Infections involving cardiac implantable electronic devices: Treatment and prevention

INTRODUCTION — 

Traditionally, cardiac implantable electronic devices (CIEDs), including pacemakers, implantable cardioverter-defibrillators (ICDs), and cardiac resynchronization therapy (CRT) devices with pacing or defibrillation capacity, have included pulse generators to provide the electrical stimulus and either transvenous or epicardial leads to deliver the stimulus to the heart.

Newer devices have been developed which operate effectively without the requirement for a transvenous or epicardial lead system; leadless pacemakers (LPM) are percutaneously placed directly inside the heart, thus avoiding a subcutaneous pocket and transvenous leads. Subcutaneous ICDs (S-ICD) with an extra-thoracic tunneled electrode have no transvenous component. Implantable loop recorders function effectively to monitor cardiac rhythm from a subcutaneous pocket without direct attachment to the heart or vasculature.

This topic focuses on treatment and prevention of infection involving traditional CIEDs – eg, those with subcutaneous pockets and transvenous leads.

The epidemiology, microbiology, clinical manifestations, and diagnosis of CIED infections, as well as noninfectious complications of CIEDs, are discussed separately.

●(See "Infections involving cardiac implantable electronic devices: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

●(See "Cardiac implantable electronic devices: Long-term complications" and "Cardiac implantable electronic devices: Periprocedural complications".)

TREATMENT

General principles — In general, successful management of a cardiac implantable electronic device (CIED) infection (systemic infection or pocket infection) requires (algorithm 1 and algorithm 2 and algorithm 3) [1]:

●Antibiotic therapy – Antibiotic therapy consists of initial empiric therapy (see 'Empiric antibiotic therapy' below), followed by definitive treatment based on culture results; the duration depends on the scope of infection (see 'Definitive antibiotic therapy' below).

●Device removal – Explantation of an infected CIED (leads, including residual leads that are non-functional, and pulse generator) remains a strong recommendation of the American Heart Association (AHA), the Heart Rhythm Society, the European Heart Rhythm Association (EHRA) and the European Society of Cardiology (ESC) [2-5]. To maximize the potential for an optimal outcome, device removal is an essential part of the management of CIED infection (ranging from isolated generator pocket infection to systemic infection with involvement of the intracardiac leads).

Device removal, particularly within seven days of diagnosis for patients with systemic CIED infection, is associated with survival benefit [6-10] (see 'Rationale for early removal' below). However, early extraction is achieved in only a minority of patients [7].

Factors that may undermine the decision to proceed with early device removal include uncertainty in the diagnosis of definite CIED infection, as well as misconceptions regarding the risk of complications related to device removal. To optimize outcomes, patients with CIED infection should be managed by clinicians with expertise in the treatment of this condition.

The details of the therapeutic approach depend upon the extent of infection, the pathogen, and individual clinical circumstances (eg. the general health of the patient and the potential complexity of device removal).

Empiric antibiotic therapy — Empiric intravenous antibiotic therapy should be initiated following collection of blood cultures (at least two or three sets) and culture of pocket drainage, if present.

Subsequently, treatment should be tailored based on antibiotic susceptibility of the implicated pathogen(s); the antimicrobial approach is derived from pathogen-specific regimens recommended for treatment of endocarditis. (See "Antimicrobial therapy of left-sided native valve endocarditis" and "Antimicrobial therapy of prosthetic valve endocarditis".)

●Empiric Gram-positive coverage

•Initial treatment with vancomycin – Empiric antibiotic therapy for patients with suspected CIED infection should consist of antistaphylococcal therapy. Given the high incidence of methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis infection, initial therapy with vancomycin (table 1) is reasonable.

•Role of daptomycin – High-dose daptomycin (8 to 10 mg/kg ideal body weight, which is higher than the US Food and Drug Administration [FDA] approved dose) is an acceptable alternative to vancomycin for treatment of CIED infection. However, caution is required in the setting of prior vancomycin failure; S. aureus that are nonsusceptible to daptomycin have been detected when the organism has persisted in spite of vancomycin therapy or when there is breakthrough bacteremia during daptomycin therapy [11]. Accordingly, susceptibility testing must be performed on these organisms to ensure continued susceptibility to daptomycin. In addition, with daptomycin exposure, emergence of resistance among Streptococcus mitis group organisms is common.

Use of daptomycin as an alternative for treatment of CIED infection is supported by a study of 25 cases of device-related infection in which high-dose daptomycin (mean 8.3 mg/kg [range 6.4 to 10.7 mg/kg]) resulted in cure or improvement in 92 percent of cases [12]. Devices were explanted in 22 patients; 2 patients with retained devices remained bacteremic during therapy. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Treatment of bacteremia".)

•Other antistaphylococcal agents – Data for use of other alternative antistaphylococcal agents (such as teicoplanin, ceftaroline, ceftobiprole, and telavancin) in treatment of CIED infections are lacking. Ceftaroline, ceftobiprole, and telavancin likely retain activity against MRSA with reduced susceptibility to vancomycin and daptomycin. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Treatment of bacteremia".)

●Empiric Gram-negative coverage – In patients presenting with hemodynamic instability, broadening of empiric therapy to include coverage of gram-negative bacteria is appropriate (reasonable additions to vancomycin include cefepime, piperacillin-tazobactam, or a carbapenem) [13].

Once a causative organism is identified (via blood and/or pocket wound cultures), the antibiotic regimen should be tailored accordingly.

Device removal — Early device removal is an important component of successful management of CIED infection.

Removal of other intravascular devices (eg central venous catheters, hemodialysis catheters) is also indicated, where feasible.

Rationale for early removal

●Benefits of early device removal – Early device removal (within <7 days) after diagnosis of CIED infection is associated with improved survival and reduced complications compared with removal later during the initial hospitalization or not removing the device. Alternative approaches (such as device retention with antibiotic therapy, or generator removal with lead retention with antibiotic therapy) are associated with increased risk of mortality.

•CIED systemic infection – Early device removal is supported by these studies as well as others:

-In a 2022 study including 6619 patients with CIED systemic infection, 52.2 percent had early device removal (within 7 days) and 47.8 percent had delayed device removal (after 7 days). Delayed device removal was associated with higher rates of in-hospital mortality in patients with systemic infection (7.5 versus 10.4 percent). With multivariate logistic regression, delayed device removal in patients with systemic infection was associated with higher odds of in-hospital mortality (aOR 1.24; 95% CI 1.04–1.49) [6].

-In a 2023 study including 11,304 patients with CIED infection, one-year mortality was greater among those who did not undergo CIED removal within 30 days (32.5 percent), relative to removal within 6 days (18.6 percent) or 7 to 30 days (23.4 percent) [7]. In a multivariable analysis, device removal (versus device retention) was associated with reduction in one-year mortality (adjusted hazard ratio [AHR] 0.82; 95% CI 0.74-0.90). In addition, in a separate multivariable model, removal within 6 days (but not removal between 7 to 30 days) was associated with decreased mortality compared to no device removal (AHR 0.69; 95% CI 0.61-0.78).

•CIED pocket infection – In a 2022 study including 6380 patients with isolated CIED pocket infection, 84.3 percent had early device removal and 15.7 percent had delayed device removal; in-hospital mortality rates were 0.9 and 1.5 percent, respectively [6]. Delayed device removal was associated with an increased risk of adverse events including major bleeding, pulmonary embolism, respiratory complications, and acute stroke.

●Device removal in patients with S. aureus bacteremia – We favor device removal in patients with a CIED and S. aureus bacteremia, even though it can be difficult to establish a definitive diagnosis of CIED infection with cardiac imaging. This approach is supported by data from 5325 patients with a CIED and S. aureus infection in the United States Nationwide Readmissions Database; in-hospital mortality rate was lower among those who underwent transvenous lead removal during hospitalization (5.6 percent versus 16.4 percent; aOR 0.31, 95% CI 0.21-0.44) [8].

The risk of relapse without device removal may be correlated with the duration of S. aureus bacteremia. In one study including 360 patients with a CIED and staphylococcal bacteremia (329 due to S. aureus), CIED infection was confirmed in 182 patients; among the remaining 178 patients, 36 died or underwent empiric device removal [14]. Of the surviving 142 patients who did not undergo device extraction, 27 patients (of whom 25 had S. aureus infection) experienced relapsed bacteremia within 6 months. The risk of relapse was greater among those with >1 day of bacteremia than among those with a single day of bacteremia (35 versus 5 percent). Among the 178 patients without detection of CIED infection on the initial hospitalization, all-cause 1-year mortality was 35 percent. In a multivariable analysis of these patients, death at one year was reduced among those who underwent empiric device removal (hazard ratio [HR] 0.28, 95% CI 0.08-0.95).

●Device removal in patients with candidemia – We favor device removal in patients with a CIED and candidemia; data are limited to case reports and case series [15-19]. In one series including 12 patients with CIED and candidemia, 4 patients had visible vegetation and underwent CIED removal; of these, 3 survived at one-year follow-up [19]. The other 8 patients were managed non-operatively; none survived.

●Device removal in patients with left-sided endocarditis – We favor device removal in the setting of left-sided endocarditis, even in the absence of definitive evidence for CIED infection – particularly in the setting of staphylococcal infective endocarditis (IE) [2,4]. In patients with prosthetic valve endocarditis, CIED removal may increase the likelihood of cure.

Data suggest that survival is improved by extraction of the entire CIED in such patients, especially those with prosthetic valve endocarditis (definite or possible) [20,21]. In one observational study including 157 patients with left-sided IE and an apparently uninfected CIED, device extraction was associated a survival benefit, hazard ratio 0.59 (0.40-0.87) [21].

Removal approach — The removal approach depends on the size of the vegetation, as outlined below.

For patients with isolated CIED pocket infection who have not already undergone transesophageal echocardiography (TEE), this study should be performed prior to or during extraction, as this facilitates assessment for vegetations (suggesting intracardiac infection). (See "Infections involving cardiac implantable electronic devices: Epidemiology, microbiology, clinical manifestations, and diagnosis", section on 'Diagnosis'.)

Arrangements should be made for managing arrhythmias until a new device can be reimplanted. Additional issues related to CIED removal are discussed separately. (See "Cardiac implantable electronic device lead removal" and "Wearable cardioverter-defibrillator", section on 'Bridge to indicated or interrupted ICD therapy'.)

Transvenous removal for most patients — The preferred approach for CIED removal consists of transvenous removal of all leads (including previously abandoned leads, if present), in conjunction with removal of the generator.

Alternative options for patients with large lead vegetations — Infrequently, transvenous removal of CIED leads with large lead vegetations (>20 mm) has been associated with hemodynamically significant pulmonary embolism (PE) in small observational studies [22-24]. Subclinical septic emboli may also occur, which may impact long-term outcomes.

In such cases, clinical approaches include transcatheter vegetation debridement prior to transvenous lead removal, or surgical removal:

●Transcatheter vegetation debridement – Transcatheter debridement of large lead vegetations prior to transvenous lead removal may reduce the risk of septic emboli; there are no comparative trials, and clinical data are limited [25,26]. The AHA states that transcatheter vegetation debridement may be considered in select patients to reduce the risk of PE with transvenous device removal, to reduce the risk of systemic emboli in patients with a patent foramen ovale or an atrial septal defect, and for source control (vegetation debridement) in patients with sepsis and persistent bacteremia who are not candidates for device removal [3].

This approach has been described in a study including 101 patients with CIED-IE and vegetation >20 mm or vegetation >10 mm with patent foramen ovale; all underwent transcatheter vegetation debridement, after which all leads were removed successfully [26]. Two patients suffered tricuspid valve injury, one of whom required tricuspid valve replacement. Mortality at 30 days was 3 percent.

●Surgical removal – Consideration of surgical management requires careful assessments of risks and benefits [2-4,13,27]. For patients with large lead vegetations, surgical removal may reduce the risk for development of PE. However, surgical removal is associated with greater morbidity than transvenous removal, and the threshold vegetation size for surgical removal is uncertain [4].

Collecting microbiology specimens — When the pocket is opened for device removal, swabs and tissue should be obtained for culture. Lead tips are typically cut and sent for culture.

For patients who have recently received antibiotics or in circumstances in which difficult–to-culture organisms are anticipated (eg Gram stain and culture of purulent drainage are unrevealing), sonication of the lead tip with culture and polymerase chain reaction (PCR) testing of the sonicate fluid may facilitate a microbiologic diagnosis [3,28,29]. However, this tool is not widely available.

Following device removal, the pocket should be debrided meticulously (including removal of the fibrous capsule and any foreign material) and irrigated with saline.

Complications — Major procedure related complications are rare (<2 percent), and extraction-related in-hospital mortality is <1 percent [13,30,31]. In general, leads that have been in place for more than two years are more difficult to remove than newer leads, and the difficulty continues to increase with increased lead dwell time. The degree of difficulty also depends on the lead type; ICD leads (particularly dual coil designs) tend to have more extensive adhesions and therefore are more difficult to explant than pacemaker leads. In most cases, even in these more difficult settings, leads can be removed safely by experienced operators. To gain the survival benefits of early extraction in such cases, the decision to attempt lead removal must be individualized, and early transfer to centers of expertise should be considered.

Definitive antibiotic therapy

CIED systemic infection — Definitive management of CIED systemic infection requires device removal and antibiotic therapy (algorithm 1 and algorithm 2) [2-5,13,32].

The clinical manifestations and diagnosis of CIED systemic infection are discussed separately. (See "Infections involving cardiac implantable electronic devices: Epidemiology, microbiology, clinical manifestations, and diagnosis", section on 'Our approach'.)

Presence of lead or valve vegetation — For patients with CIED systemic infection and echocardiography demonstrating a valve or lead vegetation, we favor presumptive treatment for endocarditis.  

In these settings, we treat with four to six weeks of parenteral therapy, depending on the implicated pathogen. This approach is particularly important when implantation of a new device is anticipated. (See "Antimicrobial therapy of left-sided native valve endocarditis" and "Antimicrobial therapy of prosthetic valve endocarditis" and "Infections involving cardiac implantable electronic devices: Epidemiology, microbiology, clinical manifestations, and diagnosis", section on 'Diagnosis'.)

For patients with bacteremia caused by an organism typically associated with endocarditis and TEE (or other imaging) demonstrating a lead vegetation but no valve vegetation, we still favor treatment for endocarditis. This is in contrast to some others (including some guideline committees) who favor a shorter duration of therapy for cases in which the vegetation only involves the lead [4,5,13,33]. We favor this approach given the limited sensitivity of TEE for excluding valvular endocarditis (or mural endocarditis at the lead implantation site).

Absence of lead or valve vegetation — For patients with no lead or valve vegetation on TEE, the approach should be guided by blood culture results, alternative imaging (fluorodeoxyglucose positron emission tomography/computed tomography [FDG-PET/CT]) and the clinical likelihood of CIED infection (algorithm 2):

●Blood culture findings warranting presumptive treatment for endocarditis – For patients with blood cultures demonstrating the following results, we favor presumptive treatment for endocarditis with four to six weeks of pathogen-specific parenteral antibiotic therapy:

•Any isolation of the following organisms:

-S. aureus

-Candida species

•High-grade bacteremia (defined as 2 or more separate blood cultures positive for the same organism, drawn ≥1 hour apart) with the following organisms:

-Coagulase-negative staphylococci, identical species

-Cutibacterium (formerly Propionibacterium) species

-Enterococcus species (particularly E. faecalis)

-Alpha-hemolytic Streptococcus species

-Non-group A beta-hemolytic Streptococcus species

-Pseudomonas aeruginosa

-Serratia marcescens

-Other organism with propensity to cause endocarditis, in the absence of a clear source

In the setting of additional sites of infection (such as discitis and/or vertebral osteomyelitis), a longer duration of therapy may be warranted. (See "Antimicrobial therapy of left-sided native valve endocarditis" and "Antimicrobial therapy of prosthetic valve endocarditis" and "Vertebral osteomyelitis in adults: Clinical manifestations and diagnosis".)

The above approach is supported by several studies. In one study including 160 patients with a CIED and bacteremia due to non-S. aureus gram positive cocci, 56 percent met EHRA criteria for CIED infection (38 percent with definite CIED and 19 percent with possible CIED infection). Increased risk of infection was associated with specific organisms (coagulase negative staphylococci, enterococci, and viridans streptococci) and clinical characteristics (presence of a prosthetic valve or a cardiac resynchronization therapy [CRT], community onset of bacteremia, and longer duration of bacteremia). Outcomes were more favorable with endocarditis targeted therapy [34].

●Blood culture findings warranting further evaluation – For patients with blood cultures demonstrating low-grade bacteremia (single positive blood culture) with one of the following organisms, further evaluation is warranted (algorithm 2):

•Coagulase-negative staphylococci

•Cutibacterium (formerly Propionibacterium) species

•Enterococcus species

•Alpha-hemolytic Streptococcus species

•Non-group A beta-hemolytic Streptococcus species

•Pseudomonas aeruginosa

•Serratia marcescens

Potential alternative sources of bacteremia should be evaluated. Blood cultures should be repeated to evaluate for high grade bacteremia. If repeat cultures are confounded by antibiotic therapy and clinical suspicion for CIED infection persists, further imaging (FDG-PET/CT) is warranted (if feasible) – given the limited sensitivity of TEE to exclude valve infection [35-40]. (See "Infections involving cardiac implantable electronic devices: Epidemiology, microbiology, clinical manifestations, and diagnosis", section on 'Diagnosis'.)

●Blood culture with organisms that do not commonly cause endocarditis – For patients with blood cultures demonstrating one of the following organisms, the approach depends on whether there is a clear alternative source:

•Gram-negative organisms (excluding P. aeruginosa and S. marcescens)

•Streptococcus pneumoniae

•Group A beta-hemolytic Streptococcus species

•Transient bacteremia due to an organism that does not commonly cause endocarditis

If there is no clear alternative source, further imaging (FDG-PET/CT) is warranted (if feasible). If there is a clear alternative source, we retain the device and administer antibiotic therapy for two weeks, followed by surveillance blood cultures and close follow up.

Antifungal therapy — The approach to selection of antifungal therapy for treatment of systemic Candida CIED infection is the same as that of native valve endocarditis (NVE) (table 2) [41]. This is discussed further separately. (See "Candida endocarditis and suppurative thrombophlebitis".)

The duration of therapy for CIED systemic Candida infection is at least six weeks following device removal.

We are in agreement with some experts who favor lifelong suppressive antifungal therapy for patients with systemic Candida CIED infection following implantation of a new CIED (even in the absence of detectable valve involvement), particularly in older adults or those with multiple comorbidities. This approach is supported by descriptions of delayed onset of IE in patients with prosthetic valves who experience candidemia [42] and descriptions of relapsed CIED fungal infection despite antifungal therapy plus device explantation [43]. In addition, cardiac imaging is not sufficiently sensitive to fully exclude intracardiac infection.

Relapse after completion of therapy should prompt repeat assessment for CIED or cardiac valve infection.

CIED pocket infection — For patients with an isolated CIED pocket infection (eg, sterile blood cultures without prior confounding antibiotic exposure, no systemic symptoms and, if performed, TEE negative for lead or valve vegetation), antibiotics should be initiated empirically (algorithm 3). If this has not been done, antibiotic therapy should be started in advance of device extraction.

Antibiotic treatment may be completed with oral antibiotics dosed for treatment of soft tissue infection, guided by pathogen susceptibility as available. Definitive antibiotic therapy should be administered for 10 to 14 days following device removal [3-5,13,33].

For fungal CIED pocket infection, the duration of antifungal therapy is four weeks following device removal (table 2). (See "Management of candidemia and invasive candidiasis in adults".)

Device reimplantation — For patients who require reimplantation of a new device, the optimal timing is uncertain. The risk of infection of a new device (which is generally low) must be balanced with the risk of monitoring with no device in place or use of a temporary device to bridge until reimplantation can be undertaken; approximately 23 to 30 percent of patients with CIED infection do not require a new device [13]. If necessary, a temporary device can be placed, although these are also associated with risk of infection. Techniques for temporary pacing are discussed separately. (See "Temporary cardiac pacing".)

●Timing – The approach to CIED reimplantation depends on TEE findings and blood culture results prior to device removal (algorithm 4):

•CIED systemic infection

-Presence of valve vegetation – For patients with valve vegetation, the new CIED may be implanted once extracardiac sites of infection have been treated effectively, symptoms and signs of infection have resolved, and surveillance blood cultures following device removal are negative for at least 14 days [3]. By that time, the valve infection should be sufficiently treated such that seeding of the new lead is unlikely.

In a retrospective study including 109 patients with CIED-IE, using a Cox regression analysis, 12-month mortality was higher among those who underwent reimplantation in <14 days after device removal than among those who underwent reimplantation ≥14 days after device removal (HR 4.03; 95% CI 1.12-13.91) [44]. Patients with a valve vegetation and reimplantation interval <14 days had lower 12-month survival than those with reimplantation interval ≥14 days (58 versus 94 percent).

-Presence of lead vegetation or no vegetation – For patients with only a lead vegetation or for patients with bacteremia in the absence of a vegetation (ie, patients with no valve nor extracardiac sites of infection), the new CIED may be implanted once surveillance blood cultures following device removal are negative for at least 72 hours of antibiotic therapy [3,4] .

•CIED pocket infection – For patients with isolated pocket CIED infection (no vegetation and negative blood cultures), the new CIED may be implanted once there is sufficient control of the local infection. The severity of infection and other clinical factors (eg, pacemaker dependence) should be considered carefully in deciding on timing of reimplantation.

For patients with minimal inflammation or device exposure due to skin erosion, same-day extraction and reimplantation on the contralateral side have been performed in small numbers of pacer-dependent patients [5,45]; however, published experience with this approach is limited.

Contralateral CIED implant is favored in most scenarios [3,4]. The new CIED should not be placed at the site of the previously infected device if any alternative exists.

●Alternative devices – Devices with lower risk of intravascular infection include subcutaneous ICDs (S-CID) or leadless pacemakers (LPM) [46-48]. For patients with prior CIED infection or patients at high risk of bacteremia (such as patients on hemodialysis), use of one of these devices warrants consideration [3,4]. These devices also might be considered if use of a contralateral reimplantation site is not feasible. (See "Implantable cardioverter-defibrillators: Choosing a device and system descriptions", section on 'Factors favoring subcutaneous ICD placement' and "Permanent cardiac pacing: Overview of devices and indications", section on 'Leadless systems'.)

CIED infection managed with device retention — In spite of consensus guidelines recommending device extraction for management of definite CIED infection, there are occasional patients who are managed with device retention. This situation may arise due to patient refusal of extraction or consideration of the risk-benefit balance and the patient's life expectancy or goals of care. These patients are at high risk of treatment failure with subsequent relapse and increased mortality [33,49].

In patients with isolated CIED pocket infection who do not undergo device removal, direct instillation of antibiotics is a last resort strategy; data to support this approach are very limited. In one study, 80 patients with CIED pocket infection (excluding patients with growth of S. aureus in pocket cultures at time of recruitment) were treated with pocket debridement (including skin flap closure or submuscular device placement in some cases) and continuous instillation of antibiotics into the pocket for at least 14 days through an implanted catheter; 8 patients underwent multiple repeat treatments. With a median follow-up of 3 years (IQR 1.0-6.8 years), all cause one-year mortality was 15 percent and clinical resolution of infection was observed in 85 percent of patients [50].

Device retention with antibiotic therapy is generally an approach of last resort. In such cases, an aggressive approach to antibiotic therapy is warranted; evidence to guide management is lacking. We favor a six-week course of therapy as would be used for prosthetic valve endocarditis. Thereafter, long-term oral suppressive antibiotic therapy may be used, targeted to the implicated pathogen [3,13,33]. In one study including 37 patients with CIED infection managed with chronic antibiotic suppression, the estimated median survival was 1.43 years (95%, CI 0.27-2.14); relapse within one year occurred in 18 percent of cases [49]. (See "Antimicrobial therapy of prosthetic valve endocarditis".)

For patients who experience persistent, progressive, or relapsed infection during attempted management with device retention, device removal should be reconsidered.

Presumed non-CIED source of bacteremia — For patients with bacteremia and negative cardiac imaging, it can be difficult to distinguish CIED infection from infection at other sites.

Initial management with device retention and antibiotic therapy is reasonable in the following circumstances (algorithm 2) [51,52]:

●Bacteremia due to the following organisms:

•Gram-negative bacteremia (excluding P. aeruginosa or Serratia marcescens)

•Streptococcus pneumoniae

•Group A beta-hemolytic Streptococcus

•Transient bacteremia due to an organism that does not commonly cause endocarditis

●No clinical, TEE, or other imaging (if available) evidence of lead or valve infection

●No evidence of pocket infection

Antibiotic therapy should be administered for at least two weeks, using a regimen appropriate for the organism and primary site of infection [4,53].

Patients managed with device retention who have continued unexplained bacteremia despite appropriate antibiotic therapy or who relapse after appropriate antibiotic therapy likely have CIED infection and warrant device removal [33,54,55]. After completion of antibiotic therapy, blood cultures (two sets) should be obtained along with close clinical follow-up. (See "Gram-negative bacillary bacteremia in adults" and "Invasive pneumococcal (Streptococcus pneumoniae) infections and bacteremia in adults" and "Invasive group A streptococcal infection and toxic shock syndrome: Treatment and prevention".)

OUTCOMES — 

Patients with cardiac implantable electronic devices (CIEDs) are often elderly and have multiple comorbidities; when admitted for CIED infection, they experience significant mortality. Mortality is reduced with early extraction of the infected CIED during the initial hospitalization.

●Among 27,257 patients hospitalized with CIED-IE in the 2003 to 2017 United States National Inpatient Sample, a longitudinal analysis demonstrated a reduction in CIED-IE in-hospital mortality between 2003 and 2017, from 15 to 9.7 percent [56].

●A 2018 study included more than 3400 patients undergoing initial CIED placement or replacement who experienced device infection during the following year; among 2109 patients who underwent device removal and replacement, one-year mortality was observed in 17 percent of cases [57]. Among 1355 patients who underwent device removal in the absence of replacement, one-year mortality was observed in 34 percent of cases.

●The Spanish Collaboration on Endocarditis, using a national observational registry based in multiple referral centers, found among 424 patients with CIED-IE, in-hospital and 1-year mortality rates of 14.6 percent and 20 percent, respectively [58].

PREVENTION — 

Cardiac implantable electronic devices (CIED) placement should be performed with assiduous aseptic and surgical techniques in a controlled environment; the same is true of changing pulse-generators [4,33,59,60]. CIED placement should be deferred in the setting of active infection elsewhere [5].

Operator experience affects outcome; ideally, the procedure should be performed by an experienced operator [4,61,62]. (See "Cardiac implantable electronic devices: Periprocedural complications", section on 'Operator characteristics' and "Infections involving cardiac implantable electronic devices: Epidemiology, microbiology, clinical manifestations, and diagnosis", section on 'Risk factors'.)

Anticoagulation or antiplatelet therapy — Pocket hematomas are associated with a significantly increased risk of CIED infection. Accordingly, careful attention should be directed to current anticoagulation or antiplatelet therapy.

For patients with CHA₂DS₂-VASc <4 (calculator 1) (eg, those not at high risk for embolic events), anticoagulation should be held prior to the procedure. For patients at higher risk, bridging anticoagulation with heparin is not recommended; but rather continued warfarin with an INR between 2 to 3.5 is reasonable [3,4]. For patients with CHA₂DS₂VASc ≥2, direct acting oral anticoagulants (DOAC) may be continued [3].

Antiplatelet therapy appears associated with hematoma formation and exacerbates anticoagulation; ideally, antiplatelet agents should be held for five to ten days before the procedure [4,63]. Bridging anticoagulation with heparin is not recommended. In device replacement procedures, total capsulectomy (as compared to partial or no capsulectomy) has been associated with increased bleeding and infection [64]. (See "Cardiac implantable electronic devices: Periprocedural complications", section on 'Bleeding'.)

Antibiotic prophylaxis at device implantation — Systemic antibiotic prophylaxis is warranted for surgical implantation of foreign devices.

●Preoperative antibiotic prophylaxis

•Antibiotic regimen – We are in agreement with the American Heart Association (AHA), the Heart Rhythm Society, and the European Heart Rhythm Association (EHRA) which recommend prophylaxis with cefazolin or a similar first generation cephalosporin when CIEDs are implanted or pulse generators exchanged [3-5,33].

Dosing consists of cefazolin 2 g (3 g for those weighing >120 kg) intravenously within 60 minutes of the surgical incision; if during the procedure, the interval from the preoperative dose exceeds four hours, an additional dose should be administered [3].

Vancomycin should not be used routinely; however, if there is concern about cephalosporin allergy, prior infection or colonization with methicillin resistant staphylococci, or high institutional rates of methicillin-resistant S. aureus (MRSA) infection, vancomycin 1 g (15 mg/kg actual body weight) intravenously 120 minutes before the incision may be given [3,33,64,65].

For patients who cannot tolerate beta-lactam antibiotics or vancomycin, daptomycin or linezolid are alternatives [33]. (See "Antimicrobial prophylaxis for prevention of surgical site infection in adults", section on 'Antibiotic selection'.)

•Efficacy – Contamination with skin flora is responsible for a significant proportion of CIED infections; antibiotic prophylaxis reduces risk for device infection [66-70]. In a controlled trial including 1000 patients randomized to receive either cefazolin or placebo prior to CIED implantation, those who received cefazolin had a lower infection rate than those who received placebo (0.6 versus 3.3 percent) [69].

●No role for incremental perioperative antibiotics – Administration of incremental perioperative antibiotics does not appear to confer benefit over conventional administration of preoperative antibiotic prophylaxis for CIED implantation.

In the PADIT trial (Prevention of Arrhythmia Device Infection Trial), a cluster randomized trial including 19,603 patients undergoing CIED procedures at 28 centers (including 12,842 "high risk" patients undergoing any repeat CIED procedure or cardiac resynchronization therapy procedure), patients were randomized to incremental treatment (which included preprocedural cefazolin plus vancomycin, intraprocedural bacitracin pocket wash, and oral cephalexin for two days following the procedure) or conventional prophylaxis (preprocedural cefazolin) [70]. Compared with cefazolin prior to the procedure, there was no significant difference in the overall hospitalization rate for CIED infection within one year (odds ratio [OR] 0.77, 95% CI 0.56-1.05) nor within the risk-related subpopulations (high-risk patients: OR 0.82, 95% CI 0.59-1.15) or low-risk patients (OR 0.54, 95% CI 0.26-1.10). There was no correlation between the device type and the intervention strategy.

Use of antibiotic-impregnated envelopes — For patients at increased risk of CIED infection (eg, patients undergoing CIED generator replacement, lead revision, system upgrade, or cardiac resynchronization therapy-defibrillator [CRT-D] placement), we suggest using an antibiotic-impregnated absorbable envelope at the time of CIED implantation [3,4,71]. In such cases, preprocedure systemic antibiotic prophylaxis should also be administered. (See 'Antibiotic prophylaxis at device implantation' above.)

At the time of implantation, the CIED pulse generator is placed in an absorbable envelope impregnated with minocycline and rifampin. These antibiotics are released slowly over seven days into the generator pocket. This strategy has reduced major CIED infections in high-risk patients, specifically infections originating in the generator pocket, as shown in the WRAP-IT trial [3,72]. Reduced body mass index (BMI) has been associated with increased frequency of procedure-related pocket hematoma and thus increased risk for infection; accordingly, low BMI might justify envelope use [63].

Data regarding the efficacy of antibiotic-impregnated envelopes are derived from one randomized trial and multiple nonrandomized cohort studies [72-75]:

●The WRAP-IT trial randomized 6983 patients who were considered at increased risk for major CIED infection to either have the device encased in an antibiotic-impregnated absorbable envelope or not (control group) [72]. The study population was comprised of patients undergoing CIED generator replacement, system upgrade, pocket or lead revision, or those undergoing initial CRT-D. Standard-of-care infection prevention was provided to all patients. During the 12-month postprocedure follow-up, the primary end point of a major device infection (defined as infection causing CIED removal or revision without removal, prolonged antibiotic therapy in lieu of removal, or death) occurred in 25 (0.7 percent) of envelope recipients and 42 patients (1.2 percent) in the control group (hazard ratio [HR] 0.60, 95% CI 0.36-0.98). Among the major infections, pocket infections were the predominant clinical event (occurring in 14 [0.4 percent] of the envelope patients and 36 patients [1.0 percent] in the control patients [HR 0.39, 95% CI 0.21-0.72]); the rate of bacteremia or endocarditis did not differ significantly between the groups. In subgroup analyses, the only significant difference in major infections was noted among the implantable cardioverter-defibrillators (ICD) or CRT-D recipients (HR 0.51, 95% CI 0.29-0.90).

An in-depth analysis of the microbiology of infections in the WRAP-IT trial demonstrated that patients who received an envelope had a 76 percent reduction in staphylococcus-related pocket infection (HR 0.24, 95% CI 0.08-0.71) with no major difference in staphylococcal systemic infections (HR 4.0, 95% CI 0.87-19.32) [76]. Subsequent publication of longer-term follow-up (mean 21 months) demonstrated a sustained reduction in major CIED infections (HR 0.66) among recipients of the antibiotic-impregnated envelope, an effect that was driven mostly by a reduction in major pocket infections [77].

●Further support of the WRAP-IT trial is seen in systematic reviews and meta-analyses. In a meta-analysis of six studies including 11,899 patients, the 5844 who underwent implantations with an antibiotic-impregnated envelope experienced significantly fewer major CIED infections in both the pooled and propensity matched analyses (OR 0.34 [95% CI 0.13-0.86] and OR 0.29 [95% CI 0.10-0.82], respectively) [71]. Mortality rates were not significantly reduced in envelope recipients.

The efficacy of antibiotic-impregnated envelopes accrues in patients at high risk for infection; there is no benefit in subgroup analyses of low-risk envelope recipients. Cost considerations have prompted further efforts to better define the patient population at greatest likelihood of benefit from these envelopes [78]. Assessment of the cost effectiveness ratio for envelope use has been determined for patients undergoing CIED revision or reimplantation based on PADIT risk scores and WRAP-IT trial benefits. A review of cost effectiveness indicates significant variability relative to specific devices and country specific infection data [78].

In addition to the procedure-related factors mentioned above, additional risks for CIED infection include end-stage kidney disease, prior CIED infection, fever prior to implantation, and immune suppression [78]. It is not known if antibiotic envelopes would reduce infection in these circumstances, particularly those in which the infection is bloodborne rather than related to the implantation procedure.

No role for prophylaxis for other procedures — There is no role for routine prophylaxis at times of mucosal trauma or manipulation for patients with CIEDs, unless there is another independent indication for endocarditis prophylaxis [33,79]. Transient bacteremia associated with mucosal trauma rarely results in CIED infection. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)

Some experts favor deferring elective procedures that pose a risk for bacteremia (such as colonoscopy or dental work) for 8 to 12 weeks following CIED implantation if possible; however, there are no data regarding the benefit of this practice.

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Infections involving cardiac implantable electronic devices".)

SUMMARY AND RECOMMENDATIONS

●Empiric antibiotic therapy – Empiric therapy for suspected cardiac implantable electronic device (CIED) infection should cover staphylococci (methicillin-susceptible and methicillin-resistant); we suggest vancomycin (Grade 2C). For patients with hemodynamic instability, we also include coverage of gram-negative bacteria; cefepime is a reasonable agent. Other regimens with comparable spectrum of activity are also acceptable. Antimicrobial therapy should be tailored to culture results, when available. (See 'Empiric antibiotic therapy' above.)

●Patients with systemic manifestations – Evaluation for CIED systemic infection is outlined in the algorithms (algorithm 1 and algorithm 2) (see 'CIED systemic infection' above):

•CIED systemic infection confirmed or likely – For these patients, we recommend device removal (Grade 1B), and administer antibiotic therapy according to the approach for endocarditis. (See 'Rationale for early removal' above and "Overview of management of infective endocarditis in adults".)

•CIED systemic infection unlikely – For patients in whom bacteremia may be attributable to an alternative (non-CIED) source of infection, we retain the device and administer antibiotic therapy for two weeks, followed by surveillance blood cultures and close follow up.

●Patients with isolated CIED pocket infection – For patients with CIED pocket infection, we recommend device removal (Grade 1B), and administer antimicrobial therapy for two weeks (four weeks for fungal infection) (algorithm 3). (See 'CIED pocket infection' above.)

●Device reimplantation – The approach to CIED reimplantation depends on transesophageal echocardiography (TEE) findings and blood culture results prior to device removal (algorithm 4). (See 'Device reimplantation' above.)

●Prevention

•Preprocedure prophylaxis – At the time of all CIED implantations, generator exchanges, or upgrades, we administer recommend systemic preprocedure antimicrobial prophylaxis. (See 'Antibiotic prophylaxis at device implantation' above and "Overview of the evaluation and management of surgical site infection".)

•Role of antibiotic-impregnated envelope – In patients at increased risk of CIED infection (eg, patients undergoing CIED generator replacement, lead revision, system upgrade, or cardiac resynchronization therapy-defibrillator [CRT-D] placement), we suggest using an antibiotic-impregnated absorbable envelope at the time of CIED implantation (Grade 2B). (See 'Use of antibiotic-impregnated envelopes' above.)

•No role for other prophylaxis – In the absence of an independent indication for endocarditis prophylaxis, we do not administer antimicrobial prophylaxis at times of mucosal trauma or manipulation. (See 'No role for prophylaxis for other procedures' above and "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)