INFECTIVE ENDOCARDITIS Michael Sales 200213 Infective Endocarditis Colonisation

INFECTIVE ENDOCARDITIS Michael Sales 20/02/13

Infective Endocarditis • • • Colonisation or invasion of heart valves or mural endocardium by microbes Formation of vegetations composed of thrombotic debris & organisms Often associated with destruction of underlying cardiac tissue Aorta, aneurysmal sacs, other blood vessels & prosthetic devices can be involved Most cases bacterial

Acute IE • • • Infection of previously normal heart valve by a highly virulent organism that produces necrotising, ulcerative, destructive lesions Difficult to cure with Abx & usually require Sx Death can occur within days to weeks despite Rx

Subcute IE • • Organisms are usually of lower virulence Cause insidious infections of deformed (native) valves that are less destructive Can take prolonged course: weeks to months More amenable to treatment with antibiotics

Aetiology & Pathogenesis • • Incidence 1. 7 -7. 2 cases per 100 000 Female to male 1: 2 Median age has increased from 30 -40 to 47 -69 yrs Rheumatic HD is no longer the major risk factor in Western countries

Aetiology & Pathogenesis • More common causes now: • • • Mitral valve prolapse Degenerative calcific valvular stenosis Bicuspid aortic valve Prosthetic valves Congenital defects

Aetiology & Pathogenesis • • Majority of cases of IE are caused by gram +ve bacteria Staphylococcus aureus is now more common (31 -54%) than oral Streptococci MSSA is more frequent in community-acquired IE, infects mainly native valves & is associated with bacteraemia of unknown origin MRSA is more related to nosocomial infection, wound infection, permanent IV catheters or surgery in previous 6/12

Aetiology & Pathogenesis • • Strep viridans is now less common (12 -26%) but difficult to isolate & confers partial resistance to ABx Coag -ve Staph were main cause of prosthetic valve endocarditits in the past, esp within first 6 -12/12 after valve surgery, MRSA is now more common

Aetiology & Pathogenesis • • • Enterococci HACEK group: • • • Haemophilus group Actinobacillus group Cardiobacterium hominis Eikenella corrodens Kingella kingae All commensals in the oral cavity

Other Causes • • • Candida & Aspergillus species cause the majority of fungal IE (1 -3% of IE) Patients with IVDU, prosthetic valve & long-term CVC are more likely to have fungal IE: needs to be considered in presence of bulky vegetations, metastatic infection, perivalvular invasion, or embolisation to large blood vessels despite -ve BC In 10 -15% of all cases of endocarditis no organism can be isolated from BC (“culture-negative” endocarditis)

Other Causes • Whenever BC -ve IE is suspected other organisms such as Coxiella burnetti, Legionella spp, Brucella spp, Bartonella spp &, Chlamydiae spp, must be considered

Aetiology & Pathogenesis • The most common factors predisposing to IE are those that cause bacteraemia: • • Dental/surgical procedures Needle sharing amongst IVDU Breaks in skin The risk in those with predisposing factors (eg valve abnormalities) can be lowered by using prophylactic Abx however the use of prophylactic Abx is no longer recommended (discussed further later)

Morphology • • • Presence of friable, bulky, potentially destructive vegetations containing fibrin, inflammatory cells & infective organism (ie bacteria, fungi) on heart valves Aortic & mitral most common sites Right heart more common in IVDU Vegetations can be single or multiple & may involve more than one valve Vegetations can erode into underlying myocardium producing abscesses (ring abscess)

Morphology • • • Emboli can break off vegetations causing abscesses at distant sites where they lodge leading to sequelae such as septic infarcts or mycotic aneurysms Vegetations of subacute endocarditis are associated with less valvular destruction than acute endocarditis Gram +ve bacteria are particularly resistant to pts innate antibacterial activity (eg complement) which facilitates the adhesion & formation of vegetations

Morphology • • When the left heart is involved vegetations most often develop on the ventricular aspect of the aortic valve & atrial surface of mitral valve, usually along the valve leaflets Septic embolism has usually occurred before diagnosis Up to 30% of patients have renal or splenic infarcts at the time of diagnosis Septic emboli can also occur in the heart, brain, intestine & other large organs

Diagnosis • The modified Duke criteria based on clinical, microbiological & echo findings providing high sensitivity & specificity (~80%) for diagnosis of IE when applied to patients with native valve IE with +ve BC

Modified Duke Criteria Major Criteria: • Posititive blood cultures • Positive echocardiogram for IE defined as • Oscillating intracardiac mass • Intracardiac abscess • New partial dehiscence of prosthetic valve Minor Criteria: • Predisposition such as a heart condition or IV drug use • Fever • Vascular phenomena or immunological phenomena such as major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial haemorrhage, conjunctival haemorrhage, & Janeway lesions • Other microbial evidence such as PCR, serological tests, or a positive blood cuture but does not meet a major criterion

Diagnosis • • The dx is confirmed in presence of 2 major criteria, 1 major + 2 minor or 5 minor criteria IE considered in presence of 1 major + 1 minor or 3 minor

Clinical Features & Diagnosis • • The modified Duke criteria have low sensitivity when BC -ve, infection affecting prosthetic valve/pacing system & when IE effects right heart It’s not always useful for rapid diagnosis: one of its major criteria includes +ve blood cultures

Clinical Features • • • Fever, chills, weakness, lethargy, weight loss, flu-like illness (not always present) Longstanding IE (rarely seen now with earlier diagnosis): splinter haemorrhages, Janeway lesions, Osler nodes, Roth spots Murmurs are present in 90% of patients with left sided IE

Splinter Haemorrhages

Janeway Lesions

Osler Nodes

Roth Spots

Clinical Features • In IVDU right sided IE usually affect the tricuspid valve & occasionally the pulmonary valve, instead of systemic issues pulmonary embolism is the most important complication which can evolve into: • • • Pulmonary infarction Pulmonary abscess Bilateral pneumothoraces Pleural effusion Empyema

Clinical Features • • The severity of valvular destruction depends on virulence of infecting organism & infection duration Heart failure can be the initial presentation

Micro • • +ve BC still the best method for identifying the causative agent: considered a major diagnostic criteria BC are +ve in ~80% of cases BC -ve in cases of intracellular or fastidious pathogens or after prior Abx treatment BC are important in suspected IE (eg T > 38, new regurgative murmur, hx of valvular disease, IVDU): in cases where Abx have been commenced prior to BC the recovery rate is only ~ 35 -40%

Micro • • It is recommended to draw 3 sets of cultures Culture -ve IE delays diagnosis + initiation of treatment/correct treatment Using PCR has been proposed in these cases PCR of excised valve tissue or embolic material should be performed in culture -ve IE (in cases of valve surgery or embolectomy)

Echo • • • Important non-invasive technique for diagnosis & management Sensitivity of TTE ranges from 45 -60% TOE offers better quality & sensitivity ranges from 90 -100%, it is necessary whenever perivalvular complications or mitral valve involvement is suspected

Echo • Findings: • • • Vegetation (hallmark lesion of IE): mobile echodense mass attached to valvular leaflets or mural endocardium. Sensitivity TTE 75% TOE 90% Periannular abscess New dehiscence of valvular prosthesis

Echo Findings • • • ~10% of IE involves right side of heart: most commonly the triscupid valve alone (98%), although the pulmonary valve & Eustachian valve (junction of IVC & RA) can be involved Isolated right sided involvement is well detected by TTE & in those cases a TOE isn’t necessary However ~15% IVDU associated IE affects left-sided valves & a TOE should be considered

Echo Findings • • An abscess usually affects the aortic root & presents as a perivalvular zone of reduced echo density without blood flow. TTE (45 -50%) TOE (>90%) Important because the diagnosis of an abscess is an indication for early surgery Aortic/mitral regurg is secondary to valvular necrosis, perforation or prolapse ~50 -60% of pts with IE develop HF secondary to valvular destruction & require early surgery (mortality without surgery ~80%)

Echo Findings • • Vegetation size & mobility is important Stroke complicates 20 -40% of left-sided IE & is the second most common cause of death *Vegetation > 10 mm &/or high vegetation mobility are associated with increased embolic risk, & early surgery (within 1/52 of dx) is associated with improved long-term outcomes through reduction in systemic embolic events* If vegetations are small or have already embolised, echo can provide false -ve results in ~15%. When suspicion is high a TOE can be repeated in 7 -10 days

Echo • In the emergency department bedside USS is starting to be used in patients suspected of IE to help speed up diagnosis: it has its limitations (should be used to rule in IE not rule out) & must be followed up with a formal USS

Prophylaxis • • 2008 National Institute of Clinical Excellence (NICE) produced guidelines re: antimicrobial prophylaxis for IE in pts undergoing interventional procedures The guidelines suggest there is weak evidence to support routine preop Abx for pts at risk of IE They state risk of allergic reaction, cost & resistance implications from Abx overuse Therefore the routine use of Abx prophylaxis is no longer recommended

Prophylaxis • However in the case of infection at the operative site, Abx prophylaxis is still recommended in high-risk patients eg: • • • Acquired valvular HD Previous valve replacement Structural congenital HD (excluding repaired ASD, VSD or PDA)

Antibiotics • • • Empirical treatment; flucloxacillin & gentamicin are the usual first line Adjusted according to MCS Vancomycin is used in pts with intracardiac prosthetic material or suspected MRSA Benzylpenicillin is the first choice for Streptococcus or Enterococcus penicillin-susceptible strains For vanc-resistant MRSA: teicoplanin, lipopeptide daptomycin or oxazilidones (linezolid) is recommended

Fungal IE • • Usually requires surgery Amphotericin B doesn’t penetrate well into vegetations however is used successfully against Candida endocarditis Fluconazole is a fungistatic & only active against Candida spp Caspofungin is usually fungicidal for Candida spp but its penetration into vegetations is unknown

Treatment Course • • IV Abx is normally continued for 4 -6 weeks, with the aim of sterilising the vegetations ID should be involved in BC -ve IE

Surgery • • Antimicrobial therapy can only offer curative treatment in ~50% The other 50% require surgery The surgical goal is valve repair but most require valve replacement Pts with IE + large vegetations, intracardiac abscess (9 -14%) or persisting infection (9 -11%) almost always require surgery

Surgery • • • Anaesthetic can be complicated secondary to haemodynamic instability Mitral or aortic regurg particularly challenging Induction often complicated by hypotension despite hyerdynamic left ventricle & hypoxaemia secondary to severe pulmonary oedema Some pts may develop acute RV dysfunction & severe tricuspid regurg These pts require arterial pressure & CVP monitoring & may require inotropes/vasopressors

Surgery • • • Pts with peri-annular abscess have higher risk of para-valvular regurgitation & valve dehiscence after OT Current IE perioperative mortality is 5 -15% If sepsis is under control the mortality is similar to non-infected valve replacement

Surgery • Most common complications: • • • Persistent septic shock Coagulopathy Acute renal failure Stroke Refractory heart failure Conduction abnormalities

• • • Summary Challenging diagnosis therefore diagnosis often delayed Need to have a high index of suspicion: esp high risk pts Clinical examination is still very important Cultures are extremely important for diagnosis/treatment The use of TTE/TOE is vital for Dx & Tx planning • Bedside USS is now being used for rapid assessment in ED Treatment needs to be started early to reduce morbidity/mortality Many pts require surgical intervention Pts can be haemodynamically unstable peri-operatively ID involvement is useful esp in BC -ve IE

References • • • Martinez, G. , Valchanov, K. , Infective Endocarditis, Continuing Education in Anaesthesia, Critical Care & Pain, 2012; 12: 3 Kumar. , Abbas. , Fausto. , Aster. , Robbins and Cotran Pathological Basis of Disease, 8 th Edition, 2010 Deng, H. , Ma, Y. , Zhia, H. , Miao, Q. , Surgical valve repair of isolated pulmonary valve endocarditis, Interactive Cardiovascular and Thoracic Surgery, 2013; 16: 384 -386 Seif, D. , Meeks, A. , Mailhot, T. , Perera, P. , Emergency department diagnosis of infective endocarditis using bedside emergency ultrasound, Clinical Ultrasound Journal, 2013; 5: 1 Kang, D. , Kim, s. , Yun, S. , Choo, S. , Song, J. , Sohn, D. , Early Surgery versus conventional treatment for infective endocarditis, The New England Journal of Medicine, 2012; 366: 2466 -73

References • Wikipedia (images) • Dermnet. nz (images) • Beaulieu, A. , Rehman, H. , Janeway Lesions, Canadian Medical Association Journal, 2010; 182: 10 (images)