Antibiotic Prophylaxis and Infective Endocarditis Incidence Following Invasive Dental Procedures (2024)

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    Original Investigation

    April6, 2024

    FrancescaSperotto,MD, PhD1,2; KatherineFrance,DMD, MBE3; MargheritaGobbo,DMD, MSc4; et al MohammedBindakhil,DDS, MS5; KununyaPimolbutr,DDS, MSc, PhD6; HalyHolmes,BDS, MSc, MChD7; LuisMonteiro,DDS, MSc, PhD8; LaurelGraham,MLS, ML9; Catherine H. L.Hong,BDS, MS10; Thomas P.Sollecito,DMD3; GiovanniLodi,PhD11; Peter B.Lockhart,DDS12; MartinThornhill,MBBS, BDS, PhD13; PedroDiz Dios,MD, DDS, PhD14; FedericaTurati,PhD15; ValeriaEdefonti,PhD16

    Author Affiliations Article Information

    • 1Department of Cardiology, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts

    • 2Department of Pediatrics, Harvard Medical School, Boston, Massachusetts

    • 3Department of Oral Medicine, University of Pennsylvania, Philadelphia

    • 4Unit of Oral and Maxillofacial Surgery, Ca’Foncello Hospital, Treviso, Italy

    • 5Division of Oral Medicine, Department of Oral Biology and Diagnostic Sciences, Augusta University, Augusta, Georgia

    • 6Department of Oral Medicine and Periodontology, Mahidol University, Bangkok, Thailand

    • 7Department of Oral Medicine and Periodontology, University of the Western Cape, Cape Town, South Africa

    • 8UNIPRO, Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences (IUCS-CESPU), Gandra, Portugal

    • 9Dental Medicine Library, University of Pennsylvania, Philadelphia

    • 10Faculty of Dentistry, National University of Singapore, Singapore

    • 11Dipartimento di Scienze Biomediche, Chirurgiche e Odontoiatriche, Università degli Studi di Milano, Milan, Italy

    • 12Department of Otolaryngology, Wake Forest University School of Medicine, Atrium Health, Charlotte, North Carolina

    • 13Department of Oral and Maxillofacial Medicine, Surgery and Pathology, University of Sheffield School of Clinical Dentistry, Sheffield, United Kingdom

    • 14Medical-Surgical Dentistry Research Group, Health Research Institute of Santiago de Compostela, School of Medicine and Dentistry, Santiago de Compostela University, Santiago de Compostela, Spain

    • 15Branch of Medical Statistics, Biometry, and Epidemiology G.A. Maccacaro, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy

    • 16Fondazione IRCCS, Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    JAMA Cardiol. Published online April 6, 2024. doi:10.1001/jamacardio.2024.0873

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    Key Points

    Question Is antibiotic prophylaxis associated with decreased risk of infective endocarditis after invasive dental procedures?

    Findings This systematic review and meta-analysis including data on 1 152 345 cases of infective endocarditis found that antibiotic prophylaxis was associated with a reduced risk of infective endocarditis following invasive dental procedures in individuals at high risk but not in those at moderate or low/unknown risk.

    Meaning These findings support the use of antibiotic prophylaxis for individuals at high risk undergoing invasive dental procedures, supporting current American Heart Association and European Society of Cardiology guidelines.

    Abstract

    Importance The association between antibiotic prophylaxis and infective endocarditis after invasive dental procedures is still unclear. Indications for antibiotic prophylaxis were restricted by guidelines beginning in 2007.

    Objective To systematically review and analyze existing evidence on the association between antibiotic prophylaxis and infective endocarditis following invasive dental procedures.

    Data Sources PubMed, Cochrane-CENTRAL, Scopus, Web of Science, Proquest, Embase, Dentistry and Oral Sciences Source, and ClinicalTrials.gov were systematically searched from inception to May 2023.

    Study Selection Studies on the association between antibiotic prophylaxis and infective endocarditis following invasive dental procedures or time-trend analyses of infective endocarditis incidence before and after current antibiotic prophylaxis guidelines were included.

    Data Extraction and Synthesis Study quality was evaluated using structured tools. Data were extracted by independent observers. A pooled relative risk (RR) of developing infective endocarditis following invasive dental procedures in individuals who were receiving antibiotic prophylaxis vs those who were not was computed by random-effects meta-analysis.

    Main Outcomes and Measures The outcome of interest was the incidence of infective endocarditis following invasive dental procedures in relation to antibiotic prophylaxis.

    Results Of 11 217 records identified, 30 were included (1 152 345 infective endocarditis cases). Of them, 8 (including 12 substudies) were either case-control/crossover or cohort studies or self-controlled case series, while 22 were time-trend studies; all were of good quality. Eight of the 12 substudies with case-control/crossover, cohort, or self-controlled case series designs performed a formal statistical analysis; 5 supported a protective role of antibiotic prophylaxis, especially among individuals at high risk, while 3 did not. By meta-analysis, antibiotic prophylaxis was associated with a significantly lower risk of infective endocarditis after invasive dental procedures in individuals at high risk (pooled RR, 0.41; 95% CI, 0.29-0.57; P for heterogeneity = .51; I2, 0%). Nineteen of the 22 time-trend studies performed a formal pre-post statistical analysis; 9 found no significant changes in infective endocarditis incidence, 7 demonstrated a significant increase for the overall population or subpopulations (individuals at high and moderate risk, streptococcus-infective endocarditis, and viridans group streptococci–infective endocarditis), whereas 3 found a significant decrease for the overall population and among oral streptococcus-infective endocarditis.

    Conclusions and Relevance While results from time-trend studies were inconsistent, data from case-control/crossover, cohort, and self-controlled case series studies showed that use of antibiotic prophylaxis is associated with reduced risk of infective endocarditis following invasive dental procedures in individuals at high risk, while no association was proven for those at low/unknown risk, thereby supporting current American Heart Association and European Society of Cardiology recommendations. Currently, there is insufficient data to support any benefit of antibiotic prophylaxis in individuals at moderate risk.

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    April 8, 2024

    Deepening the Narrative on Antibiotic Prophylaxis for Endocarditis: A Critical Appraisal of Recent Findings

    Víctor Acuña, MD | Universidad Autonoma de Nuevo León, Departamento de Medicina Interna, Hospital "Dr José Eleuterio González".

    I have read the recent systematic review and meta-analysis conducted by Francesca Sperotto and her team. Their work astutely navigates the complex terrain at the confluence of dental and cardiovascular health, shedding light on the role of antibiotic prophylaxis in preventing infective endocarditis subsequent to invasive dental procedures. The meticulousness of their methodological framework, coupled with their expansive data synthesis and discerning analysis, warrants applause.

    Nevertheless, I would like to draw attention to a few aspects that, if addressed, could augment the interpretative depth and practical utility of their findings. The disparities observed between the time-trend analyses and the

    results from case-control and cohort studies present an intricate picture. A detailed commentary on the underlying reasons for such divergences, potentially rooted in the variability of antibiotic prescription practices and the fluctuating incidence of infective endocarditis across regions and periods, would undoubtedly enrich our collective insight.

    Additionally, the delineation of the advantages of antibiotic prophylaxis is well-articulated for high-risk patients, yet the implications for individuals with moderate or indeterminate risk are less clear. The impetus for subsequent studies should be to illuminate these grey areas, thereby empowering clinicians to apply more customized guidelines in their practices.

    The practical application of this research into everyday clinical settings also presents its own set of intricacies. Given the inherent limitations of observational studies and the possible biases therein, a discussion regarding how these factors might sway the formulation of guidelines and the stratagems of patient care is of paramount importance for both practitioners and decision-makers.

    To encapsulate, Sperotto et al.'s scholarly contribution is a vital addition to the ongoing discourse concerning the prophylactic use of antibiotics to thwart infective endocarditis in dental care. It lays a robust foundation for forthcoming inquiry and the refinement of guidelines. Contemplating the points I've raised could serve to bolster the impact and relevance of this pivotal study for a spectrum of stakeholders in the medical community.

    CONFLICT OF INTEREST: None Reported

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    April 11, 2024

    Revisit infective endocarditis

    Peppino Peppino, MD, Former Professor | Post Graduate Medical School of Cardiology, Ped Cardiolgist University of Palermo, Italy

    In the respected evidence of the role of antibiotic prophylaxis in preventing infective endocarditis succeeding invasive dental procedures, we suggest a somewhat original approach (infective endocarditis triangle), considering three different key elements, namely:
    One. Anatomical substrate, patient ‘a risk’;
    Second. Initiating factor/trigger, trigger factor is always largely accepted a transient bacteraemia;
    Third. Modulating factors, a very complex varying network, consistently of innate and adaptive immunities, genetic and environmental determined (age, sex, inflammation state, hormonal secretion, glucocorticoid, epinephrine, and norepinephrine levels, together with those of pro-inflammatory cytokines including tumour necrosis factor and interleukin-1β peak during onset of the
    active phase, which heavily influences individual susceptibility to all infections, including Infective E).

    The same subject, having fixed first and second component of triangle, responds differently at different times based on a circadian rhythm (from the Latin ‘circa diem’, meaning ‘for
    about a day’) and it is difficult to predict the personal biological response.

    References
    1. Wilson W, Taubert KA, Gewitz M, et al; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee; American Heart Association Council on Cardiovascular Disease in the Young; American Heart Association Council on Clinical Cardiology; American Heart Association Council on Cardiovascular Surgery and Anesthesia; Quality of Care and Outcomes Research Interdisciplinary Working Group. Prevention of infective endocarditis: Guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation. 2007;116(15):1736-1754. doi:10.1161/CIRCULATIONAHA.106.183095.
    2. Sperotto F, France K, Gobbo M, et al. Antibiotic Prophylaxis and Infective Endocarditis Incidence Following Invasive Dental Procedures: A Systematic Review and Meta-Analysis. JAMA Cardiol. Published online April 06, 2024. doi:10.1001/jamacardio.2024.0873.

    3. Calcaterra G, Crisafulli A, Guccione P, Di Salvo G and Bassareo PP. Infective endocarditis triangle. Is it the time to revisit infective endocarditis susceptibility and indications for its antibiotic prophylaxis? European Journal of Preventive Cardiology 2019:
    DOI: 10.1177/2047487319856126.

    Giuseppe Calcaterra MD
    Former Professor of Paediatric Cardiology
    Postgraduate Medical School of Cardiology
    University of Palermo Italy

    CONFLICT OF INTEREST: None Reported

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    Sperotto F, France K, Gobbo M, et al. Antibiotic Prophylaxis and Infective Endocarditis Incidence Following Invasive Dental Procedures: A Systematic Review and Meta-Analysis. JAMA Cardiol. Published online April 06, 2024. doi:10.1001/jamacardio.2024.0873

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