Native Valve Endocarditis

Infection of the endocardium of a native heart valve, forming a vegetation of platelets, fibrin and organisms with tissue destruction. Incidence is about 3 to 10 per 100,000 per year, higher in older adults and in people who inject drugs. In hospital mortality is about 15 to 20%, and 5-year mortality about 30 to 40%.

• Organisms: Staphylococcus aureus (about 25 to 35%, commonest in healthcare related disease and injection drug use), viridans streptococci (about 20%, dental source), enterococci (about 10%, genitourinary and gastrointestinal source), coagulase negative staphylococci, Streptococcus gallolyticus (colonic neoplasia), HACEK organisms, Gram negative bacilli and fungi.
• Predisposition: rheumatic and degenerative valve disease, congenital heart disease, mitral valve prolapse with regurgitation, injection drug use, indwelling vascular catheters, haemodialysis, HIV, diabetes, and prior endocarditis. In many cases no predisposing lesion is known.
• Mechanism: damaged endothelium forms a sterile platelet fibrin thrombus, bacteraemia seeds it, and infection spreads locally (leaflet destruction, abscess) and distally (emboli, immune complex disease).

• Fever (about 90%), chills, night sweats, anorexia, weight loss, malaise, myalgia, arthralgia.
• New or changed regurgitant murmur (about 80%), heart failure (30 to 40%), splenomegaly, clubbing (late), petechiae, conjunctival haemorrhages, splinter haemorrhages, Osler nodes, Janeway lesions, Roth spots, glomerulonephritis, embolic stroke (15 to 25%), splenic or renal infarction, mycotic aneurysm, and discitis or vertebral osteomyelitis. Staphylococcus aureus is acute and destructive; streptococci are subacute.
• Differential diagnosis: sepsis from another source, Libman-Sacks and marantic endocarditis, rheumatic fever, left atrial myxoma, vasculitis, systemic lupus, lymphoma, tuberculosis, brucellosis, and drug fever.
• Complications: heart failure from valve destruction, perivalvular abscess (aortic valve in 30 to 40%), conduction block, stroke, intracranial haemorrhage, mycotic aneurysm, splenic abscess, acute kidney injury, and relapse.

• Blood cultures: three sets from separate sites over at least 1 hour (aerobic and anaerobic, 8 to 10 mL each), before antibiotics. Bacteraemia is continuous, so timing of draws is less important than avoiding prior antibiotics.
• The diagnosis uses major criteria (typical organisms in two separate cultures, or imaging with vegetation, abscess or new valve regurgitation) and minor criteria (predisposition, fever of 38.0 degrees Celsius or more, embolic or immunological phenomena, culture not meeting major criteria).
• Transthoracic echocardiography first, then transoesophageal echocardiography if transthoracic is negative with high suspicion, or if complications are suspected. Repeat after 5 to 7 days if negative. Cardiac CT for abscess and pseudoaneurysm. Brain, chest and abdominal imaging for embolic complications. Spine MRI for back pain.
• ECG daily (PR prolongation indicates root abscess). CRP, ESR, full blood count, creatinine, urinalysis, rheumatoid factor and complement if glomerulonephritis. HIV, hepatitis B and C tests. Colonoscopy after Streptococcus gallolyticus or enterococcal infection with no urinary source. Dental assessment.

• Admit and treat in a unit with cardiology, infectious disease and cardiac surgery input.
• Empirical therapy while awaiting cultures (native valve, community onset):
  • Ampicillin 2 g IV every 4 hours plus cloxacillin or flucloxacillin 2 g IV every 4 hours plus gentamicin 3 mg/kg/day IV in 1 dose (trough less than 1 mg/L).
  • Penicillin allergy or suspected methicillin resistant Staphylococcus aureus: vancomycin 30 mg/kg/day IV in 2 doses (trough 15 to 20 mg/L) plus gentamicin 3 mg/kg/day.
• Directed therapy:
  • Penicillin susceptible viridans streptococci (minimum inhibitory concentration 0.125 mg/L or less): benzylpenicillin 12 to 18 million units/day IV in 4 to 6 doses or ceftriaxone 2 g IV daily for 4 weeks; or benzylpenicillin plus gentamicin 3 mg/kg/day for 2 weeks in uncomplicated disease with no abscess, no renal impairment and no extracardiac focus.
  • Relatively resistant streptococci (minimum inhibitory concentration 0.125 to 2 mg/L): benzylpenicillin 24 million units/day (or ampicillin 200 mg/kg/day) for 4 weeks plus gentamicin 3 mg/kg/day for the first 2 weeks.
  • Methicillin susceptible Staphylococcus aureus: cloxacillin or flucloxacillin 2 g IV every 4 hours for 4 to 6 weeks (gentamicin is not added in native valve disease because it adds nephrotoxicity without clear benefit). Penicillin allergy that is not severe: cefazolin 2 g IV every 8 hours; severe allergy: vancomycin.
  • Methicillin resistant Staphylococcus aureus: vancomycin 30 to 60 mg/kg/day in 2 to 3 doses (trough 15 to 20 mg/L) or daptomycin 10 mg/kg IV once daily (weekly creatine kinase) for 4 to 6 weeks.
  • Enterococcus faecalis: ampicillin 2 g IV every 4 hours plus ceftriaxone 2 g IV every 12 hours for 6 weeks (or ampicillin plus gentamicin 3 mg/kg/day for 2 to 6 weeks when no high level gentamicin resistance).
  • HACEK organisms: ceftriaxone 2 g IV daily for 4 weeks.
  • Gram negative bacilli: a susceptible beta lactam plus ciprofloxacin 400 mg IV every 8 to 12 hours, for 6 weeks or longer, with early surgery.
  • Fungal: liposomal amphotericin B 3 to 5 mg/kg/day IV, surgery, then lifelong suppression with fluconazole 400 to 800 mg daily.
  • Selected stable patients with cleared bacteraemia, no abscess and a reliable follow up can finish treatment orally after at least 10 days of IV therapy, for example amoxicillin 1 g every 6 hours for streptococci (evidence is limited).
• Monitor: repeat blood cultures every 48 hours until negative; vancomycin troughs, gentamicin levels and creatinine twice weekly; full blood count and liver function weekly; ECG daily; echocardiography weekly if aortic valve infection with root involvement is suspected.
• Surgery (during the same admission, within days) for:
  • Heart failure from severe regurgitation, obstruction or fistula: emergency within 24 hours for refractory pulmonary oedema or shock, urgent within 3 to 5 days otherwise.
  • Uncontrolled infection: abscess, pseudoaneurysm, fistula, enlarging vegetation, or persistent bacteraemia or fever for 7 to 10 days despite effective antibiotics, and fungal or multidrug resistant organisms.
  • Embolism prevention: vegetation greater than 10 mm with an embolic event despite antibiotics (urgent), or an isolated vegetation greater than 30 mm.
  • Repair is preferred to replacement where possible. Operative mortality about 10 to 20%.
  • After ischaemic stroke without haemorrhage, surgery can proceed within days if damage is not extensive; after intracranial haemorrhage, wait at least 4 weeks unless life threatening.
• Heart failure: furosemide 40 to 80 mg IV, afterload reduction with ramipril 1.25 to 2.5 mg daily as blood pressure allows, and avoid beta blockers in severe aortic regurgitation.
• Anticoagulation and antiplatelet drugs do not prevent embolism in native valve disease. Do not start them without another indication; stop anticoagulation after central nervous system embolism or haemorrhage.
• Mycotic aneurysm: vascular imaging after any neurological event; endovascular coiling or surgery for unruptured or ruptured aneurysm.
• People who inject drugs: offer opioid agonist therapy (methadone starting at 20 to 30 mg daily with specialist titration, or buprenorphine sublingual 2 to 4 mg initially titrated to 8 to 16 mg daily), a naloxone supply, needle exchange, and addiction and psychosocial support. Do not refuse surgery because of drug use.
• Pregnancy: avoid gentamicin where possible; use ampicillin, ceftriaxone and vancomycin; urgent surgery with bypass carries fetal risk (about 20 to 30% loss), so reserve it for maternal indications.
• Renal impairment: adjust vancomycin by trough, avoid gentamicin and use a beta lactam combination.
• Children: vancomycin 40 mg/kg/day in 3 to 4 doses, gentamicin 3 mg/kg/day, flucloxacillin 200 mg/kg/day in 4 to 6 doses (maximum 12 g), benzylpenicillin 200,000 units/kg/day in 4 to 6 doses, ceftriaxone 100 mg/kg/day (maximum 4 g).
• Prevention: amoxicillin 2 g orally (50 mg/kg in children) 30 to 60 minutes before dental procedures involving the gingiva, only for patients with a prosthetic valve, previous endocarditis, unrepaired cyanotic congenital heart disease, or repair with prosthetic material within 6 months; azithromycin or clarithromycin 500 mg (15 mg/kg in children) if allergic to penicillin (clindamycin is no longer recommended). Everyone benefits from good dental hygiene.
• Red flags: heart failure, syncope or new block, new neurological deficit, persistent fever after 7 days, rising creatinine, shock.
• Follow up: echocardiography at the end of treatment, 3, 6 and 12 months; blood cultures at 2 and 4 weeks after treatment; dental clearance; patient education about early fever.