Heart & Lung xxx (2014) 1e4
Contents lists available at ScienceDirect
Heart & Lung journal homepage: www.heartandlung.org
Endocarditis 2014: An update Kristin L. Thanavaro, MD, J.V. (Ian) Nixon, MD * Pauley Heart Center, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
a r t i c l e i n f o
a b s t r a c t
Article history: Received 3 February 2014 Received in revised form 16 March 2014 Accepted 23 March 2014 Available online xxx
The epidemiology of infective endocarditis is changing due to a number of factors, including more frequent and varied antibiotic use, the emergence of resistant microorganisms, and an increase in the implantation of cardiovascular devices. This review outlines and consolidates the most recent guidelines, including the 2007 and 2010 AHA/ACC guidelines and scientific statements for the prevention and management of infective endocarditis and for the management of cardiovascular device infections. The evidence-based guidelines, including the 2009 HRS consensus document, for the treatment of patients with cardiovascular device-related infections are also reviewed. Only patients with prosthetic valves, patients with prior endocarditis, cardiac transplant patients with a valvulopathy, and certain congenital heart disease patients now require endocarditis prophylaxis. There is an increasing incidence of cardiovascular device-related infections due to the higher frequency of implanted devices and higher morbidity and mortality rates in older patients. Ó 2014 Elsevier Inc. All rights reserved.
Keywords: Endocarditis Cardiac valve disease Cardiac device infections
Introduction Infective endocarditis has been recognized as a clinical entity since the 1950s. In 1955, the American Heart Association (AHA) first established guidelines for the treatment of infective endocarditis.1 Since that time, the development of powerful antimicrobial therapy and implantable cardiac devices has changed the face of this disease. Today, patients with endocarditis are older and have more comorbidities. These changes present challenges for the prevention and management of endocarditis. This monograph reviews these challenges while continuing to incorporate the current AHA guidelines for the prevention of infective endocarditis1 and for the management of implantable cardiovascular device infections.2 Diagnosis of infective endocarditis Infective endocarditis (IE) is a clinical diagnosis and requires a high index of suspicion because patients may present with nonspecific symptoms such as fevers, chills, fatigue, malaise, and weight loss. Some patients may present with stroke-like symptoms due to embolic events or with congestive heart failure. Elderly patients, patients with renal failure or patients previously treated with antibiotics may not present with fevers, creating a diagnostic challenge. The Duke Criteria for the diagnosis and management of IE
* Corresponding author. VCU Medical Center, 1200 East Marshall Street, Gateway Building, 2nd Floor, #291, Richmond, VA 23298-0051, USA. Tel.: þ1 804 828 7915. E-mail address: [email protected] (J.V.(Ian) Nixon). 0147-9563/$ e see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.hrtlng.2014.03.009
were initially drafted in 1994 for use in clinical trials and epidemiology studies e however, they were not designed for use in clinical patients.3 Nonetheless, the Duke Criteria have become the gold standard for the diagnosis of IE and were subsequently modified in 2002 to include echocardiographic evidence of IE (Table 1).4 A definitive diagnosis of IE may be made with either pathological or clinical criteria. The two major clinical criteria are abnormal blood cultures and evidence of endocardial involvement. The five minor clinical criteria are a predisposition to IE, fever of greater than 38 C, vascular phenomena, immunologic phenomena, or microbiological evidence of IE not meeting major criteria (Table 1). Requirement for a clinical diagnosis of IE are 2 major clinical criteria, 1 major and 3 minor clinical criteria, or 5 minor clinical criteria.
Endocarditis prevention guidelines The most recent revision of the AHA Guidelines for IE was published in 2007.1 They were a clarification of the previous guidelines from 1997.5 There were several logical rationale for the revision of the guidelines. Firstly, regarding oral hygiene and procedures, IE was more likely to occur with everyday activities such as teeth brushing and flossing rather than with a single medical or dental procedure. Secondly, prophylaxis with antibiotics for dental procedures prevented very few IE cases. Furthermore, the risk of adverse events and cost of antibiotic therapy significantly outweighed the benefit of such prophylaxis. Thirdly, consistently good oral hygiene is more beneficial in preventing IE than a single dose of antibiotics.
2
K.L. Thanavaro, J.V.(Ian) Nixon / Heart & Lung xxx (2014) 1e4
Table 1 Modified Duke Criteria for the diagnosis of infective endocarditis. Pathological criteria (1 needed) 1. Microorganism identified by culture or histology from a vegetation, an embolized vegetation or in a cardiac abscess. 2. A histological specimen from a vegetation or an intracardiac abscess showing active endocarditis. Clinical criteria (2 major, 1 major and 3 minor, or 5 minor needed) Major criteria 1. Two positive blood cultures with typical microorganisms drawn at least 12 h apart (or one positive blood culture for Coxiella Burnetii) 2. Evidence of endocardial involvement (new murmur, echocardiographic evidence of a cardiac mass, abscess or valve dehiscence) Minor criteria 1. Feve > 38 C 2. Vascular phenomena (systemic emboli, Janeway lesions) 3. Immunological phenomena (Osler’s nodes, Roth spots) 4. Predisposition to infective endocarditis (previous infective endocarditis or intravenous drug abuse) 5. Microbiological evidence not meeting major criteria Adapted from Li JS, Sexton DJ, Mick N, et al. Clin Infect Dis 2000; 30:633e638.4
The number of patients requiring IE prophylaxis according to the 2007 guidelines has been greatly reduced.1 Only the four following groups now require prophylaxis: patients with prosthetic valves, patients with prior IE, cardiac transplant patients with a valvulopathy, and certain congenital heart disease patients. These groups include patients with cyanosis, palliative shunts and conduits, patients with residual defects around a cardiovascular patch site and patients within 6 months of a complete repair of a congenital anomaly. For patients with a successful cardiovascular repair, adequate endothelialization of the repair is assumed after 6 months and prophylaxis is no longer needed. Patients with mitral valve prolapse with or without mitral regurgitation and patients with bicuspid aortic valves no longer require prophylaxis under the revised 2007 guidelines. The number of dental procedures that require prophylaxis under the 2007 guidelines is also reduced. Antibiotic prophylaxis is a Class IIa (LOE C) recommendation for dental procedures that involve manipulation or perforation of the oral mucosa.1 This does not include routine anesthetic injections through non-infected tissue, dental radiographs, placement or adjustment of orthodontic devices or trauma to the lips and teeth. For respiratory procedures, antibiotic prophylaxis is a Class IIa (LOE C) recommendation for any invasive procedures that involves incision or biopsy of the respiratory mucosa (such as tonsillectomy). An exception is bronchoscopy, which requires no prophylaxis. Antibiotic choices are influenced by the patient’s ability to tolerate oral medication, by medication allergies, and by the most likely pathogen. For dental and respiratory procedures, the most common bacteria are the various streptococcus viridans species. The recommended prophylactic antibiotic is amoxicillin 2 g orally 1 h prior to the procedure.1 If the patient requires intravenous medication, ampicillin or ceftriaxone may be substituted. Cephalexin, clindamycin or azithromycin may be used in patients with a penicillin allergy. However, there is emerging penicillin resistance of the streptococcus viridans species, with percentage resistances in some studies ranging from 17% to 50%.6e10 The prescribing physician must consider the resistance in his/her area of practice when selecting the appropriate antibiotic. In cases where staphylococcus aureus is suspected, an anti-staphylococcal penicillin or vancomycin is recommended.1 There are no published data linking gastrointestinal (GI) and genitourinary (GU) procedures to IE.11 Consequently the 2007 guidelines recommend that antibiotic prophylaxis is no longer necessary during these procedures (Class III, LOE B).1 It is stated, however, that if a patient has an established GI or GU infection and is undergoing elective GI or GU tract manipulation, any infection
should be eradicated prior to the procedure (Class IIb, LOE B).1 The most common pathogens causing a GI or GU infection are the enterococcus species, which also have emerging antibiotic-resistant strains.1 Penicillins are preferred for these infections, although piperacillin and vancomycin should be considered when a resistant enterococcus is suspected. In these cases, consultation with an infectious disease specialist may be warranted. Currently, there is no indication for dental, GI or GU procedural prophylaxis for patients with implantable cardiovascular devices (Class III, LOE C).2 However, prophylaxis with an anti-staphylococcal antibiotic is indicated at the time of a cardiovascular device implantation and any subsequent manipulation of the surgical created device pocket (Class I, LOE A).2 Treatment of endocarditis Treatment of IE should be tailored to in-vitro susceptibility of the pathogen identified, and consultation with an infectious disease specialist can be considered. In general, antibiotics such as penicillin, ampicillin, ceftriaxone, rifampin, vancomycin and daptomycin are used. The length of treatment is dependent on the pathogen and type of valve (native vs. prosthetic). Antibiotic selection and duration of therapy is addressed in the 2005 AHA Scientific Statement.3 Viridans group streptococci endocarditis should be treated for 4 weeks for native valve IE and 6 weeks for prosthetic valve IE. For the more virulent staphylococcus aureus, treatment duration is 6 weeks, regardless of valve type. However, prosthetic valves require the addition of rifampin or gentamicin for synergy. Enterococcus endocarditis requires combination antimicrobial therapy for 4e6 weeks, regardless of valve type. Generally, ampicillin is used in combination with either gentamicin or ceftriaxone, depending on the patient’s renal function. Treatment duration for the HACEK organisms (Hemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella) is 4 weeks for native valves and 6 weeks for prosthetic valves. Cardiovascular non-valvular device infections IE associated with a cardiac pacemaker was first reported in the early 1970s.12 Infection rates of these implanted devices in the 1970se1980s ranged from less than 1%e19.9%.13,14 Subsequently, the numbers of implanted cardiac devices has significantly increased.15 Defibrillators are now implanted for primary prevention, and cardiac-resynchronization therapy has increased the total number of implanted intracardiac leads. Furthermore, the average patient with an implanted cardiac device is older and sicker. Zhan and colleagues have reported that among the patients receiving implantable cardiovascular devices, 70% are older than 65 years and at least 75% have more than one coexisting disease.15 Inevitably these characteristics lead to an increasing number of cardiovascular device-related infections, and a significant increase in associated morbidity and mortality. Guidelines were initially drafted for the management of cardiovascular device-related infections by the ACC/AHA in 2003.16 Since the publication of these guidelines, there has been a substantial increase in the number of reports reviewing the incidence and clinical management of patients with cardiovascular device-related infections.17e19 As a result, a scientific statement from the AHA issued in 2010 updated the evidence-based guidelines for treatment of patients with cardiovascular device-related infections.2 Clinical presentation and diagnosis The clinical presentation of a patient with a cardiac devicerelated infection can be subtle and patients may present with
K.L. Thanavaro, J.V.(Ian) Nixon / Heart & Lung xxx (2014) 1e4
vague symptoms such as fatigue and malaise.2 Pain may occur at the pocket site. However, aspiration of the pocket is not recommended (Class III, LOE B). Patients with lead or valve endocarditis may present with fevers and other stigmata of IE such as systemic embolization, immunologic phenomena, a new murmur on examination or congestive heart failure. Risk factors for a devicerelated infection include immunosuppression, oral anticoagulation, diabetes mellitus, end-stage renal disease, the absence of periprocedural antibiotics, the necessity for a device revision or replacement, an increased number of implanted devices, a lack of operator experience and the presence of a bloodstream infection.2 The following Class I recommendations were established for the diagnosis of device-related infections in the 2010 guidelines2: 1. All patients should have two sets of blood cultures drawn before the administration of antimicrobial agents (Class I, LOE C). 2. After extraction of the cardiovascular device, a gram stain and culture should be performed on the lead tips (Class I, LOE C). 3. Patients with positive blood cultures should undergo transesophageal echocardiography for the evaluation of lead endocarditis (Class I, LOE C) and the possibility of left-sided valvular endocarditis (Class I, LOE B).
Patient management Compared to traditional endocarditis, which has a high incidence of streptococcus viridans, cardiac device-related infections are more commonly caused by either coagulase-negative staphylococci (CNS) or staphylococcus aureus.2 These bacteria possess adherence molecules, and the creation of biofilm on the surface of the device forms a protected environment that antimicrobials cannot penetrate.16 Thus, once the bacteria are attached to the device, the whole system must be removed for eradication of the infection. In 2009, the Heart Rhythm Society (HRS) put forth an expert consensus document addressing the indications for and management of patients requiring transvenous lead extraction for any indication.20 Though this document predated the current ACC/AHA guidelines, it stated that complete device removal was recommended in all patients with infection of the pocket, leads, cardiac valves, and patients with gram-positive bacteremia (Class I, LOE B). When the ACC/AHA Guidelines were published the following year,2 the recommendations echoed those of the HRS. The 2010 guidelines recommend the following for total cardiac device removal2: 1. Device removal is recommended (Class I) for all patients with definite lead infection or sepsis (LOE A), a pocket infection (LOE B), valvular endocarditis without lead involvement (LOE B) and occult staphylococcal bacteremia (LOE B). 2. Device removal is reasonable for persistent occult gramnegative bacteremia despite appropriate antibiotic therapy (Class II). 3. Removal of the device is not recommended for superficial skin infections above the pocket site (Class III). Device removal should be performed by experienced physicians with surgical backup, because it carries an increased morbidity and mortality risk.2 Institutions performing system extraction should have adequate training of personnel (including cardiologists, cardiac anesthesiologists, echocardiographers and nurses), as well as an internal review of patient outcomes.20 Cardiothoracic surgeons should be immediately available for surgical backup, and a protocol
3
should be established so that emergencies can be managed quickly and efficiently.20 Complications may include hemorrhage, damage to the tricuspid valve, myocardial infarction and pulmonary embolism. To reduce the risk of septic pulmonary emboli, surgical removal rather than laser extraction should be considered if a vegetation larger than 2 cm is present on the device lead.2 After removal of the device and leads, patients should complete a course of intravenous antibiotics. However, there are no evidencebased data on the duration of antibiotic therapy or when reimplantation is appropriate. Since device-related infection has only recently emerged as a clinical entity, the current treatment guidelines are uncertain and need to be readdressed in future revisions of the guidelines. The current Class I recommendations for antimicrobial treatment are as follows2: 1. The choice of antibiotics should be based on in-vitro susceptibility of the pathogen (Class I, LOE B). 2. The duration of therapy after system removal for a pocket infection should be 10e14 days (Class I, LOE C). 3. The duration of therapy after system removal for a bloodstream infection should be at least 14 days (Class I, LOE C). 4. The duration of therapy after system removal for lead endocarditis or other complicated infections should be at least 4e6 weeks (Class I, LOE C). The timing of a new device reimplantation remains uncertain and the 2010 guidelines allow for the discretion of the treating physician.2 1. When considering reimplantation, the clinician should evaluate if a new device is required (Class I, LOE C). 2. The new device should be implanted on the contralateral side to the extraction site (Class I, LOE C). 3. The patient should have negative blood cultures for at least 72 h prior to the reimplantation of a new device (Class IIa, LOE C). 4. If the patient has evidence of valve involvement, device reimplantation should be delayed at least 14 days after the original device removal (Class IIa, LOE C)
Endocarditis in special populations For over fifty years, chronic hemodialysis (HD) has been recognized as a risk factor for IE.21 HD patients have a 50e180 fold higher risk of acquiring IE compared to the general population.22 These patients often have indwelling catheters and suppressed immune function, which make them susceptible to infections from transient bacteremia related to repetitive vascular access. In addition, the systemic vascular calcification that occurs as a consequence of renal dysfunction leads to valvular damage, which is a predisposition for IE. Generally, the left-sided valves (mitral and aortic) are more commonly affected than the right-sided valves.23 In a recent study, the most common pathogens identified were coagulase-negative staphylococcus aureus, methicillin-resistant staphylococcus aureus and fungi.24 The morbidity and mortality of IE in this population is very high. There is a 30% in-hospital mortality for IE in dialysis patients and the one year survival after IE is approximately 50%.21 It is also important to note that the risk of sudden cardiac death is high in this patient population, and many dialysis patients have defibrillators and are at risk for CIED infections. As opposed to nonHD patients who generally present with isolated pocket infection, HD patients will more frequently have fever, bacteremia and leukocytosis without pocket inflammation.24 The increasing prevalence of heart failure has led to great advancements in mechanical circulatory device support. These new
4
K.L. Thanavaro, J.V.(Ian) Nixon / Heart & Lung xxx (2014) 1e4
technologies have led to many new types of infections. Left ventricular assist device (LVAD) infections can encompass the pump, driveline, cannula, or mediastinum. While the second-generation continuous-flow LVADs have less infection compared to the firstgeneration pulsatile devices, the overall rate is still high, ranging from 30 to 50%.25 LVAD-related IE occurs from seeding of the valves or pump during implantation or via extension of driveline, pocket, lung or mediastinal infections.25 While bacterial IE usually occurs in the first month following implantation, fungal endocarditis generally presents 2e3 months later.25 The diagnosis of IE in LVAD patients may be difficult because metallic reflections on transesophageal echocardiography can obscure the visualization of vegetations.26 The treatment of LVAD-associated IE is complete device removal with prolonged pathogen-directed antimicrobial therapy. There are no guidelines on the duration of antibiotic therapy after pump removal, but IE is not considered a contraindication to heart transplantation.25 Summary The epidemiology of IE is constantly changing due to increased antibiotic use and the emergence of resistant microorganisms. The 2007 ACC/AHA Prevention and Treatment Guidelines are more comprehensive than previous versions, making management less complicated and confusing for the treating physician. However, there is an increasing incidence of cardiovascular device-related infections due to the higher frequency of implanted devices and higher morbidity and mortality rates in older patients. Nevertheless, the need for further evidence-based studies continues to exist, including studies for the management of cardiovascular devicerelated infections, in addition to the need for continued updating of treatment guidelines for the prevention and treatment of infective endocarditis. References 1. Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council of Clinical Cardiology, Council on Cardiovascular Surgery, and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation. 2007;116:1736e1754. 2. Baddour LM, Epstein AE, Erickson CC, et al, on behalf of the American Heart Association’s Rheumatic Fever, Endocarditis and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, Council on Cardiovascular Surgery and Anesthesia, Council on Cardiovascular Nursing, Council on Clinical Cardiology, and the Interdisciplinary Council on Quality of Care and Outcomes Research. Update on cardiovascular implantable electronic device infections and their management: a scientific statement from the American Heart Association. Circulation. 2010;121:458e477. 3. Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation. 2005;111:e394ee434.
4. Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis. 2000;30:633e638. 5. Dajani AS, Taubert KA, Wilson W, et al. Prevention of bacterial endocarditis: recommendations by the American Heart Association. J Am Med Assoc. 1997;277:1794e1801. 6. Diekema DJ, Beach ML, Pfaller MA, Jones RN, SENTRY Participants Group. Antimicrobial resistance in viridans group streptococci among patients with and without the diagnosis of cancer in the USA, Canada and Latin America. Clin Microbiol Infect. 2001;7:152e157. 7. Groppo FC, Castro FM, Pacheco AB, et al. Antimicrobial resistance of Staphylococcus aureus and oral streptococci strains from high-risk endocarditis patients. Gen Dent. 2005;53:410e413. 8. Teng LJ, Hsueh PR, Chen YC, Ho SW, Luh KT. Antimicrobial susceptibility of viridans group streptococci in Taiwan with an emphasis on the high rates of resistance to penicillin and macrolides in streptococcus oralis. J Antimicrob Chemother. 1998;41:621e627. 9. Tuohy M, Washington JA. Antimicrobial susceptibility of viridans group streptococci. Diagn Microbiol Infect Dis. 1997;29:277e280. 10. Prabhu RM, Piper KE, Baddour LM, Steckelberg JM, Wilson WR, Patel R. Antimicrobial susceptibility patterns among viridans group streptococcal isolates from infective endocarditis patients from 1971 to 1986 and 1994 to 2002. Antimicrob Agents Chemother. 2004;48:4463e4465. 11. Strom BL, Abrutyn E, Berlin JA, et al. Dental and cardiac risk factors for infective endocarditis: a population-based, case control study. Ann Intern Med. 1998;129:761e769. 12. Schwartz IS, Pervez N. Bacterial endocarditis associated with a permanent transvenous cardiac pacemaker. J Am Med Assoc. 1971;218:736e737. 13. Conklin EF, Giannelli Jr S, Nealon Jr TF. Four hundred consecutive patients with permanent transvenous pacemakers. J Thorac Cardiovasc Surg. 1975;69:1e7. 14. Bluhm G. Pacemaker infections: a clinical study with special reference to prophylactic use of some isoxazolyl penicillins. Acta Med Scand Suppl. 1985;699:1e62. 15. Zhan C, Baine WB, Sedrakyan A, Steiner C. Cardiac device implantation in the United States from 1997 through 2004: a population-based analysis. J Gen Intern Med. 2008;23(suppl 1):13e19. 16. Baddour LM, Bettmann MA, Bolger AF, et al. Nonvalvular, cardiovascular device-related infections. Circulation. 2003;108:2015e2031. 17. Uslan DZ, Sohail MR, St Sauver JL, et al. Permanent pacemaker and implantable cardioverter defibrillator infection: a population-based study. Arch Intern Med. 2007;167:669e675. 18. Voigt A, Shalaby A, Saba S. Rising rates of cardiac rhythm management device infections in the United States: 1996 through 2003. J Am Coll Cardiol. 2006;48: 590e591. 19. Sohail MR, Uslan DZ, Khan AH, et al. Management and outcome of permanent and implantable cardioverter-defibrillator infections. J Am Coll Cardiol. 2007;49:1851e1859. 20. Wilkoff BL, Love CJ, Byrd CL, et al. Transvenous lead extraction: Heart Rhythm Society expert consensus on facilities, training, indications and patient management: endorsed by the American Heart Association. Heart Rhythm. 2009;6: 1085e1104. 21. Doulton T, Sabharwal N, Cairns HS, et al. Infective endocarditis in dialysis patients: new challenges and old. Kidney Int. 2003;64:720e727. 22. Jones DA, McGill LA, Rathod KS, et al. Characteristics and outcomes of dialysis patients with infective endocarditis. Nephron Clin Pract. 2013;123: 151e156. 23. Rekik S, Trabelsi I, Hentati M, et al. Infective endocarditis in hemodialysis patients: clinical features, echocardiographic data and outcome. Clin Exp Nephrol. 2009;13:350e354. 24. Hickson LJ, Gooden JY, Le KY, et al. Clinical presentation and outcomes of cardiovascular implantable electronic device infections in hemodialysis patients. Am J Kidney Dis. article in press and published online, http://dx.doi.org/ 10.1053/j.ajkd.2013.11.018; 2014. 25. Nienaber J, Wilhelm MP, Sohali MZ. Current concepts in the diagnosis and management of left ventricular assist device infections. Exp Rev Anti Infect Ther. 2013;11(2):201e210. 26. Nienaber J, Kusne S, Riaz T, et al. Clinical manifestations and management of left ventricular assist device-associated infections. Clin Infect Dis. 2013;3(57): 1438e1448.
Contents lists available at ScienceDirect
Heart & Lung journal homepage: www.heartandlung.org
Endocarditis 2014: An update Kristin L. Thanavaro, MD, J.V. (Ian) Nixon, MD * Pauley Heart Center, Virginia Commonwealth University School of Medicine, Richmond, VA, USA
a r t i c l e i n f o
a b s t r a c t
Article history: Received 3 February 2014 Received in revised form 16 March 2014 Accepted 23 March 2014 Available online xxx
The epidemiology of infective endocarditis is changing due to a number of factors, including more frequent and varied antibiotic use, the emergence of resistant microorganisms, and an increase in the implantation of cardiovascular devices. This review outlines and consolidates the most recent guidelines, including the 2007 and 2010 AHA/ACC guidelines and scientific statements for the prevention and management of infective endocarditis and for the management of cardiovascular device infections. The evidence-based guidelines, including the 2009 HRS consensus document, for the treatment of patients with cardiovascular device-related infections are also reviewed. Only patients with prosthetic valves, patients with prior endocarditis, cardiac transplant patients with a valvulopathy, and certain congenital heart disease patients now require endocarditis prophylaxis. There is an increasing incidence of cardiovascular device-related infections due to the higher frequency of implanted devices and higher morbidity and mortality rates in older patients. Ó 2014 Elsevier Inc. All rights reserved.
Keywords: Endocarditis Cardiac valve disease Cardiac device infections
Introduction Infective endocarditis has been recognized as a clinical entity since the 1950s. In 1955, the American Heart Association (AHA) first established guidelines for the treatment of infective endocarditis.1 Since that time, the development of powerful antimicrobial therapy and implantable cardiac devices has changed the face of this disease. Today, patients with endocarditis are older and have more comorbidities. These changes present challenges for the prevention and management of endocarditis. This monograph reviews these challenges while continuing to incorporate the current AHA guidelines for the prevention of infective endocarditis1 and for the management of implantable cardiovascular device infections.2 Diagnosis of infective endocarditis Infective endocarditis (IE) is a clinical diagnosis and requires a high index of suspicion because patients may present with nonspecific symptoms such as fevers, chills, fatigue, malaise, and weight loss. Some patients may present with stroke-like symptoms due to embolic events or with congestive heart failure. Elderly patients, patients with renal failure or patients previously treated with antibiotics may not present with fevers, creating a diagnostic challenge. The Duke Criteria for the diagnosis and management of IE
* Corresponding author. VCU Medical Center, 1200 East Marshall Street, Gateway Building, 2nd Floor, #291, Richmond, VA 23298-0051, USA. Tel.: þ1 804 828 7915. E-mail address: [email protected] (J.V.(Ian) Nixon). 0147-9563/$ e see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.hrtlng.2014.03.009
were initially drafted in 1994 for use in clinical trials and epidemiology studies e however, they were not designed for use in clinical patients.3 Nonetheless, the Duke Criteria have become the gold standard for the diagnosis of IE and were subsequently modified in 2002 to include echocardiographic evidence of IE (Table 1).4 A definitive diagnosis of IE may be made with either pathological or clinical criteria. The two major clinical criteria are abnormal blood cultures and evidence of endocardial involvement. The five minor clinical criteria are a predisposition to IE, fever of greater than 38 C, vascular phenomena, immunologic phenomena, or microbiological evidence of IE not meeting major criteria (Table 1). Requirement for a clinical diagnosis of IE are 2 major clinical criteria, 1 major and 3 minor clinical criteria, or 5 minor clinical criteria.
Endocarditis prevention guidelines The most recent revision of the AHA Guidelines for IE was published in 2007.1 They were a clarification of the previous guidelines from 1997.5 There were several logical rationale for the revision of the guidelines. Firstly, regarding oral hygiene and procedures, IE was more likely to occur with everyday activities such as teeth brushing and flossing rather than with a single medical or dental procedure. Secondly, prophylaxis with antibiotics for dental procedures prevented very few IE cases. Furthermore, the risk of adverse events and cost of antibiotic therapy significantly outweighed the benefit of such prophylaxis. Thirdly, consistently good oral hygiene is more beneficial in preventing IE than a single dose of antibiotics.
2
K.L. Thanavaro, J.V.(Ian) Nixon / Heart & Lung xxx (2014) 1e4
Table 1 Modified Duke Criteria for the diagnosis of infective endocarditis. Pathological criteria (1 needed) 1. Microorganism identified by culture or histology from a vegetation, an embolized vegetation or in a cardiac abscess. 2. A histological specimen from a vegetation or an intracardiac abscess showing active endocarditis. Clinical criteria (2 major, 1 major and 3 minor, or 5 minor needed) Major criteria 1. Two positive blood cultures with typical microorganisms drawn at least 12 h apart (or one positive blood culture for Coxiella Burnetii) 2. Evidence of endocardial involvement (new murmur, echocardiographic evidence of a cardiac mass, abscess or valve dehiscence) Minor criteria 1. Feve > 38 C 2. Vascular phenomena (systemic emboli, Janeway lesions) 3. Immunological phenomena (Osler’s nodes, Roth spots) 4. Predisposition to infective endocarditis (previous infective endocarditis or intravenous drug abuse) 5. Microbiological evidence not meeting major criteria Adapted from Li JS, Sexton DJ, Mick N, et al. Clin Infect Dis 2000; 30:633e638.4
The number of patients requiring IE prophylaxis according to the 2007 guidelines has been greatly reduced.1 Only the four following groups now require prophylaxis: patients with prosthetic valves, patients with prior IE, cardiac transplant patients with a valvulopathy, and certain congenital heart disease patients. These groups include patients with cyanosis, palliative shunts and conduits, patients with residual defects around a cardiovascular patch site and patients within 6 months of a complete repair of a congenital anomaly. For patients with a successful cardiovascular repair, adequate endothelialization of the repair is assumed after 6 months and prophylaxis is no longer needed. Patients with mitral valve prolapse with or without mitral regurgitation and patients with bicuspid aortic valves no longer require prophylaxis under the revised 2007 guidelines. The number of dental procedures that require prophylaxis under the 2007 guidelines is also reduced. Antibiotic prophylaxis is a Class IIa (LOE C) recommendation for dental procedures that involve manipulation or perforation of the oral mucosa.1 This does not include routine anesthetic injections through non-infected tissue, dental radiographs, placement or adjustment of orthodontic devices or trauma to the lips and teeth. For respiratory procedures, antibiotic prophylaxis is a Class IIa (LOE C) recommendation for any invasive procedures that involves incision or biopsy of the respiratory mucosa (such as tonsillectomy). An exception is bronchoscopy, which requires no prophylaxis. Antibiotic choices are influenced by the patient’s ability to tolerate oral medication, by medication allergies, and by the most likely pathogen. For dental and respiratory procedures, the most common bacteria are the various streptococcus viridans species. The recommended prophylactic antibiotic is amoxicillin 2 g orally 1 h prior to the procedure.1 If the patient requires intravenous medication, ampicillin or ceftriaxone may be substituted. Cephalexin, clindamycin or azithromycin may be used in patients with a penicillin allergy. However, there is emerging penicillin resistance of the streptococcus viridans species, with percentage resistances in some studies ranging from 17% to 50%.6e10 The prescribing physician must consider the resistance in his/her area of practice when selecting the appropriate antibiotic. In cases where staphylococcus aureus is suspected, an anti-staphylococcal penicillin or vancomycin is recommended.1 There are no published data linking gastrointestinal (GI) and genitourinary (GU) procedures to IE.11 Consequently the 2007 guidelines recommend that antibiotic prophylaxis is no longer necessary during these procedures (Class III, LOE B).1 It is stated, however, that if a patient has an established GI or GU infection and is undergoing elective GI or GU tract manipulation, any infection
should be eradicated prior to the procedure (Class IIb, LOE B).1 The most common pathogens causing a GI or GU infection are the enterococcus species, which also have emerging antibiotic-resistant strains.1 Penicillins are preferred for these infections, although piperacillin and vancomycin should be considered when a resistant enterococcus is suspected. In these cases, consultation with an infectious disease specialist may be warranted. Currently, there is no indication for dental, GI or GU procedural prophylaxis for patients with implantable cardiovascular devices (Class III, LOE C).2 However, prophylaxis with an anti-staphylococcal antibiotic is indicated at the time of a cardiovascular device implantation and any subsequent manipulation of the surgical created device pocket (Class I, LOE A).2 Treatment of endocarditis Treatment of IE should be tailored to in-vitro susceptibility of the pathogen identified, and consultation with an infectious disease specialist can be considered. In general, antibiotics such as penicillin, ampicillin, ceftriaxone, rifampin, vancomycin and daptomycin are used. The length of treatment is dependent on the pathogen and type of valve (native vs. prosthetic). Antibiotic selection and duration of therapy is addressed in the 2005 AHA Scientific Statement.3 Viridans group streptococci endocarditis should be treated for 4 weeks for native valve IE and 6 weeks for prosthetic valve IE. For the more virulent staphylococcus aureus, treatment duration is 6 weeks, regardless of valve type. However, prosthetic valves require the addition of rifampin or gentamicin for synergy. Enterococcus endocarditis requires combination antimicrobial therapy for 4e6 weeks, regardless of valve type. Generally, ampicillin is used in combination with either gentamicin or ceftriaxone, depending on the patient’s renal function. Treatment duration for the HACEK organisms (Hemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella) is 4 weeks for native valves and 6 weeks for prosthetic valves. Cardiovascular non-valvular device infections IE associated with a cardiac pacemaker was first reported in the early 1970s.12 Infection rates of these implanted devices in the 1970se1980s ranged from less than 1%e19.9%.13,14 Subsequently, the numbers of implanted cardiac devices has significantly increased.15 Defibrillators are now implanted for primary prevention, and cardiac-resynchronization therapy has increased the total number of implanted intracardiac leads. Furthermore, the average patient with an implanted cardiac device is older and sicker. Zhan and colleagues have reported that among the patients receiving implantable cardiovascular devices, 70% are older than 65 years and at least 75% have more than one coexisting disease.15 Inevitably these characteristics lead to an increasing number of cardiovascular device-related infections, and a significant increase in associated morbidity and mortality. Guidelines were initially drafted for the management of cardiovascular device-related infections by the ACC/AHA in 2003.16 Since the publication of these guidelines, there has been a substantial increase in the number of reports reviewing the incidence and clinical management of patients with cardiovascular device-related infections.17e19 As a result, a scientific statement from the AHA issued in 2010 updated the evidence-based guidelines for treatment of patients with cardiovascular device-related infections.2 Clinical presentation and diagnosis The clinical presentation of a patient with a cardiac devicerelated infection can be subtle and patients may present with
K.L. Thanavaro, J.V.(Ian) Nixon / Heart & Lung xxx (2014) 1e4
vague symptoms such as fatigue and malaise.2 Pain may occur at the pocket site. However, aspiration of the pocket is not recommended (Class III, LOE B). Patients with lead or valve endocarditis may present with fevers and other stigmata of IE such as systemic embolization, immunologic phenomena, a new murmur on examination or congestive heart failure. Risk factors for a devicerelated infection include immunosuppression, oral anticoagulation, diabetes mellitus, end-stage renal disease, the absence of periprocedural antibiotics, the necessity for a device revision or replacement, an increased number of implanted devices, a lack of operator experience and the presence of a bloodstream infection.2 The following Class I recommendations were established for the diagnosis of device-related infections in the 2010 guidelines2: 1. All patients should have two sets of blood cultures drawn before the administration of antimicrobial agents (Class I, LOE C). 2. After extraction of the cardiovascular device, a gram stain and culture should be performed on the lead tips (Class I, LOE C). 3. Patients with positive blood cultures should undergo transesophageal echocardiography for the evaluation of lead endocarditis (Class I, LOE C) and the possibility of left-sided valvular endocarditis (Class I, LOE B).
Patient management Compared to traditional endocarditis, which has a high incidence of streptococcus viridans, cardiac device-related infections are more commonly caused by either coagulase-negative staphylococci (CNS) or staphylococcus aureus.2 These bacteria possess adherence molecules, and the creation of biofilm on the surface of the device forms a protected environment that antimicrobials cannot penetrate.16 Thus, once the bacteria are attached to the device, the whole system must be removed for eradication of the infection. In 2009, the Heart Rhythm Society (HRS) put forth an expert consensus document addressing the indications for and management of patients requiring transvenous lead extraction for any indication.20 Though this document predated the current ACC/AHA guidelines, it stated that complete device removal was recommended in all patients with infection of the pocket, leads, cardiac valves, and patients with gram-positive bacteremia (Class I, LOE B). When the ACC/AHA Guidelines were published the following year,2 the recommendations echoed those of the HRS. The 2010 guidelines recommend the following for total cardiac device removal2: 1. Device removal is recommended (Class I) for all patients with definite lead infection or sepsis (LOE A), a pocket infection (LOE B), valvular endocarditis without lead involvement (LOE B) and occult staphylococcal bacteremia (LOE B). 2. Device removal is reasonable for persistent occult gramnegative bacteremia despite appropriate antibiotic therapy (Class II). 3. Removal of the device is not recommended for superficial skin infections above the pocket site (Class III). Device removal should be performed by experienced physicians with surgical backup, because it carries an increased morbidity and mortality risk.2 Institutions performing system extraction should have adequate training of personnel (including cardiologists, cardiac anesthesiologists, echocardiographers and nurses), as well as an internal review of patient outcomes.20 Cardiothoracic surgeons should be immediately available for surgical backup, and a protocol
3
should be established so that emergencies can be managed quickly and efficiently.20 Complications may include hemorrhage, damage to the tricuspid valve, myocardial infarction and pulmonary embolism. To reduce the risk of septic pulmonary emboli, surgical removal rather than laser extraction should be considered if a vegetation larger than 2 cm is present on the device lead.2 After removal of the device and leads, patients should complete a course of intravenous antibiotics. However, there are no evidencebased data on the duration of antibiotic therapy or when reimplantation is appropriate. Since device-related infection has only recently emerged as a clinical entity, the current treatment guidelines are uncertain and need to be readdressed in future revisions of the guidelines. The current Class I recommendations for antimicrobial treatment are as follows2: 1. The choice of antibiotics should be based on in-vitro susceptibility of the pathogen (Class I, LOE B). 2. The duration of therapy after system removal for a pocket infection should be 10e14 days (Class I, LOE C). 3. The duration of therapy after system removal for a bloodstream infection should be at least 14 days (Class I, LOE C). 4. The duration of therapy after system removal for lead endocarditis or other complicated infections should be at least 4e6 weeks (Class I, LOE C). The timing of a new device reimplantation remains uncertain and the 2010 guidelines allow for the discretion of the treating physician.2 1. When considering reimplantation, the clinician should evaluate if a new device is required (Class I, LOE C). 2. The new device should be implanted on the contralateral side to the extraction site (Class I, LOE C). 3. The patient should have negative blood cultures for at least 72 h prior to the reimplantation of a new device (Class IIa, LOE C). 4. If the patient has evidence of valve involvement, device reimplantation should be delayed at least 14 days after the original device removal (Class IIa, LOE C)
Endocarditis in special populations For over fifty years, chronic hemodialysis (HD) has been recognized as a risk factor for IE.21 HD patients have a 50e180 fold higher risk of acquiring IE compared to the general population.22 These patients often have indwelling catheters and suppressed immune function, which make them susceptible to infections from transient bacteremia related to repetitive vascular access. In addition, the systemic vascular calcification that occurs as a consequence of renal dysfunction leads to valvular damage, which is a predisposition for IE. Generally, the left-sided valves (mitral and aortic) are more commonly affected than the right-sided valves.23 In a recent study, the most common pathogens identified were coagulase-negative staphylococcus aureus, methicillin-resistant staphylococcus aureus and fungi.24 The morbidity and mortality of IE in this population is very high. There is a 30% in-hospital mortality for IE in dialysis patients and the one year survival after IE is approximately 50%.21 It is also important to note that the risk of sudden cardiac death is high in this patient population, and many dialysis patients have defibrillators and are at risk for CIED infections. As opposed to nonHD patients who generally present with isolated pocket infection, HD patients will more frequently have fever, bacteremia and leukocytosis without pocket inflammation.24 The increasing prevalence of heart failure has led to great advancements in mechanical circulatory device support. These new
4
K.L. Thanavaro, J.V.(Ian) Nixon / Heart & Lung xxx (2014) 1e4
technologies have led to many new types of infections. Left ventricular assist device (LVAD) infections can encompass the pump, driveline, cannula, or mediastinum. While the second-generation continuous-flow LVADs have less infection compared to the firstgeneration pulsatile devices, the overall rate is still high, ranging from 30 to 50%.25 LVAD-related IE occurs from seeding of the valves or pump during implantation or via extension of driveline, pocket, lung or mediastinal infections.25 While bacterial IE usually occurs in the first month following implantation, fungal endocarditis generally presents 2e3 months later.25 The diagnosis of IE in LVAD patients may be difficult because metallic reflections on transesophageal echocardiography can obscure the visualization of vegetations.26 The treatment of LVAD-associated IE is complete device removal with prolonged pathogen-directed antimicrobial therapy. There are no guidelines on the duration of antibiotic therapy after pump removal, but IE is not considered a contraindication to heart transplantation.25 Summary The epidemiology of IE is constantly changing due to increased antibiotic use and the emergence of resistant microorganisms. The 2007 ACC/AHA Prevention and Treatment Guidelines are more comprehensive than previous versions, making management less complicated and confusing for the treating physician. However, there is an increasing incidence of cardiovascular device-related infections due to the higher frequency of implanted devices and higher morbidity and mortality rates in older patients. Nevertheless, the need for further evidence-based studies continues to exist, including studies for the management of cardiovascular devicerelated infections, in addition to the need for continued updating of treatment guidelines for the prevention and treatment of infective endocarditis. References 1. Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council of Clinical Cardiology, Council on Cardiovascular Surgery, and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation. 2007;116:1736e1754. 2. Baddour LM, Epstein AE, Erickson CC, et al, on behalf of the American Heart Association’s Rheumatic Fever, Endocarditis and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, Council on Cardiovascular Surgery and Anesthesia, Council on Cardiovascular Nursing, Council on Clinical Cardiology, and the Interdisciplinary Council on Quality of Care and Outcomes Research. Update on cardiovascular implantable electronic device infections and their management: a scientific statement from the American Heart Association. Circulation. 2010;121:458e477. 3. Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation. 2005;111:e394ee434.
4. Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis. 2000;30:633e638. 5. Dajani AS, Taubert KA, Wilson W, et al. Prevention of bacterial endocarditis: recommendations by the American Heart Association. J Am Med Assoc. 1997;277:1794e1801. 6. Diekema DJ, Beach ML, Pfaller MA, Jones RN, SENTRY Participants Group. Antimicrobial resistance in viridans group streptococci among patients with and without the diagnosis of cancer in the USA, Canada and Latin America. Clin Microbiol Infect. 2001;7:152e157. 7. Groppo FC, Castro FM, Pacheco AB, et al. Antimicrobial resistance of Staphylococcus aureus and oral streptococci strains from high-risk endocarditis patients. Gen Dent. 2005;53:410e413. 8. Teng LJ, Hsueh PR, Chen YC, Ho SW, Luh KT. Antimicrobial susceptibility of viridans group streptococci in Taiwan with an emphasis on the high rates of resistance to penicillin and macrolides in streptococcus oralis. J Antimicrob Chemother. 1998;41:621e627. 9. Tuohy M, Washington JA. Antimicrobial susceptibility of viridans group streptococci. Diagn Microbiol Infect Dis. 1997;29:277e280. 10. Prabhu RM, Piper KE, Baddour LM, Steckelberg JM, Wilson WR, Patel R. Antimicrobial susceptibility patterns among viridans group streptococcal isolates from infective endocarditis patients from 1971 to 1986 and 1994 to 2002. Antimicrob Agents Chemother. 2004;48:4463e4465. 11. Strom BL, Abrutyn E, Berlin JA, et al. Dental and cardiac risk factors for infective endocarditis: a population-based, case control study. Ann Intern Med. 1998;129:761e769. 12. Schwartz IS, Pervez N. Bacterial endocarditis associated with a permanent transvenous cardiac pacemaker. J Am Med Assoc. 1971;218:736e737. 13. Conklin EF, Giannelli Jr S, Nealon Jr TF. Four hundred consecutive patients with permanent transvenous pacemakers. J Thorac Cardiovasc Surg. 1975;69:1e7. 14. Bluhm G. Pacemaker infections: a clinical study with special reference to prophylactic use of some isoxazolyl penicillins. Acta Med Scand Suppl. 1985;699:1e62. 15. Zhan C, Baine WB, Sedrakyan A, Steiner C. Cardiac device implantation in the United States from 1997 through 2004: a population-based analysis. J Gen Intern Med. 2008;23(suppl 1):13e19. 16. Baddour LM, Bettmann MA, Bolger AF, et al. Nonvalvular, cardiovascular device-related infections. Circulation. 2003;108:2015e2031. 17. Uslan DZ, Sohail MR, St Sauver JL, et al. Permanent pacemaker and implantable cardioverter defibrillator infection: a population-based study. Arch Intern Med. 2007;167:669e675. 18. Voigt A, Shalaby A, Saba S. Rising rates of cardiac rhythm management device infections in the United States: 1996 through 2003. J Am Coll Cardiol. 2006;48: 590e591. 19. Sohail MR, Uslan DZ, Khan AH, et al. Management and outcome of permanent and implantable cardioverter-defibrillator infections. J Am Coll Cardiol. 2007;49:1851e1859. 20. Wilkoff BL, Love CJ, Byrd CL, et al. Transvenous lead extraction: Heart Rhythm Society expert consensus on facilities, training, indications and patient management: endorsed by the American Heart Association. Heart Rhythm. 2009;6: 1085e1104. 21. Doulton T, Sabharwal N, Cairns HS, et al. Infective endocarditis in dialysis patients: new challenges and old. Kidney Int. 2003;64:720e727. 22. Jones DA, McGill LA, Rathod KS, et al. Characteristics and outcomes of dialysis patients with infective endocarditis. Nephron Clin Pract. 2013;123: 151e156. 23. Rekik S, Trabelsi I, Hentati M, et al. Infective endocarditis in hemodialysis patients: clinical features, echocardiographic data and outcome. Clin Exp Nephrol. 2009;13:350e354. 24. Hickson LJ, Gooden JY, Le KY, et al. Clinical presentation and outcomes of cardiovascular implantable electronic device infections in hemodialysis patients. Am J Kidney Dis. article in press and published online, http://dx.doi.org/ 10.1053/j.ajkd.2013.11.018; 2014. 25. Nienaber J, Wilhelm MP, Sohali MZ. Current concepts in the diagnosis and management of left ventricular assist device infections. Exp Rev Anti Infect Ther. 2013;11(2):201e210. 26. Nienaber J, Kusne S, Riaz T, et al. Clinical manifestations and management of left ventricular assist device-associated infections. Clin Infect Dis. 2013;3(57): 1438e1448.
