Pacemaker Lead Endocarditis

Pacemaker lead endocarditis is infection of the endocardial part of a transvenous cardiac implantable electronic device system, with vegetation on a lead, the tricuspid valve or the right atrial and ventricular endocardium, usually with bacteraemia. The same process occurs with defibrillator and resynchronisation leads. It is part of the spectrum of device infection that ranges from pocket infection to lead endocarditis and device related valve endocarditis.

Device infection occurs in about 0.5 to 2% of implants, and most often after generator replacement, upgrade or revision, pocket haematoma, early re-intervention, long procedures and absent antibiotic prophylaxis. Patient risk factors are diabetes, chronic kidney disease or dialysis, oral anticoagulation, corticosteroids and other immunosuppression, malignancy, heart failure and skin disease.

Staphylococci cause 70 to 90% of cases (coagulase negative species in about 35 to 40% and Staphylococcus aureus in about 30%). Others are streptococci, enterococci, Gram negative bacilli, Candida species and non-tuberculous mycobacteria.

Mortality is about 5 to 15% in hospital and is roughly doubled when the device is not fully removed. Relapse is common if hardware is retained.

Pathophysiology.

Bacteria form a biofilm on the device surface, which protects them from host defences and antibiotics, so antibiotics alone rarely cure infection.

Infection arises from contamination of the pocket at implantation, from erosion of the generator or leads through skin, or from haematogenous seeding from a distant source. Pocket infection can track along the leads to the endocardium.

Vegetations on leads and the tricuspid valve embolise to the lungs, causing septic pulmonary emboli. Contact of the lead with the tricuspid leaflets damages the valve and causes regurgitation.

Pocket infection: erythema, swelling, warmth, pain, purulent discharge, sinus tracts, adherence and erosion with exposed generator or lead. Pocket signs may be absent in lead endocarditis.

Systemic features: fever, rigors, malaise and weight loss. Pulmonary signs from septic emboli (pleuritic pain, cough, haemoptysis, multifocal consolidation) occur in up to half of patients with lead endocarditis. A tricuspid regurgitation murmur and right heart failure may be present. Some patients have only unexplained fever or Staphylococcus aureus bacteraemia months or years after implantation.

• Blood cultures: at least 3 sets before antibiotics, repeated to document clearance. Do not aspirate the pocket with a needle (it risks seeding), and do not rely on superficial swabs.
• At extraction, send pocket tissue, pocket fluid, the generator and the lead tips for culture, with sonication of hardware where available.
• Echocardiography: transthoracic then transoesophageal (and intracardiac echocardiography where available) for lead and valve vegetations, tricuspid regurgitation, and left sided valve disease. Measure vegetation size, because it directs the extraction method. Normal echocardiography does not exclude lead infection.
• CT chest for septic pulmonary emboli. Fluorodeoxyglucose PET-CT improves detection of pocket infection and, less reliably, lead infection when echocardiography is unrevealing.
• Chest radiograph to count leads and show abandoned leads.
• Modified Duke criteria apply, with pocket infection and pulmonary emboli added as supportive findings.
• Inflammatory markers, creatinine, full blood count, liver tests. Check for other septic foci, and check for coexisting left sided valve disease.

Differential diagnosis.

• Sterile pocket haematoma or seroma, and generator erosion without infection.
• Lead thrombus or fibrin sheath, and right atrial myxoma.
• Pulmonary embolism or pneumonia.
• Bacteraemia from another source with device colonisation, and non-device endocarditis of the tricuspid valve.

Core principle: complete removal of all hardware (generator and every lead, including abandoned leads) is indicated for definite device infection, lead endocarditis, valve endocarditis with a device, and persistent or recurrent Staphylococcus aureus bacteraemia without another source. Long term suppression with antibiotics alone is reserved for patients unfit for extraction or in palliative care.

Empirical antibiotics (after cultures).

• Vancomycin 25 mg/kg intravenously as a loading dose, then 30 to 60 mg/kg daily in 2 to 3 doses (trough 15 to 20 mg/L); monitor creatinine and troughs; adjust to creatinine clearance.
• Add Gram negative cover when septic, health care related or immunosuppressed: ceftazidime 2 g intravenously every 8 hours, or piperacillin with tazobactam 4.5 g intravenously every 6 hours (reduce at creatinine clearance under 40 mL/min).
• Change to the directed regimen once the organism and susceptibilities are known.

Directed antibiotics.

• Methicillin susceptible Staphylococcus aureus: flucloxacillin 2 g intravenously every 4 hours (12 g daily), or cefazolin 2 g every 8 hours. Methicillin resistant strains: vancomycin 25 mg/kg intravenous loading dose, then 30 to 60 mg/kg daily in 2 to 3 doses (trough 15 to 20 mg/L), or daptomycin 10 mg/kg intravenously once daily (every 48 hours when creatinine clearance is under 30 mL/min), with creatine kinase weekly.
• Coagulase negative staphylococci: chosen by the susceptibility result, using flucloxacillin 2 g intravenously every 4 hours or vancomycin at the dose given for methicillin resistant strains. Rifampicin 900 to 1200 mg daily in 2 to 3 doses is added for retained prosthetic material (such as a prosthetic valve) after bacteraemia has cleared, with attention to interactions with warfarin and direct oral anticoagulants.
• Streptococci, enterococci and HACEK organisms: the regimens used for native valve endocarditis (benzylpenicillin 12 to 18 million units daily, or ampicillin 2 g every 4 hours with ceftriaxone 2 g every 12 hours for enterococci, or ceftriaxone 2 g daily).
• Candida: liposomal amphotericin B 3 to 5 mg/kg daily with or without flucytosine 25 mg/kg four times daily, or an echinocandin (caspofungin 70 mg once, then 50 mg daily), followed by long term fluconazole 400 to 800 mg daily; extraction is mandatory.

Duration (counted from device removal and the first negative blood culture).

• Pocket infection without bacteraemia: 10 to 14 days.
• Bacteraemia, or lead vegetation: at least 4 weeks (6 weeks for Staphylococcus aureus or complicated disease).
• Valvular involvement: 6 weeks of organism directed intravenous therapy.

Extraction.

• Percutaneous transvenous lead extraction by an experienced team with cardiac surgical back up is the usual method, including for vegetations under 20 mm.
• Surgical removal is considered for vegetations of 20 mm or more, severe tricuspid valve destruction needing repair or replacement, residual lead fragments, failed percutaneous extraction, or other cardiac indications for surgery. Embolic protection devices may be used in selected patients.
• Pocket debridement with capsulectomy and irrigation, with negative pressure wound therapy for open pockets.
• Major complications of extraction (vascular tear, tamponade, death) occur in under 1% in experienced centres.

Pacing dependence and reimplantation.

• Many patients do not need a new device (about half). Reassess the indication after extraction.
• When pacing is needed, do not reimplant until blood cultures are negative for at least 72 hours, and for at least 14 days after extraction when there is vegetation or valve involvement. Implant on the contralateral side.
• Pacing dependent patients need temporary pacing during the interval, using an active fixation lead connected to an externalised permanent generator, which carries less infection risk than a passive lead.
• Alternatives: leadless pacemaker (when there is no lead or valve vegetation), epicardial leads, and a subcutaneous defibrillator when pacing is not needed.

Anticoagulation. Continue warfarin where indicated, with INR under 3.0 at any procedure; avoid heparin bridging, which increases pocket haematoma.

Prevention.

• Cefazolin 1 to 2 g intravenously (3 g when weight is over 120 kg) within 60 minutes before incision; vancomycin 15 mg/kg intravenously, starting 90 to 120 minutes before incision, for severe beta lactam allergy or MRSA colonisation. No routine antibiotics after the procedure.
• Skin preparation with chlorhexidine in alcohol, nasal decolonisation of Staphylococcus aureus carriers, meticulous haemostasis, avoidance of unnecessary generator changes and early re-entry, and an antibacterial envelope in high risk implants (generator replacement, upgrade, resynchronisation defibrillator).

Monitoring. Blood cultures 48 to 72 hours after extraction and until negative, then 2 weeks after stopping antibiotics. Inflammatory markers and creatinine twice weekly during treatment. Echocardiography before discharge and at 1, 3 and 6 months. Wound review at 1 and 2 weeks. Relapse surveillance for 6 to 12 months.

Referral and escalation. Refer to a centre with lead extraction capability and an endocarditis team. Urgent referral for bacteraemia, a vegetation on echocardiography, sepsis, septic emboli, a pacing dependent patient, or generator erosion.

Special groups.

• Pregnancy: extraction is done when lifesaving; use penicillins and cephalosporins; avoid fluoroquinolones and tetracyclines.
• Dialysis and kidney impairment: high risk group; avoid aminoglycosides, dose vancomycin and daptomycin by creatinine clearance, and preserve veins.
• Older adults and frailty: the same indications for removal apply, with decisions made jointly on reimplantation.
• Region specific: extraction centres are few in many regions, so early transfer is needed; surgical removal is the fallback.