Open research questions in Infective Endocarditis Diagnosis and Management

What the literature leaves open

• The reasons underlying this finding remain uncertain: this reduction may be attributed to the interruption of progressive fibrosis affecting the cardiac conduction system, which may result from both infection and prolonged antibiotic exposure. Further studies are warranted to clarify the mechanisms involved and to better define the optimal timing of surgery in this setting.

  Influence of Surgical Timing on the Risk of Permanent Pacemaker Implantation in Acute Aortic Valve Endocarditis · 2026 · DOI

• Splenic embolism and splenic infarc- tion are established complications of left-sided IE, yet they may be underrecognized because abdominal pain is non-specific and may ini- tially direct attention toward primary intra-abdominal pathology rather than occult endocardial infection (8–10).

  Atypical mitral valve infective endocarditis presenting with fever and left upper abdominal pain due to splenic infarction: a case report · 2026 · DOI

• This is a notable limitation, as the Infectious Diseases Society of America (IDSA) has reported that 34% of native vertebral osteomyelitis cases are initially misdiagnosed as degenerative disease.

  A Diagnostic Challenge Involving Enterococcus faecalis Bacteremia: A Case Report · 2026 · DOI

• The clinical manifestations of MRSA-associated IE vary widely, ranging from fever and bacteremia to more severe complications such as embolic events, heart failure, and neurological damage.

  Infective Endocarditis by Biofilm-Producing Methicillin-Resistant Staphylococcus aureus—Pathogenesis, Diagnosis, and Management · 2024 · DOI

• MRSA-associated IE is a complex and evolving clinical problem, with biofilm-mediated resistance posing persistent challenges in both diagnosis and treatment. While current therapeutic regimens are essential, they often require supplementation with surgical inter- Antibiotics 2024, 13, 1132 16 of 22 vention, and emerging targeted strategies may offer important additional tools to address the limitations imposed by biofilms. The integration of novel therapies alongside estab- lished clinical practices offers a promising future for improving patient outcomes and reducing the high morbidity and mortality associated with MRSA IE. Continued research and innovation in diagnostics and therapeutics are essential for combating MRSA IE, one of the most difficult infections in modern medicine. Author Contributions: Concept and design: all authors. Acquisition, analysis, or interpretation of data: A.K., H.K., S.G., M.S., C.T., B.W.S. and M.P. Drafting of the manuscript: A.K., H.K., M.S., S.G., C.T., B.W.S. and M.P. Critical revision of the manuscript for important intellectual content: A.K., H.K., M.S., S.G., B.W.S., C.T. and M.P. Administrative, technical, or material support: A.K. and S.G. Supervision: A.K., H.K. and S.G. None of the authors have any financial disclosures or other conflicting relationships. The authors fully acknowledge and comply with the Journal’s Conflict of Interest policy. All authors have read and agreed to the published version of the manuscript. Funding: This research received no external funding. Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable. Data Availability Statement: No new data were created or analyzed in this study. Acknowledgments: We would like to thank Naomi Hein, from the Harvard Medical School, for editing this manuscript. Conflicts of Interest: The authors declare no conflicts of interest.

  Infective Endocarditis by Biofilm-Producing Methicillin-Resistant Staphylococcus aureus—Pathogenesis, Diagnosis, and Management · 2024 · DOI

• The first aspect that holds significant interest for future endeavors is aimed at reducing the occurrence of infective endocarditis and subsequently mitigating the risk of emboliza- tion. One of these preventative measures involves combating IVDA. As mentioned earlier, right-sided endocarditis commonly arises as a consequence of IVDA, and yet IVDA can also be linked to left-sided endocarditis [21,25,27,46,47]. The literature highlights a concerning statistic: approximately 15,000 patients are admitted annually in the United States due to endocarditis secondary to opioid use disorder. Tragically, the mortality rates among these individuals are alarmingly high, necessitating prolonged hospital stays and accumulating over USD700 million in annual hospitalization costs for completing the requisite six-week course of intravenous antibiotic therapy. Interestingly, despite individuals with IVDA often presenting with iron deficiency and anemia, administering iron supplementation paradoxically heightens their susceptibility to bacterial infections and exacerbates the sever- ity of various infectious conditions [74]. Despite the existence of effective opioid-agonist therapies like methadone and buprenorphine, their continuity or initiation during and after hospitalization remains inadequate for most patients. Moreover, a significant proportion of patients fail to complete their prescribed regimen of intravenous antibiotics, a critical component for averting endocarditis-associated mortality and morbidity [75]. The second area of interest for future explorations seeking to mitigate complications like infective endocarditis involves delving into autoimmune diseases. In a previous dis- cussion involving Banerjee S., a compelling case emphasized the importance of remaining vigilant for Libman–Sacks endocarditis (LSE) when managing patients with autoimmune disorders such as systemic lupus erythematosus (SLE), especially in the presence of valvu- lar dysfunction. LSE typically manifests without symptoms; yet, its potential for grave complications necessitates prompt diagnosis and intervention [34]. Autoimmune diseases emerge when the body’s defense mechanisms mistakenly target its tissues, leading to structural and functional anomalies across diverse organs. A complex interplay of genetic predisposition, environmental factors, and immune dysregulation, sometimes triggered by infections, underpins the onset of these conditions. There exist nearly a hundred recognized autoimmune disorders, with some of the most prevalent ones including SLE, multiple sclerosis (MS), rheumatoid arthritis (RA), Graves’ disease (GD), type 1 diabetes mellitus (T1D), and inflammatory bowel disease (IBD). Also, there are cases in the literature of the association between thyroid autoimmune disease and infective endocarditis. Therefore, Antibiotics 2024, 13, 513 24 of 30 the investigation of thyroid status in the management of endocarditis remains extremely important. This associatio

  Multidisciplinary Perspectives of Challenges in Infective Endocarditis Complicated by Septic Embolic-Induced Acute Myocardial Infarction · 2024 · DOI

• Despite substantial advances in the medical and surgical management of IE, the optimal timing of surgery remains controversial.

  Influence of Surgical Timing on the Risk of Permanent Pacemaker Implantation in Acute Aortic Valve Endocarditis · 2026 · DOI

• Environmental cultures at our haemodialysis unit were sterile, but as data from other dialysis facilities were unavailable, the route of acquisition could not be established.

  From Water to Bloodstream: Aeromonas dhakensis as an Emerging Cause of Catheter-Related Bloodstream Infection · 2026 · DOI

• The present study shows widespread antibiotic prescriptive heterogeneity among the sample of dentists analyzed, especially in conditions where international guidelines are lacking.

  Antibiotic-Prescribing Habits in Dentistry: A Questionnaire-Based Study · 2024 · DOI

• Conventional The relationship between oral dysbiosis, periodontal disease, and IE remains incompletely understood.

  Exploring links between oral health and infective endocarditis · 2024 · DOI

• limited research output from de- veloping countries and the predominance of single- center reports make contemporary comparisons difficult.

  Exploring the clinical and microbiological landscape of pediatric infective endocarditis: a 3-year single-center review · 2026 · DOI

• In veterinary medicine, the role of Providencia species remains poorly defined [8].

  Feline Endocarditis Caused by Carbapenem-Resistant Providencia rettgeri: Clinicopathological, Echocardiographic, and Genomic Investigation · 2026 · DOI

• These findings suggest that improving diagnostic timeliness alone is insufficient to optimise outcomes.

  Impact of the COVID-19 Pandemic on Presentation, Microbiology, and Outcomes of Infective Endocarditis: A Romanian Retrospective Cohort Study · 2026 · DOI

• The Bayesian WISCA demonstrated that adequate empirical coverage is achievable without routine broad-spectrum agents, offering institution-specific guidance for stewardship-compatible regimen selection; multicenter validation is warranted.

  In-Hospital Mortality Predictors and a Bayesian Weighted-Incidence Antibiogram in Infective Endocarditis: A Seven-Year Cohort Study from a Mexican Tertiary University Hospital · 2026 · DOI

• Data on IE treatment and outcomes in centers without on-site cardiac surgery remain scarce.

  The burden of infective endocarditis in a center without cardiac surgery: a retrospective analysis · 2026 · DOI

• However, the extent to which valve-related complications independently drive the development of AHF, beyond patient-related factors, remains unclear.

  Valve-related complications and acute heart failure in infective endocarditis: beyond structural damage · 2026 · DOI

• Circulating cholesterol levels generally decrease in severe infections but have not been analyzed in depth in IE.

  Hypocholesterolemia as a predictor of mortality in infective endocarditis · 2026 · DOI

• AIMS: The prognostic impact of vegetation size in infective endocarditis (IE) remains unclear.

  Prognostic impact of vegetation size in infective endocarditis · 2026 · DOI

• Abstract Background Aortic valve injury during cardiac catheterisation is an under-recognised complication that may present with new-onset aortic regurgitation or valvular masses, and mimic infective endocarditis or primary valve tumours (1, 2).

  Iatrogenic aortic valve injury following invasive cardiac procedures: a case series of six patients · 2026 · DOI

• However, its real-world clinical utility and cost-effectiveness remain uncertain.

  A Cell-Free DNA Plasma Next-Generation Sequencing Test—Is It Worth the Cost? · 2025 · DOI

• However, the role of antibiotic prophylaxis in preventing endocarditis following dental procedures remains controversial.

  Mapping Review of the Correlations Between Periodontitis, Dental Caries, and Endocarditis · 2025 · DOI

• Although limited evidence is available, cardiovascular imaging techniques are valuable in diagnosing and managing cardiac manifestations of TDs.

  Cardiac imaging in patients with tropical diseases—a scientific statement of the European Association of Cardiovascular Imaging (EACVI) of the European Society of Cardiology and the Cardiovascular Imaging Department of the Brazilian Society of Cardiology (DICSBC) · 2025 · DOI

• However, cardiovascular complications of TDs are often under-recognized and understudied.

  Cardiac imaging in patients with tropical diseases—a scientific statement of the European Association of Cardiovascular Imaging (EACVI) of the European Society of Cardiology and the Cardiovascular Imaging Department of the Brazilian Society of Cardiology (DICSBC) · 2025 · DOI

• Despite the potential of epidemiology to identify high-risk IE patients, there remains a significant lack of data on the prevalence of IE according to microbiological etiology in BSIs.

  Prevalence of infective endocarditis in patients with bloodstream infections and deployment of echocardiographic resources in a single-center registry · 2025 · DOI

• However, the use of some methods is supported by very limited data; as a result, they still cannot be widely used.

  Novel Diagnostic Methods for Infective Endocarditis · 2024 · DOI

Most-cited papers in Infective Endocarditis Diagnosis and Management

• Clinical Presentation, Etiology, and Outcome of Infective Endocarditis in the 21st Century · Archives of Internal Medicine · 2009 · 2,055 citations
• Staphylococcus aureus Endocarditis · JAMA · 2005 · 956 citations
• Prevention of Bacterial Endocarditis · JAMA · 1997 · 917 citations
• Changing Profile of Infective Endocarditis<SUBTITLE>Results of a 1-Year Survey in France</SUBTITLE> · JAMA · 2002 · 776 citations
• Using Multiple Intelligence Theory to Teach K-2 Geography · Social studies and the young learner · 2003 · 752 citations
• The 2023 Duke-International Society for Cardiovascular Infectious Diseases Criteria for Infective Endocarditis: Updating the Modified Duke Criteria · Clinical Infectious Diseases · 2023 · 749 citations
• The Gulstonian Lectures, on Malignant Endocarditis · BMJ · 1885 · 536 citations
• A HITHERTO UNDESCRIBED FORM OF VALVULAR AND MURAL ENDOCARDITIS · Archives of Internal Medicine · 1924 · 425 citations
• Changing Patient Characteristics and the Effect on Mortality in Endocarditis · Archives of Internal Medicine · 2002 · 389 citations
• Neurologic Manifestations of Infective Endocarditis · Archives of Internal Medicine · 2000 · 328 citations

Most recent work

• Diagnostic and Prognostic Relevance of Valve Strands in Patients With Suspected Infective Endocarditis · Clinical Infectious Diseases · 2026
• JCS 2026 Guideline on the Management of Infective Endocarditis · Circulation Journal · 2026
• Infective Endocarditis and Complications; Surgical Indications and Management: An Integrative Review · Journal of Personalized Medicine · 2026
• Intramuscular penicillin prophylaxis and valve progression in adults with mild rheumatic heart disease: a propensity score-matched cohort study · Acta Cardiologica · 2026
• Infections of Selected Nonvalvular Cardiovascular Devices: A Science Advisory From the American Heart Association · Journal of the American Heart Association · 2026
• Evaluation of the MEFIER Score in Identifying Patients at High Risk of Endocarditis in Enterococcus faecalis Bacteremia · Open Forum Infectious Diseases · 2026
• Enterococcus endocarditis in an infant with congenital renal duplex anomaly: A case report · Forensic Science, Medicine and Pathology · 2026
• An important change in infective endocarditis prevention guidance · British Dental Journal · 2026
• Enterococcus faecalis–associated infective aortic endocarditis as a cause of arterial thromboembolism in a cat · Veterinary Research Communications · 2026
• Kodamaea ohmeri–associated mitral valve endocarditis complicated by septic embolism of the right femoral artery: A case report · International Journal of Infectious Diseases · 2026

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