Microbiology of CIED infections

Staphylococcal species (coagulase-negative staphylococci and Staphylococcus aureus) are the predominant organism responsible for CIED infection. CIED infections that present early (within 4 weeks of device implantation) generally are related to device or wound contamination at the time of surgery. S. aureus is the most common microorganism encountered in this situation. However, pocket infection with coagulase-negative staphylococcus can present weeks or months after device implantation. In contrast, the majority of late-onset CIED lead infections are caused by hematogenous seeding of device leads from remote sources of bloodstream infection. In published series, up to 30% of the patients with CIEDs who have blood cultures that are positive for S. aureus have underlying CIED lead infection, even when the generator pocket has no obvious inflammatory signs. Therefore, transesophageal echocardiography (TEE) is recommended in patients with CIEDs and positive blood cultures with S. aureus. In contrast, CIED lead infection with gram-negative bacteria is an exceedingly rare complication of gram-negative bacteremia and routine use of TEE is not recommended in these cases. Moreover, gram-negative bacteria are also an uncommon cause of CIED pocket infections but may be seen in patients with multiple comorbid conditions and those with long-term central venous catheters (e.g., hemodialysis populations). Mycobacterial or fungal CIED infections are exceedingly rare and subject of case reports.

Clinical presentation and diagnosis

CIED infections primarily manifest in two distinct ways. Local infection, limited to the generator pocket; or systemic infection involving CIED leads, heart valves, or both. Pocket infection is the most common manifestation of device infection and these patients typically present with inflammatory changes at the pocket site that may include localized pain, erythema, drainage, or cellulitis around the pocket site. Occasionally, erosion of the device generator or leads through the skin is the sole manifestation of chronic smoldering infection. Systemic findings may or may not accompany local infections.

Systemic symptoms and signs such as fever, chills, rigors, malaise, or diaphoresis are hallmarks of CIED lead infection or endocarditis. Blood cultures are typically positive in these cases, but could be negative especially if drawn after administration of antibiotics. Patients with CIED lead infection or endocarditis could present with evidence of septic emboli to the lungs or other organs, especially if left-sided heart valves are also involved.

Diagnosis of CIED pocket infection is relatively straightforward based on inflammatory changes at the generator pocket site. However, blood cultures should be obtained in all cases prior to initiating antibiotic therapy, even if systemic symptoms are not overt. In cases where blood cultures are reported positive, echocardiography should be performed to look for evidence of CIED lead or valvular vegetations. TEE is preferred because it has a sensitivity of about 95% for the detection of lead or valve vegetation, compared with a sensitivity of about 30% with transthoraic echocardiography (TTE). Occasionally, additional testing such as computed tomography (CT), magnetic resonance imaging (MRI), or gallium scanning may be necessary to evaluate complications of CIED infection such as deep abscesses or metastatic foci of infection in the spine, brain, or other organs.

A particularly challenging aspect of diagnosing CIED infection is the cases where blood cultures are positive for staphylococci (especially S. aureus) but there are no inflammatory changes around the generator pocket and TEE shows no evidence of vegetations on CIED leads. Whether these devices should be left in place or taken out is a complex decision. Based on published series, the following factors increase the likelihood that the CIED is seeded with S. aureus: (1) no other identifiable source of infection, (2) persistently positive blood cultures for 72 hours or longer, (3) community-onset S. aureus bacteremia (SAB), and (4) SAB within 3 months of device implantation. If any of these factors are present, we favor removal of the CIED. In the absence of any of these features, it may be reasonable to treat for 2 to 4 weeks depending on the presumed source of SAB and closely follow-up for any evidence of relapse of infection. If the patient has relapse of SAB, the CIED should then be removed.

Management

For patients who present with systemic manifestations of infection, it is reasonable to start empiric antibiotic therapy once blood cultures have been obtained. However, for cases where infection is limited to the generator pocket without any systemic signs, it is prudent to wait until pocket and device cultures are submitted at the time of explantation and then start empiric therapy. Empiric coverage should include antimicrobials with activity against S. aureus and coagulase-negative staphylococci. Until sensitivities are known, vancomycin is a reasonable choice as it is active against methicillin-resistant staphylococci. If vancomycin cannot be clinically tolerated,

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