Infective endocarditis

Infective endocarditis is an endovascular infection of cardiovascular structures, including: Cardiac valves Atrial and ventricular endocardium Large intrathoracic vessels Intracardiac foreign bodies eg prosthetic valves, pacemaker leads, surgical conduits (tubes)

Two types:Acute bacterial endocarditis Fulminant illness over days to weeks Likely Staph aureus Affects normal valves Causes necrotising, ulcerative, destructive lesions

Subacute bacterial endocarditis Mild to moderate illness, protracted course Streptococci of low virulence Affects abnormal valves eg post Rheumatic heart disease, congenital valve defects, degenerative calcific aortic valveAetiology and risk factorsEndocarditis requires two things: bacteraemia and abnormal cardiac endothelium facilitating bacterial growth.

Damaged endocardium promotes platelet and fibrin deposition which allows organisms to adhere and grow, leading to an infected vegetation. Aortic and mitral valves are most commonly involved, apart from IVDU who acquire right-sided lesions more commonly.

Risk factors: bacteraemia Previous dental work IVDU Soft tissue infection eg cellulitis Diabetes Renal infection

Risk factors: cardiac lesions Damaged native valve Congenital heart disease (unrepaired, repaired within 6 months, repaired with defects), cardiac transplant with valve disease (surgically constructed systemic-to-pulmonary shunts Foreign bodies: prosthetic valves, intravascular cannulas, cardiac surgery, permanent pacemakers Rheumatic heart disease

Frequency of valve involvement: MV >>AV > TV (50% of IVDU) >PV

Clinical presentation

Fever + new murmur = infective endocarditis until proven otherwise.

Symptoms: fever, sweats, rigors, fatigue, weight loss, palpitations, shortness of breath

SignsSeptic signs Fever, rigors, night sweats, malaise, weight loss Anaemia, splenomegaly, clubbing (subacute)

Cardiac New murmur or change in pre-existing murmur Can be regurgitationvalve destruction; or valve obstruction (signs of stenosis) An aortic root (valve ring) or septal abscess causes prolongation of the PR interval, and may lead to a complete AV block Rareinfarct due to emboli Left ventricular failure is a common cause of death (2 to AR, MR)

Immune complex deposition Vasculitis of any vessel, but microscopic haematuria is common and GN and ARF may occur Arthritis Roth spots (boat-shaped retinal haemorrhage with pale centre)immunological Oslers nodespainful red-brown, 3-15mm, pulp infarcts in the fingers or toespathognomonic; caused by immunological complex deposition

Embolic phenomena Janeway lesionspainless 5mm palmar or plantar maculespathognomonic; caused by septic emboli Petechiae, splinter haemorrhages Splenomegaly (subacute) Microscopic haematuria, flank pain (renal emboli) +/- active sedimenttakes 10-14 days to develop (subacute) CNS embolifocal neurological signs, mycotic aneurysmheadache Abscesses in brain, heart, kidney, spleen, gut (or lung in right-sided)

Janeway lesions

IVDU There may be associated Septic pulmonary emboli (esp. with TR involvement) Beware the young person with bilateral chest disease Fever, dyspnoea, cough, haemoptysis Imaging Radiograph: nodular/infiltrative densities, pleural effusion, empyema CT: vessel sign (peripheral nodules), subpleural nodules necrosis Metastatic infection E.g. kidney, CNS, spine, other bones Comorbid viral infection HIV, Hep B, Hep C There is often no Cardiac murmur Peripheral stigmata (seen more in left-sided)OrganismsDental disease or procedures: alpha haemolytic streptococcus viridans eg strep. mutans

Native and prosthetic valve: Early (during surgery, poor prognosis) Occurring within 60 days of valve surgery and acquired in theatre or soon after on ICU Staph aureus, staph epidermitis Poor outcome with MRSA

Late (haematogenous spread) Occurring more than 60 days after valve surgery and presumed to have been acquired in the community Strep viridans (50-70%), staph aureus (25%)

Soft tissue infections: Susceptible groups: diabetics and IVDU, patients with long-standing intravascular cathertersstaphylococci

IVDU Dissolve heroin in infected lemon juice Staph aureus, candida (rare)

Gut and perineum Underlying genitourinary disease or procedures Prolonged hospitalisation 1/5 of cases may have urinary sepsis Enterococci eg E. faecalis Bowel malignancy, cirrhosis Strep bovis (rare)

Rare (HACEK)5-10% The usual cause is prior antibiotic therapy More common in children Typically slow-growing Gram ve oropharyngeal flora

Haemophilus species eg H parainfluezae Actinobacillus actinomycetemcomitans Cardiobacterium hominis Eikenella corrodens Kingella Kingae

Treat with ceftriaxone, or ampicillin and low-dose gentamicin

Some others: Coxiella burnetti, Chlamyxdia species, Bartonella species and Legionella

Fungal: candida, aspergillus, histoplasma

Viral: SLE (Libman-Sacks endocarditis), malignancy

ComplicationsCardiac Heart Failure Heart failure remains the most common cause of death secondary to IE. Usually caused by valvular insufficiency, but may also be due to embolism of vegetation fragments into the coronary circulation, causing infarction and failure Perivalvular abscess Aortic valve is most susceptible to abscess formation Abscess can extend to adjacent cardiac conduction tissues, possibly leading to heart block (most common in abscesses of the aortic valve) Get regular ECGs Patients with perivalvular abscesses seem to have higher rates of systemic embolism and fatal outcomes Other Pericarditis Aortic valve dissection

Embolisation A very common complication of IE Emboli can damage virtually any blood vessels Stroke Blindness Peripheral gangrene Acute myocardial infarction Hypoxia (due to pulmonary emboli in right-sided IE) Unusual pain syndromes (due to splenic/renal infarction)renal abscess, cerebral abscess Appears to be more common in fungal IE

Mortality In-hospital mortality = 18-23%* Six-month mortality = 22-27%* Predictors of death: Persistent bacteraemia Heart failure Diabetes mellitus Presence of embolus or perivalvular abscesses Large vegetation size Female genderDiagnostic criteria (Duke criteria)

Fulfil 2 major criteria, 1 major and 3 minor or 5 minor.

Only possible diagnosis if only 1 major and 1 minor criteria or if only 3 minor.

Major criteria: Positive blood culture (need Viridans, bovis or HACEK) Typical organism in 2/3 separate cultures out of 4, and the first and last culture must be at least one hour apart, from different sites Persistently positive blood cultures >12 hours apart, two different parts Coxiella is so hard to culture that serology is ok Endocardium involved: Positive echocardiogram (vegetation, abscess, dehiscence of prosthetic valve) OR New valvular regurgitation (not just change in murmur) Positive serological test for Q fever, with an immunofluorescence assay showing phase 1 IgG antibodies at titre >1: 800

Minor criteria: (FIVPM) Fever >38C Immunological signsGN, Oslers nodes, Roth spots, positive Rh factor Vascular phenomenamajor arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial haemorrhage, conjunctival haemorrhage, janeway lesions Predisposition (cardiac lesion, IVDU) Microbiological--Positive blood culture that does not meet the major criteriaInvestigationsMicrobiology Blood cultures are key. Six bottles or three sets should be taken from different venepuncture sites. Do not use indwelling cathether lines on these patients. Serology: when suspected but blood cultures are negative. They aid diagnosis when the organisms cannot be grown in standard blood cultures: Coxiella, Bartonella, Legionella, Chlamydia

Other lab tests FBE: mild normochromic normocytic anaemia, polymorphonuclear leucocytosis are common. Thrombocytopenia or thrombocytosis can occur. Blood culture Urea and electrolytes: renal dysfunction is common in sepsis. LFT: serum ALP may be increased. CRP: monitor response to therapy/relapse. Urinalysis: proteinuria and haematuria occur frequently, along with red cell casts. PCR: may be useful in culture-negative infective endocarditis.

Non-lab tests: ECG: MI due to emboli or new AV block (including increased PR interval) is suggestive of abscess formation CXR: evidence of heart failure, or in right-sided endocarditis, multiple pulmonary emboli, (which raises the suspicion of right-sided endocarditis when coupled with fever) Echo: TTE to image vegetations, documenting valvular dysfunction and other local complications such as aortic root abscesses. Sensitivity is 60-75% Echo: TOE has a higher sensitivity (>90%) and specificity for abscess formation because of the close physical proximity of the transducer to the aortic root. TOE enhances the visualisation of prosthetic valves and is recommended for all cases of prosthetic valve endocarditis. Inadequate in 20% (obesity, COPD, chest wall deformities) Arrows indicate vegetations

TreatmentPenicillin is essential; therefore always check allergies and what sortanaphylaxis or just GI upset? Alternative is glycopeptide antibioticsvancomycin or teicoplanin.

Serum levels of gentamicin and vancomycin need to be monitored to ensure adequate therapy and prevent nephrotoxicity.

Bactericidal and IV antibiotics are given because it is very hard to penetrate the vegetations.

Please take blood culturesenough of them

Empirical--Clinical endocarditis, culture results awaited, no suspicion of staphBenpen, fluclox and gent

Vanc and gent4 instances: Prosthetic cardiac valve, pacemaker, intracardiac device in situ Healthcare associated infection Immediate penicillin hypersensitivity Community acquired MRSA suspected

Staph endocarditis (IVDU, recent intravascular devices or cardiac surgery, acute infection)Flucloxacillin 2g 4-hourly for 4-6 weeks OR

Vancomycin 1.5g 12-hourly for 6 weeks

Streptococcal endocarditis

Enterococci (All enterococci isolates require penicillin MIC testing and aminoglycoside resistance)More resistant to drugs cf Viridans streptococci

Staphylococcal endocarditis

Enteric Gram Negative or Pseudomonas aeruginosa Cardiac therapy + antimicrobial therapy based on sensitivity testing

Candidal endocarditis IV amphotericin or fluconazole

Most patients with infective endocarditis should respond within 48 hours of initiation of antibiotics. The fever resolves, serum markers of infection decrease and the systemic symptoms are relieved. If this fails to occur, serious shit is going on, which might be:

Perivalvular extension of infection and possible abscess formation Drug reaction (fever should be ok after drug withdrawal) Nosocomial infection (some other infection from an IVC or UTI) Pulmonary embolism (secondary right-sided endocarditis or immobilization)

In such cases, samples for culture should be taken from all possible sites and a septic workup commenced. Changing antibiotic dosage or regimen should be avoided unless there is a drug reaction or positive culture of another bacterium.

Surgery: this is basically a valve replacement, which could predispose the patient to developing infective endo again, and so must take into account these factors: Patient-related: Age, comorbidities, pre-existing prosthesis, cardiac failure Disease-related: Infective organism, vegetation size, presence of perivalvular infection, systemic embolizationPrognosis and prophylaxis Dont use IV drugs yo!! Outcome depends on various factors: Comorbidities Organism involved Endocarditis related end organ damage (embolisation) Prosthetic vs native valve IVDU Degree of damage to the heart itself (a person with severe valvular lesion is more likely to develop cardiac complications later on) Many more Survival rates: 85-90% for native valve endocarditis due to viridans streptococci and HACEK organisms 55-70% for native valve endocarditis due to staphylococcus aureus in patients who are non IVDU

Prophylaxis Usually advised before dental procedures: for those dental procedures that involve gingival manipulation, bleeding, perforation of oral mucosa (this includes respiratory tract surgery) Certain high risk group of people who are highly recommended to take prophylaxis: Prosthetic valves or prosthetic material used for cardiac valve repair Prior endocarditis Congenital heart disease, including shunts or conduits Completely repaired congenital heart defects during the 6 months after repair Underlying valvular heart lesions Other cardiac comorbidities: CCF, IHD etc Cardiac transplantation with subsequent development of cardiac vavulopathy

Concern that minor procedures are using up antibiotics eg minor dental work, so those who get a high-risk heart lesion or high-risk procedure Eg colonoscopy and biopsy cf gastroscopy. Dental proceduresextraction

Prophylactic antibiotics Standard regimen Amoxicillin: 2g PO 1 hour before procedure If unable to take oral medication Amoxycillin or ampicillin, 2g IV or IM within 1 hour before procedure Penicillin allergy Clarithromycin or azithromycin 500mg PO 1 hour before procedure Cephalexin: 2g PO 1 hour before procedure Clindamycin: 600mg PO 1 hour before procedure Penicillin allergy and unable to take oral medication Cefazolin or ceftraixone: 1g IV or IM 30 min before procedure Clindamycin: 600mg IV or IM 1 hour before procedure

Prognosis Adverse prognostic factors: CHF, prosthetic valve infection, valvular/myocardial abscess Mortality up to 30%Non-bacterial thrombotic endocarditisSuspect when chronically ill patients develop arterial emboli

Causes (marantic vegetations) Vascular: DIC, hypercoagulable states eg pregnancy Chronic infections Metastatic cancer Connective tissue: SLELibman-Sacks (verrucous lesions), granulomatosis polyangiitis, antiphospholipid syndrome Iatrogenic: heart catheter, central line

Infective vs non-infective NBTE is often caused by malignancy. Patients often complain of systemic symptoms associated with their malignancy Patients may also report symptoms of underlying hypercoagulable state such as recurrent DVT, accelerated atherosclerosis, pre-mature CAD, AMI, or stroke NBTE may or may not present with a new murmur on clinical examination. Instead, NBTE may be picked up on echocardiograph or an embolic stroke may be the initial presentation

Investigations NBTE is associated with a previously undamaged heart valve unlike IE. Additionally NBTE does not cause an inflammatory response in the body and the vegetations are small, sterile and aggregate around the edges of the valve. Lesions are generally symmetric with a smooth orverrucoid(warty) texture. Histologically, lesions are composed offibrin and plateletsbut, unlikebacterialaetiologies, contain little evidence ofpolymorphonuclear leukocytes,microorganismsorinflammation CT scan or chest, abdomen and pelvis may demonstrate a primary tumour responsible for underlying pathology, which is thought to be secondary to mucin production with subsequent embolic phenomenon. Blood culture should come back negative for diagnosis to be made