7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Infections involving cardiac implantable electronic devices: Treatment and prevention : Adolf W Karchmer, MD, Vivian H Chu, MD, MHS, Jay A Montgomery, MD : Stephen B Calderwood, MD : Elinor L Baron, MD, DTMH, Todd F Dardas, MD, MS All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Mar 10, 2023. INTRODUCTION Traditionally, cardiac implantable electronic devices (CIEDs), including pacemakers, implantable cardioverter-defibrillators (ICDs), and cardiac resynchronization therapy (CRT) devices with or without 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 are percutaneously placed directly inside the heart, thus avoiding a subcutaneous pocket and transvenous leads. Subcutaneous ICDs with an extrathoracic 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. The clinical presentation and management of CIED infections varies according to the location and extent of infection and the clinical characteristics of the patient [1-5]. This topic focuses on treatment and prevention of infection involving traditional CIEDs, 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. https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 1/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate (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 CIED infection (systemic infection or pocket infection) requires ( algorithm 1 and algorithm 2 and algorithm 3 and algorithm 4) [2,5,6]: Antibiotic therapy Explantation of the entire CIED (leads, including residual leads that are non-functional, and pulse generator) Reimplantation of a new device (through an uninfected route), if indication for CIED persists 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, the potential complexity of device removal). Consultation with physicians with expertise in the care of patients with CIED infection is desirable. Antibiotic therapy The antibiotic regimen is based upon the extent of infection and the causative organism, if identified. In general, initial antibiotic empiric therapy assumes systemic infection and utilizes regimens designed to treat endocarditis. Once the extent and etiology of infection are defined, antibiotic therapy should be tailored accordingly. Empiric 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. Obtaining blood cultures prior to initiating empiric therapy is particularly important in patients who present with hypotension or criteria for a systemic inflammatory syndrome response (tachycardia, tachypnea, fever or hypothermia, leukocytosis or leukopenia) because these features are associated with bloodstream infection [7]. Once a causative organism is identified (via blood and/or pocket wound cultures), the antibiotic regimen should be tailored accordingly. 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. In patients presenting with hemodynamic instability, broadening of https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 2/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate therapy to include gram-negative bacteria is appropriate (reasonable additions to vancomycin include piperacillin-tazobactam, cefepime, a carbapenem, or gentamicin) [4]. High-dose daptomycin (8 to 10 mg/kg ideal body weight, which is higher than the US Food and Drug Administration approved dose) is an acceptable alternative to vancomycin for treatment of device infection. However, caution is required in the setting of foreign-body infection or 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 [8]. Accordingly, susceptibility testing must be performed on these persisting organisms to ensure continued susceptibility to daptomycin. 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 [8]. 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".) Data for use of other alternative antistaphylococcal agents (such as teicoplanin, ceftaroline, and telavancin) in treatment of CIED infections are lacking. Ceftaroline 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".) Definitive therapy Bacterial infection Once a causative organism is identified (via blood and/or pocket wound cultures), the antibiotic regimen should be tailored accordingly. Definitive antibiotic therapy is based on the antibiotic susceptibility of the implicated pathogen(s) and is derived from pathogen-specific regimens recommended for treatment of endocarditis. The duration of antimicrobial infection is determined by the pathogen and the extent of infection (pocket versus systemic) ( algorithm 4 and algorithm 1 and algorithm 3). (See "Antimicrobial therapy of left-sided native valve endocarditis" and "Antimicrobial therapy of prosthetic valve endocarditis".) Imaging with a lead or valve vegetation For patients with echocardiography demonstrating a valve or lead vegetation, we favor presumptive treatment for endocarditis; the antibiotic choice and duration of therapy is based upon the organism recovered from blood cultures. 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 https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 3/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate implantable electronic devices: Epidemiology, microbiology, clinical manifestations, and diagnosis", section on 'Diagnostic evaluation'.) In patients with bacteremia with an organism typically associated with endocarditis, with transesophageal echocardiography (TEE) demonstrating a lead vegetation in the absence of valve vegetation, we still favor treatment as for endocarditis; this is in contrast to some others (including some guideline committees) who favor a shorter duration of therapy in such cases [1,2,4,5]. We favor this approach given the less than perfect sensitivity of TEE for excluding valvular endocarditis (or mural endocarditis at the lead implantation site). If the TEE is nondiagnostic or cannot be done, we pursue an alternative imaging modality (eg, computed tomography [CT] angiography, fluorodeoxyglucose [FDG] positron emission tomography [PET], or single-photon emission CT) in an attempt to establish a diagnosis. The choice of a particular diagnostic modality will be guided by local availability and expertise. Imaging with no lead or valve vegetation For patients with no lead or valve vegetation on TEE (or other imaging) and bacteremia due to S. aureus, Candida species coagulase-negative Staphylococcus (high grade), Cutibacterium (formerly Propionibacterium) species (high grade), or high-grade bacteremia due to another organism with a propensity to cause endocarditis (in the absence of clear alternative source), we favor presumptive treatment for endocarditis, four to six weeks of pathogen-specific parenteral antibiotic. High-grade bacteremia is defined as two or more separate blood cultures positive for the same organism, drawn 1 hour apart. A single positive blood culture for coagulase-negative staphylococci or Cutibacterium species may represent skin contamination. In such cases, 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, consider pursuing further imaging (FDG-PET/CT) if available; further management should be guided by consultation with infectious disease expertise. (See "Infections involving cardiac implantable electronic devices: Epidemiology, microbiology, clinical manifestations, and diagnosis", section on 'Diagnostic evaluation'.) The above approach is preferred because approximately half of patients with CIED infection have concurrent valvular infection, and because the sensitivity of TEE (or other imaging) to exclude valve infection is limited [9,10]. Furthermore, S. aureus bacteremia (community onset or nosocomial) among patients with a CIED, even limited to a single positive blood culture, is associated with a significant risk of complicated infection, which mandates additional imaging (such as fluorine-18-FDG-PET/CT, if available) as well as intensive antimicrobial therapy [11,12]. (See "Infections involving cardiac implantable electronic devices: Epidemiology, microbiology, clinical manifestations, and diagnosis", section on 'Diagnostic evaluation'.) https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 4/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate In the setting of additional sites of infectious involvement (such as discitis and/or vertebral osteomyelitis), extension of 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 and discitis in adults".) For patients with no lead or valve vegetation on TEE (or other imaging) and bacteremia due to alpha-hemolytic streptococci, non-Group A beta-hemolytic streptococci, or enterococcus (high grade and/or no clear alternative source), we favor presumptive treatment for endocarditis. This approach is based on the predilection of these organisms to cause endocarditis and the significant frequency of endocarditis when these organisms cause bloodstream infection in patients with anatomic predispositions for endocarditis, recognizing that TEE (or other imaging technologies) are not 100 percent sensitive for detection of vegetations [13-16]. This approach is supported by one study including 12 patients with pacemakers who had valve infection in the absence of pacemaker involvement; besides S. aureus, pathogens included other organisms typically associated with endocarditis (such as streptococci, enterococci, and HACEK [Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella]) in more than half of the cases [17]. For patients with no lead or valve vegetation on TEE and gram-negative bacteremia (non- Pseudomonas aeruginosa/non-Serratia), Streptococcus pneumoniae, or transient bacteremia from a clear alternative source due to an organism that does not commonly cause endocarditis, antibiotics should be administered for at least two weeks using a regimen appropriate for the organism and primary site of infection [5,18]. After completion of antibiotic therapy, blood cultures (two sets) should be obtained, with close follow-up. (See "Invasive pneumococcal (Streptococcus pneumoniae) infections and bacteremia in adults" and "Gram-negative bacillary bacteremia in adults".) For patients with an isolated CIED pocket infection (eg, TEE negative for lead or valve vegetation, sterile blood cultures, and no symptoms to suggest systemic infection) ( algorithm 1), antibiotics should be administered for two weeks following device removal [1,2,4]. Empiric intravenous antibiotic therapy should be initiated until bacteremia has been excluded. Upon clarification of the pathogens causing pocket infection, device removal, and control of infection, pathogen-specific antibiotic treatment may be completed orally. If antibiotics have been administered prior to obtaining blood cultures, clinicians should be cognizant that recent antibiotic therapy can render blood cultures falsely negative. Fungal infection The approach to selection of antifungal therapy for treatment of systemic Candida CIED infection is the same as that of native valve endocarditis ( table 2) https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 5/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate [19,20]. This is discussed further separately. (See "Candida endocarditis and suppurative thrombophlebitis".) We are in agreement with guidelines which recommend prompt removal of the entire device in the setting of Candida infection involving any component of the CIED [1,5,21,22]. Systemic CIED fungal infection has been associated with a very high mortality rate and occasional relapse after therapy, and medical therapy alone has been associated with treatment failure [23-27]. The duration of antifungal therapy for CIED pocket infection is four weeks following device removal. The duration of therapy for CIED systemic infection is at least six weeks following device removal. Relapse after completion of therapy should prompt repeat assessment for CIED or cardiac valve infection. We are in agreement with some experts who favor lifelong suppressive antifungal therapy for patients with systemic Candida CIED infection following new CIED implantation (even in the absence of detectable valve involvement), particularly in older adults or those with multiple comorbidities. This approach merits consideration because of the risk for recurrent CIED Candida infection and its associated high mortality rate and is supported by descriptions of delayed onset IE in patients with prosthetic valves who experience candidemia [28] and descriptions of relapsed CIED fungal infection despite antifungal therapy plus device explantation [29]. In addition, cardiac imaging is not sufficiently sensitive to fully exclude intracardiac infection. Device removal versus retention Removal indications Removal of the entire CIED, as well as any residual nonfunctional leads, is indicated in any of the following circumstances ( algorithm 4 and algorithm 1 and algorithm 3) [1,2,5]: TEE demonstrating valve or lead vegetation in the presence of known or suspected bacteremia (as distinguished from noninfected fibrin stranding, which is often seen with long-duration leads) [30,31] Blood cultures demonstrate: Any isolation of the following organisms: S. aureus (especially in the absence of a clear portal of entry, occurring within three months of device manipulation, or persisting or recurring in spite of appropriate antimicrobial therapy) (see "Infections involving cardiac implantable electronic devices: Epidemiology, microbiology, clinical manifestations, and diagnosis", section on 'Bacteremia') https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 6/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate Candida species High-grade bacteremia (defined as two or more separate blood cultures positive for the same organism, drawn 1 hour apart) with the following organisms: Coagulase-negative staphylococci. Cutibacterium (formerly Propionibacterium) species. Other high-grade bacteremia without clear portal of entry (especially due to an organism that commonly causes endocarditis, such as alpha-hemolytic streptococci, beta-hemolytic streptococci, enterococci). A single positive blood culture for coagulase-negative staphylococci or Cutibacterium species may represent skin contamination. In such cases, 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, consider pursuing further imaging (FDG-PET/CT) if available; further management should be guided by consultation with infectious disease expertise. Presence of pocket infection (based on clinical manifestations of pain or tenderness, erythema, swelling, purulent drainage, pocket deformation, adherence or threatened erosion, and/or percutaneous exposure/erosion of the generator and/or leads), with or without positive culture of pocket drainage or bacteremia. The preferred approach for CIED removal consists of transvenous extraction of all leads (including previously abandoned leads, if present), in conjunction with removal of the generator. Major complications are infrequent (<2 percent), and extraction-related in-hospital mortality is <1 percent [4]. Presence of large lead vegetation(s) (>2 cm) prompt concern for development of pulmonary embolism (PE) in association with transvenous CIED removal. Surgical removal may be warranted to avoid PE; the threshold vegetation size for surgical removal is uncertain. In small observational studies, transvenous removal of CIED leads with large vegetations was associated with hemodynamically significant PEs relatively infrequently [32-34], and surgical removal is associated with greater morbidity than transvenous extraction. However, subclinical septic emboli may also occur, which may impact long-term outcomes. Accordingly, consideration of surgical management requires careful risk-benefit assessment [4,35]. To reduce the risk of PE while avoiding cardiac surgery, percutaneous suction removal of large lead vegetations prior to transvenous lead extraction has been used increasingly in recent years https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 7/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate [36,37]. The technical aspects of vegetation debulking and lead removal are discussed separately; arrangements should be made for managing arrhythmias until a new device can be reasonably reimplanted. (See "Cardiac implantable electronic device lead removal" and "Wearable cardioverter-defibrillator", section on 'Bridge to indicated or interrupted ICD therapy'.) In addition to device explantation, the pocket, if infected, should be meticulously debrided including removal of the fibrous capsule and any foreign material. The pocket should be irrigated with sterile saline. Removal of other intravascular devices, where feasible, is indicated as well. The above approach to device removal in patients with S. aureus bacteremia is supported by the following studies: In a retrospective cohort including 360 patients with CIED and staphylococcal bacteremia (329 due to S. aureus), CIED infection was confirmed on initial evaluation in 182 patients; among the remaining 178 patients, 36 died or underwent empiric device removal [12]. Of the surviving 142 patients, 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). In a multivariable analysis, the hazard of death at one year was reduced among those who underwent empiric device removal (hazard ratio [HR] 0.28, 95% CI 0.08-0.95). In a study of 110 patients with a CIED and S. aureus bacteremia [38], patients were classified using the European Heart Rhythm Association 2019 definition for CIED infection [5,38]. Device infection was definite in 57 patients, possible in 31 patients, and rejected in 22 patients. The median duration of bacteremia was four days, three days, and two days, respectively; device removal occurred in 80, 39, and 33 percent of patients respectively. Recurrence of S. aureus bacteremia recurred in two patients with definite or possible infection (both of whom underwent device removal) and two patients with rejected device infection (neither of whom underwent device removal). Device removal was associated with a significant survival benefit at one year among those with definite infection (HR 0.17 [0.06- 0.47]), but not among those with possible infection (HR 0.33 [0.07-1.51]) or rejected infection (HR 0.83 [0.17-4.03]). In most cases, the risks of recurrent infection and mortality significantly outweigh the risks of immediate extraction [39,40]. Alternative approaches (such as device retention with antibiotic therapy or generator removal with lead retention and antibiotic therapy) are associated with increased risk of mortality [39,40]. In one study including 415 patients with CIED infection, patients who did not undergo device removal experienced a sevenfold increase in 30-day mortality relative to those who https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 8/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate underwent device removal (HR 6.97, 95% CI 1.36-35.6) [39]. Immediate CIED removal (in contrast with removal after failure of antimicrobial therapy or no removal) was associated with a threefold reduction in mortality at one year (HR 0.35, 95% CI 0.16-0.75). In another study of 177 patients with CIED infection, device removal during the index hospitalization was associated with decreased mortality at one year (20 versus 38 percent) [40]. In a study including 80 patients with an isolated pocket infection who were not candidates for CIED extraction (or who elected not to undergo CIED extraction) who were treated with pocket debridement and infusion of antibiotics directly into the pocket for at least 14 days, 85 percent of patients had clinical resolution of infection [41]. There are circumstances in which CIED removal addresses only one of multiple possible sites of intravascular infection. While removing the CIED site of infection may increase the probability of a cure, presence of any other retained intravascular device or prosthesis raises the possibility of residual infection. As an example, in the setting of prosthetic valve endocarditis, CIED removal may increase the probability of cure of PVE without valve removal, but this cannot be considered definitive. Such situations require consultation with physicians who have experience treating complex patients with intravascular infection in the setting of intravascular devices or prostheses. In general, ease of lead extraction is inversely related to lead dwell time; leads that have been in place for more than two years are more difficult to extract than newer leads, and the risk seems to continue to increase with increased time. However, such leads can be removed safely by experienced operators in most cases. The degree of explant difficulty also depends on the lead type; implantable cardioverter-defibrillator (ICD) leads (particularly dual coil designs) tend to have more extensive adhesions and therefore are more difficult to explant than pacemaker leads. In such cases, the decision to attempt lead removal must be individualized. (See 'Removal warranted but not feasible' below and "Cardiac implantable electronic device lead removal".) Rarely, CIED infection may be complicated by stroke or systemic embolus in the apparent absence of concurrent left-sided endocarditis. In such cases, or in cases in which there are other suggestions of right to left shunting, evaluation for a patent foramen ovale should be undertaken; if found, efforts to prevent paradoxical embolization at the time of device extraction should be considered [42]. (See "Cardiac implantable electronic device lead removal", section on 'Embolism'.) Removal warranted but not feasible CIED removal may not be feasible for patients in whom the intervention would pose significant risks (for example, patients with major https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 9/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate comorbidities and limited life expectancy who have longstanding devices and who require continuous pacemaker support). In such cases, or if patients refuse CIED removal, an aggressive approach to antibiotic therapy is warranted, although evidence to guide therapy is lacking. We favor a six-week course of therapy as would be used for prosthetic valve endocarditis caused by the implicated organism. (See "Antimicrobial therapy of prosthetic valve endocarditis".) This approach is associated with a high risk of relapse [43] and no way to test for cure before discontinuing antibiotics: Among patients who are candidates for CIED removal if the infection relapses, close monitoring following completion of antibiotic therapy is indicated [2,4]. If there is evidence of persistent or progressive infection or relapse despite appropriate intravenous antibiotic therapy, the device should be removed. Among patients for whom CIED removal is not an option, long-term suppressive antibiotic therapy can be used, but this is a last resort [2,4]. These patients are at high risk of failure with subsequent relapse and increased mortality [2,43]. In one retrospective study including 37 patients with CIED infection managed with chronic antibiotic suppression, the estimated median overall survival was 1.43 years (95% CI 0.27-2.14); relapse within one year occurred in 18 percent of cases [43]. Retention criteria Device retention may be reasonably attempted in the following circumstances, since such patients may not have CIED infection ( algorithm 4 and algorithm 1 and algorithm 3): Bacteremia due to a pathogen other than S. aureus from a defined source other than the device or valvular infection, if: There is no clinical, TEE, or other imaging (if available) evidence of lead or valve infection There is no evidence of pocket infection The device has not been manipulated recently (ie, within three months) Gram-negative bacteremia (other than that caused by P. aeruginosa or Serratia), pneumococcal bacteremia, and transient bacteremia due to organisms that do not commonly cause endocarditis may be managed with device retention when there is a clear alternative source or portal of entry and no evidence of CIED infection. However patients managed with device retention who have continued unexplained bacteremia despite https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 10/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate appropriate antibiotic therapy or who relapse after appropriate antibiotic therapy likely have CIED infection and warrant device removal [2,17,44]. Presence of superficial cellulitis or a stitch abscess at the incision site, typically shortly after implant or generator replacement, with no involvement of the generator pocket [2]. This distinction is often difficult to make, and patients managed with device retention require close observation for subsequent evidence of device infection. Device reimplantation The optimal timing for CIED reimplantation is uncertain; an approach is summarized in the algorithm ( algorithm 2) [2]. For patients who require reimplantation of a new CIED, the risk of infection of a new device must be balanced with the risk of monitoring with no device in place. Approximately 23 to 30 percent of patients with CIED infection do not require a new device [4]. If necessary, a temporary device can be placed, although these are also associated with risk of infection. The techniques for temporary pacing are discussed separately. (See "Temporary cardiac pacing".) For patients with systemic CIED infection, the approach depends on TEE, blood culture results, and the presence of systemic infection: CIED infection and valvular endocarditis In patients with a CIED infection and TEE evidence of valve vegetation, the new CIED may be implanted once surveillance blood cultures following device removal are negative for at least 14 days. By that time, the valve infection should be sufficiently treated such that seeding of the new lead is unlikely. This is a generally accepted practice with limited data to support it. In one study including 109 patients with CIED-related infectious endocarditis (CIED-IE; defined as echocardiographically reported device lead or valve vegetation), patients with a reimplantation interval <14 days had the lowest 12-month survival (58 percent), particularly if there was a valve vegetation [45]. CIED infection and with extracardiac infection In patients with a CIED infection and extracardiac sites of infection, treatment prior to reimplantation should be sufficient to make relapse and recurrent bacteremia highly unlikely. For patients with TEE demonstrating only lead vegetation and for patients with bacteremia but no vegetation on TEE (ie, patients with no valve or 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 therapy. Isolated pocket infection For patients with isolated pocket CIED infection (no vegetation on TEE and negative blood cultures), the new CIED may be implanted once there is sufficient control of the local infection. For patients with pocket infection with minimal https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 11/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate inflammation or device exposure due to erosion, same-day reimplantation on the contralateral side place has been performed in small numbers of pacer dependent patients [1,46]; however, published experience with this approach is limited, and the severity of infection and other clinical factors (eg, pacemaker dependence) should be considered carefully in deciding on timing of reimplantation. The new CIED should not be placed at the site of the previously infected device if any alternative exists. Contralateral CIED implant is reasonable in many scenarios. In addition to intravascular CIEDs, subcutaneous ICDs or leadless pacemakers, when clinically appropriate, pose a lower risk of intravascular infection [47-49]. (See "Subcutaneous implantable cardioverter defibrillators", section on 'When to consider the S-ICD' and "Permanent cardiac pacing: Overview of devices and indications", section on 'Leadless systems'.) PREVENTION Implantation of CIEDs (ie, pacemakers or implantable cardioverter-defibrillators [ICDs]) should be performed with assiduous aseptic and surgical techniques in a controlled environment; the same is true of changing pulse-generator units [2,5,50]. CIED implantation should be deferred in the setting of active infection elsewhere [1]. Efforts to prevent CIED infection have been reviewed in detail; the major considerations are noted below [51]. Operator experience affects outcome; ideally, the procedure should be performed by an individual who has done many CIED implantations [5,52,53]. (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 CHA DS -VASc <4 (calculator 1) 2 2 (eg, those not at high risk for embolic events), anticoagulation should be held prior to the procedure. Bridging anticoagulation with heparin is not recommended. Ideally, antiplatelet therapy should be held for 5 to 10 days before the procedure [5]. (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. We are in agreement with the American Heart Association and the Heart Rhythm Society, which recommend prophylaxis with antistaphylococcal antimicrobial drugs at the time CIEDs are implanted or generator units https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 12/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate exchanged [1,2,5]. The dosing regimens are similar to those used for cardiac surgery (eg, cefazolin 2 g [3 g for those weighing >120 kg] intravenously within 60 minutes of surgical incision or, if there is concern about cephalosporin allergy or colonization by methicillin-resistant staphylococci, vancomycin 1 g intravenously within 90 to 120 minutes before the incision) ( table 3) [2,54]. For patients who cannot tolerate beta-lactam antibiotics or vancomycin, daptomycin or linezolid are alternatives [2]. (See "Antimicrobial prophylaxis for prevention of surgical site infection in adults", section on 'Antibiotic selection'.) Contamination with skin flora is responsible for a significant proportion of CIED infections; antibiotic prophylaxis reduces risk for device infection [55-59]. In a randomized 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) [58]. Administration of incremental perioperative antibiotics does not appear to confer benefit over conventional administration of preoperative antibiotic therapy for prevention of CIED infection. In the PADIT (Prevention of Arrhythmia Device Infection Trial) 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 therapy (preprocedural cefazolin) [59]. Compared with cefazolin prior to the procedure, there was no significant difference in the hospitalization rate for CIED infection within one year overall (odds ratio [OR] 0.77, 95% CI 0.56-1.05) or within the risk-related subpopulations (high-risk patients: OR 0.82, 95% CI 0.59-1.15; low-risk patients: OR 0.77, 95% CI 0.56-1.05). Antibiotic prophylaxis for other clinical 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 [2,60]. 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. Use of antibiotic-impregnated envelopes We suggest using an antibiotic-impregnated absorbable envelope at the time of CIED implantation or generator replacement in patients at increased risk for CIED infection wherein benefit has been established in a prospective https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 13/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate randomized trial [5,61]. This approach is based on the reduction in major CIED infections in certain higher-risk populations in the WRAP-IT trial [62]. Utilizing an antibiotic-impregnated absorbable envelope consists of placing the CIED pulse generator in an absorbable mesh envelope that is impregnated with minocycline and rifampin such that these antibiotics are slowly released in the generator pocket. All CIED recipients, including those whose device is placed in an envelope, should still receive preprocedure systemic antibiotic prophylaxis. Data regarding the efficacy of antibiotic-impregnated envelopes are derived from one randomized trial and nonrandomized cohort studies [62-65]. Published in 2019, 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) [62]. The study population was comprised of patients undergoing CIED generator replacement, system upgrade, pocket or lead revision, or those undergoing initial cardiac resynchronization-defibrillator (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