Infective Endocarditis M Armstrong

Infective endocarditis- annual incidence of 3-9/100,000 in industrialized countries Male to female case ration is more then 2:1 While 50% of cases occur in people with no known valve disease, the highest rates occur in people with prosthetic valves, intra-cardiac devices, unrepaired cyanotic congenital heart diseases or a history of infective endocarditis Other risk factors include degenerative valve disease, RHD, haemodialysis, diabetes, HIV, IVDA

Microbiology Staphylococcus sp. and Streptococcus sp. account for 80% of infective endocarditis -portions vary according to valve infected (native vs prosthetic), source of infection, patient age and co-existing medical conditions -the proportion of health care associated endocarditis (Staphylococcus sp.) has increased, while endocarditis 2nd to oral organisms (Streptococcus sp.) has decreased

“Culture negative endocarditis” (10%) Usually 1 of 2 situations -previous antibiotic use -fastidious organisms Serology, histologic examination of surgical specimens including the valve, PCR testing and 16S studies can be useful (obtaining a diagnosis in 60% of cases)

“Culture negative” organisms Bartonella sp. , Brucella sp “Culture negative” organisms Bartonella sp., Brucella sp., Coxiella burnetii, HACEK group bacteria (Haemophilus sp., Aggregatobactor [previously Actinobacillus] actinomycetemcomitans, Cardiobacterium hominis, Eikenella corodens, Kingella kingae *Tropheryma whipplei

Pathogenesis Usually endocardium is resistant to bacterial colonization and infection. With native valve endocarditis conventionally bacteraemia can lead to colonization of damaged valvular endocardium. -insults to the endocardium can be from mechanical manipulation, “jet lesions” (turbulent blood flow), repeated intravenous injection (solid particle damage) -chronic rheumatoid heart disease and degenerative lesions can also promote endocarditis *immune mediated damage may also play a significant role in endocarditis caused by intracellular organisms

Classification Classically divided in acute, sub-acute and chronic Now tend to classify according to underlying cardiac lesions, location, presence of intra-cardiac devices, or the mode of acquisition

Outcomes Contemporary studies in industralised countries show in hospital mortality rates of 15-22%, and 5 year mortality at 40% This varies widely according to infecting organisms, underlying prosthetic valves (e.g. S aureus in a prosthetic valve vs native valve lesions from oral Streptococcus sp.) Age, co-morbidities and complications also plays a prominent role in outcome

Clinical approach Diagnosis -clinical, microbiologic and echocardiographic findings Duke criteria (sens and spec over 80%) -ref criteria for diagnosis

History -fever -IVDU -heart failure symptoms -night sweats -weight loss

History continued Sepsis, meningitis, unexplained heart failure, septic pulmonary emboli, stroke, acute peripheral arterial occlusion and renal failure can also be causes of presentation

Examination -fever (80%) -new murmur (48%) -worsening murmur (20%) -splenomegaly (11%) -splinter haemorrhages (8%) -Janeway’s lesions (5%) -Roth’s spots (5%) -conjunctival haemorrhage (5%)

Complications Mostly embolic -cerebral (15-20%): ischaemic and haemorrhagic stoke, TIA, mycotic aneurysm, brain abscess, meningitis Increased size of vegetations, how mobile they are, location on the mitral valve, and Staphylococcus aureus infection all increase the risk of embolism MRI can reveal cerebral abnormalities in up to 80% of patients Other non-embolic -Inflammatory/ Immune disorders (such as arthritis, myositis, glomerulonephritis), CHF from ruptured valve cusps/ severe valve lesions, cardiac arrhythmia, sinus of Valsalva aneurysm

Investigations -elevated CRP/ ESR in ~2/3rd of cases -leukocytosis ~1/2 of cases -anaemia ~1/2 of cases Further investigations: -blood cultures (ideally 3 sets prior to antibiotics drawn from different locations and 1 hour apart) (can detect up to 90% of pathogens) -TTE>>>TOE (combined tests shows vegetation's in 90%, regurgitation in 60% and para-valvular abscess in 20%) *May need serial studies, and a study after treatment completion -serology (culture negative to consider includes Bartonella, Coxiella, Brucella, Legionella, Chlamydia) -MRI/MRA (cerebral events) -CT scans if required to assess for other embolic events (abdomen for spleen, kidneys and/ or chest if pulmonary lesions suspected in right sided endocarditis) -histopathology/ immuno-staining/ PCR / 16S

Modified Duke criteria for IE

Management Intra-disciplinary approach: Antibiotic treatment- guideline approach (empiric vs directed) e.g. eTG Concept of “Synergy” Duration is dependent on the time from the first negative culture results (continue daily blood cultures until negative for approximately 48 hours) Native valve 2-6 weeks IV Prosthetic valve 6 weeks, consider rifampicin for Staphylococcal endocarditis If surgery is performed- total duration of therapy is from day of appropriate antibiotic therapy and not the day of surgery *If however valve cultures are positive then treatment should be continued for full length from day of surgery

Management Surgical treatment- The rate of early surgical intervention (repair or replacement of valves during antibiotic treatment for endocarditis has increased to ~50% in the last 3 decades) Main indications -heart failure -uncontrolled infection -prevention of embolic events Major benefit of early surgery is reduction of embolic complications

Management Anti-platelet and anti-coagulant therapy “Increased risk of death from cerebral hemorrhage in patients with prosthetic valve endocarditis with Staphylococcus aureus on anticoagulation (and no reduction in embolic risk)” European Society of Cardiology guidelines recommend that in patients already receiving oral anticoagulant therapy in whom IE develops that is complicated by ischaemic and non-haemorrhagic stroke, the oral anticoagulant agent be replaced with heparin for 2 weeks *but evidence for this is weak Anti-platelet agents are not routinely recommended but do not need to be ceased in the absence of bleeding if taken for other indications

Prophylaxis Recent changes with down sizing of indications -prosthetic valve -history of IE -unrepaired congenital cyanotic heart disease who are planning on undergoing an invasive dental procedure *in the UK prophylaxis not recommended for IE in any circumstance!! Good oral, skin and dental care may reduce risk of IE

Uncertain areas Duration of antibiotic therapy -especially aminoglycosides Appropriate timing of surgery (possible increased rates of relapse and prosthetic valve dysfunction if performed in first week of antibiotic therapy) Management of mycotic aneurysm- imaging and endovascular intervention

References NEJM Endocarditis review article 2013 The 5-Minute Clinical Consult 2011