Culture-negative Endocarditis Research Articles

Predictors of infective endocarditis associated in-hospital mortality in Ayder Comprehensive Specialized Hospital, Tigray, North Ethiopia: Microbiological,clinical features, and management profiles.

Infective endocarditis (IE) is a continuously evolving disease with a high mortality rate despite different advances in treatment. In Ethiopia, there is a paucity of data regarding IE. Therefore, this study is aimed at assessing IE-related in-hospital mortality and characterization of IE patients based on their microbiological, clinical features, and management profiles in the Ayder Comprehensive Specified Hospital (ACSH). We conducted a hospital-based prospective follow-up study with all consecutive sampling techniques for suspected infective endocarditis patients admitted to ACSH from January 2020 to February 2022. Echocardiography was performed, and three sets of blood samples for blood culture were taken as per the standard protocol. We also performed isolation of microbial etiologies and antimicrobial susceptibility tests. The data was analyzed using STATA version 16. Stepwise logistic regression was run to identify predictors of in-hospital mortality. Effects were measured through the odds ratio at the 5% level of significance. Seventy-four cases of suspected infective endocarditis were investigated; of these, 54 episodes fulfilled modified Duke's criteria. Rheumatic heart disease (RHD) (85.2%) was the most common underlying heart disease. Murmur (94.4%), fever (68.5%), and pallor (57.4%) were the most common clinical findings. Vegetation was present in 96.3% of episodes. Blood culture was positive only in 7 (13%) episodes. Complications occurred in 41 (75.9%) cases, with congestive heart failure being the most common. All patients were managed medically, with no surgical intervention. The in-hospital mortality was 14 (25.9%). IE-related in-hospital mortality was significantly associated with surgery recommendation and myalgia clinical symptoms. IE occurred relatively in a younger population, with RHD as the most common underlying heart disease. There was a high rate of culture-negative endocarditis, and the majority of patients were treated empirically. Mortality was high. The establishment of cardiac surgery and strengthening microbiology services should be given top priority.

Endocarditis and ischemic stroke of rare cause

A60-year-old male patient presented with ischemic-embolic stroke. Transesophageal echocardiography revealed the cause to be aortic valve endocarditis with highly eccentric aortic valve regurgitation. The blood cultures taken several times remained sterile. The indication for surgical aortic valve replacement was made. Conventional microbiological work-up of the heart valve did not reveal any pathogens. The additional molecular genetic testing using eubacterial PCR ("polymerase chain reaction" [PCR]) finally demonstrated the presence of Tropheryma whipplei. Anumber of therapeutic options were available. The authors decided on intravenous antibiotic therapy with ceftriaxone for 14days and follow-up therapy with oral trimethoprim/sulfamethoxazole for 1year. The case illustrates the importance of additional molecular diagnostics beyond the conventional methods in blood culture-negative endocarditis to identify the pathogen and initiate appropriate therapy.

Secretome analysis and virulence assessment in Abiotrophia defectiva

Background Abiotrophia defectiva, although infrequently occurring, is a notable cause of culture-negative infective endocarditis with limited research on its virulence. Associated with oral infections such as dental caries, exploring its secretome may provide insights into virulence mechanisms. Our study aimed to analyze and characterize the secretome of A. defectiva strain CCUG 27639. Methods Secretome of A. defectiva was prepared from broth cultures and subjected to mass spectrometry and proteomics for protein identification. Inflammatory potential of the secretome was assessed by ELISA. Results Eighty-four proteins were identified, with diverse subcellular localizations predicted by PSORTb. Notably, 20 were cytoplasmic, 12 cytoplasmic membrane, 5 extracellular, and 9 cell wall-anchored proteins. Bioinformatics tools revealed 54 proteins secreted via the ‘Sec’ pathway and 8 via a non-classical pathway. Moonlighting functions were found in 23 proteins, with over 20 exhibiting potential virulence properties, including peroxiredoxin and oligopeptide ABC transporter substrate-binding protein. Gene Ontology and KEGG analyses categorized protein sequences in various pathways. STRING analysis revealed functional protein association networks. Cytokine profiling demonstrated significant proinflammatory cytokine release (IL-8, IL-1β, and CCL5) from human PBMCs. Conclusions Our study provides a comprehensive understanding of A. defectiva‘s secretome, laying the foundation for insights into its pathogenicity.

Culture-negative endocarditis with multifocal spread and flail mitral valve leaflet: a case report

Introduction: Blood culture-negative infective endocarditis is the condition in which a causative organism cannot be identified after inoculation of at least three samples using standard blood-culture systems for 7 days. It has a low reported incidence of about 2.5–31%. Causes may be infectious or non-infectious; use of prior antibiotic therapy is usually the leading factor. Case presentation: The authors present a case of true culture-negative endocarditis involving the mitral valve, with multiple foci of spread including brain, spleen, liver, and Intervertebral disc, which remained persistent despite treatment with intravenous broad-spectrum antibiotics on an inpatient and outpatient basis but eventually improved after upgrading alternative broad-spectrum antibiotic for an extended duration. The patient had complications in the form of a flail mitral valve with persistent mitral regurgitation, requiring mitra-clip placement. Discussion: Positive blood culture is one of the major diagnostic criteria to establish infective endocarditis. Patients may have persistent negative cultures due to previous antibiotic use, the presence of fastidious organisms, or the use of inappropriate techniques or media. Involvement of a multidisciplinary team, use of multimodal investigations, and appropriate antibiotic stewardship are crucial. Extended duration of treatment and upgrading antibiotics can be helpful next steps in highly suspicious cases. With multifocal spread as in our case, it further becomes challenging to control and treat the infection as it is frequently connected with higher morbidity and mortality. Conclusion: Blood culture-negative endocarditis is an entity that can present with early complications. It is diagnostically and therapeutically challenging to treat such patients. Multimodal approaches for early diagnosis and appropriate treatment are crucial owing to its high morbidity and mortality.

Rare Case of Chronic Coxiella Endocarditis Without Fever or Classic Risk Factors

Background: “Q-fever” is a zoonotic infectious disease caused by Coxiella burnetii which is most commonly transmitted globally through unpasteurized animal products or aerosolized fluid. This zoonosis is not thought to be common in developed countries due to modern utilization of pasteurization but risk for transmission remains high in those with extended contact with livestock and cattle. Acute Q-fever presents with an illness characterized by high fevers, myalgias, and segmental pneumonia, but rarely it may progress to chronic Q-fever. Chronic Q-fever most often presents with a culture-negative endocarditis with or without renal impairment and can be fatal if left untreated. Case Report: In this case report, we present a 72-year-old male with a 3-month history of body pain, cough, and weight loss who was eventually discovered to have an afebrile presentation of Coxiella endocarditis. This patient was found to have a mitral valve vegetation diagnosed through transesophageal echocardiography and had positive serology for chronic Q-fever. Surprisingly, this patient had no classical exposures, no history of valvular dysfunction or prosthesis, and no clinical signs suggesting endocarditis, making his case markedly atypical. He was placed on a 12 -18-month course of antibiotics and was monitored on an outpatient basis. Conclusion: Although chronic Q-fever is rare its variable presentation may cause diagnostic error if it is not kept on the differential. A transesophageal echocardiogram should be strongly preferred due to its superior visualization of heart valves. Serology remains the gold standard for diagnosis of Coxiella. When dealing with culture-negative endocarditis, clinicians should retain a high index of suspicion of Coxiella and obtain serologies for diagnosis

Blood culture-negative infective endocarditis caused by <i>Bartonella henselae</i> diagnosed through repeated echocardiography: A case report

Blood culture-negative infective endocarditis caused by <i>Bartonella henselae</i> diagnosed through repeated echocardiography: A case report

Mitral Valve Culture Negative Endocarditis Complicated by Severe Mitral Regurgitation and Chordae Tendinea Rupture

Infective endocarditis has a high mortality rate. Criterion for diagnosis is a positive blood culture, however, some cases present with negative blood culture. We present a 65-year-old male complaining of palpitations. EKG showed atrial fibrillation with RVR. Transthoracic echocardiogram showed severe mitral regurgitation and possible vegetation. Transesophageal echocardiogram revealed endocarditis with ruptured chordae and vegetation on the posterior leaflet. All obtained blood cultures remained negative. Cardiothoracic surgery and infectious disease specialties were consulted. Patient was started on broad spectrum antibiotics. Patient underwent a mitral valve replacement and pathology showed focal myxoid degeneration with no inflammation and cultures of the specimen were negative. The hospital course was complicated by hemopericardium, treated by pericardial window, and drain placement. The patient was ultimately discharged to an acute rehabilitation center. Culture-negative endocarditis presents a diagnostic and therapeutic dilemma for clinicians and should be promptly identified and treated to avoid complications.

Fastidious Bacterial Pathogens in Replaced Heart Valves: The First Report of Bartonella quintana and Legionella steeli in Blood Culture-Negative Endocarditis from Iran

Background: Infectious endocarditis is a rare infectious disease of the cardiac endothelium, but blood culture-negative endocarditis (BCNE) should be considered. Objectives: This study aims to determine the prevalence of possible infectious agents of BCNE. Methods: Real-time PCR and PCR sequencing were used to identify Coxiella burnetii, Tropheryma whipplei, Brucella spp., Legionella spp., and Bartonella spp. 16srRNA sequencing was used for the samples with negative results of PCR sequencing and real-time PCR. Results: Among the 59 positive results, the rates of Bartonella spp., Legionella spp., and Brucella spp. were 8.5%, 5.1%, and 3.4%, respectively. C. burnetii and T. whipplei were not detected. 16srRNA sequencing revealed 1 Stenotrophomonas maltophilia, 1 Aeribacillus spp. and 1 uncultured bacterium. Conclusions: The rate of some bacteria that are difficult to detect with routine laboratory tests was high in our study, and it seems that hospitals should use dedicated technology to detect BCNE pathogens.

Abstract 17436: A Diagnostic Copycat: Culture Negative Endocarditis of A Bioprosthetic Valve Presenting as ANCA Vasculitis

A 59-year-old female with a history of bicuspid aortic valve (AV) complicated by aortic stenosis and ascending aortic aneurysm s/p bioprosthetic AV and ascending aorta replacement presented with a 6-month history of weight loss, fatigue, and lower extremity rash. Initial laboratory workup identified anemia, leukopenia, and acute kidney injury with proteinuria and microscopic hematuria. Further workup included negative blood cultures, elevated inflammatory markers, elevated rheumatoid factor, hypocomplimentemia, and ANCA positivity (PR3 Ab positive). Biopsy of her palpable purpuric rash demonstrated vascular immune deposition pattern consistent with leukocytoclastic vasculitis. Renal biopsy revealed focal and crescentic glomerulonephritis with immune complex deposition. CT abdomen noted mesenteric lymphadenopathy with fluid surrounding the thoracic aortic graft. Surface echocardiogram showed bioprosthetic AV replacement with diffuse cusp thickening without stenosis or regurgitation. At this point, a multidisciplinary team offered a broad differential diagnosis of inflammatory vasculitis versus culture-negative endocarditis with plan for further testing. Follow-up whole-body and cardiac PET scan identified FDG-avid abnormalities involving the aortic graft and AV with hypermetabolic soft tissue thickening surrounding the aortic root. Transesophageal echocardiogram confirmed AV thickening with a 1 cm mobile echodensity. Additional serologic testing identified positive Bartonella henselae IgG (1:8192) and IgM (>1:20) titers. The final diagnosis was B. henselae prosthetic AV endocarditis and ascending aortic graft infection. She underwent repeat AV and ascending aortic graft replacement, with graft material positive for B. henselae PCR and was treated with a course of doxycycline and rifampin. B. henselae is a fastidious gram-negative bacterium that can cause culture negative endocarditis but is very rarely associated with aortic graft infection. This case highlights (1) a rare example of B. henselae aortic graft infection, (2) the difficulty in differentiating B. henselae endocarditis from inflammatory vasculitis, and (3) the importance of engaging multidisciplinary teams to solve difficult diagnostic cases.

A Diagnostic CopyCat: Culture-Negative Infective Endocarditis of a Bioprosthetic Valve Presenting as ANCA Vasculitis.

A Diagnostic CopyCat: Culture-Negative Infective Endocarditis of a Bioprosthetic Valve Presenting as ANCA Vasculitis.

Comparison of Blood-Based Shotgun and Targeted Metagenomic Sequencing for Microbiological Diagnosis of Infective Endocarditis.

Shotgun and targeted metagenomic sequencing have been shown in separate studies to be potentially useful for culture-free pathogen identification in blood and/or plasma of patients with infective endocarditis (IE). However, the 2 approaches have not been directly compared. The aim of this study was to compare shotgun metagenomic sequencing with targeted metagenomic sequencing (tMGS) for organism identification in blood or plasma of patients with IE. Patients with possible or definite IE were prospectively enrolled from October 2020 to July 2021. Shotgun metagenomic sequencing was performed with the Karius test, which uses microbial cell-free DNA (mcfDNA) sequencing to detect, identify, and quantitate DNA-based pathogens in plasma. tMGS was performed using a 16S ribosomal RNA (rRNA) polymerase chain reaction assay targeting the V1 to V3 regions of the 16S rRNA gene. Results were compared using the McNemar test of paired proportions. Samples from 34 patients were investigated. The Karius test was positive in 24/34 (71%), including 3/6 (50%) with blood culture-negative endocarditis (BCNE), which was not significantly different from the positivity rate of tMGS (P = .41). Results of the Karius test were concordant with tMGS in 75% of cases. The Karius test detected 2 cases of methicillin-resistant Staphylococcus aureus among the 7 S. aureus detections, in accordance with results of phenotypic susceptibility testing. The combination of blood cultures, the Karius test, and tMGS found a potential causative pathogen in 33/34 (97%), including 5/6 with BCNE. The Karius test and tMGS yielded comparable detection rates; however, beyond organism identification, the Karius test generated potentially useful antibiotic resistance data.

A Rare Case of HACEK Endocarditis in the Context of a Permanent Pacemaker

Introduction: Infective endocarditis (IE) is a serious medical condition that can lead to high morbidity and mortality rates. The prevalence of healthcare-associated IE is increasing due to the use of therapeutic devices, such as intravascular catheters and cardiac devices. The HACEK group of bacteria, are commonly found in human respiratory and genitourinary tracts, are low virulence and fastidious organisms that are associated with blood culture-negative endocarditis. Proper diagnosis requires a combination of clinical, microbiological, and imaging results. The following study presents a case of atypical device-associated IE caused by Haemophilus influenzae in a 56-year-old man with a permanent pacemaker. Methodology: description of a clinical problem, its diagnosis, management, and outcome, accompanied with a literature review. Conclusion: This study highlights the importance of considering the HACEK group of bacteria in culture-negative IE cases and the use of advanced imaging techniques in diagnosis to prevent further complications and improve patient outcomes.

Microbiological Etiology in Patients with IE Undergoing Surgery and for Patients with Medical Treatment Only: A Nationwide Study from 2010 to 2020.

Microbiological etiology has been associated with surgery for infective endocarditis (IE) during admission, especially Staphylococcus aureus. We aimed to compare patient characteristics, microbiological characteristics, and outcomes by treatment choice (surgery or not). We identified patients with first-time IE between 2010 and 2020 and examined the microbiological etiology of IE according to treatment choice. To identify factors associated with surgery during initial admission, we used the Aalen-Johansen estimator and an adjusted cause-specific Cox model. One-year mortality stratified by microbiological etiology and treatment choice was assessed using unadjusted Kaplan-Meier estimates and an adjusted Cox proportional hazard model. A total of 6255 patients were included, of which 1276 (20.4%) underwent surgery during admission. Patients who underwent surgery were younger (65 vs. 74 years) and less frequently had cerebrovascular disease, cardiovascular disease, diabetes, and chronic kidney disease. Patients with Staphylococcus aureus IE were less likely to undergo surgery during admission (13.6%) compared to all other microbiological etiologies. One-year mortality according to microbiological etiology in patients who underwent surgery was 7.0%, 5.3%, 5.5%, 9.6%, 13.2, and 11.2% compared with 24.2%, 19.1%, 27,6%, 25.2%, 21%, and 16.9% in patients who received medical therapy for Staphylococcus aureus, Streptococcus spp., Enterococcus spp., coagulase-negative Staphylococci, "other microbiological etiologies", and blood culture-negative infective endocarditis, respectively. Patients with IE who underwent surgery differed in terms of microbiology, more often having Streptococci than those who received medical therapy. Contrary to expectations, Staphylococcus aureus was more common among patients who received medical therapy only.

Case series of 12 Bartonella quintana endocarditis from the Southwest Indian Ocean.

Bartonella spp. are fastidious bacteria frequently identified as the cause of blood culture-negative (BCN) endocarditis. However, Bartonella infections are difficult to diagnose in routine laboratory testing and their incidence is probably underestimated. We investigated the epidemiological and clinical features of Bartonella endocarditis cases diagnosed between 2009 and 2021 on Reunion Island (Southwest Indian Ocean). We retrospectively included all patients diagnosed with Bartonella endocarditis at Reunion Island University Hospital during this period. Endocarditis was diagnosed on the basis of microbiological findings, including serological tests (IFA) and PCR on cardiac valves, and the modified Duke criteria. We used then the multispacer typing (MST) method to genotype the available Bartonella strains. We report 12 cases of B. quintana endocarditis on Reunion Island (83.3% in men, median patient age: 32 years). All the patients originated from the Comoros archipelago. The traditional risk factors for B. quintana infection (homelessness, alcoholism, exposure to body lice) were absent in all but two of the patients, who reported head louse infestations in childhood. Previous heart disease leading to valve dysfunction was recorded in 50% of patients. All patients underwent cardiac valve surgery and antimicrobial therapy with a regimen including doxycycline. All patients presented high C-reactive protein concentrations, anemia and negative blood cultures. The titer of IgG antibodies against Bartonella sp. exceeded 1:800 in 42% of patients. Specific PCR on cardiac valves confirmed the diagnosis of B. quintana endocarditis in all patients. Genotyping by the MST method was performed on four strains detected in preserved excised valves and was contributive for three, which displayed the MST6 genotype. Bartonella quintana is an important cause of infective endocarditis in the Comoros archipelago and should be suspected in patients with mitral valve dysfunction and BCN from this area.

Updates in Culture-Negative Endocarditis.

Blood culture-negative infective endocarditis (BCNE) is a challenging condition associated with significant morbidity and mortality. This review discusses the epidemiology, microbiology, diagnosis, and treatment of BCNE considering advancements in molecular diagnostics and increased access to cardiac surgery. BCNE can be categorized into bacterial endocarditis with sterilized blood cultures due to previous antibiotic treatment, endocarditis caused by fastidious microorganisms, and true BCNE caused by intracellular organisms that cannot be cultured using traditional techniques. Non-infectious causes such as nonbacterial thrombotic endocarditis should also be considered. Diagnostic approaches involve thorough patient history; blood and serum testing, including appropriate handling of blood cultures; serological testing; and molecular techniques such as targeted and shotgun metagenomic sequencing. Where available, evaluation of explanted cardiac tissue through histopathology and molecular techniques is crucial. The therapy for BCNE depends on the likely causative agent and the presence of prosthetic material, with surgical intervention often required.

Catheter related atrial thrombus caused by Abiotrophia defectiva: A case series and review of literature.

Catheter related atrial thrombus (CRAT) is a devastating complication associated with tunneled hemodialysis catheter. Abiotrophia defectiva is a rare fastidious pathogen implicated predominantly in culture negative infective endocarditis. Here we report three cases of CRAT in maintenance hemodialysis patients with variable clinical presentation caused by Abiotrophia defectiva. Video assisted thoracoscopic retrieval of atrial thrombus is a novel technique which is scarcely reported in medical literature for surgical management of large atrial thrombus. Our cases were managed by timely administration of antibiotics and anticoagulants followed by surgical retrieval of atrial thrombus with removal of tunneled dialysis catheter. This case series illustrates the importance of prompt diagnosis, appropriate anticoagulation with antibiotics, and mini-invasive surgical removal of atrial thrombus for the management of CRAT.

Viability and Desiccation Resistance of Bartonella henselae in Biological and Non-Biological Fluids: Evidence for Pathogen Environmental Stability.

Pathogen environmental stability is an often-neglected research priority for pathogens that are known to be vector-transmitted. Bartonella henselae, the etiologic agent of Cat Scratch Disease, has become a "pathogen of interest" in several serious human illnesses, which include neoplastic, cardiovascular, neurocognitive, and rheumatologic conditions. Survival in the flea gut and feces as well as the association with a biofilm in culture-negative endocarditis provides insight into this organism's ability to adjust to environmental extremes. The detection of B. henselae DNA in blood and tissues from marine mammals also raises questions about environmental stability and modes of pathogen transmission. We investigated the ability of B. henselae to survive in fluid matrices chosen to mimic potential environmental sources of infective materials. Feline whole blood, serum and urine, bovine milk, and physiologic saline inoculated with a laboratory strain of B. henselae San Antonio 2 were subsequently evaluated by culture and qPCR at specified time intervals. Bacterial viability was also assessed following desiccation and reconstitution of each inoculated fluid matrix. Bartonella henselae SA2 was cultured from feline urine up to 24 h after inoculation, and from blood, serum, cow's milk, and physiologic saline for up to 7 days after inoculation. Of potential medical importance, bacteria were cultured following air-desiccation of all fluid inoculates. The viability and stability of Bartonella within biological and non-biological fluids in the environment may represent a previously unrecognized source of infection for animals and human beings.

"Let the Cat Out of the Heart": Clinical Characteristics of Patients Presenting With Blood Culture-Negative Endocarditis Due to Bartonella Species.

Patients with blood culture-negative endocarditis due to Bartonella infection frequently presented with fever, cytopenias, kidney failure, and positive PR3-ANCA. Bartonella IgG titers were variable. Patients commonly underwent surgery with overall low mortality.

Clinical Significance of a 16S-rDNA Analysis of Heart Valves in Patients with Infective Endocarditis: a Retrospective Study.

A substantial proportion of patients with infective endocarditis (IE) are subjected to heart valve surgery. Microbiological findings on valves are important both for diagnostics and for tailored antibiotic therapy, post-operatively. The aims of this study were to describe microbiological findings on surgically removed valves and to examine the diagnostic benefits of 16S-rDNA PCR and sequencing (16S-analysis). Adult patients who were subjected to heart valve surgery for IE between 2012 and 2021 at Skåne University Hospital, Lund, where a 16S-analysis had been performed on the valve, constituted the study population. Data were gathered from medical records, and the results from blood cultures, valve cultures, and 16S-analyses of valves were compared. A diagnostic benefit was defined as providing an agent in blood culture negative endocarditis, providing a new agent in episodes with positive blood cultures, or confirming one of the findings in episodes with a discrepancy between blood and valve cultures. 279 episodes in 272 patients were included in the final analysis. Blood cultures were positive in 259 episodes (94%), valve cultures in 60 episodes (22%), and 16S-analyses in 227 episodes (81%). Concordance between the blood cultures and the 16S-analysis was found in 214 episodes (77%). The 16S-analyses provided a diagnostic benefit in 25 (9.0%) of the episodes. In blood culture negative endocarditis, the 16S-analyses had a diagnostic benefit in 15 (75%) of the episodes. A 16S-analysis should be routinely performed on surgically removed valves in blood culture negative endocarditis. In patients with positive blood cultures, 16S-analysis may also be considered, as a diagnostic benefit was provided in some patients. IMPORTANCE This work demonstrates that it can be of importance to perform both cultures and analysis using 16S-rDNA PCR and sequencing of valves excised from patients undergoing surgery for infective endocarditis. 16S-analysis may help both to establish a microbiological etiology in cases of blood culture negative endocarditis and to provide help in situations where there are discrepancies between valve and blood cultures. In addition, our results show a high degree of concordance between blood cultures and 16S-analyses, indicating that the latter has a high sensitivity and specificity for the etiological diagnosis of endocarditis in patients who were subjected to heart valve surgery.

Abiotrophia defectiva: A rare and lethal but an easy miss!

Abiotrophia defectiva is a nutritionally deficient streptococci, a rare pathogen of infective endocarditis (IE) in children but is frequently known to cause valvular dysfunction and embolic complications. Only nine cases of A. defectiva endocarditis have been reported so far in world literature. We report a case of A. defectiva endocarditis in a 7-year old girl, with a small peri membranous ventricular septal defect with congenital bilateral sensorineural hearing loss status post left-sided cochlear implantation who presented with prolonged fever. A. defectiva should be considered in children with endocarditis with a subacute course and atypical presentations. Although fastidious in growth it is a virulent bacterium preferentially affecting endovascular structures and is implicated in many culture negative endocarditis. Our case reiterates the possibility of a rare cause of this common disease and the challenges encountered while isolating this nutritionally deficient organism and its treatment.