Cardiac Implantable Electronic Device Infection

Cardiac implantable electronic device (CIED) infection covers infection of the generator pocket and of the transvenous leads, with or without bloodstream infection and endocarditis of the lead, tricuspid valve or other valves.

It follows about 0.5 to 2% of first implants and more of generator replacements, upgrades and revisions (about 2 to 4%), and it is more frequent with defibrillators and resynchronisation devices than with simple pacemakers.

Early infection (within about 1 month) usually reflects contamination at surgery, and late infection reflects erosion or haematogenous seeding. Staphylococci cause about 60 to 80% of cases: coagulase negative staphylococci (about 35 to 40%) and Staphylococcus aureus (about 25 to 35%, more in late and bacteraemic disease).

Gram negative bacilli account for under 10%, and the rest are Cutibacterium, enterococci, streptococci, Candida and non-tuberculous mycobacteria.

Risk factors are generator replacement or revision, pocket haematoma, anticoagulation with heparin bridging, renal failure, diabetes, immunosuppression, corticosteroids, malignancy, multiple leads, temporary pacing wires, fever at implantation, absent antibiotic prophylaxis, and previous device infection.

Pathophysiology. Bacteria adhere to the device and form a biofilm that resists antibiotics and immune clearance. Antibiotics alone therefore do not cure infection with the hardware in place. Pocket contamination spreads along the leads to the vein and tricuspid valve, producing lead vegetations and septic pulmonary emboli.

Bloodstream infection from a remote source can also seed an intact device.

• Pocket infection: local erythema, swelling, warmth, pain, tenderness, wound dehiscence, purulent discharge, a sinus tract, or erosion with visible generator or lead. Fever is often absent.
• Lead or valve endocarditis: fever, rigors, malaise, weight loss, pleuritic chest pain and cough (septic pulmonary emboli), new tricuspid regurgitation, embolic phenomena, and sepsis.
• Occult infection: unexplained fever or positive blood cultures in a patient with a device and no pocket signs.

Red flags.

• Positive blood cultures, particularly Staphylococcus aureus, in any patient with a device
• Fever with pocket signs
• Septic shock or sepsis
• Lead or valve vegetation, or vegetation over 10 mm on echocardiography
• Septic pulmonary emboli
• Exposed generator or lead through the skin
• A pacemaker dependent patient or a defibrillator patient with an acute infection
• Persistent bacteraemia more than 72 hours after antibiotics are started

• Blood cultures. At least 3 sets from separate venepunctures before any antibiotic, each with an aerobic and an anaerobic bottle.
• Pocket and lead specimens. Take pocket tissue and the lead tips at extraction for culture, and send leads for sonication where available. Do not aspirate the pocket or swab a closed wound, because swabs mislead and aspiration risks seeding the pocket.
• Echocardiography. Transthoracic first, then transoesophageal even if the transthoracic study is normal, to look for lead and valve vegetations. Intracardiac echocardiography when available. Vegetation size directs the choice of extraction route.
• Modified Duke criteria assist diagnosis, with lead vegetation and persistent positive cultures counted as major features.
• 18F-fluorodeoxyglucose PET-CT when echocardiography is negative and suspicion is high (more sensitive for pocket than for lead infection).
• CT chest for septic emboli. Laboratory: full blood count, CRP, creatinine, liver function, procalcitonin when sepsis is suspected.

Differential diagnosis.

• Pocket haematoma or sterile postoperative inflammation or seroma
• Skin cellulitis or contact dermatitis unrelated to the device
• Device allergy (titanium or nickel)
• Erosion from pressure or twiddler's syndrome without infection
• Bacteraemia from another source
• Native valve endocarditis
• Lead related thrombus without infection
• Pulmonary embolism
• Pericarditis
• Drug fever and other causes of fever of unknown origin

Complete device removal is the core of treatment for definite pocket infection, lead or valve endocarditis, and Staphylococcus aureus bacteraemia with no other source. Remove the generator and all leads, including abandoned leads.

• Extraction.
  • Percutaneous transvenous lead extraction as soon as possible, ideally within 3 days of diagnosis, in a centre with cardiac surgical back up.
  • Percutaneous extraction is used for vegetations up to 20 mm. Surgical extraction is considered for larger vegetations, severe tricuspid valve disease, and failed percutaneous extraction.
  • Do not incise and drain the pocket or revise it with the device left in place.
  • Complications: tamponade, vascular tears, pulmonary embolism. In high volume centres, major complications are about 1 to 2% and procedure related mortality under 1%.
• Empirical antibiotics after blood cultures:
  • Vancomycin 25 to 30 mg/kg intravenously as a loading dose (maximum 3 g), then 15 to 20 mg/kg every 8 to 12 hours (usual maximum 2 g for each dose), adjusted to a trough of 15 to 20 mg/L or an AUC of 400 to 600 mg·h/L. Lengthen the interval and use levels in renal impairment. Monitor creatinine, and hearing on long courses.
  • Add piperacillin-tazobactam 4.5 g intravenously every 6 hours for sepsis or Gram negative risk. Give 4.5 g every 8 hours at creatinine clearance 20 to 40 mL/min and every 12 hours under 20 mL/min.
• Directed therapy.
  • Methicillin susceptible staphylococci: flucloxacillin 2 g intravenously every 4 hours (maximum 12 g daily) or cefazolin 2 g intravenously every 8 hours. Monitor liver enzymes. Reduce flucloxacillin in severe renal impairment (creatinine clearance under 10 mL/min).
  • Methicillin resistant staphylococci: continue vancomycin, or use daptomycin 8 to 10 mg/kg intravenously once daily. At creatinine clearance under 30 mL/min give every 48 hours, and check creatine kinase weekly, with a statin withheld during treatment.
  • Candida: remove the whole system and use caspofungin 70 mg intravenously as a loading dose, then 50 mg once daily (35 mg in moderate liver impairment), with liver enzyme monitoring, for at least 4 to 6 weeks after extraction. Involve infectious diseases.
• Duration (counted from extraction):
  • Pocket infection without bacteraemia: 10 to 14 days.
  • Bacteraemia without lead or valve vegetation: at least 14 days.
  • Lead endocarditis or valve involvement, or complicated infection: 4 to 6 weeks.
• Reimplantation. Reassess the indication, because a substantial minority no longer need a device. If needed, wait for at least 72 hours of negative blood cultures, and at least 14 days after extraction when there was a vegetation or valve endocarditis. Implant on the contralateral side, or use epicardial or leadless devices.
• Pacemaker dependent patients. Bridge with a temporary active fixation lead connected to an externalised permanent pacemaker, or use a leadless pacemaker. For defibrillator patients with a high arrhythmic risk, use inpatient monitoring or a wearable defibrillator.
• Suppressive antibiotics without extraction are a last resort only when extraction is refused or impossible. Relapse is common.
• Prevention.
  • Cefazolin 2 g intravenously as a single dose 30 to 60 minutes before incision (3 g if over 120 kg). Use vancomycin 15 mg/kg intravenously, infused over 60 to 120 minutes and finishing before incision, for severe penicillin allergy or MRSA colonisation.
  • Prolonged postoperative antibiotics add no benefit.
  • Continue warfarin without heparin bridging at the time of implantation, and use an absorbable antibacterial envelope in high risk procedures (generator replacement, upgrade, resynchronisation and defibrillator devices).

Special groups. Patients with prosthetic valves are at higher risk of valve involvement. In renal impairment, lengthen the dosing interval of vancomycin to maintain a trough of 15 to 20 mg/L, reduce piperacillin-tazobactam and daptomycin by creatinine clearance, and check levels and creatinine twice weekly.

Monitoring. Blood cultures 48 to 72 hours after extraction and daily until negative, and again 2 weeks after completing therapy. CRP weekly. Vancomycin levels and creatinine twice weekly. Echocardiography before discharge and before reimplantation. Clinical review for relapse at 1, 3 and 6 months.

Referral and escalation. Refer urgently to an electrophysiology centre with extraction expertise and surgical back up, with infectious diseases input. Escalate immediately for sepsis, large vegetation, or a pacemaker dependent patient.