66. Sohail MR, Corey GR, Wilkoff BL, et al. Clinical Presentation, Timing, and Microbiology of CIED Infections: An Analysis of the WRAP-IT Trial. JACC Clin Electrophysiol 2021; 7:50. 67. Mittal S, Wilkoff BL, Kennergren C, et al. The World-wide Randomized Antibiotic Envelope Infection Prevention (WRAP-IT) trial: Long-term follow-up. Heart Rhythm 2020; 17:1115. 68. Traykov V, Blomstr m-Lundqvist C. Antibiotic-Eluting Envelopes for the Prevention of Cardiac Implantable Electronic Device Infections: Rationale, Efficacy, and Cost-Effectiveness. Front Cardiovasc Med 2022; 9:855233. Topic 116021 Version 18.0 https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 23/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate GRAPHICS Approach to evaluation and management of suspected infection limited to cardiac implantable electronic device (CIED) pocket in adults https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 24/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate TEE: transesophageal echocardiogram; FDG PET/CT: fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography; SPECT/CT: radiolabeled autologous white blood cell single-photon emission computed tomography with computed tomography; MRSA: methicillin- resistant Staphylococcus aureus. https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 25/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate Refer to separate UpToDate algorithm for approach to patients with systemic symptoms, positive blood cultures, and/or vegetation on TEE. FDG PET/CT may be useful to distinguish between CIED pocket infection and superficial site infection in some circumstances; refer to the UpToDate topic on diagnosis of CIED infection for further discussion. Oral antibiotic dosing as follows: Cephalexin 500 mg orally 4 times daily Clindamycin 300 to 450 mg orally 4 times daily (use higher dose for patients with weight >120 kg) Dicloxacillin 500 mg orally 4 times daily Doxycycline 100 mg orally twice daily Linezolid 600 mg orally twice daily Minocycline 200 mg orally once, then 100 mg orally every 12 hours Trimethoprim-sulfamethoxazole 1 to 2 double-strength tablets orally every 12 hours We favor initial therapy with vancomycin (15 to 20 mg/kg/dose intravenously every 8 to 12 hours [not to exceed 2 g per dose]); refer to UpToDate text for discussion of alternative agents. Graphic 117258 Version 5.0 https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 26/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate Approach to reimplantation of cardiac implanted electronic device (CIED) following removal of an infected device (for patients who require CIED reimplantation) TEE: transesophageal echocardiogram. Refer to separate UpToDate algorithms for approach to diagnosis and antibiotic therapy for management of CIED infection. Temporary pacing may be required; refer to the UpToDate text for further discussion. Graphic 117259 Version 1.0 https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 27/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate Approach to management of adults with suspected CIED infection and negative UpToDate algorithm for approach to initial diagnostic evaluation) CIED: cardiac implantable electronic device; TEE: transesophageal echocardiogram; FDG PET/CT: fluorine-18 f tomography/computed tomography; SPECT/CT: single photon emission computed tomography/computed to High-grade bacteremia is defined as multiple (2 or more) separate blood cultures positive for the same orga for coagulase-negative staphylococci or Cutibacterium species may represent skin contamination. In such cas grade bacteremia. If repeat cultures are confounded by antibiotic therapy and clinical suspicion for CIED infec PET/CT) if available; further management should be guided by consultation with infectious disease expertise. Clinical suspicion is increased for organisms that commonly cause endocarditis. FDG PET/CT may be useful to establish a diagnosis of CIED infection in some circumstances. Other potentia https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 28/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate The choice and duration of antibiotic therapy is based on regimens for treatment of endocarditis caused by implicated (refer to UpToDate text and related topics). The duration of antibiotic therapy (usually 4 to 6 weeks warranted. The choice of antibiotic therapy is guided by culture results. Graphic 131691 Version 2.0 https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 29/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate Approach to evaluation and management of suspected infection of a cardiac implantable electronic device (CIED) in adults TTE: transthoracic echocardiogram; TEE: transesophageal echocardiogram. Signs and symptoms of an isolated CIED pocket infection include pocket erythema, discomfort, swelling, incision dehiscence, deformation, and erosion. Signs and symptoms of endocarditis include new murmur, new regurgitation, vegetation, paravalvular leak, evidence of pulmonary or systemic emboli, and immune phenomena. https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 30/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate Vancomycin dosing consists of 15 to 20 mg/kg/dose intravenously every 8 to 12 hours (not to exceed 2 g per dose); in patients presenting with severe sepsis, broadening of parenteral therapy to include gram-negative bacteria is appropriate. Refer to UpToDate text for further discussion. The choice of antibiotic regimen is guided by blood culture results (refer to UpToDate text). The duration of antibiotic therapy (4 to 6 weeks) should be counted from the day of device explantation, if warranted. Graphic 117257 Version 7.0 https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 31/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate Approach to vancomycin dosing for adults with normal kidney function* Loading dose (for patients with known or Load 20 to 35 mg/kg (based on actual body suspected severe Staphylococcus aureus weight, rounded to the nearest 250 mg infection) increment; not to exceed 3000 mg). Within this range, we use a higher dose for critically ill patients; we use a lower dose for patients who are obese and/or are receiving vancomycin via continuous infusion. Initial maintenance dose and interval Typically 15 to 20 mg/kg every 8 to 12 hours for most patients (based on actual body weight, rounded to the nearest 250 mg increment). In general, the approach to establishing the vancomycin dose/interval is guided by a nomogram. Subsequent dose and interval adjustments Based on AUC-guided (preferred for severe [1] infection) or trough-guided serum concentration monitoring. AUC: area under the 24-hour time-concentration curve. Refer to the UpToDate topic on vancomycin dosing for management of patients with abnormal kidney function. For patients with known or suspected severe S. aureus infection, we suggest administration of a loading dose to reduce the likelihood of suboptimal initial vancomycin exposure. Severe S. aureus infections include (but are not limited to) bacteremia, endocarditis, osteomyelitis, prosthetic joint infection, pneumonia warranting hospitalization, infection involving the central nervous system, or infection causing critical illness. If possible, the nomogram should be developed and validated at the institution where it is used to best reflect the regional patient population. Refer to the UpToDate topic on vancomycin dosing for sample nomogram. Refer to the UpToDate topic on vancomycin dosing for discussion of AUC-guided and trough- guided vancomycin dosing. For patients with nonsevere infection who receive vancomycin for <3 days (in the setting of stable kidney function and absence of other risk factors for altered vancomycin kinetics), vancomycin concentration monitoring is often omitted; the value of such monitoring prior to achieving steady state (usually around treatment day 2 to 3) is uncertain. Reference: 1. Rybak MJ, Le J, Lodise TP, et al. Therapeutic Monitoring of Vancomycin for Serious Methicillin-Resistant Staphylococcus Aureus Infections: A Revised Consensus Guideline and Review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm 2020; 77:835. Graphic 128911 Version 5.0 https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 32/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate Management of Candida infections involving cardiac implantable electronic devices in adults Condition or treatment Therapy group Primary Step-down Comments Candida infections involving cardiac implantable electronic devices Implantable A lipid formulation of For patients who are Removal of the entire cardiac amphotericin B (3 to 5 clinically stable, have device is strongly defibrillator mg/kg IV daily) with or isolates that are recommended. or pacemaker without flucytosine* susceptible to For infections limited (25 mg/kg orally four fluconazole, and have to generator pockets, times daily); negative repeat blood 4 weeks of antifungal cultures following therapy following OR initiation of a lipid device removal is High-dose formulation of recommended. echinocandin amphotericin B or For infections (caspofungin 150 mg high-dose involving device wires, IV daily, micafungin echinocandin therapy, antifungal therapy 150 mg IV daily, or transition to oral should continue for at anidulafungin 200 mg fluconazole 400 to least 6 weeks after IV daily). 800 mg (6 to 12 wire removal. Some mg/kg) daily is specialists prefer appropriate. lifelong oral Oral voriconazole suppressive therapy 200 to 300 mg (3 to 4 after lead removal, mg/kg) twice daily or especially if there is posaconazole possible endocardial delayed-release infection or if a new tablets 300 mg daily device is implanted. can be used for step- down therapy in clinically stable patients who have isolates susceptible to these agents but not susceptible to fluconazole. The doses above are intended for adults with normal organ function. The dose of fluconazole and flucytosine must be adjusted in the setting of renal insufficiency; the caspofungin and voriconazole dose may require adjustment in hepatic insufficiency. Refer to the Lexicomp drug-specific monographs for additional information including specific dose adjustment recommendations. https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 33/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate IV: intravenous; VAD: ventricular assist device. Toxic effects on bone marrow and liver require careful monitoring preferably with frequent serum flucytosine levels; refer to accompanying text for discussion of benefits and risks of combined flucytosine and amphotericin B therapy. Since fluconazole is highly bioavailable, oral therapy is appropriate for most patients. IV therapy (at the same dose) should be given to patients who are unable to take oral medications, who are not expected to have good gastrointestinal absorption, or who are severely ill. Therapeutic drug monitoring should be considered; refer to the topic review on pharmacology of azoles for details. In patients with endocarditis caused by a Candida species that is not susceptible to fluconazole, oral voriconazole (200 or 300 mg [3 to 4 mg/kg] twice daily) or delayed-release posaconazole tablets (300 mg daily) should be used for chronic suppressive therapy if the organism is susceptible. Data from: Pappas PG, Kau man CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 2015; 62:e1. Graphic 107269 Version 1.0 https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 34/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate Antimicrobial prophylaxis for cardiac surgery in adults Usual adult Nature of operation Recommended antimicrobials Redose interval Common pathogens dose* Cardiac Staphylococcus Cefazolin <120 kg: 2 4 hours procedures: aureus, Staphylococcus epidermidis g IV coronary artery 120 kg: 3 g IV bypass, cardiac device insertion OR cefuroxime 1.5 g IV 4 hours procedures (eg, pacemaker OR vancomycin 15 mg/kg N/A implantation), IV (max 2 placement of g) ventricular OR clindamycin 900 mg IV 6 hours assist devices IV: intravenous. Parenteral prophylactic antimicrobials can be given as a single IV dose begun within 60 minutes before the procedure. If vancomycin is used, the infusion should be started within 60 to 120 minutes before the initial incision to have adequate tissue levels at the time of incision and to minimize the possibility of an infusion reaction close to the time of induction of anesthesia. For prolonged procedures (>3 hours) or those with major blood loss or in patients with extensive burns, additional intraoperative doses should be given at intervals 1 to 2 times the half-life of the drug for the duration of the procedure in patients with normal renal function. Cefazolin is preferred over cefuroxime, given increasing resistance to second-generation cephalosporins. Indications for vancomycin are summarized in footnote . Clindamycin may be used for patients unable to tolerate the other agents listed. Some experts recommend an additional dose when patients are removed from bypass during open-heart surgery. Use of vancomycin is appropriate in hospitals in which methicillin-resistant S. aureus (MRSA) and S. epidermidis are a frequent cause of postoperative wound infection, in patients previously colonized with MRSA, or for those who are allergic to penicillins or cephalosporins. Rapid IV administration may cause hypotension, which could be especially dangerous during induction of anesthesia. Even when the drug is given over 60 minutes, hypotension may occur; treatment with diphenhydramine and further slowing of the infusion rate may be helpful. For procedures in which enteric gram-negative bacilli are common pathogens, many experts would add another drug such as an aminoglycoside (gentamicin 5 mg/kg IV), aztreonam (2 g IV), or a fluoroquinolone (ciprofloxacin 400 mg IV or levofloxacin 500 mg IV). https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 35/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate Adapted from: 1. Antimicrobial prophylaxis for surgery. Med Lett Drugs Ther 2016; 58:63. 2. Bratzler DW, Dellinger EP, Olsen KM, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Surg Infect (Larchmt) 2013; 14:73. Graphic 76499 Version 16.0 https://www.uptodate.com/contents/infections-involving-cardiac-implantable-electronic-devices-treatment-and-prevention/print 36/37 7/6/23, 10:53 AM Infections involving cardiac implantable electronic devices: Treatment and prevention - UpToDate Contributor Disclosures Adolf W Karchmer, MD Equity Ownership/Stock Options: AbbVie [Pharmaceuticals]; Johnson and Johnson [Pharmaceuticals]; Lilly [Pharmaceuticals]; Merck [Pharmaceuticals]; Pfizer [Pharmaceuticals]. Grant/Research/Clinical Trial Support: Karius [Endocarditis]. Consultant/Advisory Boards: Debio International [Antibiotic development]; Pfizer [Rheumatologic diseases, ulcerative colitis]. Other Financial Interest: Board of Directors [Winter Course in Infectious Diseases]. All of the relevant financial relationships listed have been mitigated. Vivian H Chu, MD, MHS No relevant financial relationship(s) with ineligible companies to disclose. Jay A Montgomery, MD No relevant financial relationship(s) with ineligible companies to disclose. Stephen B Calderwood, MD Consultant/Advisory Boards: Day Zero Diagnostics [Whole genome sequencing for microbial identification and determination of antimicrobial susceptibility]. All of the relevant financial relationships listed have been mitigated. Elinor L Baron, MD, DTMH No relevant financial relationship(s) with ineligible companies to disclose. Todd F Dardas, MD, MS No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. 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