the management of hydrocephalus [49].
Nosocomial endocarditis has been defined as a diagnosis of IE made more than 72 hours after admission in patients with no evidence of IE on admission or IE that develops within 60 days of a previous hospital admission during which there was risk for bacteremia or IE [41]. In one report from Minnesota, health care-associated IE accounted for 50 percent of all IE cases during the period 2001 to 2006; of these, 7.5 percent were nosocomial and 42.5 percent were community acquired [8].
Cardiac implantable electronic device — Infection of a cardiac implantable electronic device (CIED) is a risk factor for IE [28]. CIED-related IE can manifest as lead vegetation and/or valve vegetation. (See "Infections involving cardiac implantable electronic devices: Epidemiology, microbiology, clinical manifestations, and diagnosis".)
Chronic hemodialysis — Chronic hemodialysis patients are at significant risk for IE [50,51]. Predisposing factors include intravascular access, calcific valvular disease, and immune impairment [51]. The incidence of IE in hemodialysis patients has been estimated to be 308 per 100,000 patient-years [50-52]. However, the accuracy of such estimates is difficult to assess given potential bias related to variable use of echocardiography for evaluation of access-related bloodstream infections, the infrequency of postmortem exams in hemodialysis patients following bacteremia, inconsistent follow-up, and the retrospective design of most studies.
HIV infection — It has been suggested that human immunodeficiency virus (HIV) infection is an independent risk factor for IE in injection drug abusers [53]; however, this has not been confirmed in other reports [54]. Unusual organisms such as Salmonella and Listeria may cause IE in HIV-infected patients [54,55].
Cardiac bypass surgery — Nosocomial endocarditis due to nontuberculous mycobacteria, in particular Mycobacterium chimaera, has occurred following open-chest surgery in patients from the United States, United Kingdom, and several European countries [56]. This has been linked to the use of specific heater-cooler devices [57]. (See "Overview of nontuberculous mycobacterial infections", section on 'M. chimaera associated with cardiac surgery'.)
MICROBIOLOGY — A variety of microorganisms can cause infective endocarditis (IE), and the microbiology of IE can vary depending on the population.
The microbiology of IE in patients who use intravenous drugs and in patients with prosthetic valves is discussed separately. (See "Prosthetic valve endocarditis: Epidemiology, clinical manifestations, and diagnosis", section on 'Microbiology' and "Right-sided native valve infective endocarditis", section on 'Microbiology'.)
The three most common causes of IE worldwide are staphylococci, streptococci, and enterococci. In the United States and most developed countries, Staphylococcus aureus is the most common cause of IE [58]; while streptococci has been shown to be the most common cause in some older, population-based studies [4,8]. Staphylococcal IE is a common cause of health care-associated IE [46]; streptococcal IE is a common cause of community-acquired IE [13].
Among 2781 patients with IE in a large cohort, the distribution of pathogens was as follows [47,59,60]:
●S. aureus – 31 percent
●Viridans group streptococci – 17 percent
●Enterococci – 11 percent
●Coagulase-negative staphylococci – 11 percent
●Streptococcus bovis – 7 percent
●Other streptococci (including nutritionally variant streptococci) – 5 percent
●Non-HACEK gram-negative bacteria – 2 percent
●Fungi – 2 percent
●HACEK – 2 percent; organisms in this category include a number of fastidious gram-negative bacilli: Haemophilus aphrophilus (subsequently called Aggregatibacter aphrophilus and Aggregatibacter paraphrophilus); Actinobacillus actinomycetemcomitans (subsequently called Aggregatibacter actinomycetemcomitans); Cardiobacterium hominis; Eikenella corrodens; and Kingella kingae
The remaining cases included culture-negative endocarditis (8 percent), polymicrobial (1 percent), and a variety of other organisms (3 percent). The higher incidence of S. aureus relative to viridans group streptococci is likely because this study was conducted in large, tertiary care centers and may not reflect the epidemiology of IE in more rural communities.
In the setting of streptococcal bacteremia, species differentiation can be useful to determine the likelihood of IE. As an example, in a study including more than 6000 streptococcal bloodstream infections, using Streptococcus pneumoniae as a reference, the risk of IE with Streptococcus mutans (odds ratio [OR] 81.3 [37.6-176]), Streptococcus gordonii (OR 80.8 [43.9-149]), and Streptococcus sanguinis (OR 59.1 [32.6-107]) bacteremia (among others) was high, while the risk for IE with Streptococcus pyogenes bacteremia (OR 1.57 [0.78-3.18]) was comparatively low [61]. Differential risk for IE among streptococcal bloodstream isolates has been shown in other studies, as well [62,63].
Nutritionally variant streptococci, Abiotrophia spp and Granulicatella spp, account for a small proportion of streptococcal IE cases. The clinical presentation of IE due to these pathogens is similar to that of viridans group streptococci. Diminished susceptibility to penicillins and cephalosporins in these species has been described [59,60].
Between 2000 and 2011, the incidence of streptococcal IE in the United States increased significantly, from 26 to 42 cases per million population [2]; it is uncertain whether this observation is a reflection of changes to guidelines regarding antimicrobial prophylaxis for prevention of IE published in 2007. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)
The HACEK organisms, colonizers of the oral cavity and gastrointestinal tract, are rare causes of IE. IE due to these organisms typically occurs in younger patients, has a propensity to cause prosthetic valve IE, and is associated with relatively good outcomes [64,65]. In one retrospective study including 118 episodes of HACEK bacteremia, 23 percent were associated with IE; in particular, there was a significant association between A. actinomycetemcomitans bacteremia and IE (OR 7.2 [2.1-2.5]) [66]. Clinical features of HACEK bacteremia associated with IE included community acquisition, presence of a cardiac implantable electronic device, prosthetic valve, native valve disease, and unknown origin of infection [66].
Gram-negative bacteria such as Escherichia coli and Klebsiella pneumoniae adhere less readily to heart valves than gram-positive organisms [67].
Brucella is an important cause of IE in regions where it is endemic [68]. (See "Brucellosis: Treatment and prevention", section on 'Endocarditis'.)
Patients with ulcerative lesions of the colon due to carcinoma or inflammatory bowel disease have a predilection to develop IE due to S. bovis [69,70]. (See "Infections due to Streptococcus bovis/Streptococcus equinus complex (SBSEC; formerly group D streptococci)", section on 'Association with colonic neoplasia'.)
Fungal IE is rare. Candida spp [71-73] and Aspergillus spp [74,75] are the major causes of fungal IE. (See "Candida endocarditis and suppurative thrombophlebitis" and "Epidemiology and clinical manifestations of invasive aspergillosis", section on 'Endocarditis'.)
Interpretation of culture results in the setting of known or suspected IE is discussed further separately. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Endocarditis (The Basics)")
SUMMARY
●Approximately 10,000 to 15,000 new cases of infective endocarditis (IE) are diagnosed in the United States each year. The precise incidence of IE is difficult to ascertain because case definitions are variable over time between authors and between clinical centers. In addition, the incidence of predisposing conditions such as rheumatic heart disease or injection drug use is variable over time and between regions. (See 'Epidemiology' above.)
●Patient risk factors for IE include age >60 years, male sex, injection drug use, and poor dentition or dental infection. (See 'Patient factors' above.)
●Comorbid conditions that confer increased risk for IE include structural heart disease, presence of prosthetic heart valve(s), history of IE, presence of an intravascular device, chronic hemodialysis, and HIV infection. Structural heart disease includes valvular disease and congenital heart disease. (See 'Comorbid conditions' above.)
●A variety of microorganisms can cause IE; staphylococci account for the majority of cases of health care-associated IE. However, streptococci are the most prominent in community-acquired IE. (See 'Microbiology' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Daniel J Sexton, MD, who contributed to an earlier version of this topic review.
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