OS 213LEC 11: INFECTIVE ENDOCARDITIS

OS 210LEC 0X: TITLE

OS 213: Circulation and Respiration (Cardiovascular Module)LEC 11: INFECTIVE ENDOCARDITIS Quiz 1 | Dr. Anonuevo | September 26, 2012

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OUTLINE1. Definition1. Acute vs. Sub-acute Endocarditis1. Native vs. Prosthetic Valve Endocarditis1. Right vs. Left Endocarditis1. Predisposing Conditions1. Etiologic MicroorganismsA. Streptococcus viridansB. EnterococcusC. Staphylococcus D. Gram-Negative Bacteremia1. Pathogenesis1. Presentations of IE1. Clinical Manifestations1. Peripheral Manifestations1. The Dukes Clinical Criteria for IE1. Treatment 1. Prophylaxis1. Risk Categories1. Updated AHA Recommendations (2008)

DEFINITION

Microbial infection of the endothelium of the heart (can also involve the valves, chamber walls, and even the vascular tree) But endocarditis may also arise without microbial involvement just like in systemic lupus erythematosus (mantaric endocarditis) Vegetation is the characteristic lesion (more than 90% diagnostic of infective endocarditis/IE) An amorphous substance of variable size containing platelets, fibrin, coagulation factors, microorganisms (usually bacteria) and inflammatory cells Heart valves are most commonly involved, though any part containing endothelium is a possible site of infection(interatrial or interventricular septum in ASD or VSD) with the mitral valve most often infected (next is the aortic valve) One of the most important disease entities one has to know when going to the wards very important to diagnose and treat Not very common in the Philippines, but typically seen in third-world countries where prevention is lacking and the incidence of rheumatic heart disease promotes its occurrence

Acute vs. Sub-acute Endocarditis

1. History as main basis for differentiation1. Differentiation needed for appropriate use of antibiotics

ACUTESUB-ACUTE

DurationFew days to few weeksWeeks to months

Symptoms High-grade fever Very toxic and sick patient Low-grade fever Lingering illness Malaise Depressed appetite

Etiologic OrganismStaphylococcus aureusStreptococcus viridans

TreatmentGentamicin (3-5 days) + Nafcillin/Oxacillin/ Vancomycin for 4 weeksGentamicin (2 weeks) + Penicillin G or Ampicillin (4 weeks)

Other Characteristics More valvular destruction and metastatic lesions/infections Rarely causes metastatic lesions Non-specific symptoms make it hard to diagnose

Native vs. Prosthetic Valve Endocarditis

Native ValveEndocarditis (NVE)Prosthetic ValveEndocarditis (PVE)

Valves you were born with will develop infection Mechanical or bioprosthetic valve used to replace damaged native valve develops endocarditis Usually derived from pericardium or bovine material Identified by chest cars and mechanical clicks on auscultation

Right vs. Left Endocarditis

Right EndocarditisLeft Endocarditis

Involves the tricuspid and/or pulmonic valves Involves the mitral and/or aortic valves

PREDISPOSING CONDITIONS FOR NVE

1. Rheumatic Heart Disease (RHD) most common in Philippines (95% of IE cases)2. Congenital heart disease (e.g. bicuspid aortic valve) most common in developed countries3. Mitral valve prolapse (next is Bicuspid aortic valve) also common in developed countries4. Degenerative heart disease Significant in the elderly (30% in 60 year-old patients) Thickening of the valves as part of the aging process5. Parenteral drug abuse 15-35% Can cause IE even in the absence of valve problems Use of parenteral needles can deliver bacteria found in the skin to the heart and cause IE Endocarditis, especially those on the tricuspid valve, are often caused by strains of S. aureus which are methicillin-resistant6. Others7. Spontaneous IE 25-45% Develop IE without predisposing factors

ETIOLOGIC ORGANISMS

Results of bacterial culture for IE takes 4-5 days to come out, thus prophylaxis is given based on what the organism most likely is Etiologic organism is usually dependent on the circumstances of the patient, e.g. dental procedure = S. viridians Most common associated etiologic organism for sub-acute IE1. Streptococci2. Enterococci3. Staph aureus4. Coagulase-negative Staph (Staphylococcus epidermidis)5. Gram negative bacteria6. Fungi7. Culture negative

For NVEFor PVE

#1 Streptococci (viridans): 45-65% #2 Enterococci: 5-8% Staphylococci (aureus): 35-40% (#2 if with history of IV abuse) Fungi

Early post-operation (12 mos.): Streptococci

Streptococcus Viridans

30-65% of NVE unrelated to drug use Normal inhabitants of the oropharynx Most common sub-acute IE Not a species but a group of species: Streptococci mitior(31%), sanguis (24%), bovis(20-40%), mutans (7%) May result from bacteremia Can occur via dental procedures in patients with cardiac conditions S. bovis originates from the GIT, associated with polyps and colonic tumors; enters bloodstream from the genitourinary tract Susceptible to penicillin Usually present with long-standing low-grade fever and anorexia, but with no toxic manifestations

Enterococcus

Enterococcus faecalis, faecium Part of normal the GI/GU flora Occurs with genitourinary manipulation Second most common cause of NVE unrelated to drug abuse 5-15% of chronic NVE , but may also cause prosthetic and acute IE Resistant tosemi-synthetic penicillinase-resistant penicillin, cyclosporinsand therapeutic concentrations of aminoglycosides Also resistant to oxacillin, nafcillin and cephalosporins, and are actually inhibited by penicillin, ampicillin, vancomycin and teicoplanin (Harrisons, 16thed, vol. 1, p. 737) Usually treated by combination therapy of cell wall active agents, e.g. penicillin + aminoglycosides like gentamicin Common in UTI, catherized patients and those recovering from surgery

Staphylococcus

Coagulase-Positive (S. aureus)

More likely present with sub-acute IE Major cause of IE in all populations especially health care associated and in drug abuse Characterized by a highly toxic febrile illness, frequent focal metastatic infection and central nervous system complication Primarily a right-sided infection (e.g. skin infection goes to the right part of the heart first) Treated progressively with antibiotics Oxacillin, not ampicillin Resistant to penicillin and methicillin sincepenicillinase is produced by 95% of staphylococci

Coagulase-Negative (S. epidermidis)

Cause 3-5% of NVE Major cause of PVE during first year after valve surgery- nosocomial IE PVE usually occurs within the first 60 days following valve replacement

Gram-Negative Bacteria

HACEK organisms: Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella Pseudomonas aeruginosa most common gram-negative bacillus cause of IE; one of the most common cause of septicemia in hospitalized patients Large vegetations with high incidence of emboli Very rare, usually seen in: Immunocompromised patients Those staying in the wards for a long time Persons who have undergone multiple invasive procedures Patients in the ICUs who are intubated, with indwelling catheters, central lines, etc.

PATHOGENESIS

Figure 1. Development of Infective Endocarditis. Endothelial injury caused by (any rheumatic, congenital or degenerative heart condition causing abnormal flow of blood): Flow of blood through a narrow orifice (ex: aortic stenosis) Flow of blood across high pressure chamber High stream flow through VSD and ASD Therefore, IE is often associated with an existing heart problem, but IE may also occur without an existing heart condition (as in degenerative valves without congenital anomaly). Seen when patients undergo dental manipulation, oropharyngeal manipulation, invasive procedures, etc. Injury to the endothelium causes aberrant flow and allows either direct infection by virulent organism or the development of the uninfected platelet-fibrin thrombus Platelet-fibrin complex is more sensitive to colonization by bacteria NBTE is a hemostatic mechanism of the body; commonly found in autopsy Also arises from a hypercoagulable state in a condition called marantic (wasting away) endocarditis, consisting of uninfected vegetations in patients with malignancies and chronic diseases, or bland vegetations that could complicate diseases such as systemic lupus erythematosus and anti-phospholipid antibody syndrome Bacteremia may occur after a dental, GU or GI procedure, or in IV drug abuse because of the needle used Antibiotic is then important to give to patients with predisposing factors before they undergo certain medical procedures to prevent infection (e.g. patient with RHD about to have dental work done)

PRESENTATIONS OF IE

Clinical Manifestations

Local destructive effects Infection of vegetations can form abscesses in valves Infected mitral valve (MV) leaflet can perforate and lead to regurgitation Embolizations Can occur in vital organs with dire consequences Lungs- pneumonia Brain- stroke Kidney, renal artery- acute renal failure GIT- acute mesenteric ischemia Peripheral system- peripheral occlusive disease Right sided emboli (from tricuspid valve) can go to the lungs Left-sided emboli (from mitral valve and aortic valve) can go to the systemic circulation Hematogenous seeding Due to persistent bacteremia Abscesses in other parts of the body secondary to metastatic infections Antibody response Immune complex formation can lead to glomerulonephritis

PresentationOccurrence

SYMPTOMSFeverAnorexiaWeight lossMalaiseMyalgia and arthralgia80-85%25-55%25-35%25-40%15-30%

SIGNSFeverMurmur (Acute IE)Neurologic abnormalitiesSplenomegaly (chronic IE)Peripheral Manifestations80-90%80-85%30-40%15-50%

1. Fever is the most common presentation0. Sub-acute: Low-grade, rarely exceeds 39.4 C0. Acute: High- grade, 39.4 - 40 C1. Neurologic abnormalities secondary to septic embolism of the vegetation

Peripheral Manifestations

1. Subconjunctival petechiae2. Due to infections by Staphylococcus aureus1. Splinter Hemorrhages3. Linear reddish-brown lesion in the nail bed due to group B Strep1. Oslers Nodes4. Tender, erythematous papulopustules located in the pulp of the fingers or toes of patients with Staphylococcus aureus1. Janeway Lesions5. Macular, painless, non-tender, blanching lesions on the palms and soles due to Streptococcus bovis1. Figure 2.Oslers Nodes, Janeway Lesions and Roth Spots. (From top to bottom)Roth Spots6. Retinal hemorrhages with a pale white center seen in fundoscopy1. Septic Embolizations7. Can cause obstructions to blood flow

The Dukes Clinical Criteria for IE

Major Criteria

1. Persistently positive blood cultures8. Recovery of a microorganism consistent with infective endocarditis from0. Blood cultures drawn >12 hours apart OR0. All of 3 or a majority of 4 or more separate blood cultures, with the first and the last drawn at least an hour apart8. Blood cultures should not be related to peak of fever8. Blood samples should be obtained prior antibiotic therapy8. Source of blood can be venous or arterial8. Samples should be from two different sites1. Evidence of endocardial involvement9. Presence of vegetations in echocardiogram0. May be trans-thoracic (TTE) or trans-esophageal (TEE)9. Oscillating intracardiac mass on valve or supporting structures, or in the path of regurgitant jets, or in implanted material in the absence of an alternative explanation9. Abscesses9. New partial dehiscence of a prosthetic valve9. New valvular regurgitation 4. Increase or change in preexisting murmur not sufficient

Minor Criteria

1. Predisposing heart condition (e.g. mitral valve prolapse, degenerative conditions) Exception: Spontaneous IE1. Fever >38 C1. Vascular phenomena12. Major arterial emboli12. Septic pulmonary infarcts12. Mycotic aneurysm12. Intracranial hemorrhage12. Conjunctival hemorrhages 12. Janeway lesions1. Immunological phenomena13. Glomerulonephritis13. Oslers nodes13. Roth spots1. Microbiological evidence14. (+) Culture meeting major criterion as noted below14. Serologic evidence of active infection with organism consistent with infective endocarditis1. Echocardiogram consistent but not meeting major criteria

DEFINITE IE1. Pathological criteria0. Microorganisms: demonstrated by culture or histology in a vegetation, embolized vegetation or intracardiac abscess0. Pathological lesions: vegetation or intracardiac abscess present confirmed by histology as active endocarditis 1. Clinical criteria1. Two major criteria,OR1. One major & three minor, OR 1. Five minor criteria

POSSIBLE IEFindings consistent with IE falling short of definite endocarditis but not rejected

REJECTED IE0. Firm alternative diagnosis for manifestations of endocarditis, OR0. Sustained resolution of symptoms of endocarditis with antibiotic therapy for < 4days, (bacteremia is much that more than 4d is needed), OR0. No pathological evidence of IE at surgery or autopsy after antibiotic treatment for < 4 days

TREATMENT

0. Hard to remember all, and one would inevitably have to refer to books; nonetheless, it should be known that a doctor needs to consider patient conditions and history in determining most likely etiologic agent and thus in deciding empirical treatment0. Goals: eradicate bacteria and correct any resultant destructions0. To ensure that all bacteria are killed, therapy must be bactericidal and must be given for prolonged periods5. It is difficult to eradicate bacteria from avascular regions in infective endocarditis because the site is relatively inaccessible to host defenses5. The bacterial burden is very high (109-1010 bacteria per grams of tissue involved)5. They are established colonizers (dormant)0. Antibiotics must be given parenterally, never by oral route, and must reach high concentrations at the depths of the vegetation0. Anaphylactic reaction most common adverse effect of the treatment of IE

SUMMARY0. Streptococci: Penicillin0. Enterococci: Penicillin + Aminoglycoside0. If allergic to Penicillin: Vancomycin0. Staphylococci without prosthesis: Naficillin or oxacillin0. Staphylococci with prosthesis: Vancomycin

Table 1. Treatment for NVE due to penicillin-susceptible S. viridians and Streptococci bovi. (Minimum inhibitory concentration 0.1g/ml)ANTIBIOTICDOSAGE AND ROUTEDURATION (Wks)

Aqueous penicillin G12-18 million U/24hrs IV either continuously or every 4 hrs in 6 equally divided doses4

Ceftriaxone* usually done in an out- patient basis not done here in the Philippines2gm once daily IV or IM4

Aqueous penicillin G plus Gentamicin*for earlier discharge

1mg/kg IM or IV every 8hrs2

Vancomycin*given if Px has allergy to penicillin or ceftriaxone30mg/kg per 24hrs IV in two equally divided doses, not to exceed 2gm/24hrs unless serum levels are monitored4

Table 2. Standard therapy for endocarditis due to enterococci.ANTIBIOTICDOSAGE AND ROUTEDURATION (Wks)

Aqueous penicillin G plus Gentamicin18-30 million U/24hrs IV either continuously or every 4hrs in 6 equally divided doses4-6

1mg/kg IM or IV every 8hrs4-6

Ampicillinplus Gentamicin12gm/24hrs IV either continuously or every 4hrs in 6 equally divided doses4-6

1mg/kg IM or IV every 8hrs4-6

Vancomycinplus Gentamicin20mg/kg/24hrs IV in two equally divided doses not to exceed 2gm/24hrs unless serum levels are monitored4-6

1mg/kg IM or IV every 8hrs4-6

Table 3. Treatment for Staphylococcal endocarditis in the ABSENCE of prosthetic material.ANTIBIOTICDOSAGE AND ROUTEDURATION (Wks)

Methicillin- susceptible StaphylococciNaficillin or oxacillin2gm IV every 4hrs4-6

With optional addition of gentamicin1mg/kg IM or IV every 8hrs3-5 days

Cefazolin (or other 1st gen cephalosporin in equivalent dosages)2gm IV every 8hrs4-6

With optional addition of gentamicin1mg/kg IM or IV every 8hrs3-5 days

Vancomycin30mg/kg/24hrs IV in two equally divided doses, not to exceed 2gm/24hrs unless serum levels are monitored4-6

Methicillin-resistant StaphylococciVancomycin30mg/kg/24hrs IV in two equally divided doses, not to exceed 2gm/24hrs unless serum levels are monitored4-6

Table 4. Treatment for Staphylococcal endocarditis in the PRESENCE of prosthetic material.ANTIBIOTICDOSAGE AND ROUTEDURATION (Wks)

Methicillin- resistant StaphylococciVancomycin30mg/kg/24hrs IV in two equally divided doses, not to exceed 2gm/24hrs unless serum levels are monitored6

plus Rifampicin and Gentamicin300mg p.o. every 8hrs6

1.0mg/kg IM or IV every 8hrs2

Naficillin or Oxacillin2gm IV every 4hrs6

Methicillin- susceptible StaphylococciPlus Rifampicin300mg p.o. every 8hrs6

And Gentamicin1.0mg/kg IM or IV every 8hrs2

Cardiac Surgery

0. Considered when:13. Patient is not responding to antibiotics13. There is no improvement in the condition after 1 week

Table 5. Deciding factors for surgery in IE patients.ABSOLUTE INDICATIONSRELATIVE INDICATIONS

0. Moderate to severe congestive heart failure due to valve dysfunction1. Usually regurgitant and insufficiencies0. Unstable prosthesis0. Uncontrolled infection1. Persistent bacteremia1. Ineffective anti-microbial therapy1. Fungal endocarditis0. Relapse after optimal therapy (prosthetic valves)0. Peri-valvular extension of infection1. Abscess around the valve0. Staphylococcus aureus endocarditis1. For aortic, mitral prosthetic valves0. Relapse after optimal antimicrobial therapy1. For native valves0. Culture-negative endocarditis with persistent unexplained fever 1. 10 days0. Large (>10mm) vegetations1. Puts the patient at risk for septic embolizations

PROPHYLAXIS

1. Prophylaxis to prevent the natural progression of the pathophysiology of IE, especially in patients with predispositions1. Most adverse effect in giving prophylaxis: anaphylactic reaction (Better to be safe than sorry in considering whether to administer)Risk Categories

Most of the conditions listed here may already have NBTE thus they only require bacteremia for IE to be established

Table 6. Categories of risk of cardiac conditions associated with endocarditis.HIGH RISK0. Prosthetic valves (bioprosthetic and homograft)0. Previous bacterial endocarditis0. Complex cyanotic congenital heart disease0. Surgically constructed systemic pulmonary shuntsProphylaxis RECOMMENDED

MODERATE RISK0. Other congenital cardiac malformations0. Acquired valvular dysfunction0. Hypertrophic cardiac myopathy0. MVP with regurgitation and/or thickened leafletsProphylaxis NOT RECOMMENDED

NEGLIGIBLE RISK

0. Isolated secundum atrial septal defect0. Surgical repair of ASD, VSD or PDA without residua within 6 months0. Previous coronary artery bypass graft0. MVP without regurgitation0. Physiologic, functional or innocent cardiac murmurs0. Previous Kawasaki disease without valvular dysfunction0. Previous rheumatic fever without valvular dysfunction0. Cardiac pacemakers (intravascular and epicardial) and implanted defibrillatorsProphylaxis NOT RECOMMENDED

PROPHYLAXIS IN DENTAL PROCEDURES

Among medical procedures, this has the strongest possibility of developing bacteremia

0. Reasonable only for patients without underlying cardiac conditions associated with highest risk of adverse outcome from IE0. Reasonable for all dental procedures that involve manipulation of either gingival tissue or the periapical region of teeth or perforation of oral mucosa0. Not recommended solely on the basis of an increase lifetime risk of acquisition of IE

Who should receive IE prophylaxis during dental procedures?

0. Patients with prosthetic cardiac valves or material used for cardiac valve repair0. Patients with previous IE0. Patients with unrepaired cyanotic CHD, including palliative shunts and conduits0. Patients with completely repaired CHD during the first 6 months after surgery or catheter-guided procedure0. Patients with repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or device0. Cardiac transplant recipients with valve regurgitation due to a structurally abnormal valve

Table 7.Prophylactic regimens for dental procedures.Regimen Single Dose 30 to 60m before procedure

SituationAgentAdultChildren

OralAmpicillin2g50mg/kg

Unable to take oral medicationAmpicillin

OR

Cefazolin or ceftriaxone2g IM or IV

1g IM or IV

50mg/kg IM or IV

50mg/kg IM or IV

Allergic to Penicillins or Ampicillins OralCephalexin

OR

Clindamycin

OR

Azithromycin or clarithromycin2mg

600mg

500mg

50mg/kg IM or IV

20mg/kg IM or IV

15mg/kg IM or IV

Allergic and unable to take oralCefazolin or ceftriaxone

OR

Clindamycin1g IM or IV

600 mg IM or IV50mg/kg IM or IV

20mg/kg IM or IV

IE Prophylaxis and Other Procedures

0. No longer recommended for gastrointestinal or genitourinary tract procedures0. In the absence of infection, not necessary for non-dental procedure that do not penetrate the mucosa such as:49. Trans-esophageal echocardiography49. Echocardiography49. Diagnostic bronchoscopy49. Esophagogastroscopy49. Colonoscopy

Is there such a thing as viral endocarditis? So far, no reports. There could be viral infection of the myocardium which could invade the whole muscle layer of the heart and may extend to the endocardium but a viral infection limited to the endocardium has not been reported.________________________________________________________END OF TRANSCRIPTION

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