Infectious disease management of Staphylococcus aureus bacteremia (SAB) was surveyed through the Emerging Infections Network. While there were areas of consensus, we found substantial practice variation in diagnostic evaluation and management of adult patients with SAB. These findings highlight opportunities for further research and guidance to define best practices

Beekmann, Susan E.

Chambers, Henry F.

Liu, Catherine

Polgreen, Philip M.

Strnad, Luke

English

Infectious disease management of Staphylococcus aureus bacteremia (SAB) was surveyed through the Emerging Infections Network. Although there were areas of consensus, we found substantial practice variation in diagnostic evaluation and management of adult patients with SAB. These findings highlight opportunities for further research and guidance to define best practices

Beekmann, Susan E

Polgreen, Philip M

Chambers, Henry F

eScholarship - University of California

UCSFUC San Francisco Previously Published WorksTitleClinical Practice Variation Among Adult Infectious Disease Physicians in the Management of Staphylococcus aureus BacteremiaPermalinkhttps://escholarship.org/uc/item/9ww2208bJournalClinical Infectious Diseases, 69(3)ISSN1058-4838AuthorsLiu, CatherineStrnad, LukeBeekmann, Susan Eet al.Publication Date2019-07-18DOI10.1093/cid/ciy1144 Peer reviewedeScholarship.org Powered by the California Digital LibraryUniversity of CaliforniaB R I E F  R E P O R TClinical Infectious Diseases530 • cid 2019:69 (1 August) • BRIEF REPORTB R I E F  R E P O R T Received 28 October 2018; editorial decision 19 December 2018; accepted 31 December 2018; published online January 2, 2019.Correspondence: C. Liu, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, MS E4-100, Seattle, WA 98109 (catherine.liu@fredhutch.org).Clinical Infectious Diseases®  2019;69(3):530–3© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.DOI: 10.1093/cid/ciy1144Clinical Practice Variation Among Adult Infectious Disease Physicians in the Management of Staphylococcus aureus BacteremiaCatherine Liu,1,2,  Luke Strnad,3,4 Susan E. Beekmann,5,6 Philip M. Polgreen,5,6 and Henry F. Chambers71Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, and 2Division of Allergy and Infectious Diseases, University of Washington, Seattle; 3Division of Infectious Diseases, Oregon Health and Science University, and 4Epidemiology Programs, Oregon Health and Science University–Portland State University School of Public Health, Oregon; 5University of Iowa Carver College of Medicine, Iowa City; 6Emerging Infections Network; and 7Division of Infectious Diseases, San Francisco General Hospital, University of California, San FranciscoInfectious disease management of Staphylococcus aureus bac-teremia (SAB) was surveyed through the Emerging Infections Network. Although there were areas of consensus, we found substantial practice variation in diagnostic evaluation and man-agement of adult patients with SAB. These findings highlight opportunities for further research and guidance to define best practices.Keywords. Staphylococcus aureus; bacteremia; infectious disease physicians.Staphylococcus aureus bacteremia (SAB) is associated with high morbidity, mortality, and healthcare costs [1]. Infectious disease (ID) consultation for SAB has been associated with significant improvement in patient outcomes and increased adherence to best practices in SAB management such as follow-up blood cultures, echocardiography, source identification/control, and appropriate antibiotic therapy [2, 3]. However, little is known about practice patterns among ID physicians in scenarios where data are limited or inconclusive. We distributed a survey to members of the Emerging Infections Network (EIN) to assess physician practices in the management of SAB.METHODSThe Infectious Diseases Society of America’s (IDSA) EIN is a network of practicing ID physicians in the United States and Canada, funded by the Centers for Disease Control and Prevention [4]. We developed an 11-question multiple-choice survey (Supplementary Materials) to assess adult ID specialist opinions and practice patterns in the management of SAB. The EIN distributed the survey via emailed weblink or fac-simile on 5 January 2017. Two reminders at 1-week intervals were provided. Survey responses were analyzed using SAS version 9.4. A  P value of < .05 was considered statistically significant.RESULTSCharacteristics of ParticipantsOf 1286 active EIN physician members with an adult ID prac-tice, 723 (56%) responded to this survey. Respondents (220/723 [30%]) were more likely than nonrespondents (117/563 [21%]) to have ≥25 years of ID experience (P < .0001). No other signif-icant differences were identified. Baseline practice characteris-tics including clinical experience, practice type, and geographic location are provided in Supplementary Table 1. Fifty-four (7%) respondents did not manage SAB and opted out.Diagnostic Evaluation of SABRepeat blood cultures and echocardiography are performed by the majority of respondents (Figure 1A). Most (599/667 [90%]) indicated they would always perform a transthoracic echocardiogram (TTE). Those with <15  years of experi-ence were more likely to always do a TTE (93% vs 86%; P  =  .01). A  transesophageal echocardiogram (TEE) would be performed on every patient with a negative TTE by 126 (19%) of respondents whereas 473 (71%) would only perform TEE under selected circumstances (Figure 1B). Those practicing in the Midwest, Northeast, or South [5] regions were more likely to always perform a TEE compared to those in the West or Canada/Puerto Rico (24% vs 11%; P = .009).Nafcillin or Cefazolin for Methicillin-susceptible Staphylococcus aureus EndocarditisFor treatment of left-sided methicillin-susceptible S.  aureus (MSSA) endocarditis without CNS involvement, 32% chose cefazolin and 29% favored nafcillin, whereas 32% considered the 2 equivalent. Among the 215 who chose cefazolin, 207 pro-vided a rationale, with most citing a combination of equal ef-ficacy, less toxicity, dosing convenience, and cost. Among the 193 who selected nafcillin, 169 provided a rationale, with most citing nafcillin as the “gold standard,” whereas others favored it due to inoculum effect or better CNS penetration for clini-cally silent disease. Those with <5 (vs ≥5) years of experience were more likely to use cefazolin (39% vs 33%) whereas those with ≥15 (vs <15) years of experience were more likely to use nafcillin (37% vs 26%) (P = .048).applyparastyle “fig//caption/p[1]” parastyle “FigCapt”BRIEF REPORT • cid 2019:69 (1 August) • 531Management of Methicillin-resistant S.  aureus Bacteremia and EndocarditisWhen managing a patient with methicillin-resistant S.  au-reus (MRSA) bacteremia and a vancomycin minimum in-hibitory concentration (MIC) of 2  mg/L, a majority (336/665 [51%]) of respondents would treat with vancomycin if clin-ically responding, whereas 248 (37%) favored daptomycin and 29 (4%) chose ceftaroline. Less than 1% of respondents selected linezolid, telavancin, trimethoprim-sulfamethoxazole, or daptomycin plus ceftaroline. Respondents in a university or teaching hospital were more likely to use vancomycin compared with those in a community or Veterans Affairs/Defense Department hospital (55% vs 43%; P = .03).In a patient with MRSA endocarditis and persistent bacte-remia on day 6 of vancomycin, most (504/668 [75%]) would modify therapy. Alternative monotherapy was selected by 245 (37%) respondents whereas 215 (32%) favored combina-tion therapy (Figure 1C). Among those who chose another single agent, 193 (78%) selected daptomycin while 36 (15%) chose ceftaroline. The specific combination of daptomycin and ceftaroline was chosen by 66 (10%). Those practicing in the Midwest were most likely to choose alternative monotherapy (62%). Those in the Northeast and West were most likely to use combination therapy with daptomycin (28%; P = .04), and were more likely to use daptomycin and ceftaroline (15%) compared to those in the Midwest (5%) and South (7%) (P = .004).The daptomycin dose used for MRSA bacteremia varied, with 38%, 43%, and 17% of respondents selecting 6 mg/kg, 8 mg/kg, and 10–12  mg/kg, respectively. Doses of 10–12  mg/kg were most likely to be used in the Northeast and West (21% and 20%, respectively), while 6–8 mg/kg was most likely to be used in the Midwest (91%) (P = .0002).Duration of TherapyMost respondents managed SAB with at least 14 days of intra-venous (IV) antibiotics in several scenarios. In a patient with MRSA bacteremia and a skin and soft tissue source, rapid clear-ance of blood cultures, negative TTE, and no evidence of met-astatic infection, most (491/669 [73%]) would treat with IV vancomycin for 14 days whereas 87 (13%) transitioned to oral antibiotics to complete a 14-day course. A  minority (24/669 [4%]) would treat for 5–7 days with either oral or IV antibiotics while 47 (7%) favored a longer duration of 21–28 days.A) B) C) D) 7644966111519211184216033451048543326691080 100 200 300 400 500 600 700Dilated eye examAbd/pelvis CTSpine MRITTE and/or TEERepeat blood cxNumber of RespondentsAlmost always Usually Sometimes RarelyN=666N=662N=625N=626N=61545%39%81%86%0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%Other clinical factors* (N= 209)Community-onset bacteremia (N=183)Lack of clinical improvement (N=378)Positive repeat blood cultures (N=401)Percentage of Respondents7%14%18%37%24%0% 5% 10% 15% 20% 25% 30% 35% 40%Other (N=44)Change to daptomycin and ADD another MRSAactive agent (N=95)Continue vancomycin and ADD another MRSAactive agent (N=120)Change to another single antibiotic (N=245)Continue vancomycin alonePercentage of Respondents2%16%20%35%48%52%78%84%0% 10% 20% 30% 40% 50% 60% 70% 80% 90%None of the above (N=15)Other (N=109)Diabetes (N=132)Community-onset bacteremia (N=230)Immunosuppressing conditions (N=316)Persistent fevers at 72 hours (N=342)Repeat blood cultures + at 48-96 hrs (N=517)Presence of prosthetic device implant (N=557)Percentage of RespondentsFigure 1. Practice patterns among survey respondents on the diagnostic evalu-ation and management of Staphylococcus aureus bacteremia (SAB). A, Diagnostic workup routinely performed in the evaluation of a patient with SAB. B, Respondents indicating they would perform transthoracic echocardiogram (TTE) on every patient but only perform transesophageal echocardiogram (TEE) under these selected circumstances (n  =  473). C, Management of patient with methicillin-resistant Staphylococcus aureus endocarditis and persistent SAB on day 6 of vancomycin, with therapeutic trough and vancomycin MIC of .5  mg/L. D, Factors influencing decision to extend duration of therapy from 2 weeks to 4–6 weeks assuming negative echocardiography (TTE and/or TEE). Abbreviations: Abd, abdominal; cx, culture; CT, computed tomography; MRI, magnetic resonance imaging; MRSA, methicillin-resistant Staphylococcus aureus; TEE, transesophageal echocardiogram; TTE, transthoracic echocardiogram. *Among 222 respondents who commented on other clinical factors that would prompt TEE, common responses included presence of cardiac device or prosthetic valve (58 [26%]); clinical suspicion for infective en-docarditis including embolic phenomenon or metastatic infection (43 [19%]); or TEE results would change management (eg, duration of therapy, surgical management) (36 [16%]).532 • cid 2019:69 (1 August) • BRIEF REPORTIn a patient with 1 of 2 blood cultures positive for MSSA, no obvious signs or symptoms of infection, a normal white blood cell count, negative repeat blood cultures, negative TTE, and no evidence of metastatic infection, most (445/664 [67%]) respondents would treat with IV antibiotics for 14 days whereas 51 (8%) would treat for 4–6 weeks. A  minority (10%) would consider the cultures a contaminant and stop antibiotics.Most respondents would extend treatment duration to 4–6 weeks in the setting of SAB and a negative echocardiogram for patients with a prosthetic device or positive repeat blood cultures (Figure 1D).Management of Septic ThrombophlebitisMost respondents (467/657 [71%]) recommended anticoagulation in the setting of SAB and peripherally inserted central catheter–associated deep vein thrombosis after catheter removal. Duration of antimicrobial therapy varied with 52% of respondents treating for 4 weeks while 19% chose 2 weeks and 25% chose 6 weeks.DISCUSSIONSAB is a serious disease commonly managed by ID physicians. Most respondents performed repeat blood cultures and echo-cardiography, and treated with IV therapy for at least 14 days. There were some areas of consensus, but this survey highlights considerable practice variation among respondents representing a wide breadth of ID practitioners in North America, including differences by years of experience, geographic region, and prac-tice environment.The IDSA MRSA treatment guidelines recommend echo-cardiography in all patients with SAB, with TEE being the pre-ferred modality due to its greater sensitivity [6]. Although the vast majority of respondents supported TTE as part of the di-agnostic evaluation of SAB, only 19% of respondents indicated they would always perform a TEE. These findings are consistent with other studies that suggest routine use of TEE is infrequent [7]. TEE is an invasive procedure that has complication risks, is resource intensive, and may not be available at all centers. Some studies suggest that TEE may not be necessary for all cases of SAB and that clinical prediction rules may help with risk strat-ification, but these require external validation [8]. The lack of concordance between guideline recommendations and current practice indicates a need for further research and guidance on the role of TEE among patients with SAB.There was lack of consensus regarding the treatment of MSSA endocarditis, with respondents almost evenly dis-tributed among cefazolin, nafcillin, or use of either drug, suggesting the need for evidence-based guidelines to define optimal therapy. Those with fewer years of experience fa-vored cefazolin whereas more experienced clinicians pre-ferred nafcillin. These differences may reflect a growing body of literature suggesting similar clinical outcomes and fewer drug-related adverse events with the use of cefazolin for MSSA bacteremia [9]. However, early reports of cefazolin treatment failure in the setting of endocarditis have led others to caution its use in high-inocula infections [10].Although the presence of prosthetic devices or positive re-peat blood cultures would prompt most to extend therapy to 4–6 weeks, a smaller proportion of respondents were influenced by immunosuppression, diabetes, or community-onset bacte-remia. Further guidance is needed to identify patients who are at increased risk of relapse or serious complications, in whom prolonged treatment duration may be warranted.Consistent with guideline recommendations [6], clinical response influenced 51% of respondents to continue vanco-mycin in a patient with MRSA bacteremia and vancomycin MIC of 2 μg/mL, although a substantial portion would switch to daptomycin. Observational studies examining the role of daptomycin vs vancomycin in management of MRSA bacte-remia with high vancomycin MICs have yielded mixed results [11, 12], and a randomized controlled trial designed to eval-uate this issue was recently terminated due to slow accrual [11]. Although 8  mg/kg was the most commonly selected dose of daptomycin, a sizable minority chose the US Food and Drug Administration label dose of 6 mg/kg for management of MRSA bacteremia. The substantial differences in management of the above scenario and treatment of persistent bacteremia highlight the lack of high-quality evidence in these areas.Our study has several limitations. As with all voluntary surveys, selection bias could yield results not generalizable to all ID specialists. Response bias is possible and survey answers may not accurately reflect clinical practice. Although the value of ID consultation in SAB management has been established by multiple studies, this survey demonstrates that there remains ample opportunity to further define best practices and optimize management of this complex disease.Supplementary DataSupplementary materials are available at Clinical Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.NotesAcknowledgments. The authors thank all Infectious Diseases Society of America’s Emerging Infections Network members who participated in this survey.Disclaimer. The findings and conclusions in the manuscript are those of the authors and do not necessarily represent the official views of the US Centers for Disease Control and Prevention or the Department of Health and Human Services.Financial support. This publication was supported by the Centers for Disease Control and Prevention (cooperative agreement number 1 U50 CK000477).Potential conflicts of interest. C.  L.  has served as a consultant for Theravance. H. F. C. has received grant support from Genentech and per-sonal fees from Allergan. All other authors report no potential conflicts. BRIEF REPORT • cid 2019:69 (1 August) • 533All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the con-tent of the manuscript have been disclosed.References1. Shorr  AF, Tabak  YP, Killian  AD, Gupta  V, Liu  LZ, Kollef  MH. Healthcare-associated bloodstream infection: a distinct entity? Insights from a large U.S. da-tabase. Crit Care Med 2006; 34:2588–95.2. Paulsen J, Solligard E, Damas JK, DeWan A, Asvold BO, Bracken MB. The im-pact of infectious disease specialist consultation for Staphylococcus aureus blood-stream infections: a systematic review. 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Clinical Practice Variation Among Adult Infectious Disease Physicians in the Management of Staphylococcus aureus Bacteremia

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Clinical Practice Variation Among Adult Infectious Disease Physicians in the Management of Staphylococcus aureus Bacteremia

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