Prosthetic Valve Endocarditis

Infection of a mechanical or bioprosthetic valve or of material used in valve repair or transcatheter implantation. It accounts for about 10 to 30% of endocarditis, with an incidence of about 0.3 to 1% per patient year and about 1 to 3% in the first 5 years after surgery. The risk is highest in the first 6 months.

• Early disease (within 12 months of surgery) is usually healthcare related, from perioperative contamination: coagulase negative staphylococci, Staphylococcus aureus, Gram negative bacilli, enterococci and fungi (Candida, Aspergillus). Late disease (after 12 months) resembles native valve disease: viridans streptococci, enterococci, Staphylococcus aureus and HACEK organisms.
• Mechanism: bacteria adhere to the sewing ring, annulus and adjacent tissue, forming vegetations, annular abscess, pseudoaneurysm, fistula, dehiscence and paravalvular leak. Conduction block follows aortic root abscess.
• In hospital mortality is about 20 to 40%, and 1-year mortality about 30 to 50%, higher with Staphylococcus aureus, heart failure, abscess, stroke and early disease. Transcatheter valve endocarditis occurs in about 0.5 to 1% per year with mortality of about 30 to 45%.

• Fever is often the only sign. Others: new or changed regurgitant murmur or muffled prosthetic click, heart failure, embolism (stroke in 15 to 25%), new conduction block, splenomegaly, petechiae, splinter haemorrhages, Osler nodes, Janeway lesions, Roth spots, glomerulonephritis, back pain from vertebral infection. Early disease can be acute and septic.
• Any fever in a patient with a prosthetic valve within the first year, or any unexplained fever with a prosthesis, needs three sets of blood cultures before antibiotics.
• Differential diagnosis: post-pericardiotomy syndrome, prosthetic valve thrombosis, structural valve failure, non-bacterial thrombotic vegetations, paravalvular leak with haemolysis, other bacteraemia, drug fever, and sternal wound infection.
• Complications: heart failure, abscess and fistula, dehiscence, conduction block, embolic stroke, intracranial haemorrhage, mycotic aneurysm, acute kidney injury, splenic abscess, vertebral osteomyelitis, relapse and death.

• Blood cultures: three sets from separate venepunctures over at least 1 hour (aerobic and anaerobic bottles, 8 to 10 mL each), before antibiotics. Hold bottles for 14 days if culture negative.
• Diagnosis uses major criteria (two separate cultures with a typical organism, or imaging showing vegetation, abscess or new partial dehiscence) and minor criteria (predisposition, fever of 38.0 degrees Celsius or more, embolic or immunological phenomena, a positive culture not meeting major criteria).
• Transthoracic echocardiography first, then transoesophageal echocardiography in all suspected cases (far more sensitive for prosthetic valves). Repeat transoesophageal echocardiography after 5 to 7 days if negative and suspicion is high.
• ECG daily (new PR prolongation or block suggests abscess). Cardiac CT angiography for abscess, pseudoaneurysm and dehiscence. 18F-FDG PET-CT (valve uptake) when echocardiography is inconclusive, at least 3 months after surgery to avoid false positives. Brain MRI or CT and abdominal CT for embolic disease.
• CRP, ESR, full blood count, creatinine, urinalysis (haematuria, protein). Culture and PCR of any excised valve or explanted material.

• Admit to a unit with cardiology, cardiac surgery and infectious disease input. Start antibiotics immediately after cultures in unstable patients, and delay for 24 to 48 hours in stable subacute patients only to improve culture yield.
• Empirical therapy:
  • Early (under 12 months): vancomycin 30 mg/kg/day IV in 2 divided doses (trough 15 to 20 mg/L), plus gentamicin 3 mg/kg/day IV in 1 dose (or 1 mg/kg every 8 hours; trough less than 1 mg/L), plus rifampicin 300 to 450 mg orally or IV every 8 hours, started after 3 to 5 days of effective therapy and clearing bacteraemia.
  • Late (over 12 months): ampicillin 2 g IV every 4 hours, plus cloxacillin or flucloxacillin 2 g IV every 4 hours, plus gentamicin 3 mg/kg/day IV; use vancomycin 30 mg/kg/day in place of the penicillins for penicillin allergy or suspected methicillin resistant Staphylococcus aureus.
• Directed therapy (duration at least 6 weeks, counted from the first negative blood culture, or from the day of surgery if valve culture is positive):
  • Methicillin susceptible Staphylococcus aureus: flucloxacillin 2 g IV every 4 hours, plus rifampicin 300 to 450 mg every 8 hours, plus gentamicin 3 mg/kg/day for the first 2 weeks.
  • Methicillin resistant Staphylococcus aureus and coagulase negative staphylococci: vancomycin 30 mg/kg/day IV in 2 doses (trough 15 to 20 mg/L) or daptomycin 10 mg/kg IV once daily (weekly creatine kinase), plus rifampicin 300 to 450 mg orally or IV every 8 hours and gentamicin 3 mg/kg/day IV in 1 dose.
  • Penicillin susceptible 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 6 weeks, with gentamicin 3 mg/kg/day for the first 2 weeks.
  • Enterococcus faecalis: ampicillin 2 g IV every 4 hours plus ceftriaxone 2 g IV every 12 hours for 6 weeks (avoids aminoglycoside toxicity).
  • HACEK organisms: ceftriaxone 2 g IV daily for 6 weeks.
  • Gram negative bacilli: a beta lactam chosen by susceptibility plus ciprofloxacin 400 mg IV every 8 to 12 hours or 750 mg orally every 12 hours, for at least 6 weeks.
  • Fungal: liposomal amphotericin B 3 to 5 mg/kg/day IV, with or without flucytosine 25 mg/kg every 6 hours (monitor blood counts and levels), plus surgery; then lifelong fluconazole 400 to 800 mg daily.
• Monitor: blood cultures every 48 hours until negative; vancomycin troughs, gentamicin levels, creatinine and electrolytes twice weekly; full blood count and liver function weekly; audiology if aminoglycosides run beyond 2 weeks; ECG daily.
• Surgery (early, in days, during the same admission) for:
  • Heart failure from dehiscence, severe prosthetic regurgitation or obstruction: emergency within 24 hours for refractory pulmonary oedema or shock, urgent within 3 to 5 days otherwise.
  • Locally uncontrolled infection: abscess, fistula, pseudoaneurysm, enlarging vegetation.
  • Persistent bacteraemia or fever for 7 to 10 days despite effective antibiotics.
  • Staphylococcus aureus disease, Gram negative or fungal infection, resistant organisms (surgery strongly advised).
  • Embolism with a persistent vegetation greater than 10 mm, or a vegetation greater than 30 mm.
  • Procedure: radical debridement and valve replacement, with root replacement (homograft or composite graft) for aortic root abscess. Operative mortality about 15 to 25%.
  • After ischaemic stroke without haemorrhage, surgery can proceed within days if neurological damage is not severe. After intracranial haemorrhage, wait at least 4 weeks unless the situation is life threatening.
• Anticoagulation for mechanical valves: continue warfarin to the same INR range in uncomplicated disease; after a central nervous system embolus, switch to IV unfractionated heparin (aPTT 1.5 to 2.0 times control) for about 2 weeks; stop all anticoagulation in intracranial haemorrhage and restart after specialist review (usually 2 to 4 weeks).
• Pregnancy: avoid gentamicin where possible (fetal ototoxicity); use ampicillin, ceftriaxone, vancomycin and rifampicin; seek obstetric and cardiac surgical input.
• Renal impairment: reduce vancomycin by trough and avoid gentamicin (use the 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 or periapical region, for life; azithromycin or clarithromycin 500 mg (15 mg/kg in children) if allergic to penicillin (clindamycin is no longer recommended). Dental review every 6 months, and chlorhexidine mouthwash and good hygiene.
• Red flags: heart failure, syncope or new block, new neurological deficit, persistent fever after 7 days, rising creatinine, haemodynamic instability.
• Follow up: echocardiography at completion of antibiotics, 1, 3, 6 and 12 months; blood cultures and CRP at 2 and 4 weeks after treatment (relapse is commonest within 2 months); lifelong dental care and education about fever.