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Infective Endocarditis Guidelines: The Challenges of Adherence—A Survey of Infectious Diseases Clinicians

Infective Endocarditis Guidelines: The Challenges of Adherence—A Survey of Infectious Diseases... applyparastyle “fig//caption/p[1]” parastyle “FigCapt” Open Forum Infectious Diseases MAJOR ARTICLE Infective Endocarditis Guidelines: The Challenges of Adherence—A Survey of Infectious Diseases Clinicians 1 2 3 4 5 5 4, Glen Huang, Siddhi Gupta, Kyle A. Davis, Erin W. Barnes, Susan E. Beekmann, Philip M. Polgreen, and James E. Peacock Jr. 1 2 Infectious Diseases, Department of Internal Medicine, University of California Los Angeles, Los Angeles, California, USA, Infectious Diseases, Department of Internal Medicine, Wake Forest 3 4 Baptist Health, Winston-Salem, North Carolina, USA, Department of Pharmacy, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA, Section on Infectious Diseases, Department of Internal Medicine, Wake Forest Baptist Health, Winston-Salem, North Carolina, USA, and Emerging Infections Network, University of Iowa, Iowa City, Iowa, USA Background. Guidelines exist to aid clinicians in managing patients with infective endocarditis (IE), but the degree of adherence with guidelines by Infectious Disease (ID) physicians is largely unknown. Methods. An electronic survey assessing adherence with selected IE guidelines was emailed to 1409 adult ID physician members of the Infectious Diseases Society of America’s Emerging Infections Network. Results. Five hundred fifty-seven physicians who managed IE responded. Twenty percent indicated that ID was not consulted on every case of IE at their hospitals, and 13% did not recommend transthoracic echocardiography (TTE) for all IE cases. The dura- tion of antimicrobial therapy was timed from the first day of negative blood cultures by 91% of respondents. Thirty-four percent of clinicians did not utilize an aminoglycoside for staphylococcal prosthetic valve IE (PVE). Double β-lactam therapy was “usually” or “almost always” employed by 83% of respondents for enterococcal IE. For patients with active IE who underwent valve replacement and manifested positive surgical cultures, 6 weeks of postoperative antibiotics was recommended by 86% of clinicians. Conclusions. e fin Th ding that adherence was <90% with core guideline recommendations that all patients with suspected IE be seen by ID and that all patients undergo TTE is noteworthy. Aminoglycoside therapy of IE appears to be declining, with double β-lactam regi- mens emerging as the preferred treatment for enterococcal IE. The duration of postoperative antimicrobial therapy for patients undergoing valve replacement during acute IE is poorly defined and represents an area for which additional evidence is needed. Keywords. infective endocarditis; guidelines; management; adherence; clinical practice. Guidelines for managing infective endocarditis (IE) were first exist: (1) Multiple guidelines are available, some of which oer ff introduced by the American Heart Association (AHA) in 1989 differing recommendations, thus leading to confusion rather [1], with the most recent update in 2015 [2]. The European than clarity in their application. (2) Guidelines have evolved Society of Cardiology (ESC) has developed similar guidelines from succinct, “bullet-point” documents to voluminous works [3]. The goal of both documents is to facilitate application of that are oen ft challenging to read. (3) Healthy skepticism exists knowledge and best practices for diagnosing and managing IE. about the level of evidence in many guidelines, as consensus ex- Rates of IE have recently increased in the United States and pert opinion, case series, and/or standard of care form the basis globally [4, 5]. As IE has become resurgent, old challenges in pro- for some recommendations [8]. In the 2015 AHA document, 81 viding care have resurfaced and new management dilemmas have (58.7%) of 138 recommendations were Level C in quality [2]. (4) emerged [6, 7]. Guidelines exist to address clinical uncertainties Practitioners realize that guidelines do not always reflect realities and to inform practice. However, based on our observations, of clinical practice and that compromises in care must be made, there appears to be substantial practice variation in the applica- sometimes in response to patient preferences [9]. tion of guidelines to the diagnosis and management of adult pa- Accepting the conclusion that guidelines are important ad- tients with IE. Several potential obstacles to guideline adherence juncts in management, our goal was to better understand current clinical practices in the care of patients with IE. Accordingly, we developed a survey to assess adherence to selected guidelines Received 10 June 2020; editorial decision 31 July 2020; accepted 21 August 2020. for managing IE in adults, as outlined in recent AHA and ESC Correspondence: James E.  Peacock, Jr., MD, Section on Infectious Diseases, Department documents [2, 3]. of Internal Medicine, Wake Forest Baptist Health, Winston-Salem, NC 27157 (jpeacock@ wakehealth.edu). Open Forum Infectious Diseases METHODS © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative An electronic survey consisting of 17 multiple-choice ques- Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/ by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any tions and 2 case scenarios (Supplementary Figure 1) was sent medium, provided the original work is not altered or transformed in any way, and that the to physician members of the Infectious Diseases Society of work is properly cited. For commercial re-use, please contact journals.permissions@oup.com. America’s Emerging Infections Network (EIN) [10] with adult DOI: 10.1093/ofid/ofaa342 Infective Endocarditis Guidelines • ofid • 1 ID practices in the United States, Puerto Rico, and Canada. No other significant differences were identified. Of the 631 re- The EIN is funded by the Centers for Disease Control and spondents, 74 (12%) indicated that they did not manage IE, so Prevention to serve as a provider-based surveillance net- they opted out. work for emerging infections and related phenomena. Approximately 20% of ID physicians in clinical practice in General Approaches to the Diagnosis and Management of IE the United States volunteer as EIN members. The survey was Eighty percent of respondents indicated that ID was consulted distributed by email or facsimile on February 12, 2020, with for every suspected case of IE, whereas Cardiothoracic Surgery 2 reminders at weekly intervals for nonrespondents. An opt- was consulted in only a minority of cases (17%) (Figure  1). out option was provided for those who indicated that they A designated endocarditis team existed in only 6% of hospitals. did not manage IE. Respondents were not required to an- Transthoracic echocardiography (TTE) was recommended by swer all questions, so total responses for individual questions most clinicians (87%) for all cases of IE, while only 32% of re- varied. As used in the survey, the term “some” implied <50%, spondents ordered transesophageal echocardiography (TEE) “usually” equated to 50–90%, and “almost always” referred for all IE cases. In patients with positive blood cultures, most to >90% of the time. EIN staff tabulated responses and ana- respondents (95%, 530/557) repeated cultures until negative. lyzed data. Categorical variables were compared using a χ The duration of antimicrobial therapy was generally timed from test or Fisher exact test with SAS, version 9.4 (Cary, NC). P the first day on which blood cultures were negative (91% of re- values <.05 were considered significant. spondents; 508/557). RESULTS End-of-Therapy Management Participant Characteristics End-of-therapy (EOT) echocardiography was recommended by Of 1409 active EIN physician members, 631 (45%) responded 44% of respondents, with 89% recommending TTE and 11% to the survey. Respondents were significantly more likely than TEE (Figure 1). EOT blood cultures were ordered by 181 (32%) nonrespondents to have ≥25 years of ID experience (P < .0001) physicians, with the timing of those blood cultures ranging and to be employed by a Veterans Affairs hospital (P = .009). from 48 hours to 6 weeks. Recognized risk factors for relapse General approaches to the diagnosis and management of IE (n = 557) 95%, 530 91%, 508 87%, 485 80%, 444 44%, 247 32%, 181 32%, 177 17%, 97 6%, 33 ID consulted Cardiothoracic Hospital IE TTE on all TEE on all Daily blood Duration of End of End of therapy on surgery team cases of IE cases of IE culture antibiotics, start therapy blood cultures every case consulted at first day of echocardiogram negative blood cultures Figure 1. General approaches to the diagnosis and management of infective endocarditis. Abbreviations: ID, Infectious Diseases; IE, infective endocarditis; TEE, transesophageal echocardiogram; TTE, transthoracic echocardiogram. 2 • ofid • Huang et al such as endovascular hardware, specific pathogens (ie, S.  au- indicated that they used an aminoglycoside as a component of reus), or delayed response to therapy were the identified indica- combination therapy for staphylococcal prosthetic valve endo- tions for EOT cultures. carditis (PVE). The specifics of aminoglycoside usage in this setting are shown in Table  1. For enterococcal IE, 83% of re- Treatment of Specific Pathogens Causing IE spondents (n = 461/557) stated that they “usually” (27%) or “al- For treatment of native valve IE (NVE) due to methicillin- most always” (56%) employed ampicillin and ceftriaxone (A + susceptible S. aureus (MSSA), only 4% of respondents preferred C) as their regimen of choice (Figure 2). Conversely, only 16% combination antimicrobial therapy (Table 1). When queried as selected traditional treatment with penicillin (or ampicillin or to whether cefazolin monotherapy was adequate for MSSA IE, vancomycin) plus an aminoglycoside as their preferred (“usu- 89% of respondents replied affirmatively. Only 66% of physicians ally” or “almost always”) therapy. If an aminoglycoside was used, 60% treated for 2 weeks only, whereas 39% selected 4–6 weeks. For those practitioners utilizing A + C for enterococcal Table 1. Treatment of Specific Pathogens Causing Infective IE, 44% restricted usage to E. faecalis only, while 47% used A + Endocarditis C for any enterococcal species. Seventy-six percent of respond- ents employed A + C for both NVE and PVE, whereas 17% lim- Yes, No, No Answer, ited usage to NVE only. Pathogen/Type Infective Endocarditis No. (%) No. (%) No. (%) Methicillin-susceptible Staphylococcus Case Scenarios aureus native valve IE Is combination antimicrobial therapy 23 (4) 527 (95) 7 (1) In scenario #1, a patient with mitral NVE due to methicillin- used for treatment? resistant S. aureus (MRSA) underwent valve replacement. At the Is cefazolin monotherapy adequate? 487 (89) 54 (10) 6 (1) time of surgery, 2 full weeks of therapy had been completed, 1 Enterococcal IE week of which was after bacteremia cleared. Surgical gram stain Preferred treatment (usually + almost always) β-lactam or vancomycin + 90 (16) 411 (74) 56 (10) aminoglycoside (Penicillin or Ampicillin or Vancomycin) + Ampicillin + ceftriaxone 461 (83) 92 (17) 4 (1) Aminoglycoside Do you ever use an aminoglycoside? 416 (75) 141 (25) — 23, 4% If used, what is the aminoglycoside 56, duration? 10% 2 wk 251 (60) 4–6 wk 161 (39) 67, 12% If an aminoglycoside is used, do you 177 (42) 222 (54) 17 (4) obtain a baseline audiogram? 411, 74% If you treat with A + C, is it used for: Only Enterococcus faecalis 240 (44) Any Enterococcus species 259 (47) Native valve IE only 92 (17) Prosthetic valve IE only 5 (1) Some Usually Almost always Not answered Both native and prosthetic valve IE 417 (76) (<50%) (50%–90%) (>90%) Staphylococcal prosthetic valve IE Ampicillin + Ceftriaxone Do you use an aminoglycoside for treat- 369 (66) 188 (34) ment? 4, 1% What aminoglycoside dosage is used? 3 mg/kg/d 311 (84) 5–8 mg/kg/d 39 (11) 92, 16% How do you dose the aminoglycoside? Once daily 168 (46) In divided doses 183 (50) 151, 27% How many patients complete 2 weeks? 310, 56% Some (<50%) 76 (21) Usually (50%–90%) 204 (55) Almost always (>90%) 70 (19) What dose of rifampin is used? 300 mg 2×/d 308 (55) 300 mg 3×/d 166 (30) Some Almost always Not answered Usually Other 31 (6) (<50%) (50%–90%) (>90%) Do not use 39 (7) Abbreviations: A + C, ampicillin + ceftriaxone; IE, infective endocarditis. Figure 2. Treatment strategies in enterococcal endocarditis. Infective Endocarditis Guidelines • ofid • 3 and culture were negative. Survey participants were asked how cardiothoracic surgery consultation should be obtained for all long they would continue antibiotics postoperatively. Responses patients is not addressed. Several publications have examined were diverse, with 9% choosing 2 weeks, 30% selecting 4 weeks, the benefits of an “endocarditis team,” with a general consensus 39% electing 5 weeks, and 20% treating for 6 weeks. that those teams favorably impact IE-related mortality [14]. e Th clinical features of scenario #2 were identical to #1, ex- Despite the enthusiasm for endocarditis teams in Europe, only cept that surgical cultures grew MRSA. In that scenario, 86% of 6% of US and Canadian respondents indicated that their pri- respondents chose to treat for 6 weeks aer s ft urgery. As an addi- mary hospital had such a team. In terms of routine diagnostic tional query, it was asked if respondents would treat the patient testing, 87% of respondents recommended TTE for all patients postoperatively for NVE or PVE as the prosthesis potentially with IE, which is in keeping with both US and European guide- was placed in an “infected” field. Fifty-five percent elected to lines [2, 3]. For patients with positive blood cultures, 95% of manage the patient for PVE, 33% opted for an NVE regimen, respondents repeated blood cultures on a daily or every-other- and 11% were unsure. day basis until negative, though that recommendation is not specifically delineated in the guidelines [2, 3]. Ninety-one per- cent of clinicians dated the duration of therapy as beginning on DISCUSSION the first day on which blood cultures were negative, an approach Despite decades of clinical experience and availability of guide- consistent with both US and European recommendations [2, 3]. lines since 1989 [1], management dilemmas continue to chal- EOT management of IE is largely nonstandardized. Both lenge clinicians caring for patients with IE [6, 7]. Guidelines the AHA and ESC recommend an EOT echocardiogram [2, 3] are designed to assist clinicians with meeting those challenges though the recommendation from the ESC is “stronger.” In our and, accordingly, are updated regularly [2, 3]. However, AHA survey cohort, 44% of respondents recommended EOT ech- IE guidelines are qualified by the statement that “recommenda- ocardiography, 89% of whom suggested TTE. A  recent study tions be used to support and not supplant decisions in individual by Virk et al. reported that 73% of their IE patients underwent patient management” [2]. That statement tacitly acknowledges EOT echocardiography [15]. Those authors suggested that EOT that information used to formulate guidelines may change rap- echocardiography could perhaps be targeted toward patients idly and that guidelines may reflect expert opinion rather than with new or worsening symptoms/signs at the EOT evaluation. evidence derived from clinical trials [8]. Given those limita- Whereas the AHA does not recommend routine EOT blood tions, the degree of adherence with IE guidelines in real-world cultures [2], the ESC indicates that EOT blood cultures should clinical practice may vary. Tissont-Dupont and colleagues be obtained at the initial post-therapy visit [3]. Among ID clin- examined adherence with antibiotic therapy recommendations icians taking our survey, 32% ordered EOT blood cultures, but for IE and found that overall global compliance was only 58% there was no well-defined point at which EOT blood cultures [11]. If guidelines are to improve patient outcomes, and data were obtained. No studies examining the utility of EOT blood supporting that conclusion do exist for other infections [12], cultures were identified. then higher levels of adherence with IE guidelines are desirable. Several survey questions addressed the preferred antimicro- This survey was developed to provide a “snapshot” of adherence bial therapy for specific organisms. For NVE due to MSSA, with selected IE guidelines by a representative sample of prac- monotherapy was viewed as adequate, which conforms with ticing ID clinicians in North America. recommendations [2, 3]. Eighty-nine percent of respondents As this survey reflects, general approaches to diagnosing and expressed confidence with cefazolin as monotherapy for MSSA managing IE vary and may not conform strictly with published NVE, which is listed as an alternative for penicillin-allergic guidelines [2, 3]. AHA guidelines recommend ID consultation patients in US guidelines [2] but is not mentioned as an op- for every suspected case of IE [2]. However, 20% of practitioners tion in European guidelines [3]. Of note, a recent study raised indicated that all cases of IE were not seen by ID at their hos- questions about using cefazolin in high-inoculum infections pitals. That “selective” approach is perhaps consistent with ESC such as IE [16]. Even though both AHA and ESC guidelines guidelines, which suggest that patients with “noncomplicated” recommend initial triple therapy, which includes rifampin and IE can be managed initially at nonreference centers [3]. Even an aminoglycoside, for staphylococcal PVE [2, 3], 34% of re- though no study has specifically evaluated the impact of ID spondents did not use an aminoglycoside in that setting. Based consultation on IE outcomes, numerous studies have demon- on those results, it might be concluded that aminoglycoside strated benefits of ID consultation for complex infections [13], therapy for staphylococcal PVE is perhaps “falling out of favor.” and IE is certainly 1 such infection. Only 17% of respondents A  recent retrospective study from Spain [17] and a narrative reported that cardiothoracic surgery was routinely consulted review from France [18] both suggested that aminoglycoside for every case of IE. Both AHA and ESC guidelines emphasize use in staphylococcal PVE may not be necessary. In contrast a multidisciplinary “team” approach, typically involving cardio- to the tepid embrace of aminoglycosides for staphylococcal thoracic surgery [2, 3]. Whether that implies that preemptive PVE, 91% of those surveyed reported using rifampin. Both 4 • ofid • Huang et al Ramos-Martinez et  al. [17] and Lebeaux and colleagues [18] asked whether postoperative treatment should be that utilized endorsed rifampin as the critical component of combination for NVE or for PVE. Fifty-five percent chose to treat for PVE, therapy for staphylococcal PVE. whereas 33% elected to treat as NVE. Although not oer ff ing a As reflected by this survey, therapy for enterococcal IE formal recommendation for that scenario, the AHA states that has undergone a notable evolution over the past decade. there is a lack of consensus as to whether the postsurgical reg- Aminoglycoside-containing regimens have long been the cor- imen should be the one for PVE or NVE in patients who un- nerstone for treating enterococcal IE [2], and both US and dergo implantation of prosthetic valves during treatment for European guidelines still have a β-lactam plus gentamicin as the active IE [2]. In contrast, the ESC indicates that the postoper- “first” regimen listed in their tables outlining therapy for enter - ative regimen should be that recommended for NVE, not for ococcal strains susceptible to both penicillin and gentamicin [2, PVE [3]. A  retrospective review from the Mayo Clinic exam- 3]. However, double β-lactam regimens are included as an ac- ining that issue concluded that cure rates were similar whether ceptable alternative based on accumulating evidence that sup- an NVE or PVE regimen was utilized postoperatively [24]. ports the efficacy and safety of that regimen for enterococcal This survey had strengths as well as limitations. Strengths of IE [19, 20]. It should be noted, however, that data from pro- the survey included the geographic diversity of the respondents spective clinical trials comparing β-lactam + aminoglycoside and the good response rate. Factors perhaps contributing to the therapy with A + C for the treatment of enterococcal IE are not above-average response rate were the use of a defined popula- currently available. In this survey of US and Canadian phys- tion of ID clinicians assembled from a professional organization icians, the combination of A + C was preferred by the majority who “agreed” to participate in surveys through membership in of respondents for treating enterococcal IE. In contrast, only the EIN and the topic itself, which apparently resonated with 16% of ID clinicians “usually” or “almost always” treated enter- the respondents because of its timeliness [4, 5] and the asso- ococcal IE with penicillin plus an aminoglycoside. Forty-seven ciated challenges in management [6, 7]. Limitations were sev- percent of respondents felt comfortable using A + C for any en- eral. First, it was restricted to ID clinicians in the United States terococcal species (not just E. faecalis), and 76% utilized A + C and Canada and did not include colleagues in other parts of the for both NVE and PVE. Use of A + C for all enterococcal species world whose use of guidelines may differ from practices in North is counter to ESC recommendations, which suggest that A + C America. Second, the survey was based upon self-reported data should NOT be used for E. faecium IE given the high likelihood from a subset of voluntary respondents who may not be repre- of ampicillin resistance [3]. sentative of the larger group of ID clinicians in the United States e c Th ase scenarios attempted to address management di- and Canada as a whole, thus leading to possible selection bias. lemmas that arise in patients who undergo valve replacement Response bias is a third concern, as survey answers may not ac- during active IE. In the first, the patient underwent mitral valve curately reflect practice patterns in all geographic areas. Fourth, replacement aer co ft mpleting 2 weeks of preoperative antibi- it is conceivable that respondents answered questions based otic therapy with 1 week of negative blood cultures before sur- upon their knowledge of the guidelines rather than their actual gery and negative surgical cultures. Five weeks was the most clinical practice, which was not the intent of the survey. Fifth, commonly selected duration for postoperative antimicrobial the survey focused primarily upon intravenous antimicrobial therapy and is consistent with AHA and ESC recommendations therapy for IE and did not explore the rapidly evolving use of [2, 3] but responses were quite varied. The diversity of opin- oral regimens for IE [25]. Last, the timing of the survey coin- ions likely reflects the limited evidence available to inform de- cided with onset of the COVID-19 pandemic, which may have cision-making. Studies by Morris and colleagues [21], Munoz limited participation. et al. [22], and Rao et al. [23] all concluded that 2–3 weeks of Needless to say, there are numerous other questions per- therapy aer s ft urgery was probably sufficient for most patients taining to the management of IE that were not addressed by if surgical cultures were negative. However, the AHA opted for the current survey [6]. For example, what criteria could be used a more conservative approach, stating that it was reasonable to to determine which patients might benefit from early cardio- count the days of therapy given preoperatively in the overall du- vascular surgery consultation? Should neuroimaging be per- ration of treatment for culture-negative patients [2]. Similarly, formed before valve replacement surgery in all patients or only the ESC indicated that the duration of treatment was based in selected patients, and if the latter, which patients? Is there a upon the first day of effective antibiotic therapy, which was usu- role for anticoagulation in managing patients with IE? Do alter- ally the date of the first negative blood culture [3]. native cardiac imaging modalities such as high-resolution car- In the second scenario, surgical cultures were positive at valve diac computed tomography or positron emission tomography replacement surgery. Most respondents (86%) administered 6 scanning oer a ff ny diagnostic advantages beyond echocardiog- additional weeks of therapy postoperatively, an approach con- raphy? Which patients are appropriate for outpatient parenteral sistent with both AHA and ESC guidelines [2, 3]. As an ad- antibiotic therapy or oral step-down therapy? Additionally, a ditional decision point in the second case, respondents were number of responses in the current survey might benefit from Infective Endocarditis Guidelines • ofid • 5 complications: a scientific statement for healthcare professionals from the further clarification. For example, what are the impediments to American Heart Association. Circulation 2015; 132:1435–86. establishing endocarditis teams? Why is TEE utilized less fre- 3. Habib  G, Lancellotti  P, Antunes  MJ, et  al. ESC guidelines for the management quently than might be expected? Why is A  + C used to treat of infective endocarditis. The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Eur Heart J 2015; non-faecalis enterococcal IE? A  future follow-up survey could 36:3075–23. possibly be a useful tool for further defining the basis for clin- 4. Pant S, Patel NJ, Deshmukh A, et al. Trends in infective endocarditis incidence, microbiology, and valve replacement in the United States from 2000 to 2011. J Am ical practices that are not guideline-adherent. Coll Cardiol 2015; 65:2070–6. In conclusion, this survey oer ff ed interesting insights about 5. Dayer  MJ, Jones  S, Prendergast  B, et  al. Incidence of infective endocarditis in England, 2000-13: a secular trend, interrupted time-series analysis. Lancet 2015; management of IE by ID clinicians in the United States and 385:1219–28. Canada. Importantly, guideline adherence appeared to be sub- 6. Wang  A, Gaca  JG, Chu  VH. Management considerations in infective endocar- ditis: a review. JAMA 2018; 320:72–83. optimal, as 20% of respondents reported that ID did not eval- 7. Cahill TJ, Baddour LM, Habib G, et al. Challenges in infective endocarditis. J Am uate all suspected cases of IE and 13% did not recommend TTE Coll Cardiol 2017; 69:325–44. for all IE patients. Those 2 guidelines are perhaps “essential,” 8. Fanaroff  AC, Califf  RM, Windecker  S, et  al. Levels of evidence supporting American College of Cardiology/American Heart Association and European so adherence at levels below 90% is concerning. Second, even Society of Cardiology guidelines, 2008–2018. JAMA 2019; 321:1069–80. though a “team” approach to IE management is generally em- 9. Arts DL, Voncken AG, Medlock S, et al. Reasons for intentional guideline non- adherence: a systematic review. Int J Med Inform 2016; 89:55–62. braced as an important principle, only 6% of respondents indi- 10. Pillai  SK, Beekmann  SE, Santibanez  S, Polgreen  PM. The Infectious Diseases cated that their hospitals had a designated endocarditis team. Society of America Emerging Infections Network: bridging the gap between clin- ical infectious diseases and public health. Clin Infect Dis 2014; 58:991–6. Third, it appears that aminoglycoside use in IE is declining and 11. Tissot-Dupont H, Casalta JP, Gouriet F, et al. International experts’ practice in the that double β-lactam therapy is the preferred treatment for en- antibiotic therapy of infective endocarditis is not following the guidelines. Clin Microbiol Infect 2017; 23:736–9. terococcal IE. Last, duration of postoperative therapy for pa- 12. Wilke  M, Grube  RF, Bodmann  KF. Guideline-adherent initial intravenous anti- tients undergoing valve replacement during acute IE remains biotic therapy for hospital-acquired/ventilator-associated pneumonia is clinically unclear and represents an area for additional investigation. superior, saves lives and is cheaper than non guideline adherent therapy. Eur J Med Res 2011; 16:315–23. 13. Bai  AD, Showler  A, Burry  L, et  al. Impact of infectious disease consultation on Supplementary Data quality of care, mortality, and length of stay in Staphylococcus aureus bacteremia: Supplementary materials are available at Open Forum Infectious results from a large multicenter cohort study. Clin Infect Dis 2015; 60:1451–61. Diseases online. Questions or comments should be addressed to the 14. Botelho-Nevers  E, Thuny  F, Casalta  JP, et  al. Dramatic reduction in infective corresponding author. endocarditis-related mortality with a management-based approach. Arch Intern Med 2009; 169:1290–8. 15. Virk A, Schutte KM, Steckelberg JM, et al. End-of-therapy echocardiography may Acknowledgments not be needed in all patients with endocarditis. Open Forum Infect Dis 2020; e a Th uthors wish to provide a heartfelt thanks to all the members of the 7:XXX–XX. Infectious Diseases Society of America’s Emerging Infections Network who 16. Miller WR, Soas C, Carvajal LP, et al. The cefazolin inoculum effect is associated participated in the survey. with increased mortality in methicillin-susceptible Staphylococcus aureus bacte- remia. Open Forum Infect Dis 2018; 5:XXX–XX. Financial support. This work was supported by Cooperative 17. Ramos-Martínez  A, Muñoz  Serrano  A, de  Alarcón  González  A, et  al; Spanish Agreement Number 1 U50 CK00477, funded by the Centers for Disease Collaboration on Endocarditis—Grupo de Apoyo al Manejo de la Endocarditis Control and Prevention. Infecciosa en España (GAMES). Gentamicin may have no effect on mortality of Disclaimer. e fin Th dings and conclusions presented in this manuscript staphylococcal prosthetic valve endocarditis. J Infect Chemother 2018; 24:555–62. are those of the authors and do not necessarily represent the views of the US 18. Lebeaux D, Fernandez-Hidalgo N, Pilmis B, et al. Aminoglycosides for infective Centers for Disease Control and Prevention or the Department of Health endocarditis: time to say goodbye? Clin Microbiol Infect 2020; 26:723–8. and Human Services. 19. Pericas JM, Cervera C, del Rio A, et al. Changes in the treatment of Enterococcus Potential coni fl cts of interest. J.E.P. owns common stock in Pfizer, Inc. faecalis infective endocarditis in Spain in the last 15 years: from ampicillin plus All other authors report no conflicts. All authors have submitted the ICMJE gentamicin to ampicillin plus ceftriaxone. Clin Microbiol Infect 2014; 20:1075–83. 20. El  Rafei  A, DeSimone  DC, Narichania  AD, et  al. Comparison of dual β-lactam Form for Disclosure of Potential Conflicts of Interest. Conflicts that the edi- therapy to penicillin-aminoglycoside combination in treatment of Enterococcus tors consider relevant to the content of the manuscript have been disclosed. faecalis infective endocarditis. J Infect 2018; 77:398–404. Author contributions. Concept/design: Peacock. Data analysis/in- 21. Morris AJ, Drinković D, Pottumarthy S, et al. Bacteriological outcome after valve terpretation: Beekmann, Polgreen, Peacock. Drafting article: Peacock, surgery for active infective endocarditis: implications for duration of treatment Huang. Critical revision of article: All authors. Approval of article: All au- after surgery. Clin Infect Dis 2005; 41:187–94. thors. Statistics: Beekmann. Funding secured by: Polgreen. Data collection: 22. Muñoz  P, Giannella  M, Scoti  F, et  al; Group for the Management of Infective Beekmann, Polgreen, EIN. Endocarditis of the Gregorio Marañón Hospital (GAME). 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Council on Cardiovascular Surgery and Anesthesia, and Stroke Council. Infective 25. Iversen  K, Ihlemann  N, Gill  SU, et  al. Partial oral versus intravenous antibiotic endocarditis in adults: diagnosis, antimicrobial therapy, and management of treatment of endocarditis. N Engl J Med 2019; 380:415–24. 6 • ofid • Huang et al http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Open Forum Infectious Diseases Oxford University Press

Infective Endocarditis Guidelines: The Challenges of Adherence—A Survey of Infectious Diseases Clinicians

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Oxford University Press
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© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
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2328-8957
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10.1093/ofid/ofaa342
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applyparastyle “fig//caption/p[1]” parastyle “FigCapt” Open Forum Infectious Diseases MAJOR ARTICLE Infective Endocarditis Guidelines: The Challenges of Adherence—A Survey of Infectious Diseases Clinicians 1 2 3 4 5 5 4, Glen Huang, Siddhi Gupta, Kyle A. Davis, Erin W. Barnes, Susan E. Beekmann, Philip M. Polgreen, and James E. Peacock Jr. 1 2 Infectious Diseases, Department of Internal Medicine, University of California Los Angeles, Los Angeles, California, USA, Infectious Diseases, Department of Internal Medicine, Wake Forest 3 4 Baptist Health, Winston-Salem, North Carolina, USA, Department of Pharmacy, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA, Section on Infectious Diseases, Department of Internal Medicine, Wake Forest Baptist Health, Winston-Salem, North Carolina, USA, and Emerging Infections Network, University of Iowa, Iowa City, Iowa, USA Background. Guidelines exist to aid clinicians in managing patients with infective endocarditis (IE), but the degree of adherence with guidelines by Infectious Disease (ID) physicians is largely unknown. Methods. An electronic survey assessing adherence with selected IE guidelines was emailed to 1409 adult ID physician members of the Infectious Diseases Society of America’s Emerging Infections Network. Results. Five hundred fifty-seven physicians who managed IE responded. Twenty percent indicated that ID was not consulted on every case of IE at their hospitals, and 13% did not recommend transthoracic echocardiography (TTE) for all IE cases. The dura- tion of antimicrobial therapy was timed from the first day of negative blood cultures by 91% of respondents. Thirty-four percent of clinicians did not utilize an aminoglycoside for staphylococcal prosthetic valve IE (PVE). Double β-lactam therapy was “usually” or “almost always” employed by 83% of respondents for enterococcal IE. For patients with active IE who underwent valve replacement and manifested positive surgical cultures, 6 weeks of postoperative antibiotics was recommended by 86% of clinicians. Conclusions. e fin Th ding that adherence was <90% with core guideline recommendations that all patients with suspected IE be seen by ID and that all patients undergo TTE is noteworthy. Aminoglycoside therapy of IE appears to be declining, with double β-lactam regi- mens emerging as the preferred treatment for enterococcal IE. The duration of postoperative antimicrobial therapy for patients undergoing valve replacement during acute IE is poorly defined and represents an area for which additional evidence is needed. Keywords. infective endocarditis; guidelines; management; adherence; clinical practice. Guidelines for managing infective endocarditis (IE) were first exist: (1) Multiple guidelines are available, some of which oer ff introduced by the American Heart Association (AHA) in 1989 differing recommendations, thus leading to confusion rather [1], with the most recent update in 2015 [2]. The European than clarity in their application. (2) Guidelines have evolved Society of Cardiology (ESC) has developed similar guidelines from succinct, “bullet-point” documents to voluminous works [3]. The goal of both documents is to facilitate application of that are oen ft challenging to read. (3) Healthy skepticism exists knowledge and best practices for diagnosing and managing IE. about the level of evidence in many guidelines, as consensus ex- Rates of IE have recently increased in the United States and pert opinion, case series, and/or standard of care form the basis globally [4, 5]. As IE has become resurgent, old challenges in pro- for some recommendations [8]. In the 2015 AHA document, 81 viding care have resurfaced and new management dilemmas have (58.7%) of 138 recommendations were Level C in quality [2]. (4) emerged [6, 7]. Guidelines exist to address clinical uncertainties Practitioners realize that guidelines do not always reflect realities and to inform practice. However, based on our observations, of clinical practice and that compromises in care must be made, there appears to be substantial practice variation in the applica- sometimes in response to patient preferences [9]. tion of guidelines to the diagnosis and management of adult pa- Accepting the conclusion that guidelines are important ad- tients with IE. Several potential obstacles to guideline adherence juncts in management, our goal was to better understand current clinical practices in the care of patients with IE. Accordingly, we developed a survey to assess adherence to selected guidelines Received 10 June 2020; editorial decision 31 July 2020; accepted 21 August 2020. for managing IE in adults, as outlined in recent AHA and ESC Correspondence: James E.  Peacock, Jr., MD, Section on Infectious Diseases, Department documents [2, 3]. of Internal Medicine, Wake Forest Baptist Health, Winston-Salem, NC 27157 (jpeacock@ wakehealth.edu). Open Forum Infectious Diseases METHODS © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative An electronic survey consisting of 17 multiple-choice ques- Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/ by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any tions and 2 case scenarios (Supplementary Figure 1) was sent medium, provided the original work is not altered or transformed in any way, and that the to physician members of the Infectious Diseases Society of work is properly cited. For commercial re-use, please contact journals.permissions@oup.com. America’s Emerging Infections Network (EIN) [10] with adult DOI: 10.1093/ofid/ofaa342 Infective Endocarditis Guidelines • ofid • 1 ID practices in the United States, Puerto Rico, and Canada. No other significant differences were identified. Of the 631 re- The EIN is funded by the Centers for Disease Control and spondents, 74 (12%) indicated that they did not manage IE, so Prevention to serve as a provider-based surveillance net- they opted out. work for emerging infections and related phenomena. Approximately 20% of ID physicians in clinical practice in General Approaches to the Diagnosis and Management of IE the United States volunteer as EIN members. The survey was Eighty percent of respondents indicated that ID was consulted distributed by email or facsimile on February 12, 2020, with for every suspected case of IE, whereas Cardiothoracic Surgery 2 reminders at weekly intervals for nonrespondents. An opt- was consulted in only a minority of cases (17%) (Figure  1). out option was provided for those who indicated that they A designated endocarditis team existed in only 6% of hospitals. did not manage IE. Respondents were not required to an- Transthoracic echocardiography (TTE) was recommended by swer all questions, so total responses for individual questions most clinicians (87%) for all cases of IE, while only 32% of re- varied. As used in the survey, the term “some” implied <50%, spondents ordered transesophageal echocardiography (TEE) “usually” equated to 50–90%, and “almost always” referred for all IE cases. In patients with positive blood cultures, most to >90% of the time. EIN staff tabulated responses and ana- respondents (95%, 530/557) repeated cultures until negative. lyzed data. Categorical variables were compared using a χ The duration of antimicrobial therapy was generally timed from test or Fisher exact test with SAS, version 9.4 (Cary, NC). P the first day on which blood cultures were negative (91% of re- values <.05 were considered significant. spondents; 508/557). RESULTS End-of-Therapy Management Participant Characteristics End-of-therapy (EOT) echocardiography was recommended by Of 1409 active EIN physician members, 631 (45%) responded 44% of respondents, with 89% recommending TTE and 11% to the survey. Respondents were significantly more likely than TEE (Figure 1). EOT blood cultures were ordered by 181 (32%) nonrespondents to have ≥25 years of ID experience (P < .0001) physicians, with the timing of those blood cultures ranging and to be employed by a Veterans Affairs hospital (P = .009). from 48 hours to 6 weeks. Recognized risk factors for relapse General approaches to the diagnosis and management of IE (n = 557) 95%, 530 91%, 508 87%, 485 80%, 444 44%, 247 32%, 181 32%, 177 17%, 97 6%, 33 ID consulted Cardiothoracic Hospital IE TTE on all TEE on all Daily blood Duration of End of End of therapy on surgery team cases of IE cases of IE culture antibiotics, start therapy blood cultures every case consulted at first day of echocardiogram negative blood cultures Figure 1. General approaches to the diagnosis and management of infective endocarditis. Abbreviations: ID, Infectious Diseases; IE, infective endocarditis; TEE, transesophageal echocardiogram; TTE, transthoracic echocardiogram. 2 • ofid • Huang et al such as endovascular hardware, specific pathogens (ie, S.  au- indicated that they used an aminoglycoside as a component of reus), or delayed response to therapy were the identified indica- combination therapy for staphylococcal prosthetic valve endo- tions for EOT cultures. carditis (PVE). The specifics of aminoglycoside usage in this setting are shown in Table  1. For enterococcal IE, 83% of re- Treatment of Specific Pathogens Causing IE spondents (n = 461/557) stated that they “usually” (27%) or “al- For treatment of native valve IE (NVE) due to methicillin- most always” (56%) employed ampicillin and ceftriaxone (A + susceptible S. aureus (MSSA), only 4% of respondents preferred C) as their regimen of choice (Figure 2). Conversely, only 16% combination antimicrobial therapy (Table 1). When queried as selected traditional treatment with penicillin (or ampicillin or to whether cefazolin monotherapy was adequate for MSSA IE, vancomycin) plus an aminoglycoside as their preferred (“usu- 89% of respondents replied affirmatively. Only 66% of physicians ally” or “almost always”) therapy. If an aminoglycoside was used, 60% treated for 2 weeks only, whereas 39% selected 4–6 weeks. For those practitioners utilizing A + C for enterococcal Table 1. Treatment of Specific Pathogens Causing Infective IE, 44% restricted usage to E. faecalis only, while 47% used A + Endocarditis C for any enterococcal species. Seventy-six percent of respond- ents employed A + C for both NVE and PVE, whereas 17% lim- Yes, No, No Answer, ited usage to NVE only. Pathogen/Type Infective Endocarditis No. (%) No. (%) No. (%) Methicillin-susceptible Staphylococcus Case Scenarios aureus native valve IE Is combination antimicrobial therapy 23 (4) 527 (95) 7 (1) In scenario #1, a patient with mitral NVE due to methicillin- used for treatment? resistant S. aureus (MRSA) underwent valve replacement. At the Is cefazolin monotherapy adequate? 487 (89) 54 (10) 6 (1) time of surgery, 2 full weeks of therapy had been completed, 1 Enterococcal IE week of which was after bacteremia cleared. Surgical gram stain Preferred treatment (usually + almost always) β-lactam or vancomycin + 90 (16) 411 (74) 56 (10) aminoglycoside (Penicillin or Ampicillin or Vancomycin) + Ampicillin + ceftriaxone 461 (83) 92 (17) 4 (1) Aminoglycoside Do you ever use an aminoglycoside? 416 (75) 141 (25) — 23, 4% If used, what is the aminoglycoside 56, duration? 10% 2 wk 251 (60) 4–6 wk 161 (39) 67, 12% If an aminoglycoside is used, do you 177 (42) 222 (54) 17 (4) obtain a baseline audiogram? 411, 74% If you treat with A + C, is it used for: Only Enterococcus faecalis 240 (44) Any Enterococcus species 259 (47) Native valve IE only 92 (17) Prosthetic valve IE only 5 (1) Some Usually Almost always Not answered Both native and prosthetic valve IE 417 (76) (<50%) (50%–90%) (>90%) Staphylococcal prosthetic valve IE Ampicillin + Ceftriaxone Do you use an aminoglycoside for treat- 369 (66) 188 (34) ment? 4, 1% What aminoglycoside dosage is used? 3 mg/kg/d 311 (84) 5–8 mg/kg/d 39 (11) 92, 16% How do you dose the aminoglycoside? Once daily 168 (46) In divided doses 183 (50) 151, 27% How many patients complete 2 weeks? 310, 56% Some (<50%) 76 (21) Usually (50%–90%) 204 (55) Almost always (>90%) 70 (19) What dose of rifampin is used? 300 mg 2×/d 308 (55) 300 mg 3×/d 166 (30) Some Almost always Not answered Usually Other 31 (6) (<50%) (50%–90%) (>90%) Do not use 39 (7) Abbreviations: A + C, ampicillin + ceftriaxone; IE, infective endocarditis. Figure 2. Treatment strategies in enterococcal endocarditis. Infective Endocarditis Guidelines • ofid • 3 and culture were negative. Survey participants were asked how cardiothoracic surgery consultation should be obtained for all long they would continue antibiotics postoperatively. Responses patients is not addressed. Several publications have examined were diverse, with 9% choosing 2 weeks, 30% selecting 4 weeks, the benefits of an “endocarditis team,” with a general consensus 39% electing 5 weeks, and 20% treating for 6 weeks. that those teams favorably impact IE-related mortality [14]. e Th clinical features of scenario #2 were identical to #1, ex- Despite the enthusiasm for endocarditis teams in Europe, only cept that surgical cultures grew MRSA. In that scenario, 86% of 6% of US and Canadian respondents indicated that their pri- respondents chose to treat for 6 weeks aer s ft urgery. As an addi- mary hospital had such a team. In terms of routine diagnostic tional query, it was asked if respondents would treat the patient testing, 87% of respondents recommended TTE for all patients postoperatively for NVE or PVE as the prosthesis potentially with IE, which is in keeping with both US and European guide- was placed in an “infected” field. Fifty-five percent elected to lines [2, 3]. For patients with positive blood cultures, 95% of manage the patient for PVE, 33% opted for an NVE regimen, respondents repeated blood cultures on a daily or every-other- and 11% were unsure. day basis until negative, though that recommendation is not specifically delineated in the guidelines [2, 3]. Ninety-one per- cent of clinicians dated the duration of therapy as beginning on DISCUSSION the first day on which blood cultures were negative, an approach Despite decades of clinical experience and availability of guide- consistent with both US and European recommendations [2, 3]. lines since 1989 [1], management dilemmas continue to chal- EOT management of IE is largely nonstandardized. Both lenge clinicians caring for patients with IE [6, 7]. Guidelines the AHA and ESC recommend an EOT echocardiogram [2, 3] are designed to assist clinicians with meeting those challenges though the recommendation from the ESC is “stronger.” In our and, accordingly, are updated regularly [2, 3]. However, AHA survey cohort, 44% of respondents recommended EOT ech- IE guidelines are qualified by the statement that “recommenda- ocardiography, 89% of whom suggested TTE. A  recent study tions be used to support and not supplant decisions in individual by Virk et al. reported that 73% of their IE patients underwent patient management” [2]. That statement tacitly acknowledges EOT echocardiography [15]. Those authors suggested that EOT that information used to formulate guidelines may change rap- echocardiography could perhaps be targeted toward patients idly and that guidelines may reflect expert opinion rather than with new or worsening symptoms/signs at the EOT evaluation. evidence derived from clinical trials [8]. Given those limita- Whereas the AHA does not recommend routine EOT blood tions, the degree of adherence with IE guidelines in real-world cultures [2], the ESC indicates that EOT blood cultures should clinical practice may vary. Tissont-Dupont and colleagues be obtained at the initial post-therapy visit [3]. Among ID clin- examined adherence with antibiotic therapy recommendations icians taking our survey, 32% ordered EOT blood cultures, but for IE and found that overall global compliance was only 58% there was no well-defined point at which EOT blood cultures [11]. If guidelines are to improve patient outcomes, and data were obtained. No studies examining the utility of EOT blood supporting that conclusion do exist for other infections [12], cultures were identified. then higher levels of adherence with IE guidelines are desirable. Several survey questions addressed the preferred antimicro- This survey was developed to provide a “snapshot” of adherence bial therapy for specific organisms. For NVE due to MSSA, with selected IE guidelines by a representative sample of prac- monotherapy was viewed as adequate, which conforms with ticing ID clinicians in North America. recommendations [2, 3]. Eighty-nine percent of respondents As this survey reflects, general approaches to diagnosing and expressed confidence with cefazolin as monotherapy for MSSA managing IE vary and may not conform strictly with published NVE, which is listed as an alternative for penicillin-allergic guidelines [2, 3]. AHA guidelines recommend ID consultation patients in US guidelines [2] but is not mentioned as an op- for every suspected case of IE [2]. However, 20% of practitioners tion in European guidelines [3]. Of note, a recent study raised indicated that all cases of IE were not seen by ID at their hos- questions about using cefazolin in high-inoculum infections pitals. That “selective” approach is perhaps consistent with ESC such as IE [16]. Even though both AHA and ESC guidelines guidelines, which suggest that patients with “noncomplicated” recommend initial triple therapy, which includes rifampin and IE can be managed initially at nonreference centers [3]. Even an aminoglycoside, for staphylococcal PVE [2, 3], 34% of re- though no study has specifically evaluated the impact of ID spondents did not use an aminoglycoside in that setting. Based consultation on IE outcomes, numerous studies have demon- on those results, it might be concluded that aminoglycoside strated benefits of ID consultation for complex infections [13], therapy for staphylococcal PVE is perhaps “falling out of favor.” and IE is certainly 1 such infection. Only 17% of respondents A  recent retrospective study from Spain [17] and a narrative reported that cardiothoracic surgery was routinely consulted review from France [18] both suggested that aminoglycoside for every case of IE. Both AHA and ESC guidelines emphasize use in staphylococcal PVE may not be necessary. In contrast a multidisciplinary “team” approach, typically involving cardio- to the tepid embrace of aminoglycosides for staphylococcal thoracic surgery [2, 3]. Whether that implies that preemptive PVE, 91% of those surveyed reported using rifampin. Both 4 • ofid • Huang et al Ramos-Martinez et  al. [17] and Lebeaux and colleagues [18] asked whether postoperative treatment should be that utilized endorsed rifampin as the critical component of combination for NVE or for PVE. Fifty-five percent chose to treat for PVE, therapy for staphylococcal PVE. whereas 33% elected to treat as NVE. Although not oer ff ing a As reflected by this survey, therapy for enterococcal IE formal recommendation for that scenario, the AHA states that has undergone a notable evolution over the past decade. there is a lack of consensus as to whether the postsurgical reg- Aminoglycoside-containing regimens have long been the cor- imen should be the one for PVE or NVE in patients who un- nerstone for treating enterococcal IE [2], and both US and dergo implantation of prosthetic valves during treatment for European guidelines still have a β-lactam plus gentamicin as the active IE [2]. In contrast, the ESC indicates that the postoper- “first” regimen listed in their tables outlining therapy for enter - ative regimen should be that recommended for NVE, not for ococcal strains susceptible to both penicillin and gentamicin [2, PVE [3]. A  retrospective review from the Mayo Clinic exam- 3]. However, double β-lactam regimens are included as an ac- ining that issue concluded that cure rates were similar whether ceptable alternative based on accumulating evidence that sup- an NVE or PVE regimen was utilized postoperatively [24]. ports the efficacy and safety of that regimen for enterococcal This survey had strengths as well as limitations. Strengths of IE [19, 20]. It should be noted, however, that data from pro- the survey included the geographic diversity of the respondents spective clinical trials comparing β-lactam + aminoglycoside and the good response rate. Factors perhaps contributing to the therapy with A + C for the treatment of enterococcal IE are not above-average response rate were the use of a defined popula- currently available. In this survey of US and Canadian phys- tion of ID clinicians assembled from a professional organization icians, the combination of A + C was preferred by the majority who “agreed” to participate in surveys through membership in of respondents for treating enterococcal IE. In contrast, only the EIN and the topic itself, which apparently resonated with 16% of ID clinicians “usually” or “almost always” treated enter- the respondents because of its timeliness [4, 5] and the asso- ococcal IE with penicillin plus an aminoglycoside. Forty-seven ciated challenges in management [6, 7]. Limitations were sev- percent of respondents felt comfortable using A + C for any en- eral. First, it was restricted to ID clinicians in the United States terococcal species (not just E. faecalis), and 76% utilized A + C and Canada and did not include colleagues in other parts of the for both NVE and PVE. Use of A + C for all enterococcal species world whose use of guidelines may differ from practices in North is counter to ESC recommendations, which suggest that A + C America. Second, the survey was based upon self-reported data should NOT be used for E. faecium IE given the high likelihood from a subset of voluntary respondents who may not be repre- of ampicillin resistance [3]. sentative of the larger group of ID clinicians in the United States e c Th ase scenarios attempted to address management di- and Canada as a whole, thus leading to possible selection bias. lemmas that arise in patients who undergo valve replacement Response bias is a third concern, as survey answers may not ac- during active IE. In the first, the patient underwent mitral valve curately reflect practice patterns in all geographic areas. Fourth, replacement aer co ft mpleting 2 weeks of preoperative antibi- it is conceivable that respondents answered questions based otic therapy with 1 week of negative blood cultures before sur- upon their knowledge of the guidelines rather than their actual gery and negative surgical cultures. Five weeks was the most clinical practice, which was not the intent of the survey. Fifth, commonly selected duration for postoperative antimicrobial the survey focused primarily upon intravenous antimicrobial therapy and is consistent with AHA and ESC recommendations therapy for IE and did not explore the rapidly evolving use of [2, 3] but responses were quite varied. The diversity of opin- oral regimens for IE [25]. Last, the timing of the survey coin- ions likely reflects the limited evidence available to inform de- cided with onset of the COVID-19 pandemic, which may have cision-making. Studies by Morris and colleagues [21], Munoz limited participation. et al. [22], and Rao et al. [23] all concluded that 2–3 weeks of Needless to say, there are numerous other questions per- therapy aer s ft urgery was probably sufficient for most patients taining to the management of IE that were not addressed by if surgical cultures were negative. However, the AHA opted for the current survey [6]. For example, what criteria could be used a more conservative approach, stating that it was reasonable to to determine which patients might benefit from early cardio- count the days of therapy given preoperatively in the overall du- vascular surgery consultation? Should neuroimaging be per- ration of treatment for culture-negative patients [2]. Similarly, formed before valve replacement surgery in all patients or only the ESC indicated that the duration of treatment was based in selected patients, and if the latter, which patients? Is there a upon the first day of effective antibiotic therapy, which was usu- role for anticoagulation in managing patients with IE? Do alter- ally the date of the first negative blood culture [3]. native cardiac imaging modalities such as high-resolution car- In the second scenario, surgical cultures were positive at valve diac computed tomography or positron emission tomography replacement surgery. Most respondents (86%) administered 6 scanning oer a ff ny diagnostic advantages beyond echocardiog- additional weeks of therapy postoperatively, an approach con- raphy? Which patients are appropriate for outpatient parenteral sistent with both AHA and ESC guidelines [2, 3]. As an ad- antibiotic therapy or oral step-down therapy? Additionally, a ditional decision point in the second case, respondents were number of responses in the current survey might benefit from Infective Endocarditis Guidelines • ofid • 5 complications: a scientific statement for healthcare professionals from the further clarification. For example, what are the impediments to American Heart Association. Circulation 2015; 132:1435–86. establishing endocarditis teams? Why is TEE utilized less fre- 3. Habib  G, Lancellotti  P, Antunes  MJ, et  al. ESC guidelines for the management quently than might be expected? Why is A  + C used to treat of infective endocarditis. The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Eur Heart J 2015; non-faecalis enterococcal IE? A  future follow-up survey could 36:3075–23. possibly be a useful tool for further defining the basis for clin- 4. Pant S, Patel NJ, Deshmukh A, et al. Trends in infective endocarditis incidence, microbiology, and valve replacement in the United States from 2000 to 2011. J Am ical practices that are not guideline-adherent. Coll Cardiol 2015; 65:2070–6. In conclusion, this survey oer ff ed interesting insights about 5. Dayer  MJ, Jones  S, Prendergast  B, et  al. Incidence of infective endocarditis in England, 2000-13: a secular trend, interrupted time-series analysis. Lancet 2015; management of IE by ID clinicians in the United States and 385:1219–28. Canada. Importantly, guideline adherence appeared to be sub- 6. Wang  A, Gaca  JG, Chu  VH. Management considerations in infective endocar- ditis: a review. JAMA 2018; 320:72–83. optimal, as 20% of respondents reported that ID did not eval- 7. Cahill TJ, Baddour LM, Habib G, et al. Challenges in infective endocarditis. J Am uate all suspected cases of IE and 13% did not recommend TTE Coll Cardiol 2017; 69:325–44. for all IE patients. Those 2 guidelines are perhaps “essential,” 8. Fanaroff  AC, Califf  RM, Windecker  S, et  al. Levels of evidence supporting American College of Cardiology/American Heart Association and European so adherence at levels below 90% is concerning. Second, even Society of Cardiology guidelines, 2008–2018. JAMA 2019; 321:1069–80. though a “team” approach to IE management is generally em- 9. Arts DL, Voncken AG, Medlock S, et al. Reasons for intentional guideline non- adherence: a systematic review. Int J Med Inform 2016; 89:55–62. braced as an important principle, only 6% of respondents indi- 10. Pillai  SK, Beekmann  SE, Santibanez  S, Polgreen  PM. The Infectious Diseases cated that their hospitals had a designated endocarditis team. Society of America Emerging Infections Network: bridging the gap between clin- ical infectious diseases and public health. Clin Infect Dis 2014; 58:991–6. Third, it appears that aminoglycoside use in IE is declining and 11. Tissot-Dupont H, Casalta JP, Gouriet F, et al. International experts’ practice in the that double β-lactam therapy is the preferred treatment for en- antibiotic therapy of infective endocarditis is not following the guidelines. Clin Microbiol Infect 2017; 23:736–9. terococcal IE. Last, duration of postoperative therapy for pa- 12. Wilke  M, Grube  RF, Bodmann  KF. Guideline-adherent initial intravenous anti- tients undergoing valve replacement during acute IE remains biotic therapy for hospital-acquired/ventilator-associated pneumonia is clinically unclear and represents an area for additional investigation. superior, saves lives and is cheaper than non guideline adherent therapy. Eur J Med Res 2011; 16:315–23. 13. Bai  AD, Showler  A, Burry  L, et  al. Impact of infectious disease consultation on Supplementary Data quality of care, mortality, and length of stay in Staphylococcus aureus bacteremia: Supplementary materials are available at Open Forum Infectious results from a large multicenter cohort study. Clin Infect Dis 2015; 60:1451–61. Diseases online. Questions or comments should be addressed to the 14. Botelho-Nevers  E, Thuny  F, Casalta  JP, et  al. Dramatic reduction in infective corresponding author. endocarditis-related mortality with a management-based approach. Arch Intern Med 2009; 169:1290–8. 15. Virk A, Schutte KM, Steckelberg JM, et al. End-of-therapy echocardiography may Acknowledgments not be needed in all patients with endocarditis. Open Forum Infect Dis 2020; e a Th uthors wish to provide a heartfelt thanks to all the members of the 7:XXX–XX. Infectious Diseases Society of America’s Emerging Infections Network who 16. Miller WR, Soas C, Carvajal LP, et al. The cefazolin inoculum effect is associated participated in the survey. with increased mortality in methicillin-susceptible Staphylococcus aureus bacte- remia. Open Forum Infect Dis 2018; 5:XXX–XX. Financial support. This work was supported by Cooperative 17. Ramos-Martínez  A, Muñoz  Serrano  A, de  Alarcón  González  A, et  al; Spanish Agreement Number 1 U50 CK00477, funded by the Centers for Disease Collaboration on Endocarditis—Grupo de Apoyo al Manejo de la Endocarditis Control and Prevention. Infecciosa en España (GAMES). Gentamicin may have no effect on mortality of Disclaimer. e fin Th dings and conclusions presented in this manuscript staphylococcal prosthetic valve endocarditis. J Infect Chemother 2018; 24:555–62. are those of the authors and do not necessarily represent the views of the US 18. Lebeaux D, Fernandez-Hidalgo N, Pilmis B, et al. Aminoglycosides for infective Centers for Disease Control and Prevention or the Department of Health endocarditis: time to say goodbye? Clin Microbiol Infect 2020; 26:723–8. and Human Services. 19. Pericas JM, Cervera C, del Rio A, et al. Changes in the treatment of Enterococcus Potential coni fl cts of interest. J.E.P. owns common stock in Pfizer, Inc. faecalis infective endocarditis in Spain in the last 15 years: from ampicillin plus All other authors report no conflicts. All authors have submitted the ICMJE gentamicin to ampicillin plus ceftriaxone. Clin Microbiol Infect 2014; 20:1075–83. 20. El  Rafei  A, DeSimone  DC, Narichania  AD, et  al. 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Journal

Open Forum Infectious DiseasesOxford University Press

Published: Aug 24, 2020

Keywords: infective endocarditis; guidelines; management; adherence; clinical practice

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