, Rocío M. Hurtado1 and Rajesh TIM Gandhi1, 2
(1)
Harvard Medical School Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
(2)
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA
Abstract
Infective endocarditis (IE) is a highly morbid infection with a diversity of clinical presentations and etiologies that is best managed with a multidisciplinary team. Similarly, cardiac device infections are occurring at increasing rates and require a high index of suspicion, careful workup, and a multidisciplinary treatment plan.
HIV-infected patients not on antiretroviral therapy (ART) or with low CD4 cell counts (<200 cells/mm3) are at risk for a broad array of opportunistic conditions (infections and cancers). HIV-infected patients on ART with normal CD4 cell counts are not at risk for opportunistic conditions but have an increased rate of atherosclerosis and cardiovascular events, probably because of ongoing inflammation. Drug interactions with antiretroviral medications should be considered before prescribing commonly used cardiac medications, including statins.
Abbreviations
Abx
Antibiotics
AIDS
Acquired immunodeficiency syndrome
ART
Antiretroviral therapy
AZT
Zidovudine
BCx
Blood cultures
CAD
Coronary artery disease
CHF
Congestive HF (Heart Failure)
CIED
Cardiac implantable electronic devices
CNS
Central nervous system
CT
Computed tomography
CVD
Cardiovascular disease
ECG
Electrocardiography
HIV
Human immunodeficiency virus
ICD
Implantable cardioverter defibrillator
IDU
Intravenous drug user
IE
Infective endocarditis
JVP
Jugular venous pressure
LVAD
Left ventricular assist device
NSTEMI
Non-ST elevation myocardial infarction
NVE
Native valve endocarditis
NYHA
New York Heart Association
PAH
Pulmonary arterial hypertension
PCR
Polymerase chain reaction
PPM
Permanent pacemaker
PVE
Prosthetic valve endocarditis
TEE
Trans-esophageal echocardiography
TIMI
“Thrombolysis in myocardial infarction” research group
TPN
Total parenteral nutrition
TTE
Trans-thoracic echocardiography
Introduction
Infective endocarditis (IE) is a highly morbid infection with a diversity of clinical presentations and etiologies that is best managed with a multidisciplinary team. Similarly, cardiac device infections are occurring at increasing rates and require a high index of suspicion, careful workup, and a multidisciplinary treatment plan.
HIV-infected patients not on antiretroviral therapy (ART) or with low CD4 cell counts (<200 cells/mm3) are at risk for a broad array of opportunistic conditions (infections and cancers). HIV-infected patients on ART with normal CD4 cell counts are not at risk for opportunistic conditions but have an increased rate of atherosclerosis and cardiovascular events, probably because of ongoing inflammation. Drug interactions with antiretroviral medications should be considered before prescribing commonly used cardiac medications, including statins.
Infective Endocarditis
An infection of the endocardium, which most frequently involves the heart valves but can also include chamber walls, chordae, and prosthetic tissue [1]
A.
Epidemiology and Risk Factors
Degenerative valvular heart disease is a common predisposing condition in the modern era [2]
Up to 25 % of IE cases in a large international cohort have been linked to nosocomial exposure [2]
IE continues to be common among intravenous drug users (IDU) and account for ∼10 % of hospital admissions [3]
Staphylococcus aureus is most common pathogen
Polymicrobial or unusual pathogens are also more common in IDU with IE
Right-sided IE is particularly common in IDU with presentation of tricuspid insufficiency and/or pleuritic chest pain from septic emboli
B.
Clinical Presentation and Diagnosis
IE is a heterogeneous disease with a wide range of clinical presentations, so a high index of suspicion and thorough, multidisciplinary diagnostic evaluation is often needed
Clinical signs and symptoms: Most common findings in international cohort of IE [2]:
Fever (96 %)
New murmur (48 %)
Worsening of old murmur (20 %)
Echocardiography: Characteristics suggestive of vegetation [1]
Location: amidst high velocity jet or on “upstream” side of regurgitant valve
Motion: chaotic
Shape: amorphous
Texture: grey scale in comparison to calcification on myocardium
Associated abnormalities, such as leaks, fistula, or abscess
Serial echocardiograms may be useful in the setting of high pre-test probability and an initially negative study (Table 29-1)
Sensitivity (%)
Specificity (%)
Native valve
TTE
60–65
90–98
TEE
85–95
90–98
Prosthetic valve
TTE
<50
90–98
TEE
82–90
90–98
C.
Microbiology and pathology:
Blood cultures prior to antimicrobial initiation are imperative for diagnosis
Optimally, three sets of blood cultures will be obtained over 24 h
Minimum of 10 cc in each blood culture bottle for improved yield in adults
Histologic findings on cardiac valves after surgical resection can be diagnostic [4], including the specific pattern of inflammation [5]
Current standard of care for diagnosis is the modified Duke criteria (Tables 29-2, 29-2, and 29-3)
Table 29-2
Definition of IE according to the modified Duke criteria, adopted with permission from [64]
Definite infective endocarditis
Pathologic criteria
(1) Microorganisms demonstrated by culture or histologic examination of a vegetation, a vegetation that has embolized, or an intracardiac abscess specimen; or
(2) Pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis
Clinical criteria
(1) Two major criteria; or
(2) One major criterion and three minor criteria; or
(3) Five minor criteria
Possible infective endocarditis
(1) One major criterion and one minor criterion; or
(2) Three minor criteria
Rejected
(1) Firm alternate diagnosis explaining evidence of infective endocarditis; or
(2) Resolution of infective endocarditis syndrome at surgery or autopsy, 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
Table 29-3
Definition of terms used in the modified Duke criteria for the diagnosis of infective endocarditis (IE), adopted with permission from [64]
Major criteria
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 two positive cultures of blood samples drawn > 12 h apart or single positive blood culture for Coxiella burnetii or IgG antibody titer > 1:800
Evidence of endocardial involvement:
Echocardiogram positive for IE, 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
Abscess
or
New partial dehiscence of prosthetic valve
New valvular regurgitation (worsening or changing of pre-existing murmur not sufficient)
Minor criteria
Predisposition, predisposing heart condition, or IDU
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’s nodes, Roth spots, and rheumatoid factor
Microbiological evidence: positive blood culture but does not meet a major criterion as noted above or serologic evidence
D.
Treatment
Prompt initiation of parenteral antimicrobials is the mainstay of treatment, in conjunction with surgical evaluation when indicated (Table 29-4)
Table 29-4
Guidelines for antibiotic selection and treatment duration for native valve endocarditis [3]
Pathogen | Antimicrobial (S) | Duration (weeks) |
|---|---|---|
Streptococcus (viridans group or bovis) | PCN or Ceftriaxone OR | 4 |
(dosing depends on MIC to PCN) | PCN or Ceftriaxone + Gentamicin OR | 2 |
If MIC for PCN >0.5 ug/mL | Vancomycin (PCN-allergic) use Enterococcal IE guidelines | 4 |
Staphylococci | 6 | |
If oxacillin-susceptiblea | Nafcillin or Oxacillin ± Gentamicin | 3–5 days |
If oxacillin-resistant or for PCN-allergic patients | Vancomycin ± Gentamicin (or PCN-allergic) | 6 |
Enterococcus (if susceptible to PCN, Gentamicin, and | Ampicillin or PCN + Gentamicin | 4–6 |
OR | ||
Vancomycin (in cases of resistance, ID consultation) | Vancomycin + Gentamicin | 6 |
HACEKb | Ceftriaxone OR | 4 |
Ampicillin-sulbactam OR | ||
Ciprofloxacin (PCN-allergy) | ||
Culture-negative | Ampicillin-sulbactam + Gentamicin OR | 4–6 |
Vancomycin + Gentamicin + Ciprofloxacin | ||
Culture-negative (suspected Bartonella) | Ceftriaxone + Gentamicin ± Doxycycline (Gentamicin can be discontinued at 2 weeks) | 6 |
E.
Complications
IE can pursue a fulminant or subacute clinical course that depends on host, pathogen and the rapidity of diagnosis, treatment initiation, and presence of complications from the endovascular infection.
Heart failure (HF) [3]
Most common and feared complication of IE given increased rates of morbidity and mortality
Frequency of acute HF depends on location of IE: 29 % (aortic), 20 % (mitral), versus 8 % (tricuspid)
All patients with IE and in clinical HF should be considered for immediate surgical evaluation
Timing of surgical intervention depends on clinical status; surgery earlier in clinical course is often better tolerated [7]
Worse outcomes when surgical intervention is performed in patients with advanced age, in renal failure or in NYHA Class III or IV heart failure
Embolization
Evident in 22–50 % of IE cases and associated with increased morbidity and mortality
65 % of emboli involve the central nervous system (CNS), especially in the middle cerebral artery distribution
Uncertain clinical significance to asymptomatic CNS emboli incidentally found on imaging [8]
After initial 2–3 weeks of antimicrobials, embolic events are much less likely
Risk factors for embolization may include: vegetation size, mitral valve involvement, staphylococcal species, prior emboli [9, 10]
Timing of surgery in patient with CNS emboli and/or use of anticoagulation remain a controversial topic [9, 11]
Intracranial hemorrhage remains a devastating complication (∼5 %) and contraindication to surgical intervention [8, 12] (Table 29-5)
Complication
Clinical features
Diagnostic testing (sensitivity/specificity)
Treatment recommendations
Valvular extension
Heart block
ECG to assess for conduction abnormalities (sensitivity 45 %)
Surgical evaluation
TEE (sensitivity 76–100 %; specificity 95 %)
Splenic abscess
Abdominal pain
CT or MRI (sensitivity and specificity: 90–95 %)
Percutaneous drainage or splenectomy
Pleuritic or shoulder pain
Persistent fever
Mycotic aneurysm (intracranial or extracranial)
Focal neurologic findings or mental status deterioration
CT or MRA (sensitivity and specificity: 90–95 %)
Antimicrobials with surgical or endovascular treatment if progression or rupture
F.
Surgery for IE
Although surgical interventions must always be individualized with input from the medical and surgical teams, guidelines suggest specific indications for careful consideration of surgical intervention [1, 3]. Importantly, post-operative infection of new prostheses is rare (2–3 %) even when surgical intervention is performed in active IE [3] (Table 29-6).
Vegetation | Valvular dysfunction | Perivalvular extension |
|---|---|---|
Persistent vegetation after systemic embolization | Acute aortic or mitral insufficiency with signs of ventricular failure | Valvular dehiscence, rupture, or fistula |
Anterior mitral leaflet vegetation, particularly if >10 mm | CHF that is unresponsive to medical management | New heart block |
≥1 embolic events during first 2 weeks of antimicrobial therapy | Valve perforation or rupture | Large abscess or extension of abscess despite appropriate antimicrobial therapy |
Increase in vegetation size despite appropriate antimicrobial therapy |
Class I, Level of Evidence: B
HF
Valvular dehiscence, rupture, or perforation
Perivalvular abscess or periannular extension
Fungal IE or multidrug-resistant aggressive pathogens
Persistently positive blood cultures after >1 week of targeted antimicrobials
≥1 embolic event during the initial 2 weeks of antimicrobials
Class IIa, Level of Evidence: B
Anterior mitral leaflet vegetation, especially if >10 mm
Class IIb, Level of Evidence: C
Increased vegetation size despite targeted antimicrobials
G.
Outcomes and follow–up
Almost 50 % of patients with IE require surgical intervention [2]
Inpatient mortality remains 15–20 % in the twenty first century [2]
Risk factors for death include increasing age, HF, paravalvular complications, prosthetic valve endocarditis, and Staphylococcus aureus as the causative organism
Many patients with IE on stable parenteral antimicrobial therapy can be managed in the outpatient setting with careful monitoring and follow-up [13]
TTE should be obtained as a new baseline after treatment; if cardiac windows are inadequate, then a TEE should be performed
IE prophylaxis should be prescribed for appropriate procedures in patients who have recovered from IE [14]
Special Topic – Prosthetic Valve Endocarditis (PVE)
Distinguished by early and late presentation (≤ or >1 year post-valve surgery); clinical course and causative organisms can be different [15]
Most often requires surgical intervention because frequently complicated by perivalvular abscess, leak or other valvular dysfunction
S. aureus and coagulase-negative staphylococcus are the most common etiologies, especially in early PVE; nosocomial pathogens are also more common than in NVE [16]
Antimicrobial treatment algorithms are available for PVE [3] but should be used in conjunction with Infectious Disease consultation given complexities of diagnosis and treatment in this patient population
Special Topic: Culture Negative Endocarditis
Causes [18]
Receipt of antimicrobials prior to collection of blood cultures
Right-sided endocarditis
Endocarditis with cardiac device
Non-bacterial pathogen (e.g., fungi, mycobacteria) or non-infectious etiology (e.g., neoplastic or auto-immune phenomenon)
Fastidious organisms (often intracellular) that require different diagnostic tools
Coxiella burnetii (“Q fever”)
Bartonella spp
Brucella spp
Mycoplasma spp
Tropheryma whipelii
Nutritionally deficient streptococci (non-intracellular org)
HACEK organisms (haemophilus spp; Actinobacillus spp; Cardiobacterium hominis; Eikenella corrodens; Kingella kingae)
Diagnosis [19]
Specialized culture techniques
Serology
16S and 18S ribosomal PCR (serum, valve tissue)
Treatment: in conjunction with Infectious Diseases consultation
Special Topic: Fungal Endocarditis
Fungal IE is a rare (<10 %) but increasingly prevalent form of IE
Most commonly Candida spp
Aspergillus spp, Histoplasmosis and other fungi have been reported to cause IE especially in immunocompromised hosts
Risk factors: prosthetic valves, nosocomial exposures, short-term catheters [21], immunocompromise, antibiotic use, IDU, TPN [20]
Complications: most commonly embolization and large vegetations. HF is less common [21]
Treatment: medical ± surgical
Recurrence rates are extremely high, so secondary prophylaxis with oral fluconazole is recommended for at least 2 years if not life-long [21–23]
ID Consultation is strongly advised
Special Topic: Endocarditis Prophylaxis (Tables 29-7, 29-8, and 29-9)
Prosthetic cardiac valve or prosthetic material in valve repair |
History of prior IE |
Specific forms of congenital heart disease (CHD) |
Completely repaired CHD if prosthetic material or device was placed within past 6 months |
Repaired CHD with residual defects at or adjacent to site of prosthetic material or device |
Unrepaired cyanotic CHD |
Cardiac transplant with valvulopathy |
Dental procedures: |
Any procedure that involves manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa. |
Respiratory procedures: |
If procedure is invasive with incision or biopsy. Not indicated in bronchoscopy. |
GI/GU procedures: |
No prophylaxis indicated. |
Active treatment of GI or GU infection (if present) prior to procedure is recommended. |
Regimen | Antibiotics |
|---|---|
Preferred | Amoxicillin 2 g PO |
PCN allergy | Clindamycin 600 mg PO OR Azithromycin 500 mg PO |
Unable to take oral medication | Ampicillin 2 g IV OR Cefazolin 1 g IM or IV |
Unable to take oral and PCN allergy | Cefazolin 1 g IM or IV OR Clindamycin 600 mg IM or IV |
Special Topic: Device Infections
A.
Cardiovascular implantable electronic device infection (CIED): includes ICD and PPM
B.
Epidemiology: CIED infections is a growing problem that is out of proportion to the increased rates of device implantation
Over past 20 years, there have been more infections and more hospitalizations< div class='tao-gold-member'>Only gold members can continue reading. Log In or Register to continue
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