Curr Infect Dis Rep (2014) 16:439 DOI 10.1007/s11908-014-0439-4
CARDIOVASCULAR INFECTIONS (D LEVINE, SECTION EDITOR)
Health Care-Associated Infective Endocarditis: a Growing Entity that Can Be Prevented Natividad Benito & Juan M. Pericas & Mercè Gurguí & Carlos A. Mestres & Francesc Marco & Asunción Moreno & Juan P. Horcajada & José M. Miró
# Springer Science+Business Media New York 2014
Abstract Infective endocarditis (IE) continues to be a serious disease with a poor prognosis and high mortality. Neither incidence rates nor mortality have decreased in recent decades. Because of this, it is important to prevent IE in patients at risk. In the past, prevention of IE has focused on antimicrobial prophylaxis, mainly for dental procedures. However, recent major changes in epidemiology, the most significant being the growing frequency and high mortality rate of health care-associated valve endocarditis (HAIE), mean that This article is part of the Topical Collection on Cardiovascular Infections N. Benito (*) : M. Gurguí Infectious Diseases Unit, Department of Internal Medicine. Hospital de la Santa Creu i Sant Pau—Institut d’Investigació Biomèdica Sant Pau, Universitat Autònoma de Barcelona, Sant Antoni Maria Claret, 167, 08025 Barcelona, Spain e-mail: [email protected] N. Benito : M. Gurguí : A. Moreno : J. M. Miró Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015), Instituto de Salud Carlos III, Madrid, Spain J. M. Pericas : A. Moreno : J. M. Miró (*) Infectious Diseases Service. Hospital Clínic-IDIBAPS, University of Barcelona, Villarroel, 170, 08036 Barcelona, Spain e-mail: [email protected] C. A. Mestres Department of Cardiovascular Surgery. Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain e-mail: [email protected] F. Marco Servei de Microbiologia. Centre Diagnòstic Biomèdic (CDB). Barcelona Centre for International Health Research (CRESIB), Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain J. P. Horcajada Infectious Diseases Service, Hospital del Mar, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra, Barcelona, Spain
preventive strategies against IE must also change. Since intravascular catheters are the most common source of bacteremia among patients with HAIE, significant efforts must be made to minimize the risk of catheter-related bloodstream infections. Measures for preventing the infection of prosthetic valves and cardiac implantable devices at the time of implantation also need to be implemented. Keywords Endocarditis . Infective endocarditis . Health care-associated endocarditis . Prevention . Prophylaxis . Catheter-related bloodstream infections
Introduction Infective endocarditis (IE) is one of the most feared complications of bacteremia, most frequently involving patients with predisposing cardiac conditions. In industrialized countries, the estimated annual incidence of IE is 3 to 9 cases per 100,000 persons [1–7]. Despite advances in diagnostic procedures and medical and surgical treatment, IE remains a serious disease with a poor prognosis and high mortality [8, 9]. In recent studies, in-hospital mortality ranged between 15 and 22 %, although rates across patient subgroups vary considerably [2, 7]. Thus, in-hospital mortality is less than 10 % among patients with right-sided lesions or left-sided native valve lesions due to oral streptococci, but 40 % or more among patients with prosthetic valve IE due to Staphylococcus aureus [10]. It seems that neither the incidence of the disease nor the mortality associated with it have decreased in the past few decades [1, 3, 4, 11, 12]. For all these reasons, it is important to prevent IE in patients at risk. In the last few decades, prevention of IE has focused on antimicrobial prophylaxis, mainly for dental procedures. Due to recent changes in the epidemiology of IE, however, other preventive measures must now be considered.
439, Page 2 of 9
Health Care-Associated Infective Endocarditis: a Growing Entity Several studies have shown that the profile of IE in industrialized countries has changed significantly in recent decades [2, 7, 12–14]. IE today affects an increasingly elderly population [3, 12, 15]. Underlying degenerative aortic and mitral valve disease now predominates over rheumatic disease in industrialized settings, and an increasing number of patients with IE have no known history of an underlying cardiac disorder [3, 7, 15, 16]. Furthermore, IE is developing more frequently in patients with prosthetic valves and other intracardiac devices, including permanent pacemakers and implantable cardioverter defibrillators [15–20]. However, as several studies have highlighted, the most striking change in the pattern of IE in recent years concerns its shift from an infectious disease mostly associated with dental care to one that is mainly health care-related [1, 2, 7, 21–24]. Health care-associated valve endocarditis (HAIE) currently accounts for at least 25 % of IE cases in most reports from developed countries [2, 7, 23, 25], including native valve endocarditis [21], prosthetic valve endocarditis [26], and IE involving implantable cardiac devices [27]. HAIE not only includes cases that are acquired in hospital (nosocomial), but also those that develop outside hospitals (non-nosocomial) in patients with extensive health care contact (such as day care hospitals, dialysis centers, outpatient parenteral antibiotic therapy programs, and nursing homes) [21, 23, 25]. The recently described category of non-nosocomial HAIE represented up to a half of all HAIE cases in recent cohort studies, with percentages varying significantly depending on the geographical area [1, 21, 23, 25]. As a result, S. aureus has emerged as a major cause of IE [28]. The main source of concern however is the significantly higher mortality rate among HAIE patients compared to community-acquired IE, which has been linked to significantly higher rates of staphylococcal IE, older patients, and prior comorbidities. Indeed, HAIE has been identified as an independent predictor of death in several studies [21, 23, 25, 29]. Because of the increasing frequency and high mortality rate of HAIE, preventive strategies must be adopted to help protect patients from this fatal infection. In the main, HAIE is the result of bacteremia associated with health care-based procedures, so that significant efforts must be made to minimize the risk of bacteremia in health care facilities. The most common source of bacteremia among patients with HAIE has consistently been the intravascular catheter, with reported rates of 40–50 % in recent studies [21, 23, 25, 26, 30–32], with the peripheral venous catheter being the leading source of catheter-related bacteremia in several current series [21, 23, 25]. Patients receiving hemodialysis are at greater risk of HAIE because of the frequent intravascular access through an arteriovenous fistula, vascular graft, or vascular catheter [21, 23, 33]. Genitourinary and gastrointestinal procedures are
Curr Infect Dis Rep (2014) 16:439
other less common sources of bacteremia in patients with HAIE [21, 23, 25, 30–32]. The increasing group of patients with prosthetic valves or cardiac implantable devices (CIDs) is also at risk of HAIE as a result of the device becoming contaminated at the time of implantation [17, 34, 35]. Consequently, preventive measures need to be implemented aimed at improving insertion and surgical procedures and giving antibiotic prophylaxis at the time of device placement or revision [35, 36]. The main strategies for preventing HAIE concentrate on minimizing the risk of bacteremia in health care facilities— largely by reducing catheter-related bacteremia—as well as reducing endocarditis due to infection when implanting cardiac devices.
Reduction of Catheter-Related Bloodstream Infections In recent years, measures for preventing catheter-related bloodstream infections have consistently demonstrated their efficacy and are now considered to be key to avoiding or reducing catheter-related infections [37]. These preventive measures include the following: choosing an appropriate site for catheter insertion, using appropriate procedures during insertion, ensuring proper catheter-site care, and removal of the catheter when it is no longer essential. Strict adherence to hand hygiene recommendations and the use of aseptic techniques during insertion and dressing changes continue to be the most important measures for preventing infections. These measures are emphasized in several recently published guidelines [38–40]. An upper-extremity site is recommended for insertion of a peripheral catheter in adults [38]. Infection is considered to be more common with central venous catheters in the femoral and, to a lesser extent, internal jugular veins, compared to the subclavian vein [41–43]. However, a recent meta-analysis that evaluated central venous catheter location and infection rates was unable to demonstrate differences of infection rate between femoral venous as compared to subclavian or internal jugular catheters [44]. Interestingly, differences of infection risk with respect to the site of catheterization can be minimized if an experienced physician inserts the catheter, a strict sterile technique is used, and a trained nursing staff performs catheter care [45]. There is insufficient evidence to recommend one central venous catheter type or insertion site, but experts and guidelines currently recommend avoiding femoral catheterization in adults [38, 40]. Appropriate procedures during central venous catheter insertion involve the use of maximum sterile barrier precautions: health care personnel involved in the insertion procedure should wear a mask, cap, sterile gown, and sterile gloves and the patient be fully covered with a long sterile drape during catheter insertion [40]. For skin disinfection,
Curr Infect Dis Rep (2014) 16:439
chlorhexidine-based alcohol solutions are superior to iodine compounds for reducing the risk of infection [46, 47]. For peripheral venous catheters, daily evaluation of the catheter insertion site is recommended and it should be removed if the patient develops signs of phlebitis (warmth, tenderness, erythema, or a palpable venous cord) or infection or if the catheter is malfunctioning [38]. No differences in infection rates have been demonstrated between transparent and gauze dressings. It is recommended that transparent dressings on short-term central venous catheters should be changed every 5–7 days, gauze dressings every 2 days—or immediately if the dressing is soiled, loose, or damp—and that site care be performed with a chlorhexidine-based antiseptic [40]. In addition, a recent metaanalysis of 11 randomized trials demonstrated that a chlorhexidine-impregnated dressing was beneficial in preventing catheter-related bloodstream infections [48]. Topical antimicrobial ointment has not been shown to reduce the rate of infection, except for hemodialysis catheters [49]. Disinfecting catheter hubs, needleless connectors, and injection ports with a suitable antiseptic before accessing the catheter, accessing the port with sterile devices only and capping all stopcocks when not in use are all strongly recommended for catheter access ports [40]. Some authors recommend changing peripheral catheters periodically (every 72–96 h); the routine replacement of central venous catheters is discouraged [38, 40]. As a general preventive measure, bathing patients daily with chlorhexidine can reduce the incidence of catheterrelated bloodstream infections [50]. Some experts and guidelines recommend its use in ICU patients [40]. Different antimicrobial-/antiseptic-impregnated catheters have been demonstrated to reduce infection rates [51, 52]. Current guidelines recommend that these should be used if infection rates remain high in spite of a comprehensive strategy to reduce rates of central line-associated bloodstream infections [38, 40]. Compliance with recommended measures for preventing intravascular catheter infections is a challenging issue. A systematic review and meta-analysis recently assessed the efficacy of interventions aimed at decreasing central lineassociated bloodstream infections by improving adherence to preventive measures [53]. In that review, implementation of care bundles and checklists appeared to yield stronger risk reductions. Such bundles are most likely to be successful if they are implemented in a patient safety culture that is already established and their success depends on adherence to individual measures [54].
Antimicrobial Prophylaxis for Invasive Procedures (Other than Implantation of Prosthetic Valves or Other Cardiac Devices) in Patients at Risk of Infective Endocarditis Transient bacteremia is common after many invasive procedures. Since the occurrence of bacteremia is critical to the
Page 3 of 9, 439
initiation of an IE episode, it seems reasonable to assume that preventing or promptly treating transient bacteremia will prevent the development of endocarditis. Consequently, administering antibiotics before invasive procedures—especially dental procedures—that could cause transient bacteremia in patients at risk of IE has been widely recommended for decades [55, 56]. Since 1955, the American Heart Association (AHA) has recommended giving antimicrobial prophylaxis before specific dental, gastrointestinal, and genitourinary procedures to prevent IE in patients at risk for its development [57]. Even though the idea is biologically plausible, no studies in humans have conclusively demonstrated that antimicrobial prophylaxis prevents IE after invasive procedures [55–57]. Therefore, many authorities and societies, as well as the conclusions of published studies, have questioned the efficacy of antimicrobial prophylaxis in most situations [55, 57–59]. Consequently, there has been a general tendency in recent years to reduce indications for prophylaxis. The current guidelines of the AHA (2007) [57] and the European Society of Cardiology (ESC, 2009) [59] limit their indications to patients with the highest risk of an adverse outcome from IE who are undergoing high-risk procedures (Table 1). The National Institute for Health and Clinical Excellence (NICE) in the UK recommends that at-risk patients who undergo dental and non-dental procedures (upper and lower respiratory tract, upper and lower gastrointestinal tract, and genitourinary tract) should no longer be given antibiotic prophylaxis for IE [60]. The same guidelines also recommend that patients at risk for IE receiving antibiotics because they are undergoing a gastrointestinal or genitourinary procedure at a site where there is a suspected infection should be given an agent that covers the organisms that cause IE. After the introduction of the NICE guidelines, no increase in the incidence of endocarditis was found [61]. Current guidelines agree on the importance of maintaining good oral health via good oral hygiene and regular dental checkups to reduce the risk of IE [57, 59, 60].
Specific Measures for Prevention of Prosthetic Valve Endocarditis and Endocarditis Involving Cardiac Implantable Devices Early infection of intracardiac devices is generally due to intraoperative contamination at the time of device implantation or generator replacement and is associated with microorganisms directly seeding the device or pocket [62]. Infection can spread from the pocket to the leads and ultimately to the endocardial surfaces of
Procedures for which antibiotic prophylaxis is recommended in patients at highest risk
(a) Dental procedures requiring manipulation of the gingival or periapical region of the teeth or perforation of the oral mucosa (an agent active against oral streptococci) (b) Respiratory tract procedures • Patients who undergo an invasive procedure that involves incision or biopsy of the respiratory mucosa such as tonsillectomy, adenoidectomy or bronchoscopy with biopsy (an agent active against oral streptococci) (recommendation of the AHA, not supported by the ESC) • Patients who undergo an invasive respiratory tract procedure to treat an established infection (antibiotic regimen which contains an agent active against oral streptococci and Staphylococcus aureus) (c) Gastrointestinal or genitourinary procedures: the administration of prophylactic antibiotics solely to prevent endocarditis is not recommended • In the case of an established infection or if antibiotic therapy is indicated to prevent infection associated with a gastrointestinal or genitourinary procedure, the antibiotic regimen should include an agent active against enterococci (d) Procedures on infected skin, skin structure or musculoskeletal tissue: the therapeutic regimen should contain an agent active against staphylococci and β-hemolytic streptococci
Cardiac conditions for which prophylaxis is recommended when a high risk procedure is performed
(a) Prosthetic cardiac valve or prosthetic material used for cardiac valve repair (b) Previous infective endocarditis (c) Congenital heart disease • Patients with unrepaired congenital heart disease, including palliative shunts and conduits • Patients with repaired congenital heart disease with residual defects • After surgical repair of congenital heart disease with no residual defects, prophylaxis is recommended for the first 6 months after the procedure (d) Heart transplant recipients who develop cardiac valvulopathy (recommendation of the AHA, not supported by the ESC)
Table 1 Antimicrobial prophylaxis for bacterial endocarditis, according to the recommendations of the American Heart Association (AHA) and the European Society of Cardiology (ESC) [59]
439, Page 4 of 9
Curr Infect Dis Rep (2014) 16:439
the heart. Most CID infections affect the subcutaneous generator pocket; approximately 10 to 23 % result in IE [27]. In any event, strategies that address the prevention of these surgical site infections must be developed in order to prevent early prosthetic valve endocarditis and endocarditis involving CID. Antimicrobial Prophylaxis in Cardiac Surgery (Focused on Valve Procedures and Cardiac Device Implantation) Antibiotic prophylaxis should be considered for patients undergoing surgery for implantation of prosthetic valves, intravascular prosthetic, or other foreign material because of the increased risk and adverse outcome of postoperative infections and especially early prosthetic valve endocarditis [59]. Diagnostic cardiac catheterization, use of an intra-aortic balloon pump, and transesophageal echocardiograms appear to present little risk, and prophylaxis is not recommended during these procedures [63]. The predominant organisms causing surgical site infections and early (1 year after surgery) prosthetic valve infections are skin flora, including S. aureus, coagulasenegative staphylococci, and streptococcal species. Gramnegative organisms and fungi are less commonly isolated in these patients [63]. No single antibiotic regimen is effective against all these organisms, and the use of broad-spectrum antibiotics may predispose to superinfection with resistant bacteria. The recommendations for surgical prophylaxis in cardiac surgery and for preventing device-related infections, according to current guidelines, are listed in Table 2 [63, 64]. Cefazolin is the drug of choice for most procedures. It has a desirable duration of action and spectrum of activity against organisms commonly encountered in surgery, has reasonable safety, and is low cost. Second-generation cephalosporins (such as cefuroxime) have broader coverage against gram-negative organisms but have not demonstrated their superiority over firstgeneration cephalosporins [63, 65]. The accepted alternative antimicrobial for patients who are beta-lactam allergic is vancomycin or clindamycin for grampositive coverage. Use of vancomycin may also be acceptable in patients known to be colonized with MRSA [63]. The addition of an aminoglycoside, aztreonam, or fluoroquinolone may be prudent when gramnegative pathogens are a concern [63]. Antibiotic prophylaxis should be administered to ensure adequate levels of the drug in serum and tissue during the interval when the surgical site is open. For most adults, it is acceptable to use standardized doses of
Curr Infect Dis Rep (2014) 16:439
Page 5 of 9, 439
Table 2 Antimicrobial prophylaxis for cardiac surgery (adapted from [63, 64]) Operation
Common pathogens
Recommended antimicrobials
Usual adult dosagea
Redose interval (h)
Coronary artery bypass graft procedures, valve repairs Placement of electrophysiological devices, ventricular assist devices, ventriculoatrial shunts, and arterial patches Implantation of permanent pacemakers and cardioverter defibrillators
Staphylococcus aureus Staphylococcus epidermidis
Cefazolin OR cefuroxime OR vancomycin OR clindamycin
2–3 g IVb,c 1.5 g Ic 1 g IV 900 mg IV
4 4 12 6
a
Parenteral prophylactic antimicrobials can be given as a single IV dose within 60 min of the beginning of the procedure. For prolonged procedures (>3 h) or those with major blood loss, additional intraoperative doses should be given at intervals of 1–2 times the half-life of the drug (cefazolin q4 h, cefuroxime q4 h, clindamycin q6 h, and vancomycin q12 h) for the duration of the procedure in patients with normal renal function
b
The recommended dose of cefazolin is 2 g for patients who weigh
CARDIOVASCULAR INFECTIONS (D LEVINE, SECTION EDITOR)
Health Care-Associated Infective Endocarditis: a Growing Entity that Can Be Prevented Natividad Benito & Juan M. Pericas & Mercè Gurguí & Carlos A. Mestres & Francesc Marco & Asunción Moreno & Juan P. Horcajada & José M. Miró
# Springer Science+Business Media New York 2014
Abstract Infective endocarditis (IE) continues to be a serious disease with a poor prognosis and high mortality. Neither incidence rates nor mortality have decreased in recent decades. Because of this, it is important to prevent IE in patients at risk. In the past, prevention of IE has focused on antimicrobial prophylaxis, mainly for dental procedures. However, recent major changes in epidemiology, the most significant being the growing frequency and high mortality rate of health care-associated valve endocarditis (HAIE), mean that This article is part of the Topical Collection on Cardiovascular Infections N. Benito (*) : M. Gurguí Infectious Diseases Unit, Department of Internal Medicine. Hospital de la Santa Creu i Sant Pau—Institut d’Investigació Biomèdica Sant Pau, Universitat Autònoma de Barcelona, Sant Antoni Maria Claret, 167, 08025 Barcelona, Spain e-mail: [email protected] N. Benito : M. Gurguí : A. Moreno : J. M. Miró Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015), Instituto de Salud Carlos III, Madrid, Spain J. M. Pericas : A. Moreno : J. M. Miró (*) Infectious Diseases Service. Hospital Clínic-IDIBAPS, University of Barcelona, Villarroel, 170, 08036 Barcelona, Spain e-mail: [email protected] C. A. Mestres Department of Cardiovascular Surgery. Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain e-mail: [email protected] F. Marco Servei de Microbiologia. Centre Diagnòstic Biomèdic (CDB). Barcelona Centre for International Health Research (CRESIB), Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain J. P. Horcajada Infectious Diseases Service, Hospital del Mar, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Pompeu Fabra, Barcelona, Spain
preventive strategies against IE must also change. Since intravascular catheters are the most common source of bacteremia among patients with HAIE, significant efforts must be made to minimize the risk of catheter-related bloodstream infections. Measures for preventing the infection of prosthetic valves and cardiac implantable devices at the time of implantation also need to be implemented. Keywords Endocarditis . Infective endocarditis . Health care-associated endocarditis . Prevention . Prophylaxis . Catheter-related bloodstream infections
Introduction Infective endocarditis (IE) is one of the most feared complications of bacteremia, most frequently involving patients with predisposing cardiac conditions. In industrialized countries, the estimated annual incidence of IE is 3 to 9 cases per 100,000 persons [1–7]. Despite advances in diagnostic procedures and medical and surgical treatment, IE remains a serious disease with a poor prognosis and high mortality [8, 9]. In recent studies, in-hospital mortality ranged between 15 and 22 %, although rates across patient subgroups vary considerably [2, 7]. Thus, in-hospital mortality is less than 10 % among patients with right-sided lesions or left-sided native valve lesions due to oral streptococci, but 40 % or more among patients with prosthetic valve IE due to Staphylococcus aureus [10]. It seems that neither the incidence of the disease nor the mortality associated with it have decreased in the past few decades [1, 3, 4, 11, 12]. For all these reasons, it is important to prevent IE in patients at risk. In the last few decades, prevention of IE has focused on antimicrobial prophylaxis, mainly for dental procedures. Due to recent changes in the epidemiology of IE, however, other preventive measures must now be considered.
439, Page 2 of 9
Health Care-Associated Infective Endocarditis: a Growing Entity Several studies have shown that the profile of IE in industrialized countries has changed significantly in recent decades [2, 7, 12–14]. IE today affects an increasingly elderly population [3, 12, 15]. Underlying degenerative aortic and mitral valve disease now predominates over rheumatic disease in industrialized settings, and an increasing number of patients with IE have no known history of an underlying cardiac disorder [3, 7, 15, 16]. Furthermore, IE is developing more frequently in patients with prosthetic valves and other intracardiac devices, including permanent pacemakers and implantable cardioverter defibrillators [15–20]. However, as several studies have highlighted, the most striking change in the pattern of IE in recent years concerns its shift from an infectious disease mostly associated with dental care to one that is mainly health care-related [1, 2, 7, 21–24]. Health care-associated valve endocarditis (HAIE) currently accounts for at least 25 % of IE cases in most reports from developed countries [2, 7, 23, 25], including native valve endocarditis [21], prosthetic valve endocarditis [26], and IE involving implantable cardiac devices [27]. HAIE not only includes cases that are acquired in hospital (nosocomial), but also those that develop outside hospitals (non-nosocomial) in patients with extensive health care contact (such as day care hospitals, dialysis centers, outpatient parenteral antibiotic therapy programs, and nursing homes) [21, 23, 25]. The recently described category of non-nosocomial HAIE represented up to a half of all HAIE cases in recent cohort studies, with percentages varying significantly depending on the geographical area [1, 21, 23, 25]. As a result, S. aureus has emerged as a major cause of IE [28]. The main source of concern however is the significantly higher mortality rate among HAIE patients compared to community-acquired IE, which has been linked to significantly higher rates of staphylococcal IE, older patients, and prior comorbidities. Indeed, HAIE has been identified as an independent predictor of death in several studies [21, 23, 25, 29]. Because of the increasing frequency and high mortality rate of HAIE, preventive strategies must be adopted to help protect patients from this fatal infection. In the main, HAIE is the result of bacteremia associated with health care-based procedures, so that significant efforts must be made to minimize the risk of bacteremia in health care facilities. The most common source of bacteremia among patients with HAIE has consistently been the intravascular catheter, with reported rates of 40–50 % in recent studies [21, 23, 25, 26, 30–32], with the peripheral venous catheter being the leading source of catheter-related bacteremia in several current series [21, 23, 25]. Patients receiving hemodialysis are at greater risk of HAIE because of the frequent intravascular access through an arteriovenous fistula, vascular graft, or vascular catheter [21, 23, 33]. Genitourinary and gastrointestinal procedures are
Curr Infect Dis Rep (2014) 16:439
other less common sources of bacteremia in patients with HAIE [21, 23, 25, 30–32]. The increasing group of patients with prosthetic valves or cardiac implantable devices (CIDs) is also at risk of HAIE as a result of the device becoming contaminated at the time of implantation [17, 34, 35]. Consequently, preventive measures need to be implemented aimed at improving insertion and surgical procedures and giving antibiotic prophylaxis at the time of device placement or revision [35, 36]. The main strategies for preventing HAIE concentrate on minimizing the risk of bacteremia in health care facilities— largely by reducing catheter-related bacteremia—as well as reducing endocarditis due to infection when implanting cardiac devices.
Reduction of Catheter-Related Bloodstream Infections In recent years, measures for preventing catheter-related bloodstream infections have consistently demonstrated their efficacy and are now considered to be key to avoiding or reducing catheter-related infections [37]. These preventive measures include the following: choosing an appropriate site for catheter insertion, using appropriate procedures during insertion, ensuring proper catheter-site care, and removal of the catheter when it is no longer essential. Strict adherence to hand hygiene recommendations and the use of aseptic techniques during insertion and dressing changes continue to be the most important measures for preventing infections. These measures are emphasized in several recently published guidelines [38–40]. An upper-extremity site is recommended for insertion of a peripheral catheter in adults [38]. Infection is considered to be more common with central venous catheters in the femoral and, to a lesser extent, internal jugular veins, compared to the subclavian vein [41–43]. However, a recent meta-analysis that evaluated central venous catheter location and infection rates was unable to demonstrate differences of infection rate between femoral venous as compared to subclavian or internal jugular catheters [44]. Interestingly, differences of infection risk with respect to the site of catheterization can be minimized if an experienced physician inserts the catheter, a strict sterile technique is used, and a trained nursing staff performs catheter care [45]. There is insufficient evidence to recommend one central venous catheter type or insertion site, but experts and guidelines currently recommend avoiding femoral catheterization in adults [38, 40]. Appropriate procedures during central venous catheter insertion involve the use of maximum sterile barrier precautions: health care personnel involved in the insertion procedure should wear a mask, cap, sterile gown, and sterile gloves and the patient be fully covered with a long sterile drape during catheter insertion [40]. For skin disinfection,
Curr Infect Dis Rep (2014) 16:439
chlorhexidine-based alcohol solutions are superior to iodine compounds for reducing the risk of infection [46, 47]. For peripheral venous catheters, daily evaluation of the catheter insertion site is recommended and it should be removed if the patient develops signs of phlebitis (warmth, tenderness, erythema, or a palpable venous cord) or infection or if the catheter is malfunctioning [38]. No differences in infection rates have been demonstrated between transparent and gauze dressings. It is recommended that transparent dressings on short-term central venous catheters should be changed every 5–7 days, gauze dressings every 2 days—or immediately if the dressing is soiled, loose, or damp—and that site care be performed with a chlorhexidine-based antiseptic [40]. In addition, a recent metaanalysis of 11 randomized trials demonstrated that a chlorhexidine-impregnated dressing was beneficial in preventing catheter-related bloodstream infections [48]. Topical antimicrobial ointment has not been shown to reduce the rate of infection, except for hemodialysis catheters [49]. Disinfecting catheter hubs, needleless connectors, and injection ports with a suitable antiseptic before accessing the catheter, accessing the port with sterile devices only and capping all stopcocks when not in use are all strongly recommended for catheter access ports [40]. Some authors recommend changing peripheral catheters periodically (every 72–96 h); the routine replacement of central venous catheters is discouraged [38, 40]. As a general preventive measure, bathing patients daily with chlorhexidine can reduce the incidence of catheterrelated bloodstream infections [50]. Some experts and guidelines recommend its use in ICU patients [40]. Different antimicrobial-/antiseptic-impregnated catheters have been demonstrated to reduce infection rates [51, 52]. Current guidelines recommend that these should be used if infection rates remain high in spite of a comprehensive strategy to reduce rates of central line-associated bloodstream infections [38, 40]. Compliance with recommended measures for preventing intravascular catheter infections is a challenging issue. A systematic review and meta-analysis recently assessed the efficacy of interventions aimed at decreasing central lineassociated bloodstream infections by improving adherence to preventive measures [53]. In that review, implementation of care bundles and checklists appeared to yield stronger risk reductions. Such bundles are most likely to be successful if they are implemented in a patient safety culture that is already established and their success depends on adherence to individual measures [54].
Antimicrobial Prophylaxis for Invasive Procedures (Other than Implantation of Prosthetic Valves or Other Cardiac Devices) in Patients at Risk of Infective Endocarditis Transient bacteremia is common after many invasive procedures. Since the occurrence of bacteremia is critical to the
Page 3 of 9, 439
initiation of an IE episode, it seems reasonable to assume that preventing or promptly treating transient bacteremia will prevent the development of endocarditis. Consequently, administering antibiotics before invasive procedures—especially dental procedures—that could cause transient bacteremia in patients at risk of IE has been widely recommended for decades [55, 56]. Since 1955, the American Heart Association (AHA) has recommended giving antimicrobial prophylaxis before specific dental, gastrointestinal, and genitourinary procedures to prevent IE in patients at risk for its development [57]. Even though the idea is biologically plausible, no studies in humans have conclusively demonstrated that antimicrobial prophylaxis prevents IE after invasive procedures [55–57]. Therefore, many authorities and societies, as well as the conclusions of published studies, have questioned the efficacy of antimicrobial prophylaxis in most situations [55, 57–59]. Consequently, there has been a general tendency in recent years to reduce indications for prophylaxis. The current guidelines of the AHA (2007) [57] and the European Society of Cardiology (ESC, 2009) [59] limit their indications to patients with the highest risk of an adverse outcome from IE who are undergoing high-risk procedures (Table 1). The National Institute for Health and Clinical Excellence (NICE) in the UK recommends that at-risk patients who undergo dental and non-dental procedures (upper and lower respiratory tract, upper and lower gastrointestinal tract, and genitourinary tract) should no longer be given antibiotic prophylaxis for IE [60]. The same guidelines also recommend that patients at risk for IE receiving antibiotics because they are undergoing a gastrointestinal or genitourinary procedure at a site where there is a suspected infection should be given an agent that covers the organisms that cause IE. After the introduction of the NICE guidelines, no increase in the incidence of endocarditis was found [61]. Current guidelines agree on the importance of maintaining good oral health via good oral hygiene and regular dental checkups to reduce the risk of IE [57, 59, 60].
Specific Measures for Prevention of Prosthetic Valve Endocarditis and Endocarditis Involving Cardiac Implantable Devices Early infection of intracardiac devices is generally due to intraoperative contamination at the time of device implantation or generator replacement and is associated with microorganisms directly seeding the device or pocket [62]. Infection can spread from the pocket to the leads and ultimately to the endocardial surfaces of
Procedures for which antibiotic prophylaxis is recommended in patients at highest risk
(a) Dental procedures requiring manipulation of the gingival or periapical region of the teeth or perforation of the oral mucosa (an agent active against oral streptococci) (b) Respiratory tract procedures • Patients who undergo an invasive procedure that involves incision or biopsy of the respiratory mucosa such as tonsillectomy, adenoidectomy or bronchoscopy with biopsy (an agent active against oral streptococci) (recommendation of the AHA, not supported by the ESC) • Patients who undergo an invasive respiratory tract procedure to treat an established infection (antibiotic regimen which contains an agent active against oral streptococci and Staphylococcus aureus) (c) Gastrointestinal or genitourinary procedures: the administration of prophylactic antibiotics solely to prevent endocarditis is not recommended • In the case of an established infection or if antibiotic therapy is indicated to prevent infection associated with a gastrointestinal or genitourinary procedure, the antibiotic regimen should include an agent active against enterococci (d) Procedures on infected skin, skin structure or musculoskeletal tissue: the therapeutic regimen should contain an agent active against staphylococci and β-hemolytic streptococci
Cardiac conditions for which prophylaxis is recommended when a high risk procedure is performed
(a) Prosthetic cardiac valve or prosthetic material used for cardiac valve repair (b) Previous infective endocarditis (c) Congenital heart disease • Patients with unrepaired congenital heart disease, including palliative shunts and conduits • Patients with repaired congenital heart disease with residual defects • After surgical repair of congenital heart disease with no residual defects, prophylaxis is recommended for the first 6 months after the procedure (d) Heart transplant recipients who develop cardiac valvulopathy (recommendation of the AHA, not supported by the ESC)
Table 1 Antimicrobial prophylaxis for bacterial endocarditis, according to the recommendations of the American Heart Association (AHA) and the European Society of Cardiology (ESC) [59]
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the heart. Most CID infections affect the subcutaneous generator pocket; approximately 10 to 23 % result in IE [27]. In any event, strategies that address the prevention of these surgical site infections must be developed in order to prevent early prosthetic valve endocarditis and endocarditis involving CID. Antimicrobial Prophylaxis in Cardiac Surgery (Focused on Valve Procedures and Cardiac Device Implantation) Antibiotic prophylaxis should be considered for patients undergoing surgery for implantation of prosthetic valves, intravascular prosthetic, or other foreign material because of the increased risk and adverse outcome of postoperative infections and especially early prosthetic valve endocarditis [59]. Diagnostic cardiac catheterization, use of an intra-aortic balloon pump, and transesophageal echocardiograms appear to present little risk, and prophylaxis is not recommended during these procedures [63]. The predominant organisms causing surgical site infections and early (1 year after surgery) prosthetic valve infections are skin flora, including S. aureus, coagulasenegative staphylococci, and streptococcal species. Gramnegative organisms and fungi are less commonly isolated in these patients [63]. No single antibiotic regimen is effective against all these organisms, and the use of broad-spectrum antibiotics may predispose to superinfection with resistant bacteria. The recommendations for surgical prophylaxis in cardiac surgery and for preventing device-related infections, according to current guidelines, are listed in Table 2 [63, 64]. Cefazolin is the drug of choice for most procedures. It has a desirable duration of action and spectrum of activity against organisms commonly encountered in surgery, has reasonable safety, and is low cost. Second-generation cephalosporins (such as cefuroxime) have broader coverage against gram-negative organisms but have not demonstrated their superiority over firstgeneration cephalosporins [63, 65]. The accepted alternative antimicrobial for patients who are beta-lactam allergic is vancomycin or clindamycin for grampositive coverage. Use of vancomycin may also be acceptable in patients known to be colonized with MRSA [63]. The addition of an aminoglycoside, aztreonam, or fluoroquinolone may be prudent when gramnegative pathogens are a concern [63]. Antibiotic prophylaxis should be administered to ensure adequate levels of the drug in serum and tissue during the interval when the surgical site is open. For most adults, it is acceptable to use standardized doses of
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Table 2 Antimicrobial prophylaxis for cardiac surgery (adapted from [63, 64]) Operation
Common pathogens
Recommended antimicrobials
Usual adult dosagea
Redose interval (h)
Coronary artery bypass graft procedures, valve repairs Placement of electrophysiological devices, ventricular assist devices, ventriculoatrial shunts, and arterial patches Implantation of permanent pacemakers and cardioverter defibrillators
Staphylococcus aureus Staphylococcus epidermidis
Cefazolin OR cefuroxime OR vancomycin OR clindamycin
2–3 g IVb,c 1.5 g Ic 1 g IV 900 mg IV
4 4 12 6
a
Parenteral prophylactic antimicrobials can be given as a single IV dose within 60 min of the beginning of the procedure. For prolonged procedures (>3 h) or those with major blood loss, additional intraoperative doses should be given at intervals of 1–2 times the half-life of the drug (cefazolin q4 h, cefuroxime q4 h, clindamycin q6 h, and vancomycin q12 h) for the duration of the procedure in patients with normal renal function
b
The recommended dose of cefazolin is 2 g for patients who weigh
