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Cited by 3,232Infective Endocarditis Diagnosis and ManagementStreptococcal Infections and TreatmentsCardiac Valve Diseases and Treatments

Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association

Baddour, Larry M., Wilson, Walter R., Bayer, Arnold S., Fowler, Vance G., Tleyjeh, Imad M., Rybak, Michael J., Barsic, Bruno, Lockhart, Peter B. +9 more·2015·Circulation
DOI 10.1161/cir.0000000000000296
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Abstract

BACKGROUND: Infective endocarditis is a potentially lethal disease that has undergone major changes in both host and pathogen. The epidemiology of infective endocarditis has become more complex with today's myriad healthcare-associated factors that predispose to infection. Moreover, changes in pathogen prevalence, in particular a more common staphylococcal origin, have affected outcomes, which have not improved despite medical and surgical advances. METHODS AND RESULTS: This statement updates the 2005 iteration, both of which were developed by the American Heart Association under the auspices of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of the Young. It includes an evidence-based system for diagnostic and treatment recommendations used by the American College of Cardiology and the American Heart Association for treatment recommendations. CONCLUSIONS: Infective endocarditis is a complex disease, and patients with this disease generally require management by a team of physicians and allied health providers with a variety of areas of expertise. The recommendations provided in this document are intended to assist in the management of this uncommon but potentially deadly infection. The clinical variability and complexity in infective endocarditis, however, dictate that these recommendations be used to support and not supplant decisions in individual patient management.

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Cites

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Statistics

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Claims the paper makes

102 of 369 cited sources checked · 46 supported · 4 flagged · accuracy not yet measured

  • Findingcitation

    A retrospective study of 410 patients showed good agreement (72%-90%) between the Duke criteria and clinical assessment by infectious disease experts blinded to underlying infective endocarditis risk factors.

    “a retrospective study of 410 patients showed good agreement (72%-90%) between the Duke criteria and clinical assessment by infectious disease experts blinded to underlying IE risk factors.39”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [39] 39. Fowler VG Jr, Sanders LL, Kong LK, McClelland RS, Gottlieb GS, Li J, Ryan T, Sexton DJ, Roussakis G, Harrell LJ, Corey GR. Infective endocar- ditis due to Staphylococcus aureus: 59 prospectively identified cases with follow-up. Clin Infect Dis. 1999;28:106-114. doi: 10.1086/515076. source

      The Abstract describes a prospective study of 59 patients with definite infective endocarditis, not a retrospective study of 410 patients. The Definition of IE says the authors used the Duke criteria, but our copy does not report the claimed 72%–90% agreement with blinded infectious disease experts. (LLM, conf=0.88)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Premisecitation

    Staphylococcal or fungal infective endocarditis appears to carry a high incidence rate of embolization independently of vegetation size.

    “In contrast, as confirmed above by Vilacosta et al, 278 staphylococcal or fungal IE appears to carry a high incidence rate of embolization independently of vegetation size.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [278] source

      The Discussion says earlier reports suggested increased embolization risk with Staphylococcus and fungi, but this study found no significant difference by microorganism. It also reports that, in staphylococcal endocarditis, large vegetations had a higher incidence of embolism. The Clinical and microbiologic data section identifies vegetation size—not microorganism—as the only independent predictor in its multivariate analysis. (LLM, conf=0.88)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Premisecitation

    Adjustment of the Duke criteria to require a minimum of 1 major plus 1 minor criterion or 3 minor criteria as a floor to designate a case as possible infective endocarditis has been incorporated into the modified criteria to reduce the proportion of patients assigned to the possible infective endocarditis category.

    “adjustment of the Duke criteria to require a minimum of 1 major plus 1 minor criterion or 3 minor criteria as a”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [24] 24. Li JS, Sexton DJ, Mick N, Nettles R, Fowler VG Jr, Ryan T, Bashore T, Corey GR. Proposed modifications to the Duke criteria for the diag- nosis of infective endocarditis. Clin Infect Dis. 2000;30:633-638. doi: 10.1086/313753. source
  • Premisecitation

    Daptomycin has been evaluated in the treatment of Staphylococcus aureus bacteremia and infective endocarditis in a randomized controlled trial.

    “daptomycin has been evaluated in the treatment of S aureus bacteremia and IE in a randomized, controlled trial.13”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [13] 13. Fowler VG Jr, Boucher HW, Corey GR, Abrutyn E, Karchmer AW, Rupp ME, Levine DP, Chambers HF, Tally FP, Vigliani GA, Cabell CH, Link AS, DeMeyer I, Filler SG, Zervos M, Cook P, Parsonnet J, Bernstein JM, Price CS, Forrest GN, Fätkenheuer G, Gareca M, Rehm SJ, Brodt HR, Tice A, Cosgrove SE; S aureus Endocarditis and Bacteremia Study Group. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med. 2006;355:653-665. doi: 10.1056/NEJMoa053783. source
  • Findingcitation

    The proportion of infective endocarditis patients undergoing surgery has increased over time to approximately 50%.

    “the proportion of IE patients undergoing surgery has increased over time to reach ≈50%.1,10,11”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [1] 1. Duval X, Delahaye F, Alla F, Tattevin P, Obadia JF, Le Moing V, Doco- Lecompte T, Celard M, Poyart C, Strady C, Chirouze C, Bes M, Cambau E, Iung B, Selton-Suty C, Hoen B; AEPEI Study Group. Temporal trends in infective endocarditis in the context of prophylaxis guideline modifi- cations: three successive population-based surveys. J Am Coll Cardiol. 2012;59:1968-1976. doi: 10.1016/j.jacc.2012.02.029. source
    • cites [10] 10. Lalani T, Cabell CH, Benjamin DK, Lasca O, Naber C, Fowler VG Jr, Corey GR, Chu VH, Fenely M, Pachirat O, Tan RS, Watkin R, Ionac A, Moreno A, Mestres CA, Casabé J, Chipigina N, Eisen DP, Spelman D, Delahaye F, Peterson G, Olaison L, Wang A; International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS) Investigators. Analysis of the impact of early surgery on in-hospital mortality of native valve endocarditis: use of propensity score and instrumental variable methods to adjust for treatment-selection bias. Circulation. 2010;121:1005-1013. doi: 10.1161/CIRCULATIONAHA.109.86 source

      The Results report that 720 of 1,552 eligible patients with native valve endocarditis (46%) underwent early surgery, supporting the approximate 50% figure for that study group. The paper does not establish that the proportion increased over time or that the figure applies to all infective endocarditis patients. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [11] 11. Kiefer T, Park L, Tribouilloy C, Cortes C, Casillo R, Chu V, Delahaye F, Durante-Mangoni E, Edathodu J, Falces C, Logar M, Miró JM, Naber C, Tripodi MF, Murdoch DR, Moreillon P, Utili R, Wang A. Association between valvular surgery and mortality among patients with infective endocarditis complicated by heart failure. JAMA. 2011;306:2239-2247. doi: 10.1001/jama.2011.1701. source

      The Results report that another study found surgery in 46% of patients with left-sided infective endocarditis and heart failure, a restricted group close to the claimed 50%. This paper reports surgery in 62% of its own patients with heart failure. Neither passage establishes that surgery rates increased over time or reached approximately 50% among infective endocarditis patients generally. (LLM, conf=0.77)

      Experimental — accuracy not yet measured
  • May combine two claims. 88
  • Classified as probably not a substantial claim. 18
  • The quote only partly states this claim. 2

  • May combine two claims.

    Premisenone given

    These initial studies included a limited number of patients, and risk adjustments were not performed.

    “However, these initial studies included a limited number of patients, and risk adjustments were not performed.”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [265] 265. Maruyama M, Kuriyama Y, Sawada T, Yamaguchi T, Fujita T, Omae T. Brain damage after open heart surgery in patients with acute cardioem- bolic stroke. Stroke. 1989;20:1305-1310. source
    • cites [266] 266. Gillinov AM, Shah RV, Curtis WE, Stuart RS, Cameron DE, Baumgartner WA, Greene PS. Valve replacement in patients with endocarditis and acute neurologic deficit. Ann Thorac Surg. 1996;61:1125-1129. source
    • cites [267] 267. Eishi K, Kawazoe K, Kuriyama Y, Kitoh Y, Kawashima Y, Omae T. Surgical management of infective endocarditis associated with cere- bral complications: multi-center retrospective study in Japan. J Thorac Cardiovasc Surg. 1995;110:1745-1755. source

      The Discussion (page unavailable) says earlier studies had limited numbers of cases but describes this study’s 181 analyzed patients as sufficient for examining surgical timing. Patients and methods (page unavailable) also reports stepwise regression analysis of risk factors, contrary to the unqualified claim that risk adjustments were not performed. (LLM, conf=0.83)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Extension of infective endocarditis beyond the valve annulus predicts a higher mortality rate, more frequent development of heart failure, and more frequent need for cardiac surgery.

    “Extension of IE beyond the valve annulus predicts a higher mortality rate, more frequent development of heart failure, and more frequent need for cardiac surgery.284,297,298”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [284] source

      The Abstract (page unavailable) says early echocardiographic findings were not predictive of in-hospital death. Table 1 (page unavailable) reports no statistically significant association between abscess and death (OR 1.52; P=0.525), contrary to the claimed mortality prediction. The Discussion identifies perivalvular extension as an indication for surgery, but does not show that it predicts more frequent heart failure or surgery. (LLM, conf=0.88)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites [297] 297. Middlemost S, Wisenbaugh T, Meyerowitz C, Teeger S, Essop R, Skoularigis J, Cronje S, Sareli P. A case for early surgery in native left- sided endocarditis complicated by heart failure: results in 203 patients. J Am Coll Cardiol. 1991;18:663-667. source

      The Methods define extensive infection as spread to the annulus or adjacent tissues, and the Results report five postoperative deaths among patients with extensive aortic infection versus two with limited aortic infection. But this was a surgical series of patients with heart failure; it does not establish that extension predicts more frequent heart failure or a greater need for surgery, and the authors conclude that extensive infection is not necessarily associated with high surgical risk when surgery is early (Discussion). No page number is available in our copy. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites [298] 298. Blumberg EA, Karalis DA, Chandrasekaran K, Wahl JM, Vilaro J, Covalesky VA, Mintz GS. Endocarditis-associated paravalvular abscesses: do clinical parameters predict the presence of abscess? Chest. 1995;107:898-903. source

  • May combine two claims.

    Findingcitation

    Of 59 consecutive patients with Staphylococcus aureus infective endocarditis, 45.8% had nosocomial infections, and 50.8% had a removable focus of infection.

    “of 59 consecutive patients with S aureus IE, 45.8% had nosocomial infections, and 50.8% had a removable focus of infection.39”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [39] 39. Fowler VG Jr, Sanders LL, Kong LK, McClelland RS, Gottlieb GS, Li J, Ryan T, Sexton DJ, Roussakis G, Harrell LJ, Corey GR. Infective endocar- ditis due to Staphylococcus aureus: 59 prospectively identified cases with follow-up. Clin Infect Dis. 1999;28:106-114. doi: 10.1086/515076. source

      Table 2 reports 27 hospital-acquired cases among 59 patients (45.8%). The Sources of Infection section reports that an intravascular device was the presumed source in 30 patients (50.8%), but it does not establish that all 30 had a removable focus of infection. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation

    In the predefined subgroup with MRSA bacteremia, daptomycin demonstrated a 44.4% success rate compared with 31.8% for standard therapy; this difference was not statistically significant (absolute difference 12.6%, 95% CI -7.4 to 32.6; P=0.28).

    “In the predefined subgroup of those with MRSA bacteremia, daptomycin demonstrated a 44.4% success rate compared with 31.8% for standard therapy; this difference was not statistically significant (absolute difference, 12.6%, 95% confidence interval, -7.4 to 32.6; P=0.28).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [13] 13. Fowler VG Jr, Boucher HW, Corey GR, Abrutyn E, Karchmer AW, Rupp ME, Levine DP, Chambers HF, Tally FP, Vigliani GA, Cabell CH, Link AS, DeMeyer I, Filler SG, Zervos M, Cook P, Parsonnet J, Bernstein JM, Price CS, Forrest GN, Fätkenheuer G, Gareca M, Rehm SJ, Brodt HR, Tice A, Cosgrove SE; S aureus Endocarditis and Bacteremia Study Group. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med. 2006;355:653-665. doi: 10.1056/NEJMoa053783. source

  • May combine two claims.

    Interpretationcitation

    Patterns of diffusion differ by class of antibiotic, which may have implications for therapeutic outcomes in patients being treated for IE.

    “Patterns of diffusion differ by class of antibiotic, which may have implications for therapeutic outcomes in patients being treated for IE.[98][99][100]”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [98] 98. Fantin B, Leclercq R, Ottaviani M, Vallois JM, Maziere B, Duval J, Pocidalo JJ, Carbon C. In vivo activities and penetration of the two com- ponents of the streptogramin RP 59500 in cardiac vegetations of experi- mental endocarditis. Antimicrob Agents Chemother. 1994;38:432-437. source

      The Discussion describes different diffusion patterns for RPI and RPII in rabbit cardiac vegetations, and the Results report differences in their penetration. This supports the diffusion point, but the study compares two components of one streptogramin combination, not antibiotic classes generally, and does not establish therapeutic implications in patients with infective endocarditis. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [99] 99. Mertes PM, Jehl F, Burtin P, Dopff C, Pinelli G, Villemot JP, Monteil H, Dureux JB. Penetration of ofloxacin into heart valves, myocardium, mediastinal fat, and sternal bone marrow in humans. Antimicrob Agents Chemother. 1992;36:2493-2496. 100. Nicolau DP, Freeman CD, Nightingale CH, Coe CJ, Quintiliani R. Minocycline versus vancomycin for treatment of experimental endocar- ditis caused by oxacillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 1994;38:1515-1518. 101. Rybak MJ. Pharmacodynamics: relation to antimicrobial resistance. Am J Med. 2006;119(suppl 1):S37-S44. doi: source
    • cites [100] 100. Rybak M, Lomaestro B, Rotschafer JC, Moellering R Jr, Craig W, Billeter M, Dalovisio JR, Levine DP. Therapeutic monitoring of vanco- mycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists [published correction appears in Am J Health Syst Pharm. 2009;66:887]. Am J Health Syst Pharm. 2009;66:82-98. doi: 10.2146/ajhp080434. 113. source

  • May combine two claims.

    Premisecitation

    In a post hoc analysis of the landmark clinical trial, the addition of low-dose short-course gentamicin in one arm was significantly associated with renal toxicity, which occurred early and often, and the clinical association between gentamicin dose and duration was minimal.

    “Of note, in a post hoc analysis of this landmark clinical trial, 149 the addition of even such low-dose, short-course gentamicin in 1 arm of the study was significantly associated with renal toxicity, which occurred early and often, and the clinical association between gentamicin dose and duration was minimal.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [149] 149. Cosgrove SE, Vigliani GA, Fowler VG Jr, Abrutyn E, Corey GR, Levine DP, Rupp ME, Chambers HF, Karchmer AW, Boucher HW. Initial low- dose gentamicin for Staphylococcus aureus bacteremia and endocarditis is nephrotoxic. Clin Infect Dis. 2009;48:713-721. doi: 10.1086/597031. source

  • May combine two claims.

    Premisecitation

    Use of rifampin as adjunct therapy for S aureus native valve infective endocarditis has been associated with higher rates of adverse events, primarily hepatotoxicity, and a significantly lower survival rate.

    “Moreover, use of rifampin as adjunct therapy for S aureus NVE has been associated with higher rates of adverse events (primarily hepatotoxicity) and a significantly lower survival rate.162”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [162] 162. Riedel DJ, Weekes E, Forrest GN. Addition of rifampin to standard therapy for treatment of native valve infective endocarditis caused by Staphylococcus aureus. Antimicrob Agents Chemother. 2008;52:2463- 2467. doi: 10.1128/AAC.00300-08. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The 2005 AHA document recommended streptomycin for patients with gentamicin-resistant strains of enterococci.

    “The 2005 AHA document 12 recommended streptomycin for patients with gentamicin-resistant strains of enterococci.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [12] 12. Baddour LM, Wilson WR, Bayer AS, Fowler VG Jr, Bolger AF, Levison ME, Ferrieri P, Gerber MA, Tani LY, Gewitz MH, Tong DC, Steckelberg JM, Baltimore RS, Shulman ST, Burns JC, Falace DA, Newburger JW, Pallasch TJ, Takahashi M, Taubert KA. Infective endocarditis: diagno- sis, antimicrobial therapy, and management of complications: a state- ment for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American source

      The section on enterococci resistant to gentamicin recommends a streptomycin regimen, but specifically for strains susceptible to streptomycin, penicillin, and vancomycin. It says only some gentamicin-resistant strains remain susceptible to streptomycin, so the claim is too broad without that qualification. No page number is available in our copy. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In that study, the median duration of aminoglycoside therapy was 15 days, and microbiological cure and survival rates were similar to those for patients who received longer courses of gentamicin therapy.

    “The median duration of aminoglycoside therapy was 15 days, and the microbiological cure and survival rates were similar to those for patients who received longer courses of gentamicin therapy.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [189] 189. Olaison L, Schadewitz K; Swedish Society of Infectious Diseases Quality Assurance Study Group for Endocarditis. Enterococcal endo- carditis in Sweden, 1995-1999: can shorter therapy with aminogly- cosides be used? Clin Infect Dis. 2002;34:159-166. doi: 10.1086/ 338233. source

      The Results (p. 3) report a median of 15 days of aminoglycoside therapy in episodes with clinical cure. The Discussion (pp. 6–7) describes good outcomes with shortened treatment, but our copy does not report similar microbiological-cure and survival rates compared with a longer-course gentamicin group; it discusses several aminoglycosides. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

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    Premisecitation

    In one survey, 60% of HACEK isolates did not grow adequately in control wells, and no valid in vitro susceptibility results were available.

    “In 1 survey, 60% of isolates did not grow adequately in control wells, and no valid in vitro susceptibility results were available.219”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    β-lactamase-producing strains of HACEK are appearing with increased frequency; rarely, resistance to ampicillin can occur in β-lactamase-negative strains.

    “However, β-lactamaseproducing strains of HACEK are appearing with increased frequency; rarely, resistance to ampicillin can occur in β-lactamase-negative strains.219”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [219] source

      The discussion following Table 1 reports penicillin/ampicillin resistance in one Eikenella corrodens isolate without β-lactamase production, supporting the rare-exception claim. The paper also identifies two β-lactamase-positive isolates, but it does not establish that β-lactamase-producing HACEK strains are appearing with increased frequency. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Some laboratory-based diagnostic techniques for fastidious pathogens are not available in most clinical laboratories and require considerable time if sent to a referral laboratory.

    “Moreover, some of the laboratory-based diagnostic techniques to define fastidious or unusual pathogens are not available in most clinical laboratories and require considerable time for completion of testing if specimens are sent to a referral laboratory.233”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [233] 233. Baron EJ, Miller JM, Weinstein MP, Richter SS, Gilligan PH, Thomson RB Jr, Bourbeau P, Carroll KC, Kehl SC, Dunne WM, Robinson-Dunn B, Schwartzman JD, Chapin KC, Snyder JW, Forbes BA, Patel R, Rosenblatt JE, Pritt BS. A guide to utilization of the microbiology labo- ratory for diagnosis of infectious diseases: 2013 recommendations by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM)(a). Clin Infect Dis. 2013;57:e22-e121. doi: 10.1093/cid/cit278. source

  • May combine two claims.

    Premisecitation

    When adjusted for survivor bias, analyses have shown either a statistical loss of benefit of early surgery or findings indicating that the surgical intervention may actually result in harm.

    “When adjusted for survivor bias, analyses have shown either a statistical loss of benefit of early surgery or findings indicating that the surgical intervention may actually result in harm.”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [15] 15. Bannay A, Hoen B, Duval X, Obadia JF, Selton-Suty C, Le Moing V, Tattevin P, Iung B, Delahaye F, Alla F; AEPEI Study Group. The impact of valve surgery on short-and long-term mortality in left-sided infective endocarditis: do differences in methodological approaches explain previous conflicting results? Eur Heart J. 2011;32:2003-2015. doi: 10.1093/eurheartj/ehp008. source
    • cites [16] 16. Sy RW, Bannon PG, Bayfield MS, Brown C, Kritharides L. Survivor treat- ment selection bias and outcomes research: a case study of surgery in infective endocarditis. Circ Cardiovasc Qual Outcomes. 2009;2:469-474. doi: 10.1161/CIRCOUTCOMES.109.857938. source
    • cites [258] 258. Tleyjeh IM, Ghomrawi HM, Steckelberg JM, Montori VM, Hoskin TL, Enders F, Huskins WC, Mookadam F, Wilson WR, Zimmerman V, Baddour LM. Conclusion about the association between valve surgery and mortality in an infective endocarditis cohort changed after adjusting for survivor bias. J Clin Epidemiol. 2010;63:130-135. doi: 10.1016/j. jclinepi.2008.06.022. source

  • May combine two claims.

    Premisecitation

    Emboli can occur before diagnosis, during therapy, or after therapy is completed, although most emboli occur within the first 2 to 4 weeks of antimicrobial therapy.

    “Emboli can occur before diagnosis, during therapy, or after therapy is completed, although most emboli occur within the first 2 to 4 weeks of antimicrobial therapy.58,278”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [58] 58. Steckelberg JM, Murphy JG, Ballard D, Bailey K, Tajik AJ, Taliercio CP, Giuliani ER, Wilson WR. Emboli in infective endocarditis: the prognos- tic value of echocardiography. Ann Intern Med. 1991;114:635-640. Doi: 10.7326/0003-4819-114-8-635. source
    • cites [278] source

  • May combine two claims.

    Premisecitation

    Ruttmann et al analyzed 65 patients who underwent cardiac surgery after cardioembolic stroke (median time, 4 days; range, 0-38 days); surgery in this time frame was not associated with worse patient outcomes.

    “Ruttmann et al 270 analyzed 65 patients who underwent cardiac surgery after cardioembolic (embolic) stroke (median time, 4 days; range, 0-38 days).Surgery in this time frame was not associated with worse patient outcomes.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [270] 270. Ruttmann E, Willeit J, Ulmer H, Chevtchik O, Höfer D, Poewe W, Laufer G, Müller LC. Neurological outcome of septic cardioembolic stroke after infective endocarditis. Stroke. 2006;37:2094-2099. doi: 10.1161/01. STR.0000229894.28591.3f. source

  • May combine two claims.

    Premisecitation

    Vilacosta et al confirmed the reduced frequency of embolization after 2 weeks of therapy and reemphasized the increased risk of embolization with increasing vegetation size during therapy, mitral valve involvement, and staphylococcal pathogenesis.

    “Vilacosta et al 278 confirmed the reduced frequency of embolization after 2 weeks of therapy.Moreover, the latter study reemphasized the increased risk of embolization with increasing vegetation size during therapy, mitral valve involvement, and staphylococcal pathogenesis.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [278] source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    The largest early series of operated patients with cerebral complications included 181 patients; hospital mortality rates were 66.3% when surgery was performed within 24 hours of stroke and gradually decreased every week to 7.0% with surgery more than 4 weeks after stroke.

    “The largest early series of operated patients with cerebral complications included 181 patients.267 Hospital mortality rates as a function of the interval between evidence of cerebral infarction to cardiac surgery were 66.3% when surgery was performed within 24 hours of stroke and gradually decreased every week to 7.0% with surgery >4 weeks after stroke.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [267] 267. Eishi K, Kawazoe K, Kuriyama Y, Kitoh Y, Kawashima Y, Omae T. Surgical management of infective endocarditis associated with cere- bral complications: multi-center retrospective study in Japan. J Thorac Cardiovasc Surg. 1995;110:1745-1755. source

      The Conclusion reports 181 patients with infective endocarditis and cerebral complications. The ‘Influence of cardiac surgery on preoperative cerebral infarction’ section gives the claimed 66.3% mortality within 24 hours and 7.0% after more than four weeks, but mortality did not decrease every week: it rose from 10.0% at 15–21 days to 26.3% at 22–28 days. The supplied passages have no page numbers. (LLM, conf=0.91)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Latency between the neurological event and cardiac surgery was not a significant factor with respect to the perioperative neurological complication rate or the postoperative neurological recovery rate.

    “Latency between the neurological event and cardiac surgery was not a significant factor with respect to the perioperative neurological complication rate or the postoperative neurological recovery rate.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [270] 270. Ruttmann E, Willeit J, Ulmer H, Chevtchik O, Höfer D, Poewe W, Laufer G, Müller LC. Neurological outcome of septic cardioembolic stroke after infective endocarditis. Stroke. 2006;37:2094-2099. doi: 10.1161/01. STR.0000229894.28591.3f. source

  • May combine two claims.

    Premisecitation

    Retrospective, observational studies have examined the impact of long-term antiplatelet therapy before the onset of infective endocarditis on infection-related outcomes, and findings have been mixed.

    “Retrospective, observational studies 290-296 have examined the impact, if any, of long-term antiplatelet therapy before the onset of IE on infection-related outcomes.Findings from these investigations have been mixed in terms of IE-related outcomes.”
    Quote in the paperSubstantial claim1 of 7 sources checked
    • cites [290] 290. Anavekar NS, Tleyjeh IM, Anavekar NS, Mirzoyev Z, Steckelberg JM, Haddad C, Khandaker MH, Wilson WR, Chandrasekaran K, Baddour LM. Impact of prior antiplatelet therapy on risk of embolism in infective endo- carditis [published correction appears in Clin Infect Dis. 2007;44:1398]. Clin Infect Dis. 2007;44:1180-1186. doi: 10.1086/513197. source
    • cites [291] 291. Chan KL, Tam J, Dumesnil JG, Cujec B, Sanfilippo AJ, Jue J, Turek M, Robinson T, Williams K. Effect of long-term aspirin use on embolic events in infective endocarditis. Clin Infect Dis. 2008;46:37-41. doi: 10.1086/524021. source
    • cites [292] 292. Eisen DP, Corey GR, McBryde ES, Fowler VG Jr, Miro JM, Cabell CH, Street AC, Paiva MG, Ionac A, Tan RS, Tribouilloy C, Pachirat O, Jones SB, Chipigina N, Naber C, Pan A, Ravasio V, Gattringer R, Chu VH, Bayer AS; ICE Investigators. Reduced valve replacement surgery and complication rate in Staphylococcus aureus endocarditis patients receiv- ing acetyl-salicylic acid. J Infect. 2009;58:332-338. doi: 10.1016/j. jinf.2009.03.006. source
    • cites [293] 293. Pepin J, Tremblay V, Bechard D, Rodier F, Walker C, Dufresne D, Lafontaine A, Li N, Lacroix C, Lanthier L. Chronic antiplatelet therapy and mortality among patients with infective endocarditis. Clin Microbiol Infect. 2009;15:193-199. doi: 10.1111/j.1469-0691. 2008.02665.x. source
    • cites [294] 294. Snygg-Martin U, Rasmussen RV, Hassager C, Bruun NE, Andersson R, Olaison L. The relationship between cerebrovascular complica- tions and previously established use of antiplatelet therapy in left- sided infective endocarditis. Scand J Infect Dis. 2011;43:899-904. doi: 10.3109/00365548.2011.603742. source
    • cites [295] 295. Anavekar NS, Schultz JC, De Sa DD, Thomas JM, Lahr BD, Tleyjeh IM, Steckelberg JM, Wilson WR, Baddour LM. Modifiers of symptomatic embolic risk in infective endocarditis [published correction appears in Mayo Clin Proc. 2012;87:309]. Mayo Clin Proc. 2011;86:1068-1074. doi: 10.4065/mcp.2011.0111. source
    • cites [296] 296. Omari B, Shapiro S, Ginzton L, Robertson JM, Ward J, Nelson RJ, Bayer AS. Predictive risk factors for periannular extension of native valve endocarditis: clinical and echocardiographic analyses. Chest. 1989;96:1273-1279. source

  • May combine two claims.

    Premisecitation

    No significant benefit was observed in aspirin-treated patients in terms of vegetation resolution and embolic events, and there was a trend toward more bleeding episodes in the aspirin-treated patients.

    “No significant benefit was observed in aspirin-treated patients in terms of vegetation resolution and embolic events.Moreover, there was a trend toward more bleeding episodes in the aspirin-treated patients.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [288] 288. Chan KL, Dumesnil JG, Cujec B, Sanfilippo AJ, Jue J, Turek MA, Robinson TI, Moher D; Investigators of the Multicenter Aspirin Study in Infective Endocarditis. A randomized trial of aspirin on the risk of embolic events in patients with infective endocarditis. J Am Coll Cardiol. 2003;42:775-780. source

  • May combine two claims.

    Premisecitation

    TEE dramatically improves the sensitivity for defining periannular extension of IE (76% to 100%) while retaining excellent specificity (95%) and positive and negative predictive values (87% and 89%, respectively).

    “TEE dramatically improves the sensitivity for defining periannular extension of IE (76% to 100%) while retaining excellent specificity (95%) and positive and negative predictive values (87% and 89%, respectively).54,307”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [54] 54. Daniel WG, Mügge A, Martin RP, Lindert O, Hausmann D, Nonnast- Daniel B, Laas J, Lichtlen PR. Improvement in the diagnosis of abscesses associated with endocarditis by transesophageal echocardiography. N Engl J Med. 1991;324:795-800. doi: 10.1056/NEJM199103213241203. source

      The Transesophageal Echocardiography section (p. 2) reports that TEE detected more endocarditis-associated abscesses than transthoracic echocardiography, with specificity of 94.6%—approximately the claimed 95%. It reports TEE sensitivity of 87%, positive predictive value of 90.9%, and negative predictive value of 92.1%, not the claimed sensitivity range of 76% to 100% and predictive values of 87% and 89%. (LLM, conf=0.90)

      Experimental — accuracy not yet measured
    • cites [307] source

      The case report describes echocardiographic identification of a mitral anular abscess (Course and echocardiographic findings; Discussion, pp. 953–955). Our copy does not assess TEE against another method or report the claimed sensitivity, specificity, or predictive values; searches for those terms and figures found no supporting passage. (LLM, conf=0.78)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Under conditions of extensive destruction of periannular supporting tissues, human aortic homografts, when available, can be used to replace the damaged aortic valve and to reconstruct the damaged aorta.

    “Under these conditions, human aortic homografts, when available, can be used to replace the damaged aortic valve and to reconstruct the damaged aorta.310,311”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [310] source
    • cites [311] source

  • May combine two claims.

    Findingcitation

    Fournier et al studied 20 pathologically confirmed cases of Q fever infective endocarditis; when the original Duke criteria were used, 4 of the 20 patients were classified as having possible infective endocarditis, and when Q fever serological results and a single blood culture positive for Coxiella burnetii were considered a major criterion, each of these 4 cases was reclassified from possible to

    “Fournier et al 40 studied 20 pathologically confirmed cases of Q fever IE.When the original Duke criteria were used, 4 of the 20 patients were classified as having possible IE.When Q fever serological results and a single blood culture positive for C burnetii were considered to be a major criterion, however, each of these 4 cases was reclassified from possible IE to definite IE.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [40] 40. Fournier PE, Casalta JP, Habib G, Messana T, Raoult D. Modification of the diagnostic criteria proposed by the Duke Endocarditis Service to permit improved diagnosis of Q fever endocarditis. Am J Med. 1996;100:629-633. source

  • May combine two claims.

    Findingown data

    In a reanalysis of patients in the Duke University database containing records on more than 800 cases of definite and possible infective endocarditis since 1984, the echocardiographic minor criterion was used in only 5% of cases and was never used in the final analysis of any patient who underwent transesophageal echocardiography.

    “In a reanalysis of patients in the Duke University database (containing records collected prospectively on >800 cases of definite and possible IE since 1984), this echocardiographic criterion was used in only 5% of cases and was never used in the final analysis of any patient who underwent transesophageal echocardiography (TEE).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    Cases with limited manifestations of infective endocarditis may occur early during infection, particularly among injection drug users, in whom infective endocarditis is often the result of acute Staphylococcus aureus infection of right-sided heart valves.

    “Cases with limited manifestations of IE may occur early during IE, particularly among patients who are injection drug users (IDUs), in whom IE is often the result of acute S aureus infection of right-sided heart valves.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    The overall incidence of infective endocarditis has remained stable.

    “Although the overall IE incidence has remained stable, 1,2,[5][6][7][8][9]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites 1,2,[5][6][7][8][9]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Findingnone given

    The major limitations of erythrocyte sedimentation rate and C-reactive protein are that they are nonspecific and particularly challenging to interpret in patients with comorbid conditions.

    “The major limitations of the erythrocyte sedimentation rate and C-reactive protein are that they are nonspecific and particularly challenging to interpret in patients with comorbid conditions.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Right-sided infective endocarditis can cause septic pulmonary emboli.

    “Right-sided IE, however, can cause septic pulmonary emboli.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Characteristics of infective endocarditis patients have shifted toward increased mean patient age, a higher proportion of prosthetic valves and other cardiac devices, and a decreasing proportion of rheumatic heart disease.

    “Characteristics of IE patients have also shifted toward an increased mean patient age, a higher proportion of prosthetic valves and other cardiac devices, and a decreasing proportion of rheumatic heart disease.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Direct analyses of the Duke criteria in 12 major studies including nearly 1700 patients confirmed the high sensitivity and specificity of the Duke criteria and the diagnostic utility of echocardiography in identifying clinically definite cases.

    “The studies [27][28][29][30][31][32][33][34][35][36][37][38] confirmed the high sensitivity and specificity of the Duke criteria and the diagnostic utility of echocardiography in identifying clinically definite cases.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [27][28][29][30][31][32][33][34][35][36][37][38]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S4 (based).

    Findingnone given

    Some patients will have significant valvular dysfunction at the end of otherwise successful antimicrobial treatment that will require eventual valvular surgery.

    “Some patients will have significant valvular dysfunction at the end of otherwise successful antimicrobial treatment that will require eventual valvular surgery.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Findingnone given

    All patients who have experienced an episode of infective endocarditis remain at increased risk for recurrent infection indefinitely.

    “All patients who have experienced an episode of IE remain at increased risk for recurrent infection indefinitely.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Both β-lactam therapy alone and combination therapy with nafcillin and an aminoglycoside for only 2 weeks have been effective in patients with uncomplicated right-sided IE caused by S aureus.

    “Both β-lactam therapy alone and combination therapy with nafcillin and an aminoglycoside for only 2 weeks have been effective in patients with uncomplicated right-sided IE caused by S aureus 91 ; monotherapy with a β-lactam would be selected for use in cases of uncomplicated IE. 92”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [91] 91. Chambers HF, Miller RT, Newman MD. Right-sided Staphylococcus aureus endocarditis in intravenous drug abusers: two-week combination therapy. Ann Intern Med. 1988;109:619-624. source

  • May combine two claims.

    Findingcitation

    In a prospective study of 25 infective endocarditis cases, 18F-fluorodeoxyglucose positron emission tomography/computed tomography was useful in identifying peripheral embolization in 11 patients and in detecting infective endocarditis extracardiac manifestations in 7 patients who did not demonstrate any clinical manifestations of infective endocarditis.

    “In a prospective study of 25 IE cases, 18 F-fluorodeoxyglucose positron emission tomography/ CT was useful in identifying peripheral embolization in 11 patients and in detecting IE extracardiac manifestations in 7 patients who did not demonstrate any clinical manifestations of IE. 70”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [70] 70. Van Riet J, Hill EE, Gheysens O, Dymarkowski S, Herregods MC, Herijgers P, Peetermans WE, Mortelmans L. (18)F-FDG PET/CT for early detection of embolism and metastatic infection in patients with infective endocarditis. Eur J Nucl Med Mol Imaging. 2010;37:1189-1197. doi: 10.1007/s00259-010-1380-x. source

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingnone given

    Criteria changes that add sensitivity often do so at the expense of specificity and vice versa.

    “Criteria changes that add sensitivity often do so at the expense of specificity and vice versa.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In the setting of a prosthetic valve, transthoracic images are greatly hampered by the structural components of the prosthesis and are inadequate for assessment of the perivalvular area where those infections often start.

    “In the setting of a prosthetic valve, transthoracic images are greatly hampered by the structural components of the prosthesis and are inadequate for assessment of the perivalvular area where those infections often start.48”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [48] 48. Daniel WG, Mügge A, Grote J, Hausmann D, Nikutta P, Laas J, Lichtlen PR, Martin RP. Comparison of transthoracic and transesophageal echocar- diography for detection of abnormalities of prosthetic and bioprosthetic valves in the mitral and aortic positions. Am J Cardiol. 1993;71:210-215. source

  • May combine two claims.

    Findingcitation

    An interval increase in vegetation size on serial echocardiography despite the administration of appropriate antibiotic therapy has serious implications and has been associated with an increased risk of complications and the need for surgery.

    “An interval increase in vegetation size on serial echocardiography despite the administration of appropriate antibiotic therapy has serious implications and has been associated with an increased risk of complications and the need for surgery.60”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [60] 60. Rohmann S, Erbel R, Darius H, Görge G, Makowski T, Zotz R, Mohr- Kahaly S, Nixdorff U, Drexler M, Meyer J. Prediction of rapid versus prolonged healing of infective endocarditis by monitoring vegetation size. J Am Soc Echocardiogr. 1991;4:465-474. source

  • May combine two claims.

    Findingcitation

    Several echocardiographic features identify patients at high risk for a complicated course or with a need for surgery, including large (>10 mm) vegetations, severe valvular insufficiency, abscess cavities or pseudoaneurysms, valvular perforation or dehiscence, and evidence of decompensated heart failure.

    “Several echocardiographic features identify patients at high risk for a complicated course or with a need for surgery (Table 5).These features include large (>10 mm in diameter) vegetations, severe valvular insufficiency, abscess cavities or pseudoaneurysms, valvular perforation or dehiscence, and evidence of decompensated heart failure.21”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [21] 21. Baddour LM, Epstein AE, Erickson CC, Knight BP, Levison ME, Lockhart PB, Masoudi FA, Okum EJ, Wilson WR, Beerman LB, Bolger AF, Estes NA 3rd, Gewitz M, Newburger JW, Schron EB, Taubert KA; on behalf of the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee; Council on Cardiovascular Disease in Young; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Nursing; Council on Clinical Cardiology; and Interdisciplinary Council on Quality of Care. Update on cardiovascu- lar implantable electronic device infections and their management: source

  • May combine two claims.

    Findingnone given

    Lower temporal and lateral resolution with 3-dimensional echocardiography compared with 2-dimensional echocardiography leads to an overestimation of vegetation size and technically challenging visualization of fast-moving structures.

    “the lower temporal and lateral resolution with 3D echocardiography compared with 2-dimensional echocardiography leads to an overestimation of vegetation size and technically challenging visualization of fast-moving structures.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    The role of cerebral magnetic resonance imaging and magnetic resonance angiography in the diagnosis and management of infective endocarditis has been better defined in several studies.

    “the role of cerebral MRI and magnetic resonance angiography in the diagnosis and management of IE has been better defined in several studies.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Several risk stratification models for quantifying morbidity and mortality in infective endocarditis patients overall and particularly in those undergoing valve surgeries have been developed and validated.

    “several risk stratification models for quantifying morbidity and mortality in IE patients overall and particularly in those undergoing valve surgeries have been developed and validated.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Six common but less specific findings of infective endocarditis were included as minor criteria in the original Duke schema.

    “Six common but less specific findings of IE were included as minor criteria in the original Duke schema (Tables 2 and 3).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Diagnostic innovations have emerged through new imaging techniques such as 3-dimensional echocardiography, head-to-toe multislice computed tomography, and cardiac magnetic resonance imaging.

    “diagnostic innovations have emerged through new imaging techniques such as 3-dimensional (3D) echocardiography,”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The Duke criteria gave diagnostic weight to bacteremia with staphylococci or enterococci only, on the basis of the location of acquisition and without an apparent primary focus; these types of bacteremia have the highest risk of being associated with infective endocarditis.

    “The Duke criteria gave diagnostic weight to bacteremia with staphylococci or enterococci only, on the basis of the location of acquisition and without an apparent primary focus; these types of bacteremia have the highest risk of being associated with IE. 23,25,26”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [23] 23. Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infec- tive endocarditis: utilization of specific echocardiographic findings: Duke Endocarditis Service. Am J Med. 1994;96:200-209. source
    • cites [25] 25. Bayer AS, Lam K, Ginzton L, Norman DC, Chiu CY, Ward JI. Staphylococcus aureus bacteremia: clinical, serologic, and echocardio- graphic findings in patients with and without endocarditis. Arch Intern Med. 1987;147:457-462. source
    • cites [26] 26. Fowler VG Jr, Olsen MK, Corey GR, Woods CW, Cabell CH, Reller LB, Cheng AC, Dudley T, Oddone EZ. Clinical identifiers of complicated Staphylococcus aureus bacteremia. Arch Intern Med. 2003;163:2066- 2072. doi: 10.1001/archinte.163.17.2066. source

  • May combine two claims.

    Premisecitation

    Infected vegetations are characterized by focal infection with high bacterial density, slow bacterial growth within biofilms, and low microorganism metabolic activity.

    “These characteristics include focal infection with high bacterial density, slow rate of bacterial growth within biofilms, and low microorganism metabolic activity.72”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [72] 72. Durack DT, Beeson PB. Experimental bacterial endocarditis, II: survival of a bacteria in endocardial vegetations. Br J Exp Pathol. 1972;53:50-53.

  • May combine two claims.

    Interpretationcitation

    Loss of penicillin-binding proteins during stationary-phase growth may be responsible in part for the inoculum effect observed in vivo and may account for the failure of penicillin in both experimental and human cases of severe streptococcal infections.

    “This loss of penicillin-binding proteins during stationary-phase growth may be responsible in part for the inoculum effect observed in vivo and may account for the failure of penicillin in both experimental and human cases of severe streptococcal infections.80”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [80] 80. Stevens DL, Yan S, Bryant AE. Penicillin-binding protein expression at different growth stages determines penicillin efficacy in vitro and in vivo: an explanation for the inoculum effect. J Infect Dis. 1993;167:1401-1405. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    The Duke criteria were originally developed to facilitate epidemiological and clinical research efforts so that investigators could compare and contrast the clinical features and outcomes of various case series of patients.

    “the Duke criteria were originally developed to facilitate epidemiological and clinical research efforts so that investigators could compare and contrast the clinical features and outcomes of various case series of patients.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Nafcillin-gentamicin combination therapy did not reduce mortality or the frequency of cardiac complications.

    “However, combination therapy did not reduce mortality or the frequency of cardiac complications.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [153] 153. Korzeniowski O, Sande MA. Combination antimicrobial therapy for Staphylococcus aureus endocarditis in patients addicted to paren- teral drugs and in nonaddicts: a prospective study. Ann Intern Med. 1982;97:496-503. source

  • May combine two claims.

    Interpretationcitation

    A growing body of evidence suggests that the addition of adjunctive aminoglycoside therapy is unnecessary for patients with uncomplicated right-sided native valve S aureus infective endocarditis and may cause harm.

    “A growing body of evidence suggests that the addition of adjunctive aminoglycoside therapy not only is unnecessary for patients with uncomplicated right-sided native valve S aureus IE but may cause harm.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Linezolid was reported to be effective in the treatment of persistent MRSA bacteremia, but this study had important study design weaknesses.

    “Linezolid was reported to be effective in the treatment of persistent MRSA bacteremia, 172 but this study had important study design weaknesses.173”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [172] source
    • cites [173] source

  • May combine two claims.

    Premisecitation

    In an observational study, high-dose daptomycin at approximately 9 mg/kg per dose for treatment of left-sided infective endocarditis was as effective as standard-of-care therapy and cleared MRSA bacteremia significantly faster than standard-of-care treatment.

    “However, in an observational study, high-dose daptomycin (≈9 mg/kg per dose) for treatment of left-sided IE was as effective as standard-of-care therapy and cleared MRSA bacteremia significantly faster than did standard-ofcare treatment.155”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [155] 155. Carugati M, Bayer AS, Miró JM, Park LP, Guimarães AC, Skoutelis A, Fortes CQ, Durante-Mangoni E, Hannan MM, Nacinovich F, Fernández- Hidalgo N, Grossi P, Tan RS, Holland T, Fowler VG Jr, Corey RG, Chu VH; International Collaboration on Endocarditis. High-dose daptomycin therapy for left-sided infective endocarditis: a prospective study from the International Collaboration on Endocarditis. Antimicrob Agents Chemother. 2013;57:6213-6222. doi: 10.1128/AAC.01563-13. source

  • May combine two claims.

    Premisecitation

    Compared with other patients with infective endocarditis, patients with enterococcal infective endocarditis are older, often debilitated, may have complicated underlying urological conditions including pre-existing renal failure, may have healthcare-associated infections, and have significant other underlying comorbidities common in older age groups.

    “Compared with other patients with IE, in general, patients with enterococcal IE are older; are often debilitated; may have complicated, underlying urological conditions, including pre-existing renal failure; may have healthcare-associated infections; and have significant other underlying comorbidities common in older age groups.192”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [192] source

  • May combine two claims.

    Premisecitation

    Experimental infective endocarditis models caused by methicillin-resistant staphylococci demonstrated that vancomycin combined with rifampin and gentamicin is the optimal regimen, and limited clinical reports support this approach.

    “Experimental IE models caused by methicillin-resistant staphylococci demonstrated that vancomycin combined with rifampin and gentamicin is the optimal regimen, and limited clinical reports support this approach.183”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [183] 183. Drinković D, Morris AJ, Pottumarthy S, MacCulloch D, West T. Bacteriological outcome of combination versus single-agent treatment for staphylococcal endocarditis. J Antimicrob Chemother. 2003;52:820- 825. doi: 10.1093/jac/dkg440. source

  • Classified as probably not a substantial claim.

    Premisecitation

    Because of the high mortality rate associated with S aureus prosthetic valve infective endocarditis, combination antimicrobial therapy is recommended.

    “Because of the high mortality rate associated with S aureus PVE, 136 combination antimicrobial therapy is recommended (Table 11).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [136] 136. Wang A, Athan E, Pappas PA, Fowler VG Jr, Olaison L, Paré C, Almirante B, Muñoz P, Rizzi M, Naber C, Logar M, Tattevin P, Iarussi DL, Selton-Suty C, Jones SB, Casabé J, Morris A, Corey GR, Cabell CH; International Collaboration on Endocarditis-Prospective Cohort Study Investigators. Contemporary clinical profile and outcome of pros- thetic valve endocarditis. JAMA. 2007;297:1354-1361. doi: 10.1001/ jama.297.12.1354. source

  • May combine two claims.

    Premisecitation

    In the Markowitz et al report, all treatment failures with trimethoprim-sulfamethoxazole occurred in patients infected with MSSA, whereas patients with MRSA infection were uniformly cured.

    “Interestingly, all treatment failures with trimethoprim-sulfamethoxazole occurred in patients infected with MSSA in that report, 165 whereas patients with MRSA infection were uniformly cured.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [165] 165. Markowitz N, Quinn EL, Saravolatz LD. Trimethoprim- sulfamethoxazole compared with vancomycin for the treatment of Staphylococcus aureus infection. Ann Intern Med. 1992;117:390-398. doi: 10.7326/0003-4819-117-5-390. source

  • May combine two claims.

    Premisecitation

    Increasing the dose of gentamicin in patients with normal renal function did not result in enhanced efficacy but did increase the risk of nephrotoxicity.

    “Increasing the dose of gentamicin in these patients did not result in enhanced efficacy but did increase the risk of nephrotoxicity.194”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [194] source

  • May combine two claims.

    Study design and conductcitation

    The meta-analysis included small, retrospective studies, which limits support for initial combination therapy by some experts.

    “The meta-analysis included small, retrospective studies, however, which limits support for initial combination therapy by some experts.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [154] 154. McConeghy KW, Bleasdale SC, Rodvold KA. The empirical combina- tion of vancomycin and a β-lactam for staphylococcal bacteremia. Clin Infect Dis. 2013;57:1760-1765. doi: 10.1093/cid/cit560. source

  • May combine two claims.

    Premisecitation

    Levine and Lamp reported daptomycin cure in 6 of 9 patients with E faecium IE; both daptomycin-treated patients reported by Segreti et al died.

    “Levine and Lamp 208 reported daptomycin cure in 6 of 9 patients with E faecium IE; both daptomycin-treated patients with E faecium IE reported by Segreti et al 209 died.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [208] source
    • cites [209] source

  • May combine two claims.

    Interpretationown data

    The major advantages of the ampicillin-ceftriaxone regimen are the lower risk of nephrotoxicity and the lack of need for measuring aminoglycoside serum concentrations.

    “The major advantages of the ampicillin-ceftriaxone regimen are the lower risk of nephrotoxicity and the lack of need for measuring aminoglycoside serum concentrations.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In the larger study, there were no significant differences between ampicillin-ceftriaxone and ampicillin-gentamicin in need for surgery, complications (except fewer renal failure cases in ampicillin-ceftriaxone), relapse, or mortality.

    “Sixth, in the larger study, there were no significant differences between ampicillin-ceftriaxone and ampicillin-gentamicin in the need for surgery, complications (except for fewer cases of renal failure in the ampicillin-ceftriaxone group), relapse, or mortality.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [191] 191. Fernández-Hidalgo N, Almirante B, Gavaldà J, Gurgui M, Peña C, de Alarcón A, Ruiz J, Vilacosta I, Montejo M, Vallejo N, López-Medrano F, Plata A, López J, Hidalgo-Tenorio C, Gálvez J, Sáez C, Lomas JM, Falcone M, de la Torre J, Martínez-Lacasa X, Pahissa A. Ampicillin plus ceftriaxone is as effective as ampicillin plus gentamicin for treat- ing Enterococcus faecalis infective endocarditis. Clin Infect Dis. 2013;56:1261-1268. doi: 10.1093/cid/cit052. 192. source

  • May combine two claims.

    Premisecitation

    The combination of ampicillin and imipenem acted synergistically in vitro and was effective therapy of multidrug-resistant enterococcal experimental IE.

    “The combination of ampicillin and imipenem acted synergistically in vitro and was effective therapy of multidrug-resistant enterococcal experimental IE.198”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [198] source

  • May combine two claims.

    Premisecitation

    None of the patients in either study developed nephrotoxicity with ampicillin-ceftriaxone therapy, whereas 20 of 87 (23%) ampicillin-gentamicin-treated patients developed nephrotoxicity (P<0.001).

    “Third, none of the patients in either study developed nephrotoxicity with ampicillin-ceftriaxone therapy, whereas 20 of 87 (23%) ampicillin-gentamicin-treated patients developed nephrotoxicity (P<0.001).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [190] 190. Gavaldà J, Len O, Miró JM, Muñoz P, Montejo M, Alarcón A, de la Torre-Cisneros J, Peña C, Martínez-Lacasa X, Sarria C, Bou G, Aguado JM, Navas E, Romeu J, Marco F, Torres C, Tornos P, Planes A, Falcó V, Almirante B, Pahissa A. Brief communication: treatment of Enterococcus faecalis endocarditis with ampicillin plus ceftriaxone. Ann Intern Med. 2007;146:574-579. source
    • cites [191] 191. Fernández-Hidalgo N, Almirante B, Gavaldà J, Gurgui M, Peña C, de Alarcón A, Ruiz J, Vilacosta I, Montejo M, Vallejo N, López-Medrano F, Plata A, López J, Hidalgo-Tenorio C, Gálvez J, Sáez C, Lomas JM, Falcone M, de la Torre J, Martínez-Lacasa X, Pahissa A. Ampicillin plus ceftriaxone is as effective as ampicillin plus gentamicin for treat- ing Enterococcus faecalis infective endocarditis. Clin Infect Dis. 2013;56:1261-1268. doi: 10.1093/cid/cit052. 192. source

  • May combine two claims.

    Premisecitation

    Multiple other case reports describe daptomycin failures, some due to emergence of daptomycin resistance during treatment.

    “Multiple other case reports describe daptomycin failures, some as a result of emergence of daptomycin-resistance during treatment.210,211”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [210] source
    • cites [211] source

  • May combine two claims.

    Premisecitation

    These are the largest series of E faecalis IE reported to date, 43 patients in one study and 272 in the other.

    “First, these are the largest series of E faecalis IE reported to date, 43 patients in 1 study 190 and 272 in the other study.191”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [190] 190. Gavaldà J, Len O, Miró JM, Muñoz P, Montejo M, Alarcón A, de la Torre-Cisneros J, Peña C, Martínez-Lacasa X, Sarria C, Bou G, Aguado JM, Navas E, Romeu J, Marco F, Torres C, Tornos P, Planes A, Falcó V, Almirante B, Pahissa A. Brief communication: treatment of Enterococcus faecalis endocarditis with ampicillin plus ceftriaxone. Ann Intern Med. 2007;146:574-579. source
    • cites [191] 191. Fernández-Hidalgo N, Almirante B, Gavaldà J, Gurgui M, Peña C, de Alarcón A, Ruiz J, Vilacosta I, Montejo M, Vallejo N, López-Medrano F, Plata A, López J, Hidalgo-Tenorio C, Gálvez J, Sáez C, Lomas JM, Falcone M, de la Torre J, Martínez-Lacasa X, Pahissa A. Ampicillin plus ceftriaxone is as effective as ampicillin plus gentamicin for treat- ing Enterococcus faecalis infective endocarditis. Clin Infect Dis. 2013;56:1261-1268. doi: 10.1093/cid/cit052. 192. source

  • May combine two claims.

    Premisecitation

    Mave et al compared daptomycin with linezolid for vancomycin-resistant Enterococcus bacteremia; 5 patients had E faecium IE, 1 of 2 daptomycin-treated and 2 of 3 linezolid-treated survived.

    “Mave et al 203 compared daptomycin with linezolid for vancomycin-resistant Enterococcus bacteremia.Five patients had E faecium IE; 1 of 2 daptomycin-treated patients and 2 of 3 linezolid-treated patients survived.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [203] source

  • May combine two claims.

    Premisecitation

    >90% of enterococci are reportedly susceptible in vitro to daptomycin, but daptomycin resistance is an increasing problem.

    “Although >90% of enterococci are reportedly susceptible in vitro to daptomycin, the emergence of daptomycin resistance is an increasing problem.207”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [207] source

  • May combine two claims.

    Premisecitation

    Positive blood cultures are a major diagnostic criterion in IE and key to identifying a pathogenic agent and optimal antimicrobial regimen.

    “Positive blood cultures are a major diagnostic criterion in IE and key to identifying an pathogenic agent and an optimal antimicrobial regimen.225,226”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [225] 225. Von Reyn CF, Levy BS, Arbeit RD, Friedland G, Crumpacker CS. Infective endocarditis: an analysis based on strict case definitions. Ann Intern Med. 1981;94(pt 1):505-518. source
    • cites [226] 226. Washington JA. The microbiological diagnosis of infective endocarditis. J Antimicrob Chemother. 1987;20(suppl A):29-39. source

  • May combine two claims.

    Premisecitation

    Escherichia coli and Pseudomonas aeruginosa accounted for 51% of cases, and 59% had PVE.

    “Escherichia coli and Pseudomonas aeruginosa accounted for 51% of cases, and 59% had PVE.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [221] 221. Morpeth S, Murdoch D, Cabell CH, Karchmer AW, Pappas P, Levine D, Nacinovich F, Tattevin P, Fernández-Hidalgo N, Dickerman S, Bouza E, del Río A, Lejko-Zupanc T, de Oliveira Ramos A, Iarussi D, Klein J, Chirouze C, Bedimo R, Corey GR, Fowler VG Jr; International Collaboration on Endocarditis Prospective Cohort Study (ICE-PCS) Investigators. Non-HACEK Gram-negative bacillus endocarditis. Ann Intern Med. 2007;147:829-835. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

    Premisecitation

    In-hospital mortality rate was 24% for non-HACEK Gram-negative IE.

    “Although management included cardiac surgery in 51% of cases, the in-hospital mortality rate was 24%.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [221] 221. Morpeth S, Murdoch D, Cabell CH, Karchmer AW, Pappas P, Levine D, Nacinovich F, Tattevin P, Fernández-Hidalgo N, Dickerman S, Bouza E, del Río A, Lejko-Zupanc T, de Oliveira Ramos A, Iarussi D, Klein J, Chirouze C, Bedimo R, Corey GR, Fowler VG Jr; International Collaboration on Endocarditis Prospective Cohort Study (ICE-PCS) Investigators. Non-HACEK Gram-negative bacillus endocarditis. Ann Intern Med. 2007;147:829-835. source

  • May combine two claims.

    Premisecitation

    In that analysis, serological results were positive in 47.7% of cases, primarily for Coxiella and Bartonella species.

    “Second, serological results were positive in 47.7% of cases, primarily for Coxiella and Bartonella species infection.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [236] 236. Fournier PE, Thuny F, Richet H, Lepidi H, Casalta JP, Arzouni JP, Maurin M, Célard M, Mainardi JL, Caus T, Collart F, Habib G, Raoult D. Comprehensive diagnostic strategy for blood culture-negative endocardi- tis: a prospective study of 819 new cases. Clin Infect Dis. 2010;51:131- 140. doi: 10.1086/653675. source

  • May combine two claims.

    Premisecitation

    Fungal infective endocarditis is rare but can develop in a wide range of patients.

    “Fungal IE is rare but can develop in a wide range of patients.240,241”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [240] 240. Pierrotti LC, Baddour LM. Fungal endocarditis, 1995-2000. Chest. 2002;122:302-310. source
    • cites [241] 241. Ellis ME, Al-Abdely H, Sandridge A, Greer W, Ventura W. Fungal endo- carditis: evidence in the world literature, 1965-1995. Clin Infect Dis. 2001;32:50-62. doi: 10.1086/317550. source

  • May combine two claims.

    Premisecitation

    In a large prospective analysis of referred samples, a pathogen was identified in 62.7% of 759 cases; in 2.5%, a noninfectious origin was confirmed.

    “First, there was identification of a pathogen in 62.7% of 759 cases; in 2.5%, a noninfectious origin (see below) was confirmed.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [236] 236. Fournier PE, Thuny F, Richet H, Lepidi H, Casalta JP, Arzouni JP, Maurin M, Célard M, Mainardi JL, Caus T, Collart F, Habib G, Raoult D. Comprehensive diagnostic strategy for blood culture-negative endocardi- tis: a prospective study of 819 new cases. Clin Infect Dis. 2010;51:131- 140. doi: 10.1086/653675. source

  • May combine two claims.

    Premisecitation

    Aspergillus is a cause of culture-negative infective endocarditis, and when this occurs it is usually in a patient with a prosthetic cardiac valve.

    “Thus, Aspergillus is a cause of culture-negative IE, and when this occurs, it is usually in a patient with a prosthetic cardiac valve.240”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [240] 240. Pierrotti LC, Baddour LM. Fungal endocarditis, 1995-2000. Chest. 2002;122:302-310. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Anti-phospholipid antibody syndrome has been described as both a primary and secondary syndrome and is associated with presence of APA.

    “Perhaps the one that has received the most attention is anti-phospholipid antibody (APA) syndrome, 238 which has been described as both a primary and a secondary syndrome and is associated with the presence of APA.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [238] 238. Hojnik M, George J, Ziporen L, Shoenfeld Y. Heart valve involve- ment (Libman-Sacks endocarditis) in the antiphospholipid syndrome. Circulation. 1996;93:1579-1587. source

  • May combine two claims.

    Premisecitation

    Fungal infective endocarditis has been recognized as a cause of early prosthetic valve endocarditis, but in a single-center case series 43% of these cases had symptom onset more than 1 year after prosthetic valve placement.

    “Fungal IE has been recognized as a cause of early PVE, but a case series from a single medical center demonstrated that 43% of these cases had symptom onset >1 years after prosthetic valve placement.242”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [242] 242. Nguyen MH, Nguyen ML, Yu VL, McMahon D, Keys TF, Amidi M. Candida prosthetic valve endocarditis: prospective study of six cases and review of the literature. Clin Infect Dis. 1996;22:262-267. source

  • May combine two claims.

    Premisecitation

    Blood cultures are ultimately positive in most cases of Candida infective endocarditis, whereas they are rarely positive in cases caused by Aspergillus.

    “Blood cultures are ultimately positive in most cases caused by the former pathogen, whereas they are rarely positive in cases caused by the latter fungus.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [240] 240. Pierrotti LC, Baddour LM. Fungal endocarditis, 1995-2000. Chest. 2002;122:302-310. source
    • cites [241] 241. Ellis ME, Al-Abdely H, Sandridge A, Greer W, Ventura W. Fungal endo- carditis: evidence in the world literature, 1965-1995. Clin Infect Dis. 2001;32:50-62. doi: 10.1086/317550. source

  • May combine two claims.

    Premisecitation

    A meta-analysis of 64 reported patients with Candida infective endocarditis who did not undergo valve surgery because they were deemed unacceptable surgical candidates supports the notion that fluconazole suppressive therapy is useful; 20 of 21 patients (95%) ultimately treated with long-term suppressive therapy survived during follow-up of at least 6 months.

    “A meta-analysis that included 64 reported patients with Candida IE who did not undergo valve surgery because they were deemed to be unacceptable surgical candidates supports the notion that fluconazole suppressive therapy is useful; 20 of 21 patients (95%) who were ultimately treated with long-term suppressive therapy survived during follow-up, which was ≥6 months.244”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [244] 244. Steinbach WJ, Perfect JR, Cabell CH, Fowler VG, Corey GR, Li JS, Zaas AK, Benjamin DK Jr. A meta-analysis of medical versus surgical therapy for Candida endocarditis. J Infect. 2005;51:230-247. doi: 10.1016/j. jinf.2004.10.016. source

  • May combine two claims.

    Premisecitation

    Candida and Aspergillus species account for the large majority of fungal infective endocarditis, and Candida-related infective endocarditis is much more common than Aspergillus-related disease.

    “Candida and Aspergillus species account for the large majority of fungal IE, and Candida-related IE is much more common than Aspergillus-related disease.240,241”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [240] 240. Pierrotti LC, Baddour LM. Fungal endocarditis, 1995-2000. Chest. 2002;122:302-310. source
    • cites [241] 241. Ellis ME, Al-Abdely H, Sandridge A, Greer W, Ventura W. Fungal endo- carditis: evidence in the world literature, 1965-1995. Clin Infect Dis. 2001;32:50-62. doi: 10.1086/317550. source

  • May combine two claims.

    Premisecitation

    Patients in this trial were young, had limited comorbidity based on a EuroSCORE, a low prevalence of S aureus infective endocarditis, and lower mortality compared with most contemporary patient cohorts.

    “In addition, patients in this trial were young and had limited comorbidity based on a EuroSCORE, a calculated risk of surgical mortality (http://www.euroscore.org), a low prevalence of S aureus IE, and lower mortality compared with most contemporary patient cohorts.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] 17. Kang DH, Kim YJ, Kim SH, Sun BJ, Kim DH, Yun SC, Song JM, Choo SJ, Chung CH, Song JK, Lee JW, Sohn DW. Early surgery versus conven- tional treatment for infective endocarditis. N Engl J Med. 2012;366:2466- 2473. doi: 10.1056/NEJMoa1112843. source

  • Probably not a substantial claim: may not pass S1 (asserted), S4 (based). The quote only partly states this claim.

    Premisecitation

    Subgroup analysis indicated lower in-hospital and 1-year mortality with early surgery only in the group of prosthetic valve infective endocarditis patients with the highest surgical propensity.

    “Subgroup analysis indicated a lower in-hospital and 1-year mortality with early surgery only in the group of patients with the highest surgical propensity.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [259] 259. Lalani T, Chu VH, Park LP, Cecchi E, Corey GR, Durante-Mangoni E, Fowler VG Jr, Gordon D, Grossi P, Hannan M, Hoen B, Muñoz P, Rizk H, Kanj SS, Selton-Suty C, Sexton DJ, Spelman D, Ravasio V, Tripodi MF, Wang A; International Collaboration on Endocarditis-Prospective Cohort Study Investigators. In-hospital and 1-year mortality in patients undergoing early surgery for prosthetic valve endocarditis [published correction appears in JAMA Intern Med. 2013;173:1846]. JAMA Intern Med. 2013;173:1495-1504. doi: 10.1001/jamainternmed. 2013.8203. source

  • May combine two claims.

    Premisecitation

    Only 1 study examined the role of valve surgery in prosthetic valve infective endocarditis; after adjustment for differences in clinical characteristics and survival bias, early valve replacement was not associated with lower mortality compared with medical therapy in the overall cohort.

    “Only 1 study examined the role of valve surgery in PVE.259 After adjustment for differences in clinical characteristics and survival bias, early valve replacement was not associated with lower mortality compared with medical therapy in the overall cohort.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [259] 259. Lalani T, Chu VH, Park LP, Cecchi E, Corey GR, Durante-Mangoni E, Fowler VG Jr, Gordon D, Grossi P, Hannan M, Hoen B, Muñoz P, Rizk H, Kanj SS, Selton-Suty C, Sexton DJ, Spelman D, Ravasio V, Tripodi MF, Wang A; International Collaboration on Endocarditis-Prospective Cohort Study Investigators. In-hospital and 1-year mortality in patients undergoing early surgery for prosthetic valve endocarditis [published correction appears in JAMA Intern Med. 2013;173:1846]. JAMA Intern Med. 2013;173:1495-1504. doi: 10.1001/jamainternmed. 2013.8203. source

  • May combine two claims.

    Interpretationnone given

    After stroke, neurological deterioration can occur as a result of hemorrhagic transformation with anticoagulation during cardiopulmonary bypass or exacerbation of cerebral ischemia attributable to hypotension during cardiac surgery.

    “After stroke, neurological deterioration can occur as a result of hemorrhagic transformation with anticoagulation during cardiopulmonary bypass or exacerbation of cerebral ischemia attributable to hypotension during cardiac surgery.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The trial reported a reduction in the composite outcome of in-hospital deaths and embolic events with early surgery (3% versus 23%), but the difference between groups was driven by a significant decrease in embolic events with early surgery.

    “Although the authors 17 report a reduction in the composite outcome of in-hospital deaths and embolic events with early surgery (3% versus 23%), the differences between the 2 groups were driven by a significant decrease in embolic events with early surgery.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] 17. Kang DH, Kim YJ, Kim SH, Sun BJ, Kim DH, Yun SC, Song JM, Choo SJ, Chung CH, Song JK, Lee JW, Sohn DW. Early surgery versus conven- tional treatment for infective endocarditis. N Engl J Med. 2012;366:2466- 2473. doi: 10.1056/NEJMoa1112843. source

  • May combine two claims.

    Premisecitation

    In a study based on transesophageal echocardiography, mitral vegetations greater than 1 cm in diameter were associated with the greatest frequency of embolism, and the association was strengthened when the analysis was limited to patients who had not yet experienced a clinical embolic event.

    “In a study 57 based on TEE, mitral vegetations >1 cm in diameter were associated with the greatest frequency of embolism.The association was strengthened when the analysis was limited to those patients who had not yet experienced a clinical embolic event.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [57] 57. Mügge A, Daniel WG, Frank G, Lichtlen PR. Echocardiography in infec- tive endocarditis: reassessment of prognostic implications of vegetation size determined by the transthoracic and the transesophageal approach. J Am Coll Cardiol. 1989;14:631-638. doi: 10.1016/0735-1097(89)90104-6. source

  • May combine two claims.

    Premisecitation

    The first study to evaluate the timing of surgery after stroke in infective endocarditis that included a risk adjustment for differences in patient characteristics comprised 198 patients; 58 patients underwent surgery within 1 week of stroke and 140 underwent surgery at least 8 days after stroke.

    “The first study to evaluate the timing of surgery after stroke in IE that included a risk adjustment for differences in patient characteristics comprised 198 patients.273 Fifty-eight patients who underwent surgery within 1 week of stroke were compared with 140 patients who underwent surgery ≥8 days after stroke.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [273] source

  • May combine two claims.

    Premisecitation

    Up to 65% of embolic events involve the central nervous system, and more than 90% of central nervous system emboli lodge in the distribution of the middle cerebral artery.

    “Up to 65% of embolic events involve the CNS, and >90% of CNS emboli lodge in the distribution of the middle cerebral artery.277”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [277] source

  • May combine two claims.

    Premisecitation

    Hospital mortality was numerically but not significantly higher in the early surgery group (22.4% versus 12%).

    “Hospital mortality was numerically but not significantly higher in the early surgery group (22.4% versus 12%).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [273] source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Rates of embolization can be higher if noninvasive imaging, including MRI and CT scanning, is routinely done to detect asymptomatic emboli.

    “Rates can be higher if noninvasive imaging, including MRI and CT scanning, is routinely done to detect asymptomatic (silent) emboli.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    After hemorrhagic stroke, the risk of exacerbation by surgery is prohibitively high in the first month but can extend beyond 1 month in some patients, possibly because of the presence of undetected mycotic aneurysms.

    “After hemorrhagic stroke, the risk of exacerbation by surgery is prohibitively high in the first month but can extend beyond 1 month in some patients, possibly because of the presence of undetected mycotic aneurysms (MAs).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    A second, infrequent peak of late embolic events has been observed to occur 15 to 30 weeks after the diagnosis of infective endocarditis and has been associated with nonhealing vegetations as defined by echocardiography.

    “In addition, a second, albeit infrequent, peak of late embolic events has been observed to occur 15 to 30 weeks after the diagnosis of IE and has been associated with nonhealing vegetations (failure of a vegetation to stabilize or diminish in size) as defined by echocardiography.63”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [63] 63. Konstadt SN, Louie EK, Shore-Lesserson L, Black S, Scanlon P. The effects of loading changes on intraoperative Doppler assessment of mitral regurgitation. J Cardiothorac Vasc Anesth. 1994;8:19-23. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisereasoning

    The role of echocardiography in predicting embolic events has been controversial.

    “The role of echocardiography in predicting embolic events has been controversial.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In a survey that included 4 echocardiographers blinded to clinical data, interobserver agreement was high for the presence of vegetation (98%) and involved site (97%), but considerably less for vegetation size (73%), mobility (57%), shape (37%), and attachment (40%).

    “In 1 survey 282 that included 4 echocardiographers who were blinded to clinical data, interobserver agreement was mixed on the characterization of vegetations.Agreement was high for the presence of vegetation (98%) and involved site (97%); interobserver agreement was considerably less for vegetation size (73%), mobility (57%), shape (37%), and attachment (40%).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [282] source

  • May combine two claims.

    Interpretationcitation

    The anatomic vulnerability of the area near the membranous septum and atrioventricular node explains both why abscesses occur in this location and why heart block is a frequent sequela.

    “The anatomic vulnerability of this area explains both why abscesses occur in this location and why heart block is a frequent sequela.300”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [300] 300. Arnett EN, Roberts WC. Prosthetic valve endocarditis: clinicopathologic analysis of 22 necropsy patients with comparison observations in 74 nec- ropsy patients with active infective endocarditis involving natural left- sided cardiac valves. Am J Cardiol. 1976;38:281-292. source

  • May combine two claims.

    Interpretationreasoning

    The criterion of at least 2 major embolic events for valvular surgery is arbitrary and excludes cutaneous embolization, which is common, or embolism occurring before the institution of therapy, which is common among infective endocarditis patients who develop embolic events.

    “This criterion is arbitrary and excludes cutaneous embolization, which is common, or embolism occurring before the institution of therapy, which is common among IE patients who develop embolic events.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationnone given

    A period of at least 2 weeks after a central nervous system embolic event should allow for thrombus organization and prevent the acute hemorrhagic transformation of embolic lesions.

    “This time should allow for thrombus organization and prevent the acute hemorrhagic transformation of embolic lesions.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Early surgical intervention may preclude a primary or recurrent major embolic event but exposes the patient to both immediate and lifelong risks of valve replacement if the valve cannot be primarily repaired.

    “Early surgical intervention may preclude a primary or recurrent major embolic event but exposes the patient to both immediate and lifelong risks of valve replacement if the valve cannot be primarily repaired.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Splenic abscesses generally require splenectomy or a drainage procedure because the usefulness of antimicrobial therapy is in preventing disease extension in the spleen and treating systemic infection rather than eliminating abscesses.

    “For example, splenic abscesses generally require splenectomy or a drainage procedure because the usefulness of antimicrobial therapy is in preventing disease extension in the spleen and treating systemic infection rather than eliminating abscesses.314”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [314] source

  • May combine two claims.

    Interpretationreasoning

    Structural lesions and intracardiac fistulas from periannular infection may be catastrophic; even if their hemodynamic impact is tolerated, these lesions will not heal with medical treatment alone and require urgent operative intervention.

    “Such structural lesions and intracardiac fistulas may be catastrophic; even if their hemodynamic impact is tolerated, these lesions will not heal with medical treatment alone and require urgent operative intervention.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Perivalvular abscesses are particularly common with prosthetic valves because the annulus, rather than the leaflet, is the usual primary site of infection, especially in early prosthetic valve infective endocarditis and on bioprosthetic valves.

    “Perivalvular abscesses are particularly common with prosthetic valves because the annulus, rather than the leaflet, is the usual primary site of infection, especially in early PVE and on bioprosthetic valves.302”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [302] 302. Carpenter JL. Perivalvular extension of infection in patients with infec- tious endocarditis. Rev Infect Dis. 1991;13:127-138. source

  • May combine two claims.

    Premisecitation

    On ECG, new atrioventricular block has a positive predictive value of 88% for abscess formation but low (45%) sensitivity.

    “On ECG, new atrioventricular block has a positive predictive value of 88% for abscess formation but low (45%) sensitivity.298”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [298] 298. Blumberg EA, Karalis DA, Chandrasekaran K, Wahl JM, Vilaro J, Covalesky VA, Mintz GS. Endocarditis-associated paravalvular abscesses: do clinical parameters predict the presence of abscess? Chest. 1995;107:898-903. source

  • May combine two claims.

    Premisecitation

    Periannular extension is common, occurring in 10% to 40% of all native valve infective endocarditis and complicating aortic infective endocarditis more commonly than mitral or tricuspid infective endocarditis.

    “Periannular extension is common, occurring in 10% to 40% of all NVE and complicating aortic IE more commonly than mitral or tricuspid IE. [301][302][303][304]”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [301] 301. Fernicola DJ, Roberts WC. Frequency of ring abscess and cuspal infec- tion in active infective endocarditis involving bioprosthetic valves. Am J Cardiol. 1993;72:314-323. source
    • cites [302] 302. Carpenter JL. Perivalvular extension of infection in patients with infec- tious endocarditis. Rev Infect Dis. 1991;13:127-138. source
    • cites [303] 303. Anguera I, Miro JM, Vilacosta I, Almirante B, Anguita M, Muñoz P, Roman JA, de Alarcon A, Ripoll T, Navas E, Gonzalez-Juanatey C, Cabell CH, Sarria C, Garcia-Bolao I, Fariñas MC, Leta R, Rufi G, Miralles F, Pare C, Evangelista A, Fowler VG Jr, Mestres CA, de Lazzari E, Guma JR; Aorto-cavitary Fistula in Endocarditis Working Group. Aorto-cavitary fistulous tract formation in infective endocarditis: clinical and echocardiographic features of 76 cases and risk factors for mortality. Eur Heart J. 2005;26:288-297. doi: 10.1093/eurheartj/ehi034. 304. source

  • May combine two claims.

    Premisecitation

    Multivariate analysis demonstrated that factors associated with an increased risk of death included moderate to severe heart failure, prosthetic valve infective endocarditis, and urgent or emergency surgical intervention.

    “Multivariate analysis demonstrated that factors associated with an increased risk of death included moderate to severe heart failure, PVE, and urgent or emergency surgical intervention.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [304] source

  • May combine two claims.

    Premisecitation

    Streptococci and S aureus account for 50% and 10% of ICMA cases, respectively.

    “Streptococci and S aureus account for 50% and 10% of cases, respectively, 317,318”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [317] source
    • cites [318] source

  • May combine two claims.

    Premisecitation

    OPAT is efficacious, safe, and cost-effective for a variety of infections, including IE that requires prolonged parenteral therapy in hospitalized patients who otherwise no longer require inpatient care but do require continued parenteral antimicrobial therapy.

    “Outpatient parenteral antibiotic therapy (OPAT) is efficacious, safe, and cost-effective for a variety of infections, [323][324][325] including IE that requires prolonged parenteral therapy in hospitalized patients who otherwise no longer require inpatient care but do require continued parenteral antimicrobial therapy.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [323] source
    • cites [324] source
    • cites [325] source

  • May combine two claims.

    Premisecitation

    Neurological signs and symptoms in ICMAs are nonspecific and may suggest a mass lesion or an embolic event.

    “Neurological signs and symptoms are nonspecific and may suggest a mass lesion or an embolic event.315,317”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [315] source
    • cites [317] source
105 of 105

  • The paper relies on this without support.

    Outcomes of infective endocarditis have not improved despite medical and surgical advances.

    “changes in pathogen prevalence, in particular a more common staphylococcal origin, have affected outcomes, which have not improved despite medical and surgical advances.”

  • The paper relies on this without support.

    The modified Duke criteria are universally accepted.

    “These additional parameters have not been formally integrated into the modified Duke criteria, 24 however, which are universally accepted.”

  • The paper relies on this without support.

    Host characteristics such as impaired immunity contribute to challenges in treating IE.

    “Host characteristics such as impaired immunity also contribute to challenges in therapeutics.”

  • The paper relies on this without support.

    Antibiotics may fail to eradicate infection as a result of increased binding of the drug to serum proteins, perturbations of antibiotic penetration into the vegetation, and unique antibiotic PK/PD features.

    “In addition, antibiotics may fail to eradicate infection as a result of increased binding of the drug to serum proteins, perturbations of antibiotic penetration into the vegetation, and unique antibiotic pharmacokinetic/pharmacodynamic (PK/PD) features.”

  • The paper relies on this without support.

    For enterococci, bactericidal activity can be achieved by the combination of certain β-lactam antibiotics with an aminoglycoside.

    “For enterococci, bactericidal activity can be achieved by the combination of certain β-lactam antibiotics (eg, penicillin, ampicillin, and piperacillin) with an aminoglycoside.”

  • The paper relies on this without support.

    The rate of bactericidal activity against some other organisms can be enhanced by a combination of a β-lactam antibiotic plus an aminoglycoside.

    “The rate of bactericidal activity against some other organisms can also be enhanced by a combination of a β-lactam antibiotic plus an aminoglycoside.”

  • The paper relies on this without support.

    The addition of gentamicin sulfate to penicillin exerts a synergistic killing effect in vitro on VGS and S gallolyticus (bovis).

    “The addition of gentamicin sulfate to penicillin exerts a synergistic killing effect in vitro on VGS and S gallolyticus (bovis).”

  • The paper relies on this without support.

    The combination of penicillin or ceftriaxone with gentamicin results in synergistic killing in animal models of VGS or S gallolyticus (bovis) experimental IE.

    “The combination of penicillin or ceftriaxone with gentamicin results in synergistic killing in animal models of VGS or S gallolyticus (bovis) experimental IE.”

  • The paper relies on this without support.

    Both penicillin and ceftriaxone are overall well tolerated but have the potential for causing adverse drug events; common ones include rash, fever, diarrhea, and neutropenia.

    “Both penicillin and ceftriaxone are overall well tolerated but, like all antimicrobials, have the potential for causing adverse drug events; some of the more common ones include rash, fever, diarrhea, and neutropenia.”

  • The paper relies on this without support.

    Prolonged intravenous use of vancomycin may be complicated by thrombophlebitis, rash, fever, neutropenia, and rarely ototoxic reactions.

    “Prolonged intravenous use of vancomycin may be complicated by thrombophlebitis, rash, fever, neutropenia, and rarely ototoxic reactions.”

  • The paper relies on this without support.

    The likelihood of red man syndrome is reduced with an infusion of vancomycin over at least 1 hour.

    “The likelihood of “red man” syndrome is reduced with an infusion of vancomycin over ≥1 hour.”

  • The paper relies on this without support.

    Penicillin resistance in vitro occurs among some strains of VGS and S gallolyticus (bovis).

    “Penicillin resistance in vitro occurs among some strains of VGS and S gallolyticus (bovis).”

  • The paper relies on this without support.

    In non-IDUs, S aureus infective endocarditis involves primarily the left side of the heart.

    “In non-IDUs, S aureus IE involves primarily the left side of the heart and is associated with mortality rates ranging from 25% to 40%.”

  • The paper relies on this without support.

    In non-IDUs, S aureus infective endocarditis is associated with mortality rates ranging from 25% to 40%.

    “In non-IDUs, S aureus IE involves primarily the left side of the heart and is associated with mortality rates ranging from 25% to 40%.”

  • The paper relies on this without support.

    S aureus infective endocarditis in IDUs often involves the tricuspid valve.

    “S aureus IE in IDUs often involves the tricuspid valve.”

  • The paper relies on this without support.

    Most CoNS are resistant to methicillin.

    “Most CoNS are resistant to methicillin.”

  • The paper relies on this without support.

    S lugdunensis tends to cause a substantially more virulent form of infective endocarditis, with a high rate of perivalvular extension of infection and metastatic infection.

    “This species of CoNS tends to cause a substantially more virulent form of IE, with a high rate of perivalvular extension of infection and metastatic infection.”

  • The paper relies on this without support.

    Cefazolin has inadequate blood-brain barrier penetrability.

    “In cases of brain abscess complicating MSSA IE, nafcillin is the preferred agent rather than cefazolin, which has inadequate blood-brain barrier penetrability.”

  • The paper relies on this without support.

    Current laboratory screening procedures for detecting penicillin susceptibility may not be reliable.

    “Unfortunately, the current laboratory screening procedures for detecting penicillin susceptibility may not be reliable.”

  • The paper relies on this without support.

    Enterococci are the third leading cause of infective endocarditis and account for approximately 10% of cases in non-IDUs.

    “Enterococci are the third leading cause of IE and account for ≈10% of cases in non-IDUs.”

  • The paper relies on this without support.

    E faecalis causes approximately 97% of cases of enterococcal infective endocarditis; E faecium causes approximately 1% to 2%; and other species cause approximately 1%.

    “E faecalis causes ≈97% of cases of IE; E faecium, ≈1% to 2%; and other species, ≈1%.”

  • The paper relies on this without support.

    Killing of susceptible strains of enterococci requires the synergistic action of penicillin, ampicillin, or vancomycin in combination with either gentamicin or streptomycin.

    “Killing of susceptible strains of enterococci requires the synergistic action of penicillin, ampicillin, or vancomycin in combination with either gentamicin or streptomycin.”

  • The paper relies on this without support.

    Enterococci are relatively impermeable to aminoglycosides.

    “Enterococci are relatively impermeable to aminoglycosides.”

  • The paper relies on this without support.

    High concentrations of aminoglycosides in the extracellular environment are required to achieve sufficient concentrations of the drug at the ribosomal target within the bacterial cell for bactericidal activity.

    “High concentrations of aminoglycosides in the extracellular environment are required to achieve sufficient concentrations of the drug at the site of the ribosomal target within the bacterial cell for bactericidal activity.”

  • The paper relies on this without support.

    If an enterococcal strain is resistant to the cell wall-active agent or high concentrations of an aminoglycoside, then the combination of an aminoglycoside and the cell wall-active agent will not result in bactericidal activity in vitro or in vivo, nor predictably produce a microbiological cure in human enterococcal infective endocarditis.

    “If an enterococcal strain is resistant to the cell wall-active agent or high concentrations of an aminoglycoside (500 µg/mL gentamicin or 1000 µg/mL streptomycin), then the combination of an aminoglycoside and the cell wall-active agent will not result in bactericidal activity in vitro or in vivo (ie, in experimental IE models), nor will it predictably produce a microbiological cure in human enter”

  • The paper relies on this without support.

    Since the 2005 AHA statement on antimicrobial therapy of patients with infective endocarditis, the frequency of aminoglycoside-resistant strains of enterococci has increased significantly.

    “Since the publication of the latest (2005) AHA statement on antimicrobial therapy of patients with IE, 12 the frequency of aminoglycoside-resistant strains of enterococci has increased significantly.”

  • The paper relies on this without support.

    Approximately 97% of cases of enterococcal infective endocarditis are caused by E faecalis, and the majority of these remain susceptible to beta-lactams and vancomycin, but aminoglycoside resistance is increasing in frequency.

    “Approximately 97% of cases of enterococcal IE are caused by E faecalis, and the majority of these remain susceptible to β-lactams and vancomycin, but aminoglycoside resistance is increasing in frequency.”

  • The paper relies on this without support.

    Patients with preexisting mild or severe renal failure may not be able to safely complete a 4- to 6-week course of gentamicin therapy because of gentamicin-associated nephrotoxicity.

    “Patients with preexisting mild (creatinine clearance, 30-50 mL/min) or severe (creatinine clearance, <30 mL/min) renal failure may not be able to safely complete a 4-to 6-week course of gentamicin therapy because of gentamicin-associated nephrotoxicity.”

  • The paper relies on this without support.

    Streptomycin is less nephrotoxic than gentamicin.

    “The main advantage is that streptomycin is less nephrotoxic than gentamicin.”

  • The paper relies on this without support.

    Streptomycin has a higher risk of ototoxicity than gentamicin, which may not be reversible.

    “There are several disadvantages of using streptomycin-containing regimens, including a lack of familiarity among clinicians with streptomycin, a higher risk of ototoxicity, which may not be reversible, and drug availability limitations.”

  • The paper relies on this without support.

    Most strains of E faecalis are inhibited but not killed in vitro by penicillin or ampicillin, with MICs usually 2 to 4 µg/mL penicillin; ampicillin MICs are usually 1 dilution lower.

    “Most strains of E faecalis are inhibited but not killed in vitro by penicillin or ampicillin, with MICs usually 2 to 4 µg/ mL penicillin; ampicillin MICs are usually 1 dilution lower.”

  • The paper relies on this without support.

    Cephalosporins and antistaphylococcal penicillins have minimal or no in vitro activity against enterococci.

    “Cephalosporins and antistaphylococcal penicillins (oxacillin, nafcillin) have minimal or no in vitro activity against enterococci.”

  • The paper relies on this without support.

    The in vitro activity of carbapenems is variable, with imipenem being most active.

    “The in vitro activity of carbapenems is variable, with imipenem being most active.”

  • The paper relies on this without support.

    The likely mechanism of double-β-lactam combinations against enterococci is saturation of different penicillin-binding proteins.

    “The likely mechanism of double-β-lactam combinations against enterococci is saturation of different penicillin-binding proteins.”

  • The paper relies on this without support.

    The potential disadvantage of ampicillin-ceftriaxone is the possibility of hypersensitivity reactions to 2 separate β-lactams.

    “The potential disadvantage is the possibility of hypersensitivity reactions to 2 separate β-lactams.”

  • The paper relies on this without support.

    Aminoglycoside resistance in enterococci is most commonly the result of acquisition of plasmid-mediated aminoglycoside-modifying enzymes.

    “Aminoglycoside resistance in enterococci is most commonly the result of the acquisition of plasmid-mediated aminoglycoside-modifying enzymes.”

  • The paper relies on this without support.

    E faecalis strains resistant to high levels of gentamicin are resistant to most other aminoglycosides, although some are susceptible to streptomycin.

    “E faecalis strains resistant to high levels of gentamicin are resistant to most other aminoglycosides, although some of them are susceptible to streptomycin.”

  • The paper relies on this without support.

    The total number of cases published in European studies far exceeds the relatively small number of reported streptomycin-treated patients with enterococcal IE.

    “The total number of cases published in the European studies far exceeds the relatively small number of reported streptomycin-treated patients with enterococcal IE.”

  • The paper relies on this without support.

    Combinations of penicillin or ampicillin with gentamicin are preferable to combined vancomycin-gentamicin because of the potential increased risk of ototoxicity and nephrotoxicity with the vancomycin-gentamicin combination.

    “Combinations of penicillin or ampicillin with gentamicin are preferable to combined vancomycin-gentamicin because of the potential increased risk of ototoxicity and nephrotoxicity with the vancomycin-gentamicin combination.”

  • The paper relies on this without support.

    Combinations of penicillin or ampicillin and gentamicin are more active than combinations of vancomycin and gentamicin in vitro and in animal models of experimental IE.

    “Moreover, combinations of penicillin or ampicillin and gentamicin are more active than combinations of vancomycin and gentamicin in vitro and in animal models of experimental IE.”

  • The paper relies on this without support.

    Rarely, strains of E faecalis produce an inducible β-lactamase.

    “Rarely, strains of E faecalis produce an inducible β-lactamase.”

  • The paper relies on this without support.

    β-lactamase-producing E faecalis strains are susceptible to ampicillin-sulbactam and to vancomycin.

    “These β-lactamase-producing strains are susceptible to ampicillin-sulbactam and to vancomycin.”

  • The paper relies on this without support.

    Intrinsic penicillin resistance is uncommon in E faecalis but is common in E faecium.

    “Intrinsic penicillin resistance is uncommon in E faecalis but is common in E faecium.”

  • The paper relies on this without support.

    Most vancomycin-resistant enterococci are E faecium, and as many as 95% of strains express multidrug resistance to vancomycin, aminoglycosides, and penicillins.

    “Most of these strains are E faecium, and as many as 95% of strains express multidrug resistance to vancomycin, aminoglycosides, and penicillins.”

  • The paper relies on this without support.

    Only about 3% of E faecalis strains are multidrug resistant, and many vancomycin-resistant E faecalis are penicillin susceptible.

    “Only about 3% of E faecalis strains are multidrug resistant, and many vancomycin-resistant E faecalis are penicillin susceptible.”

  • The paper relies on this without support.

    E faecium IE is uncommon.

    “Fortunately, E faecium IE is uncommon.”

  • The paper relies on this without support.

    Linezolid and daptomycin are the only 2 antimicrobial agents currently available in the United States that may be useful for treatment of multidrug-resistant E faecium IE.

    “Linezolid and daptomycin are the only 2 antimicrobial agents currently available in the United States that may be useful for the treatment of multidrug-resistant E faecium IE.”

  • The paper relies on this without support.

    Quinupristin-dalfopristin may be active in vitro but only against E faecium and is inactive against E faecalis.

    “Quinupristin-dalfopristin may be active in vitro but only against strains of E faecium and is inactive against E faecalis.”

  • The paper relies on this without support.

    Quinupristin-dalfopristin is rarely used because of severe side effects, including intractable muscle pain.

    “Quinupristin-dalfopristin is rarely used because of severe side effects, including intractable muscle pain.”

  • The paper relies on this without support.

    Tigecycline is active in vitro against some strains of multidrug-resistant enterococci, but there are minimal published data on its clinical use.

    “Tigecycline is active in vitro against some strains of multidrug-resistant enterococci, but there are minimal published data on its use clinically.”

  • The paper relies on this without support.

    Linezolid is bacteriostatic in vitro against enterococci, and susceptibility ranges from 97% to 99%, including multidrug-resistant strains.

    “Linezolid is bacteriostatic in vitro against enterococci, and susceptibility of enterococci to linezolid ranges from 97% to 99%, including strains that are multidrug resistant.”

  • The paper relies on this without support.

    Daptomycin has bactericidal activity in vitro against susceptible strains of enterococci.

    “Daptomycin is a cyclic lipopeptide antibiotic that has bactericidal activity in vitro against susceptible strains of enterococci.”

  • The paper relies on this without support.

    HACEK microorganisms grow slowly in standard blood culture media, and recovery may require prolonged incubation.

    “These microorganisms grow slowly in standard blood culture media, and recovery may require prolonged incubation.”

  • The paper relies on this without support.

    Typically, only a small fraction of blood culture bottles in patients with HACEK IE demonstrate growth.

    “Typically, only a small fraction of blood culture bottles in patients with HACEK IE demonstrate growth.”

  • The paper relies on this without support.

    Bacteremia caused by HACEK microorganisms in the absence of an obvious focus of infection is highly suggestive of IE even without typical physical findings.

    “Bacteremia caused by HACEK microorganisms in the absence of an obvious focus of infection is highly suggestive of IE even without typical physical findings of IE.”

  • The paper relies on this without support.

    Almost all strains of the HACEK group are susceptible to ceftriaxone (or other third- or fourth-generation cephalosporins).

    “Almost all strains of the HACEK group are susceptible to ceftriaxone (or other third-or fourth-generation cephalosporins).”

  • The paper relies on this without support.

    There are only a few case reports of HACEK IE treated with a fluoroquinolone.

    “There are only a few case reports of HACEK IE treated with a fluoroquinolone, however.”

  • The paper relies on this without support.

    IE caused by non-HACEK Gram-negative aerobic bacilli is rare.

    “IE caused by non-HACEK Gram-negative aerobic bacilli (Enterobacteriaceae and Pseudomonas species) is rare.”

  • The paper relies on this without support.

    Prospective trial data are lacking to define the optimal antimicrobial regimen for IE caused by non-HACEK Gram-negative aerobic bacilli.

    “Prospective trial data are lacking to define the optimal antimicrobial regimen for the treatment of IE caused by non-HACEK Gram-negative aerobic bacilli.”

  • The paper relies on this without support.

    Medical therapy may be successful in right-sided P aeruginosa IE in 50% to 75% of cases.

    “Medical therapy may be successful in right-sided P aeruginosa IE in 50% to 75% of cases.”

  • The paper relies on this without support.

    Patients with right-sided P aeruginosa IE have typically been IDUs and have high recidivism risk.

    “Typically, these patients have been IDUs, and because of their high recidivism risk, avoidance of placement of prosthetic valves is desirable.”

  • The paper relies on this without support.

    Continuous bacteremia and a high frequency of positive blood cultures are typical hallmarks of IE.

    “Continuous bacteremia and a high frequency of positive blood cultures are typical hallmarks of this infection.”

  • The paper relies on this without support.

    Failure to culture microorganisms that cause IE can be a major problem that complicates diagnosis and timely, effective treatment.

    “Failure to culture microorganisms that cause IE can be a major problem that complicates diagnosis and timely, effective treatment.”

  • The paper relies on this without support.

    The causes of culture-negative IE may include inadequate microbiological techniques, infection with highly fastidious bacteria or fungi, noncultivatable agents, or previous administration of antimicrobial agents before blood cultures.

    “This may be attributable to inadequate microbiological techniques, infection with highly fastidious bacteria or fungi, noncultivatable agents, or the previous administration of antimicrobial agents before blood cultures were obtained.”

  • The paper relies on this without support.

    IE patients with blood cultures initially negative after only a few days of antibiotic therapy may have positive blood cultures after several days without antibiotics.

    “IE patients with blood cultures that are initially negative after only a few days of antibiotic therapy may have positive blood cultures after several days without antibiotics.”

  • The paper relies on this without support.

    The blood cultures of patients who receive longer courses of high-dose bactericidal antimicrobials may remain negative for weeks.

    “The blood cultures of patients who receive longer courses of high-dose bactericidal antimicrobials may remain negative for weeks.”

  • The paper relies on this without support.

    Certain therapeutic agents, including aminoglycosides, have potentially toxic effects that dictate limitation or avoidance of use if at all possible.

    “On the other hand, certain therapeutic agents, including aminoglycosides, have potentially toxic effects that dictate limitation or avoidance of use if at all possible.”

  • The paper relies on this without support.

    During the period between collection of blood cultures and determination of a pathogen, patients are often treated empirically for the more common bacterial causes of IE, which can result in exposure to potentially toxic therapy that could be avoided with earlier pathogen identification.

    “During this period, patients are often treated empirically for the more common bacterial causes of IE, which can result in exposure to potentially toxic therapy that could be avoided with earlier pathogen identification.”

  • The paper relies on this without support.

    During the period between collection of blood cultures and determination of a pathogen or if blood cultures are ultimately deemed culture negative, empirical therapy is generally required.

    “During the period between the collection of blood cultures and the determination of a pathogen or if blood cultures are ultimately deemed culture negative, empirical therapy is generally required.”

  • The paper relies on this without support.

    Collection of additional clinical and laboratory data often dictates subsequent revisions in initial empirical therapy.

    “Collection of additional clinical and laboratory data often dictates subsequent revisions in initial empirical therapy that will be administered over the treatment course.”

  • The paper relies on this without support.

    The organisms that have garnered the most attention as causes of culture-negative IE are Bartonella species, Chlamydia species, C burnetii, Brucella species, Legionella species, Tropheryma whipplei, Candida, and non-Candida fungi.

    “The organisms that have garnered the most attention are Bartonella species, Chlamydia species, C burnetii, Brucella species, Legionella species, Tropheryma whipplei, Candida, and non-Candida fungi (particularly Aspergillus species).”

  • The paper relies on this without support.

    The last 2 groups of organisms (Candida and non-Candida fungi) are especially relevant to PV recipients.

    “The last 2 groups of organisms are especially relevant to PV recipients.”

  • The paper relies on this without support.

    With special diagnostic techniques, Bartonella species, C burnetii, and Brucella species have been identified in the majority of cases of culture-negative IE caused by fastidious organisms.

    “With the use of special diagnostic techniques, Bartonella species, C burnetii, and Brucella species have been identified in the majority of cases of culture-negative IE caused by fastidious organisms.”

  • The paper relies on this without support.

    In some cases, serological and special blood culture techniques can be helpful for culture-negative IE.

    “In some cases, serological and special blood culture techniques can be helpful.”

  • The paper relies on this without support.

    In other cases, tissue (usually valve) screening is required for culture-negative IE.

    “In other cases, tissue (usually valve) screening is required.”

  • The paper relies on this without support.

    Diagnostic methods for resected valve tissue include microbiological, histopathological, and molecular techniques, the last of which includes gene amplification with PCR.

    “Diagnostic methods for resected valve tissue include microbiological, histopathological, and molecular techniques, the last of which includes gene amplification with PCR methods.”

  • The paper relies on this without support.

    Most clinical laboratories do not perform molecular screening, and specimens must be sent to reference laboratories.

    “Unfortunately, most clinical laboratories do not perform molecular screening, and specimens must be sent to reference laboratories.”

  • The paper relies on this without support.

    Incidence data from population-based surveys for IE caused by these organisms are lacking in the United States.

    “Incidence data from population-based surveys for IE caused by these organisms are lacking in the United States.”

  • The paper relies on this without support.

    Treatment of culture-negative IE without prior antibiotic exposure is based on limited data.

    “Treatment of the wide variety of microorganisms that cause culture-negative IE without prior antibiotic exposure has been described anecdotally, and regimens of choice are based on limited data and can be found in other publications.”

  • The paper relies on this without support.

    Noninfectious causes of valvular vegetations can produce a syndrome similar to culture-negative IE.

    “Noninfectious causes of valvular vegetations can produce a syndrome similar to culture-negative IE.”

  • The paper relies on this without support.

    Sterile valvular vegetations form and embolize, clinically mimicking culture-negative IE.

    “Sterile valvular vegetations form and embolize, clinically mimicking in many respects culture-negative IE.”

  • The paper relies on this without support.

    The mitral valve is most often affected, and valvular regurgitation is the predominant functional abnormality in APA syndrome with valvular involvement.

    “The mitral valve is most often affected, and valvular regurgitation is the predominant functional abnormality seen in APA syndrome with complicating valvular involvement.”

  • The paper relies on this without support.

    Numerous other causes of noninfective vegetative endocarditis can mimic IE.

    “Numerous other causes of noninfective vegetative endocarditis can mimic IE.”

  • The paper relies on this without support.

    The survival rate for patients with mold-related infective endocarditis is less than 20%.

    “The survival rate for patients with mold-related IE is <20%.”

  • The paper relies on this without support.

    Stroke is an independent risk factor for postoperative mortality in infective endocarditis patients.

    “Stroke is an independent risk factor for postoperative mortality in IE patients.”

  • The paper relies on this without support.

    The novel oral anticoagulants are not approved for use with either mechanical valves or bioprosthetic valves when risk factors for thromboembolism exist.

    “The novel oral anticoagulants are not approved for use with either mechanical valves or bioprosthetic valves when risk factors for thromboembolism exist (eg, atrial fibrillation).”

  • The paper relies on this without support.

    Clinical parameters for the diagnosis of perivalvular extension of IE are inadequate.

    “Clinical parameters for the diagnosis of perivalvular extension of IE are inadequate.”

  • The paper relies on this without support.

    TEE can demonstrate the distinctive flow patterns of fistulas and pseudoaneurysms and can rule out communications from unruptured abscess cavities.

    “When combined with spectral and color Doppler techniques, TEE can demonstrate the distinctive flow patterns of fistulas and pseudoaneurysms and can rule out communications from unruptured abscess cavities.”

  • The paper relies on this without support.

    The most frequent complications of IE are heart failure and systemic emboli.

    “Patients selected for OPAT should be at low risk for the complications of IE, the most frequent of which are heart failure and systemic emboli.”

  • The paper relies on this without support.

    The period of greatest risk for systemic emboli is before or within the first 1 to 2 weeks of antimicrobial therapy.

    “The period of greatest risk for systemic emboli is before or within the first 1 to 2 weeks of antimicrobial therapy, although serious complications such as heart failure and rupture of MAs may develop weeks to months after the initiation of antimicrobial therapy.”

  • The paper relies on this without support.

    Serious complications such as heart failure and rupture of MAs may develop weeks to months after the initiation of antimicrobial therapy.

    “although serious complications such as heart failure and rupture of MAs may develop weeks to months after the initiation of antimicrobial therapy.”

  • The paper relies on this without support.

    The risk for drug-related side effects usually increases with a prolonged drug exposure.

    “The risk for drug-related side effects usually increases with a prolonged drug exposure (eg, vestibular, auditory, and nephrotoxicity resulting from aminoglycosides; leukopenia caused by β-lactams and vancomycin; and nephrotoxicity resulting from the combination of vancomycin and gentamicin) and requires close monitoring by the home infusion team consisting of representatives from nursing and pha”

  • The paper relies on this without support.

    The majority of patients with IE are cured with appropriate medical and, if necessary, surgical treatment.

    “The majority of patients with IE are cured with appropriate medical and, if necessary, surgical treatment.”

  • The paper relies on this without support.

    Routine blood cultures after completion of antimicrobial therapy have a low likelihood of positive result in a patient who is otherwise without evidence of active infection.

    “Routine blood cultures are no longer recommended after the completion of antimicrobial therapy because the likelihood of a positive culture result in a patient who is otherwise without evidence of active infection is low.”

  • The paper relies on this without support.

    Developing or worsening heart failure is a complication that should be considered during short-term follow-up.

    “Developing or worsening heart failure is a second complication that should be considered during short-term followup.”

  • The paper relies on this without support.

    Valve function can deteriorate as a result of ongoing infection or mechanical stress unrelated to infection.

    “Although new onset of heart failure caused by valvular dysfunction is unlikely during this period, valve function can deteriorate as a result of ongoing infection or mechanical stress unrelated to infection.”

  • The paper relies on this without support.

    Antibiotic toxicity still can occur after the completion of treatment.

    “Antibiotic toxicity still can occur after the completion of treatment and is the third complication that should be considered during short-term follow-up.”

  • The paper relies on this without support.

    Delayed ototoxicity can occur because of previous use of aminoglycosides.

    “The first is delayed ototoxicity because of the previous use of aminoglycosides.”

  • The paper relies on this without support.

    No tools are routinely available for monitoring vestibular function.

    “No tools are routinely available for monitoring vestibular function, and patients should be told to report the onset of any symptoms of vestibular toxicity during or after treatment.”

  • The paper relies on this without support.

    Clostridium difficile infection is an antibiotic-related adverse event.

    “The second antibiotic-related adverse event is Clostridium difficile infection.”

  • The paper relies on this without support.

    Onset of C. difficile diarrhea can be delayed as long as 4 weeks after the last dose of antibiotic.

    “Onset of diarrhea can be delayed as long as 4 weeks after the last dose of antibiotic.”

  • The paper relies on this without support.

    IE can mimic a variety of febrile illnesses.

    “This is necessary because IE can mimic a variety of febrile illnesses.”

  • The paper relies on this without support.

    Antibiotics prescribed for nonspecific or unproved febrile syndromes are a major cause of culture-negative IE.

    “Antibiotics prescribed for nonspecific or unproved febrile syndromes are a major cause of (blood) culture-negative IE, and this practice should be strongly discouraged.”

  • The paper relies on this without support.

    Dental disease is almost entirely preventable if patients are compliant with 4 measures.

    “Dental disease is almost entirely preventable if patients are compliant with 4 measures.”

  • The paper relies on this without support.

    The cause of both periodontal disease and caries is bacterial plaque accumulation on teeth, and prevention is dependent on keeping teeth free of plaque.

    “First, the cause of both periodontal disease and caries is bacterial plaque accumulation on teeth, and prevention is dependent on keeping teeth free of plaque.”

  • The paper relies on this without support.

    The degree to which sugar and other refined carbohydrates are eliminated from the diet will have a major impact on the growth of pathogenic bacterial species, some of which are responsible for IE.

    “The degree to which sugar and other refined carbohydrates are eliminated from the diet will have a major impact on the growth of pathogenic bacterial species, some of which are responsible for IE.”

  • The paper relies on this without support.

    Daily use of a high-concentration fluoridated toothpaste will help to ensure that acid from plaque does not decalcify tooth structures and result in caries.

    “Finally, the daily use of a high-concentration fluoridated toothpaste will help to ensure that the acid from plaque does not decalcify tooth structures and result in caries.”

  • The paper relies on this without support.

    Fluoroquinolones are highly active in vitro against HACEK microorganisms.

    “Fluoroquinolones are highly active in vitro against HACEK microorganisms.”

  • The paper relies on this without support.

    Published data on the use of fluoroquinolones for endocarditis caused by HACEK are minimal.

    “Published data on the use of fluoroquinolones for endocarditis caused by HACEK are minimal.”

  • The paper relies on this without support.

    Intramuscular injection of ceftriaxone is painful.

    “Patientsshould be informed that intramuscular injection of ceftriaxone is painful.”
110 of 110

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • The early-surgery trial has conflicting citation numbers

    Minor

    The surgical-management section identifies the randomized early-surgery trial as reference 17. A later discussion calls the previously discussed trial reference 12, which the reference list identifies as an earlier AHA statement.

  • The recommendation class for vancomycin differs

    Minor

    For relatively penicillin-resistant VGS or S gallolyticus endocarditis in patients intolerant of β-lactams, the discussion assigns vancomycin monotherapy Class IIb, while the numbered recommendation assigns it Class IIa.

  • Daptomycin is named as an alternative to itself

    Minor

    The treatment discussion names daptomycin as an alternative to daptomycin for MRSA left-sided native-valve endocarditis. The corresponding recommendation names vancomycin as the drug it may replace.

3 of 3

Cites

Flagged first, then by citations

Research works printed but not linked: 3

  1. Kanavos K Antoniadou A Venetis C Gezerlis P Giamarellou H. Retrospective analysis of Duke’s criteria in 60 cases of infective endocarditis in Greece [abstract 138]. Paper presented at: Third International Symposium on Modern Concepts in Endocarditis; July 13–15 1995; Boston MA.
  2. 10.1016/S0025-6196(11)63302-8 · DOI
  3. 10.1016/S0025-6196(11)64307-3 · DOI

Cited by

Sorted by citations

Related

Authors
Baddour, L. M., Wilson, W. R., Bayer, A. S., Fowler, V. G., Tleyjeh, I. M., Rybak, M. J., Barsic, B., Lockhart, P. B., Gewitz, M. H., Levison, M. E., Bolger, A. F., Steckelberg, J. M., Baltimore, R. S., Fink, A. M., O’Gara, P., Taubert, K. A., & on behalf of the American Heart Association Committee on Rheumatic Fever, E.
Affiliations
American Heart Association (US)
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2015-10-13
Volume
132
Issue
15
Pages
1435-1486
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/cir.0000000000000296
OpenAlex
W1905008412
Cited by
3,232
References
338
Citations by year
2026: 265 · 2025: 337 · 2024: 350 · 2023: 337 · 2022: 348 · 2021: 344 · 2020: 346 · 2019: 301 · 2018: 258 · 2017: 207 · 2016: 120 · 2015: 12 · 2014: 3 · 2013: 1
FWCI
156.29
Type
journal article
Language
en
Update notices
Open access
closed
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
  • Touro Scholar (Touro College) (submittedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Infective Endocarditis Diagnosis and Management
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Streptococcal Infections and Treatments
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Valve Diseases and Treatments
Keywords
infective endocarditis, adults, diagnosis, antimicrobial therapy, complication management, Staphylococcus aureus, nosocomial infections, treatment guidelines
MeSH terms
Adult, Anti-Infective Agents, Anticoagulants, Candidiasis, Diagnostic Techniques, Cardiovascular, Endocarditis, Heart Valve Prosthesis, Humans, Rheumatic Heart Disease, Risk Factors, Staphylococcal Infections, Streptococcal Infections, Prosthesis-Related Infections, Bacteremia

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-11.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-11.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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