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R.C. Hyzy (ed.), Evidence-Based Critical Care, DOI 10.1007/978-3-319-43341-7_19
his blood pressure and his heart rate, with the intent of shortening diastolic filling time [1]. He underwent an emergent aortic valve replacement
with a bioprosthetic valve. He was extubated and transferred to the surgical ward on post-operative day 2, and discharged home on post-operative day 6. An echocardiogram prior to discharge showed a normally functioning aortic bioprosthe- sis with no signs of infective endocarditis.
Ceftriaxone was continued for a total of 6 weeks.
Principles of Management Epidemiology
The incidence of infective endocarditis is between 3 and 10 episodes per 100,000 person-years with a peak incidence during the ages of 70–80 of 14.5 episodes per 100,000 person-years [2–5]. Risk factors for IE include advanced age, poor denti- tion, injection drug use, structural heart disease (specifically valvular and congenital heart disease), the presence of prosthetic heart valves, and the presence of an intravascular catheter [6–10]. The
Fig. 19.1 Transthoracic echocardiogram documenting an aortic valve vegetation and severe aortic insufficiency in the parasternal long axis view and the 5-chamber apical
view. Continuous wave Doppler signal of the aortic valve with a very short pressure half time suggestive of severe aortic insufficiency
Fig. 19.2 Chest x-ray on post-admission day 2 showing severe pulmonary edema
most common micro-organisms responsible for native valve IE in order of likelihood are listed in Table 19.1 [11].
Diagnosis
Modified Duke criteria incorporate patient risk factors, physical exam findings, laboratory stud- ies, and echocardiographic imaging to diagnose IE (Table 19.2) [12]. Importantly, three sets of
peripheral venous blood cultures (aerobic and anaerobic) should be obtained from two sites (spatial separation) at 30 min intervals (temporal separation) prior to initiating antimicrobial ther- apy [1, 2]. Cultures should be investigated for typical and fastidious (e.g. HACEK organisms) pathogens. A transthoracic echocardiogram (TTE) is the first recommended imaging test in IE [1, 2]. Recognizing the TTE sensitivity of 40–63 % and specificity of 98 % [13, 14], a fol- low- up transesophageal echocardiogram (TEE)
Table 19.1 Common causative microorganisms in infec- tive endocarditis [11]
Microorganism Frequency (%)
Staphylococcus aureus 31
Coagulase-negative staphylococcus 11 Viridans group streptococci 17
Streptococcus bovis 6
Other streptococci 6
Enterococcus species 10
HACEK organisms 2
Fungi/yeast 2
Polymicrobial 1
Negative cultures 10
Other 4
Abbreviation: HACEK organisms include Haemophilus species, Aggregatibacter/Actinobacillus actinomycetem- comitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella species
Data from Murdoch et al. [11]
Table 19.2 Modified Duke criteria for infective endocarditis
Major criteria
1. Blood cultures positive for IE
a. Typical IE microorganism from two separate blood cultures
– Viridans streptococci – Streptococcus bovis – HACEK group
– Community-acquired enterococci b. Microorganism consistent with IE from
persistently positive blood cultures – Two blood cultures drawn > 12 h apart – All of three or a majority of ≥ 4 separate blood
cultures (with first and last sample drawn at least 1 h apart)
c. Single positive blood culture for Coxiella burnetii or phase 1 IgG antibody titer > 1:800
Table 19.2 (continued)
2. Evidence of endocardial involvement a. Echocardiography positive for IE
– Vegetation – Abscess
– New partial dehiscence of prosthetic valve b. New valvular regurgitation
Minor criteria 1. Predisposition
– Predisposing heart condition – Injection drug use
2. Fever – temperature > 38° Celsius 3. Vascular phenomena
– Major arterial emboli – Septic pulmonary infarcts – Mycotic aneurysm – Intracranial haemorrhages – Conjunctival haemorrhages – Janeway lesions
4. Immunologic phenomena – Glomerulonephritis – Osler’s nodes – Roth’s spots – Rheumatoid factor 5. Microbiological evidence
– Positive blood culture but does not meet a major criterion
– Serological evidence of active infection with microorganism consistent with IE
Diagnosis
Definite IE Possible IE
2 major criteria 1 major and 1 minor criteria
1 major and 3 minor criteria
3 minor criteria 5 minor criteria
Data from Li et al. [12]
is recommended when: the TTE is non- diagnostic, the TTE is negative with a high index of suspi- cion of IE, structural cardiac complications are suspected, the patient has a prosthetic heart valve or an intra-cardiac device, or there is Staphylococcus aureus bacteremia [1, 2]. The reported sensitivity of TEE is 90–100 % [14, 15].
The reported negative predictive value of the original Duke Criteria is 92 % [16].
Antimicrobial Therapy
For acutely ill patients, an empiric antibiotic regi- men of intravenous vancomycin, gentamicin, and ciprofloxacin or amoxicillin-clavulanate and gen- tamicin has been recommended [2]. However, ini- tial empiric therapy should take into account local patterns of antibiotic resistance. In patients with prosthetic valves within 1 year of surgery, empiric therapy with vancomycin, gentamicin, and rifampin is recommended; rifampin should be ini- tiated once cultures have cleared so as to reduce development of resistance [2]. Antimicrobial ther- apy and duration should be tailored to the specific organism and sensitivity according to published guidelines. The duration of therapy consists of a minimum of 4–6 weeks of intravenous antibiot- ics; the duration should be guided by guideline organism-specific recommendations [2].
Indications for Surgery
Cardiac surgery is recommended in the treat- ment of IE in the following situations [1, 17]:
(1) aortic or mitral valve obstruction or regurgi- tation with heart failure, shock, severe regurgi- tation, or echocardiographic evidence of hemodynamic deterioration (early mitral valve closure or pulmonary hypertension); (2) locally uncontrolled infection or extension (abscess, fistula, aneurysm, heart block, or enlarging veg- etation); (3) fungal, multidrug resistant, or highly resistant organisms; (4) Persistent bacte- remia > 5–10 days despite appropriate antimi- crobial therapy; (5) recurrent embolization with
persistent vegetations; (6) vegetation > 15 mm;
(7) prosthetic valves with relapsing infections.
Follow-Up Evaluation
Daily blood cultures should be drawn until the resolution of bacteremia. New infectious signs (e.g. fever) or clinical evidence of structural com- plications (e.g. heart failure or valvular regurgita- tion) merits re-initiating blood culture surveillance as described in the diagnosis section.
Electrocardiographic surveillance is particularly important in patients at risk for new atrioventric- ular block including those with aortic valve endo- carditis, microorganisms prone to peri-valvular abscess formation (e.g. Staphylococcus aureus), and patients with new atrioventricular block. We recommend routine electrocardiographic surveil- lance until blood cultures are negative and inter- mittently throughout the course of antimicrobial therapy – particularly in patients at high risk of new atrioventricular block including those with aortic valve endocarditis and microorganisms prone to peri-valvular abscess. Serial echocardio- graphic imaging has been recommended for both diagnosis and follow-up. A study in 2004 reported that in patients with a clinical suspicion of IE and a negative first TTE or TEE echocardiogram, a second or third TTE diagnosed an additional 26.7 % of patients with IE, while a second or third TEE diagnosed an additional 19.7 % [18].
Repeat imaging is also recommended when a new complication of IE is suspected (e.g. recur- rent fever, new murmur, new embolus). At the completion of therapy, current guidelines, based largely on expert opinion, recommend follow-up echocardiography to detect any new silent com- plication or any residual vegetation [1, 2].
Evidence Contour
Although antimicrobial therapy and cardiac sur- gery are well established in the management of IE, there are several aspects of IE management that remain controversial or less well defined.
Timing of Non-emergent Surgery in IE
In patients without an emergent or urgent indica- tion for cardiac surgery, there is little evidence to guide the timing of non-urgent surgery for IE. Early surgery may reduce the risk of systemic embolization of vegetations, whereas later sur- gery may facilitate the resolution of bacteremia and reduce the risk of infecting new bioprosthetic material. A recent small randomized study of patients with left sided valvular IE with severe mitral or aortic valve disease, and a vegetation
>10 mm but no other indications for surgery were randomized to early-surgery within 48 h versus conventional care. Early surgery significantly reduced the composite end point of death and embolic events (3 % versus 23 %, p =0.03) and no differences in prosthetic valve IE recurrence was observed suggesting a possible benefit with early cardiac surgery [19].
Neuroimaging in IE
A reported 22–50 % of IE cases are complicated by a systemic embolization, with 65 % of these events involving the central nervous system [20, 21]. Cerebral emboli can cause strokes, mycotic aneurysms, and lead to hemorrhagic transforma- tion. There are no guidelines for neuroimaging test selection; however we recommend the fol- lowing approach: (1) All patients with new neu- rologic signs or symptoms should initially be evaluated with a non-contrast CT scan of the head. (2) Magnetic resonance imaging can be considered in symptomatic patients with a nor- mal CT scan or to better define CT findings. (3) CT or magnetic resonance angiography can be used to evaluate mycotic aneurysms. Their role, however, in patients with early stroke symptoms to guide endovascular therapy is unclear in this population and should be made in conjunction with a neurologist [22, 23]. In neurologically asymptomatic IE patients, a small case series has reported that 79 % of patients had cerebral mag- netic resonance imaging abnormalities and these
findings upgraded the diagnosis of IE from possible to definite in 34 % of patients [24].
Pending further outcome based studies, we do not recommend routine neuroimaging in neuro- logically asymptomatic patients.
Timing of Surgery in IE with Septic Cerebral Embolic Strokes
Embolic events from IE are associated with an increase in-hospital mortality [25]. Patients who require cardiac surgery after an embolic stroke have a potential risk of hemorrhagic transforma- tion with coronary artery bypass pump anti- coagulation. Given this additional risk, the optimal timing for surgery in patients with embolic complications remains unclear. An observational study compared early surgery (1–7 days after ischemic stroke) to late surgery (>7 days after ischemic stroke) and found no dif- ference in in-hospital or 1 year mortality [26].
Other studies, however, have reported higher in- hospital mortality and cerebral exacerbation rates associated with early surgery [27]. Until ade- quately powered randomized trials are per- formed, the appropriate timing of surgery will remain uncertain and treatment timing decisions should be individualized.
Valve Repair Versus Valve Replacement
There is very little high quality evidence to guide the choice of valve repair versus valve replace- ment in the setting of IE. Valve repair is theoreti- cally more appealing given that the lack of prosthetic material reduces the risk of recurrence of IE [28–30]. A systematic review and meta- analysis of 24 observational studies compared a total of 470 patients who underwent mitral valve repair while 724 patients underwent valve replace- ment. Patients who underwent mitral valve repair had lower in-hospital (2.3 % versus 14.4 %) and long-term (7.8 % versus 40.5 %) mortality [31].
However, this evidence is limited by the potential
for residual confounding in observational studies and the lack of randomized studies.
Cardiac Device Related IE
The risk of IE in patients with pacemakers or implantable cardioverter defibrillators ranges from 1.82 to 1.90 per 1000-device years [32, 33]. The diagnosis of IE is more difficult in this population because blood cultures are negative in 23 %, the sen- sitivity of the Duke criteria is lower, and TEEs have a higher false negative rate [33]. Medical therapy alone has been associated with increased morbidity and mortality [34]. Accordingly, guidelines recom- mend that all patients with IE should have their devices removed and/or replaced; preferably percu- taneous laser lead extraction techniques should be performed followed by a 4–6 week course of antibi- otics [1, 2]. The optimal timing of both device removal and re-implantation remains unclear.
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