Ann K. Lal and Thaddeus P. Waters
•In pregnancy, the most common risk factors for infective endocarditis (IE) are intravenous drug use and congenital heart disease
•For early diagnosis and treatment, endocarditis should be considered in the differential diagnosis for any patient presenting with fever along with relevant risk factors
•Any compromise of the cardiac structure and/or function related to IE may accelerate maternal cardiovascular decompensation
•Endocarditis prophylaxis in pregnancy is indicated for the same non-obstetric procedures as nonpregnant patients in the highest risk patients (see Table 18.7)
•Prophylaxis for IE is not recommended at the time of delivery (either vaginal or cesarean) in the absence of infection
Infective endocarditis (IE) is defined as an infection of a heart valve (native or prosthetic), the endocardial surface, or an indwelling cardiac device [1–4]. The yearly incidence of IE is estimated at 3-10/100,000 in the general population , similar to that reported in pregnancy [5–8] (see Figure 18.1). IE can be a life-threatening infection associated with significant morbidity and mortality. Hospitalization rates for IE in the United States have increased from 28,195 in 1998 to 43,419 in 2009 in keeping with the increasing comorbidities and aging in the general population. While the majority of cases of IE during pregnancy are identified antepartum, it can also present up to 6 weeks postpartum or after an abortion .
Figure 18.1 Epidemiology of infective endocarditis; incidence of infective endocarditis according to (a) age and sex, and (b) previous cardiac history, in a French cohort of 497 adults. The incidence peaks at 194 cases per million in men aged 75–79 years. (Adapted from Selton-Suty C et al. Clin Infect Dis. 2012;54:1230–9.)
Pregnancy imposes significant challenges to the cardiovascular system. Any compromise of the cardiac structure and/or function related to IE may accelerate maternal cardiovascular decompensation  with an increased risk of both maternal and fetal mortality, i.e., 22.1% and 14.7%, respectively . In addition, cardiac surgery, which may sometimes be required, may lead to significant maternal mortality between 1.5%–5%, and fetal mortality of 14%–38% [11–13].
While the risk factors for IE have remained overall unchanged, the distribution has evolved over time (see Table 18.1), as is true for pregnant and nonpregnant adults. Previously, rheumatic heart disease was a major contributing factor for IE, the prevalence of which has fallen significantly in developed countries and its contribution to IE is negligible. In pregnancy, the most common risk factors are intravenous (IV) drug use and congenital heart disease that constitute 14%–43% and 12%–38% of cases of IE, respectively [9,17].
Predisposing Risk Factors for Infective Endocarditisa
Prosthetic cardiac valve
Congenital heart disease
IV drug use
Rheumatic heart disease
The microbes causing IE have also changed over the last 20 years. Currently, 50% of IE is health care–associated, with 42.5% being community-acquired and 7.5% nosocomial . The vast majority of cases of IE (80%–90%) are caused by gram-positive cocci, staphylococcus, streptococcus, or enterococcus, with 5% reported as no identifiable organism and less than 2% are polymicrobial [2,14]. Staphylococcus aureus (26%–38%) and Streptococcus viridans (19%–43%) are the most common organisms isolated in cases of IE in pregnancy [9,17] (see Table 18.2).
Organisms Associated with Infective Endocarditisa
Both Staphylococcus aureus, including methicillin-resistant strains, and coagulase-negative organisms (S. epidermidis, S. lugdunensis, S. capitis)
(oral, gastrointestinal tract, and genitourinary tract)
Streptococcus mutans, S. salivarius, S. anginosus, S. mitis, S. sanguinis
Enterococcus faecalis is most common
Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella corrodens, Kingella
Other rare organisms
Coxiella burnetii, Brucella, Bartonella, Chlamydia psittaci, Enterobacteriaceae, Propionibcaterium acnes, Lactobacillus, Acinetobacter, Pseudomonas aeruginosa, Legionella, Mycoplasma, Tropheryma whippelii
Clinical Features of Endocarditis
The clinical features of IE are varied and nonspecific, causing a diagnostic challenge in most cases [20–22]. Nonspecific symptoms may include low-grade fever, chills, weight loss, poor appetite, or low-grade sepsis. Typical physical examination findings are a new-onset cardiac murmur, splinter hemorrhages, microscopic hematuria, embolic complications, or heart failure. Electrocardiogram may reveal new-onset conduction system abnormalities. Atypical presentation is more likely to occur in older and immunocompromised patients including pregnant population . To avoid delays in diagnosis and treatment, IE should be in the differential diagnosis for any pregnant patient presenting with fever along with relevant risk factors.
The diagnosis of IE is straightforward in patients with a consistent history and classic Oslerian manifestations, including sustained bacteremia or fungemia, evidence of acute valvulitis, peripheral emboli, and immunologic vascular phenomena . However, as the majority of cases do not present with these classic signs and symptoms, initial evaluation of suspected IE includes both expeditious cardiac imaging and laboratory assessment, including:
1.Three sets of blood cultures should be taken from different venipuncture sights, with the first and last samples drawn at least 1 hour apart.
2.Echocardiogram is the main diagnostic test for the diagnosis of IE.
a.Transthoracic echocardiogram (TTE) should be done initially in all suspected IE cases.
b.Transesophageal echocardiogram (TEE) is recommended for cases with poor visualization on TTE or in patients with negative TTE, but high suspicion for IE .
The majority of cases in pregnancy involve a left-sided, either mitral or aortic valve, abnormality . Duke criteria for IE were proposed in 1994 to aid both clinicians and researchers to make this challenging diagnosis . Modified Duke criteria were subsequently published in 2000 in an attempt to decrease the number of patients classified as possible IE; these criteria are still used today  (see Tables 18.3 through 18.5).
Modified Duke Criteria for the Diagnosis of Infective Endocarditisa
1.Microorganisms demonstrated by culture or histologic examination of a vegetation, a vegetation that has embolized, or an intracardiac abscess specimen
2.Pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis
1.2 major criteria or
2.1 major criterion and 3 minor criteria or
3.5 minor criteria
1.1 major criterion and 1 minor criterion
2.3 minor criteria
1.Firm alternate diagnosis explaining evidence of infective endocarditis or
2.Resolution of infective endocarditis syndrome with antibiotic therapy for ≤4 days or
3.No pathologic evidence of infective endocarditis at surgery or autopsy, with antibiotic therapy for ≤4 days or
4.Does not meet criteria for possible infective endocarditis, as above
a See further reference .
Modified Major Duke Criteria for the Diagnosis of Infective Endocarditisa
Blood culture positive for IE
•Typical microorganisms consistent with IE from 2 separate blood cultures
•Viridans streptococci, Streptococcus bovis, HACEK group, Staphylococcus aureus, or community-acquired enterococci, in the absence of a primary focus; or
•Microorganisms consistent with IE from persistently positive blood cultures, defined as follows: At least 2 positive cultures of blood samples drawn 112 h apart; or all of 3; or a majority of >4 separate cultures of blood (with first and last sample drawn at least 1 h apart)
•Single positive blood culture for Coxiella burnetii or antiphase I IgG antibody titer 1:800
Evidence of endocardial involvement
Echocardiogram positive for IE (TEE recommended in patients with prosthetic valves, rated at least “possible IE” by clinical criteria, or complicated IE [paravalvular abscess]; TTE as first test in other patients), defined as follows
•Oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or on implanted material in the absence of an alternative anatomic explanation; or
•New partial dehiscence of prosthetic valve
New valvular regurgitation (worsening or changing of preexisting murmur not sufficient)
a See further reference .
Modified Minor Duke Criteria for the Diagnosis of Infective Endocarditisa
Predisposition, predisposing heart condition, or injection drug use
•Fever, temperature >38°C
•Vascular phenomena, major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, and Janeway lesions
•Immunologic phenomena: Glomerulonephritis, Osler nodes, Roth spots, and rheumatoid factor
•Microbiological evidence: Positive blood culture but does not meet a major criterion as noted above or serological evidence of active infection with organism consistent with IE
a See further reference .
A recent systematic review summarized maternal and fetal outcomes of pregnant or postpartum women with IE . In total, 72 articles were identified with 90 cases of IE (56.7% (n = 51) pregnant versus 43.3% (n = 39) postpartum. The modified Duke criteria  were applied to all cases included in the publication. IV drug use was the most common identified risk factor for IE (n = 13), followed by congenital heart disease (n = 11) and rheumatic heart disease (n = 11). These observed frequencies were slightly lower than reported previously in pregnancy ; however, IV drug use and congenital heart disease were the most frequent identifiable causes in both studies on IE in pregnancy. The most commonly identified pathogens were streptococcal (n = 39) and staphylococcal species (n = 23), with 8 patients being culture-negative (8.9%). Other identified pathogens included Neisseria species (n = 4), gram stain-positive cocci (n = 3), Escherichia coli (n = 3), Listeria species (n = 2), Pseudomonas species (n = 2), Salmonella species (n = 1), Rickettsia species (n = 1), Enterobacter species (n = 1), Enterococcus species (n = 1), and Haemophilus species (n = 1) with 4 not reported and 3 being polymicrobial. Surgical interventions were performed in 48 cases, with 7 of these occurring during pregnancy. Maternal mortality was 11% overall (n = 10) with a relative equal distribution of deaths antepartum or postpartum (11.5 vs. 10.5%). Mortality was highest for the 16 non-staphylococcal and non-streptococcal cases (25%) with no observed deaths in the culture-negative group. Other complications included septic pulmonary emboli for 21 patients (23.3%), CNS emboli in 11 (12.2%), and other embolic complications in 7 women (7.8%). For the 51 pregnant women, IE involved native valves in 98% (n = 50) with the mitral valve being the most commonly affected (n = 21). Seven fetal deaths were observed (13.7%) with 41 deliveries with survival to discharge (80.4%), with the remaining 3 pregnancies lost to follow up (n = 2) and 1 termination of pregnancy.
See further Figure 18.2.