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Diagnostic and Therapeutic Challenges in Infective Endocarditis
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Diagnostic and Therapeutic Challenges in Infective Endocarditis

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Cardiology".

Deadline for manuscript submissions: closed (25 March 2026) | Viewed by 6144

Special Issue Editor

Dr. Lorenzo Bertolino

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Guest Editor
Department of Precision Medicine, University of Campania ‘L. Vanvitelli’, Via de Crecchio, 7, 80138 Napoli, Italy
Interests: cardiovascular infections; infective endocarditis; CIED infection; antimicrobial therapy; gram negative MDR microorganism

Special Issue Information

Dear Colleagues

In the past two decades, Infective Endocarditis (IE) has become an extremely heterogeneous disease, accompanied by an epidemiological shift towards older comorbid patients with valve prosthesis and intracardiac devices that may present with atypical symptoms and uncommon aetiology.

Despite recent advancements in the field, the prognosis of IE remains poor, with an in-hospital mortality rate peaking at 20-25%. Clinicians dealing with cardiovascular infections are called to handle a wide number of diagnostic challenges related to possible inconclusive echocardiography and to difficulties in isolating the causative microorganism. Moreover, patients with IE need a tailored medical and surgical management, sometimes based on low-quality supporting evidence and expert opinions. In this scenario, the multidisciplinary approach represented by the Endocarditis Team is of pivotal importance.

This Special Issue aims to foster interaction between different medical specialists caring for IE patients and to facilitate the spreading of medical knowledge by welcoming the submission of observational, single-centre or multi-centre, retrospective and prospective studies together with case series, clinical case reports and narrative literature reviews focusing on the diagnostic and therapeutic management of IE.

Dr. Lorenzo Bertolino
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • infective endocarditis
  • complications
  • diagnostic challenges
  • therapeutic approach
  • epidemiology
  • clinical correlates

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Published Papers (5 papers)

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Research

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12 pages, 1074 KB  
Article
Delayed Diagnosis of Infective Endocarditis—Analysis of an Endocarditis Network
by Shekhar Saha, Benjamin Zauner, Rainer Kaiser, Konstantinos Rizas, Martin Orban, Steffen Massberg, Sven Peterss, Christian Hagl and Dominik Joskowiak
J. Clin. Med. 2026, 15(3), 924; https://doi.org/10.3390/jcm15030924 - 23 Jan 2026
Viewed by 440
Abstract
Objectives: The diagnosis of infective endocarditis (IE) is clinically challenging. This study aimed to examine an endocarditis network and the effects of delayed diagnosis. Methods: We reviewed the patients who were admitted for infective endocarditis at our institution between January 2012 [...] Read more.
Objectives: The diagnosis of infective endocarditis (IE) is clinically challenging. This study aimed to examine an endocarditis network and the effects of delayed diagnosis. Methods: We reviewed the patients who were admitted for infective endocarditis at our institution between January 2012 and December 2021. Infective endocarditis was diagnosed according to ESC/EACTS guidelines for the management of endocarditis. Details of admitting hospitals were obtained from the German Hospital Directory. Data are presented as medians (25th–75th quartiles) or absolute values (percentages) unless otherwise specified. Results: A total of 812 consecutive patients were admitted to our centre for IE. Exact records on the time to diagnosis were available for 707 patients (87.1%). The patients were divided into two groups based on the time to diagnosis, i.e., up to 7 days (n = 509; 72.0% group ED) and more than 7 days (n = 198; 28.0% group LD). The EuroSCORE II (p = 0.001) and the EndoSCORE (p = 0.019) were significantly higher in the LD group. The median time to diagnosis was shorter in university hospitals as compared to non-teaching hospitals (p = 0.008) and among patients admitted to cardiology and cardiac surgery departments (p < 0.001). Patients diagnosed later had higher rates of tracheostomy (p < 0.001), longer ICU (p = 0.004) and hospital stays (p < 0.001) and higher in-hospital mortality (p = 0.027). We found that a delayed diagnosis (p = 0.040), stroke (p = 0.004), age > 75 years (p = 0.044) and atrial fibrillation (p < 0.001) were independently associated with in-hospital mortality. Furthermore, survival at 1 and 5 years was significantly higher in the ED group (p < 0.001). Conclusions: The diagnosis of IE may be influenced by a multitude of factors. Our results indicate that a delayed diagnosis is independently associated with an increased rate of in-hospital mortality. According to our results, an early diagnosis of IE may be associated with improved outcomes. Full article
(This article belongs to the Special Issue Diagnostic and Therapeutic Challenges in Infective Endocarditis)
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9 pages, 340 KB  
Article
Fewer Minor Modified Duke Criteria on Admission Are Associated with Worse 90-Day Mortality in Patients with Confirmed Infective Endocarditis
by Felix von Sanden, Kathrin Orlovius, Stefanie Andreß, Jonathan Ihrig, Friederike Schröder, Armin Imhof, Dominik Buckert, Wolfgang Rottbauer and Sascha d’Almeida
J. Clin. Med. 2025, 14(21), 7703; https://doi.org/10.3390/jcm14217703 - 30 Oct 2025
Viewed by 697
Abstract
Background/Objectives: Timely diagnosis of infective endocarditis (IE) remains a significant challenge, and IE poses significant morbidity and mortality. Modified Duke criteria (MDC) are used for the clinical evaluation and diagnosis of IE, but their current use is dichotomous. There are no studies [...] Read more.
Background/Objectives: Timely diagnosis of infective endocarditis (IE) remains a significant challenge, and IE poses significant morbidity and mortality. Modified Duke criteria (MDC) are used for the clinical evaluation and diagnosis of IE, but their current use is dichotomous. There are no studies that associate the amount of positive MDC with the patient’s outcome. This study intends to analyze whether the amount of MDC on initial presentation can be used for prognostic assumptions. Methods: We conducted a retrospective data analysis on patients with confirmed and suspected IE who were treated at the Department of Internal Medicine II at Ulm University Heart Center from December 2009 to December 2019. Univariable and multivariable logistic regression models were used to find correlations between 90-day mortality and the number of MDC. Results: 130 patients with confirmed IE were included in the analysis. Less minor MDC (OR 1.718; 95%-CI 1.096–3.268; p = 0.022) and a history of coronary artery disease (OR 4.711; 95%-CI 1.791–12.393; p = 0.002) were independently associated with higher 90-day mortality in patients with ultimately confirmed IE. Fewer minor MDC on presentation were associated with later diagnosis (b 2.341; 95%-CI 0.312–4.370; p = 0.024) and antibiotic therapy (b 2.953; 95%-CI 0.82–5.084; p = 0.007) for IE. Conclusions: Early diagnosis of IE is essential for favorable outcomes. Fewer minor MDC on initial presentation may lead to delayed diagnosis, antibiosis, and worse outcomes. Full article
(This article belongs to the Special Issue Diagnostic and Therapeutic Challenges in Infective Endocarditis)
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Review

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13 pages, 255 KB  
Review
Gut–Heart Axis and Infective Endocarditis: How Microbiota Dysbiosis Shapes Cardiovascular Risk and Infection Susceptibility
by Livia Moffa, Claudio Tana, Tiziana Meschi, Carmine Siniscalchi, Nicoletta Cerundolo, Claudio Ucciferri, Jacopo Vecchiet and Katia Falasca
J. Clin. Med. 2026, 15(2), 597; https://doi.org/10.3390/jcm15020597 - 12 Jan 2026
Viewed by 674
Abstract
The gut–heart axis represents a key determinant of cardiovascular (CV) system health. Emerging evidence indicates that intestinal dysbiosis can induce a state of chronic systemic inflammation which, together with mechanisms of endothelial dysfunction, increases the risk of CV diseases. Infective endocarditis (IE) exemplifies [...] Read more.
The gut–heart axis represents a key determinant of cardiovascular (CV) system health. Emerging evidence indicates that intestinal dysbiosis can induce a state of chronic systemic inflammation which, together with mechanisms of endothelial dysfunction, increases the risk of CV diseases. Infective endocarditis (IE) exemplifies this concept, as microbiota alterations may promote bacterial translocation from the gut into the bloodstream, leading to colonization of cardiac valves and subsequent endocardial infection. This narrative review examines current scientific evidence on the relationship between the gut microbiota and CV diseases, with a particular focus on IE. We also summarize the mechanisms underlying impaired intestinal barrier integrity, immune activation, and the production of microbiota-derived metabolites that contribute to CV disease. Special attention is given to potential preventive and therapeutic strategies, including microbiota modulation, targeted antibiotic management, and personalized medicine approaches tailored to individual patient profiles. Full article
(This article belongs to the Special Issue Diagnostic and Therapeutic Challenges in Infective Endocarditis)
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25 pages, 1917 KB  
Review
Deciphering the Complex Relationships Between the Hemostasis System and Infective Endocarditis
by Muhammad Aamir Wahab, Atta Ullah Khan, Silvia Mercadante, Iolanda Cafarella, Lorenzo Bertolino and Emanuele Durante-Mangoni
J. Clin. Med. 2025, 14(11), 3965; https://doi.org/10.3390/jcm14113965 - 4 Jun 2025
Cited by 2 | Viewed by 2735
Abstract
Infective endocarditis (IE) arises from complex interactions between microbial pathogens and host hemostasis systems, where dysregulated coagulation mediates microbial persistence and systemic thromboembolic complications. Alterations in primary, secondary, and tertiary hemostasis in the acute IE phase have direct clinical implications for vegetation formation [...] Read more.
Infective endocarditis (IE) arises from complex interactions between microbial pathogens and host hemostasis systems, where dysregulated coagulation mediates microbial persistence and systemic thromboembolic complications. Alterations in primary, secondary, and tertiary hemostasis in the acute IE phase have direct clinical implications for vegetation formation and detachment. Staphylococcus aureus is one of the most common pathogens that causes IE, and it is capable of profoundly altering the coagulation cascade through several mechanisms, such as platelet activation, prothrombin activation through staphylocoagulase release, and plasminogen stimulation via staphylokinase production. Understanding these complex and yet unmasked mechanisms is of pivotal importance to promoting targeted therapeutic intervention aimed at reducing IE morbidity and mortality. Moreover, the management of antiplatelet and anticoagulant treatment during IE onset is a controversial issue and needs to be tailored to patient comorbidities and IE-related complications, such as cerebral embolism. This review provides a roadmap to promote clinicians’ understanding of the complex interactions between hemostasis and IE clinical manifestations and complications, discussing pathogen-specific coagulation profiles while addressing critical knowledge gaps for IE management. Full article
(This article belongs to the Special Issue Diagnostic and Therapeutic Challenges in Infective Endocarditis)
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Other

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11 pages, 2256 KB  
Case Report
Cardiac Implantable Electronic Device-Related Infective Endocarditis Caused by Bacillus cereus: A Case Report
by Denis Swolana, Danuta Łoboda, Beata Sarecka-Hujar, Rafał Sznajder, Anna Szajerska-Kurasiewicz, Tadeusz Zębik, Krzysztof S. Gołba and Robert D. Wojtyczka
J. Clin. Med. 2026, 15(1), 344; https://doi.org/10.3390/jcm15010344 - 2 Jan 2026
Viewed by 667
Abstract
Background: Globalization, increased mobility, changes in dietary habits, and a growing number of immunocompromised patients have heightened exposure to rare or opportunistic pathogens. Here, we present a case of cardiac implantable electronic device-related infective endocarditis (CIED-IE) caused by Bacillus cereus bacteremia originating in [...] Read more.
Background: Globalization, increased mobility, changes in dietary habits, and a growing number of immunocompromised patients have heightened exposure to rare or opportunistic pathogens. Here, we present a case of cardiac implantable electronic device-related infective endocarditis (CIED-IE) caused by Bacillus cereus bacteremia originating in the gastrointestinal tract. Case presentation: A 66-year-old female, who had a cardiac resynchronization pacemaker (CRT-P) implanted in 2017 due to second-degree atrioventricular block and left bundle branch block, had undergone device replacement due to battery depletion 4 months earlier and was scheduled for transvenous lead extraction (TLE) due to generator pocket infection. During the TLE procedure, transoesophageal echocardiography revealed vegetations on the leads and in the right atrium. Standard empirical therapy covering methicillin-resistant Staphylococci and Gram-negative bacteria was administered, including oritavancin and gentamicin. Surprisingly, intraoperative samples cultured B. cereus, a Gram-positive, spore-forming rod that usually causes food poisoning through contamination of rice and other starchy foods. B. cereus is generally resistant to β-lactam antibiotics except for carbapenems but is susceptible to glycopeptides. The oritavancin treatment was extended to four fractionated doses (1200, 800, 800, and 800 mg) administered at 7-day intervals. To eradicate bacteria in the gastrointestinal tract, oral vancomycin (125 mg 4 times a day) was added. After 4 weeks of effective antibiotic therapy, a CRT-P with a left bundle branch area pacing lead was reimplanted on the right subclavian area, with no recurrence of infection during the 3-month follow-up. Clinical discussion: In the patient, a diet high in rice and improper storage of rice dishes, together with habitual constipation, were identified as risk factors for the development of invasive Bacillus cereus infection. However, the long half-life lipoglycopeptide antibiotic, oritavancin, administered weekly, proved effective in treating CIED-IE. Conclusions: Infection with rare or opportunistic microorganisms may require extended microbiological diagnostics and non-standard antibiotic therapy; therefore, the medical history should consider risk factors for such infections. Full article
(This article belongs to the Special Issue Diagnostic and Therapeutic Challenges in Infective Endocarditis)
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