Cause Of Culture-negative Endocarditis Research Articles

An unusual presentation of a rare disease: acute upper limb ischemia as the presenting symptom of Whipple’s Endocarditis, a case report

BackgroundWhipple's disease is known to cause multiple varied systemic symptoms, and is a well-documented cause of culture-negative endocarditis. Endocarditis secondary to Whipple disease, however, has rarely been known to present primarily as a cause of acute limb ischemia. We describe such a case here.Case presentationA previously healthy 40 year old man presented to the emergency department with acute-onset right arm paresthesias. On exam, he was found to be tachycardic with a VI/VI systolic ejection murmur. He was diagnosed with critical limb ischemia and severe aortic regurgitation, and echocardiography showed a large mass on his bicuspid aortic valve. Thrombectomy was performed urgently, with aortic valve repair the following day. As blood cultures and valvular tissue culture remained unrevealing, the patient remained on empiric vancomycin and ceftriaxone for culture-negative endocarditis. 16 s rRNA nucleic acid amplification testing (NAAT) of his formalin-fixed, paraffin-embedded valvular tissue detected T. whipplei, after which the patient was transitioned to ceftriaxone and trimethoprim-sulfamethoxazole for a year of therapy. He continues to do clinically well.ConclusionsWe report an unusual presentation of Whipple endocarditis as an acute upper limb ischemia, absent other classic symptoms of Whipple's disease, and with diagnosis made by 16 s rRNA NAAT of valvular tissue in the setting of culture-negative endocarditis.

Molecular epidemiology of Bartonella quintana endocarditis in patients from Israel and Eastern Africa

BackgroundBartonella quintana is an important cause of culture-negative endocarditis. Although humans have been considered as its only reservoir, recent studies showed that macaque species are also reservoirs of B. quintana. Based on multi-locus sequence typing (MLST) B. quintana strains have been classified into 22 sequence types (STs), with 7 STs exclusively found in humans. Data regarding the molecular epidemiology of B. quintana endocarditis is limited to only 3 STs identified in 4 patients from Europe and Australia. We studied B. quintana endocarditis acquired in Eastern Africa or Israel to investigate the genetic diversity and clinical relatedness of B. quintana from distinct geographic regions.MethodsEleven patients with B. quintana endocarditis, 6 from Eastern Africa and 5 from Israel, were studied. DNA was extracted from cardiac tissue or blood specimens and analyzed by MLST based on 9 genetic loci. An evolutionary relationship between STs was visualized by a minimum spanning tree. A phylogenetic tree was constructed with the concatenated sequences (4271 bp) of the 9 loci using the maximum-likelihood method.ResultsSix strains were classified into previously described STs while 5 strains were identified for the first time and classified into new STs 23–27 which clustered with the previously reported STs 1–7 from human strains found in Australia, France, Germany, the USA, Russia, and the former Yugoslavia, without indication of geographical structuring. ST2 was the most prevalent ST, found in 5 of 15 patients with endocarditis (33.3%). ST26 appears to be a primary founder of the human lineage.ConclusionsThe new and previously reported human STs form a single human lineage, clearly separated from the other 3 B. quintana lineages of cynomolgus, rhesus, and Japanese macaques. From evolutionary perspectives, these findings support the assumption that B. quintana has co-evolved with host species to form a host-speciation pattern. ST26 is suggested herein as a primary founder of the human lineage and may be key to explore where B. quintana had first originated; ST2 is a dominant genetic type associated with B. quintana endocarditis. To confirm these findings, additional worldwide molecular epidemiological studies are required.

Whipple disease – an important cause of culture negative endocarditis

Whipple disease is a rare systemic disease caused by the bacterium Tropheryma whipplei with a range of clinical manifestations including diarrhoea, abdominal pain, arthralgia. There is increasing evidence that Whipple disease can present with isolated organ involvement, which may include culture negative endocarditis.1 We present a case of a 49-year-old female who presented with a prolonged history of progressive cardiac symptoms, found to have valve destruction and foamy macrophage infiltration of her aortic valve.

Culture Negative Endocarditis With Tropheryma whipplei

Tropheryma whipplei endocarditis is an increasingly recognized cause of culture negative endocarditis but is challenging to diagnose and often not accompanied by typical symptoms of Whipple disease. In this report, we describe a case of T. whipplei endocarditis and share echocardiographic images from the patient case.

A \u201ccat\u201d-astrophic case of Bartonella infective endocarditis causing secondary cryoglobulinemia: a case report

BackgroundCulture-negative infective endocarditis (IE) constitutes approximately 10% of all cases of IE. Bartonella endocarditis is a common cause of culture-negative endocarditis and is associated with a high mortality rate. To date, no cases of Bartonella IE has been reported in association with cryoglobulinemia in the UK. We present a unique case of Bartonella IE causing secondary cryoglobulinemia in a young female.Case presentationA 17-year-old female with a background of pulmonary atresia and ventricular septal defect repaired with a cardiac conduit at the age of 4, presented with a one-year history of weight loss (from 53 to 39 kg) and poor appetite. She subsequently developed a vasculitic rash and haematoproteinuria with decline in renal function, requiring urgent hospital admission. Initial blood tests showed a near normal creatinine, but a raised cystatin C. Renal biopsy showed focal necrotizing glomerulonephritis with no acute tubular necrosis or chronic change. Subsequent blood tests supported a diagnosis of cryoglobulinaemic vasculitis (high rheumatoid factor, low complement, polyclonal gammopathy, Type 3 cryoglobulin). A weak positive PR3 meant there was some uncertainty about whether this could be a primary ANCA-associated vasculitis (AAV). Initial workup for an infectious cause, including multiple blood cultures, were negative. However, an echocardiogram showed definite vegetations on her surgical conduit. The patient did not respond to empirical antimicrobials and so was referred for surgical revision of her conduit. Tissue samples obtained intra-operatively demonstrated Bartonella species. With targeted antimicrobials post-operatively, she improved with resolution of immunologic abnormalities and at last review had a normal renal profile. On reviewing her social history, she had adopted several stray cats in the preceding year; and thus, the cause of the Bartonella infection was identified.ConclusionThis is the first reported case of Bartonella endocarditis causing secondary cryoglobulinemia reported in the UK. The key learning points from this case include that Bartonella endocarditis can present as a cryoglobulinaemic vasculitis and should be considered in any differential when the cause of cryoglobulinaemia is not clear and to enquire about relevant exposures especially when culture-negative endocarditis is suspected.

Coxiella burnetii Sterol-Modifying Protein Stmp1 Regulates Cholesterol in the Intracellular Niche.

ABSTRACTCoxiella burnetii replicates in a phagolysosome-like vacuole called the Coxiella-containing vacuole (CCV). While host cholesterol readily traffics to the CCV, cholesterol accumulation leads to CCV acidification and bacterial death. Thus, bacterial regulation of CCV cholesterol content is essential for Coxiella pathogenesis. Coxiella expresses a sterol-modifying protein, Stmp1, that may function to lower CCV cholesterol through enzymatic modification. Using an Stmp1 knockout (Δstmp1), we determined that Stmp1 is not essential for axenic growth. Inside host cells, however, Δstmp1 mutant bacteria form smaller CCVs which accumulate cholesterol, preferentially fuse with lysosomes, and become more acidic, correlating with a significant growth defect. However, in cholesterol-free cells, Δstmp1 mutant bacteria grow similarly to wild-type bacteria but are hypersensitive to cholesterol supplementation. To better understand the underlying mechanism behind the Δstmp1 mutant phenotype, we performed sterol profiling. Surprisingly, we found that Δstmp1 mutant-infected macrophages accumulated the potent cholesterol homeostasis regulator 25-hydroxycholesterol (25-HC). We next determined whether dysregulated 25-HC alters Coxiella infection by treating wild-type Coxiella-infected cells with 25-HC. Similar to the Δstmp1 mutant phenotype, 25-HC increased CCV proteolytic activity and inhibited bacterial growth. Collectively, these data indicate that Stmp1 alters host cholesterol metabolism and is essential to establish a mature CCV which supports Coxiella growth.

Clinical and Microbiological Characteristics of Infective Endocarditis at a Cardiac Center in Saudi Arabia

BackgroundInfective endocarditis (IE) is a serious disease with complex pathology and significant mortality. Little information is known regarding clinical and microbiological characteristics in Saudi Arabia. This study surveyed these characteristics at a Cardiac Center in Riyadh, Saudi Arabia over a period of 5 years.MethodsThis retrospective study was done on all infective endocarditis (IE) patients admitted to Prince Sultan Cardiac Center between January 1, 2015, and December 31, 2019. Clinical characteristics, microbiological results, management, and outcomes were assessed.ResultA total of 340 cases of infective endocarditis were identified over the study period.Most patients (64%) were 50 years old or above, and 67% were males. Fever was the most common clinical presentation, and a murmur was audible in a fifth of patients. Blood cultures were positive in 177 (52%) cases. The most common organisms were Staphylococcus aureus, coagulase negative Staphylococcus and viridans group Streptococcus. Most common microbiological organisms causing native valve endocarditis were viridans group Streptococcus (32%) followed by methicillin-susceptible Staphylococcus aureus (21%), and for prosthetic valve endocarditis they were coagulase negative Staphylococcus (32%) followed by methicillin-susceptible Staphylococcus aureus (23%), the most common causes of culture negative endocarditis were Q-fever and brucellosis. Predisposing cardiac conditions were present in 127 (37%) patients, most commonly rheumatic heart disease and congenital heart disease. Surgical intervention was done in 26% of cases, with an overall in-hospital mortality rate of 6.76%.ConclusionWe demonstrate the epidemiological, clinical, and microbiological profile of infective endocarditis in a tertiary care cardiac center in Saudi Arabia. It gives information concerning the prevalence of responsible organisms. This information will be helpful in assessing patients with suspected IE and in planning management of cases knowing the relative frequency of types of microorganisms encountered.

#28: Rapid, Non-invasive Detection of Invasive Bartonella Infections in Pediatric Patients Using the Karius Test, A Next-Generation Sequencing Test for Microbial Cell-free DNA in Plasma

Abstract Background Bartonella henselae and Bartonella quintana are the etiologic agents of cat scratch disease (CSD) and “trench fever”, respectively. Both are important causes of culture-negative endocarditis and fever of unknown origin (FUO). The diagnosis of Bartonella infections is limited by (1) the nonspecific, protean manifestations of the disease and its broad differential diagnosis; (2) the fastidious nature of Bartonella spp., leading to rare detections with traditional culture based methods; (3) the insensitivity and poor specificity of Bartonella serologies. Rapid, non-invasive diagnosis of Bartonella through next-generation sequencing (NGS) of plasma microbial cell-free DNA (mcfDNA) offers a means to overcome these limitations. Here we describe the diagnosis of 23 Bartonella infections in children from August 2017 – December 2020 using plasma mcfDNA NGS. Methods The Karius Test (KT), developed and validated in Karius’ CLIA certified/CAP accredited lab, detects mcfDNA in plasma. After mcfDNA is extracted and NGS performed, human reads are removed, and remaining sequences are aligned to a curated database of > 1400 organisms. McfDNA from organisms present above a statistical threshold are reported and quantified in molecules/μL (MPM). Clinical information was included from data submitted with the requisition or obtained at the time of reporting from clinical consultations with the provider. Results KT detected Bartonella henselae mcfDNA in 22 cases and Bartonella quintana in 1. Detections included 10 cases of endocarditis (7 prosthetic valve), 12 cases of CSD/FUO, and a single case of osteomyelitis. Glomerulonephritis was reported in 5 the cases of endocarditis. Six cases had splenic involvement; three had hepatic involvement. History of cat exposure was elicited in 8 cases. The mean MPMs was highest for prosthetic valve endocarditis (mean 47,272 +/- 67,526) followed by native valve endocarditis (3,881 +/- 2,458), FUO/CSD (1,922 +/- 3,416), and osteomyelitis (119 +/- 0) (p<0.05). Three subjects had serial mcfDNA monitoring. Predictable declines in Bartonella mcfDNA were observed in response to therapy in all three patients. The duration of positive Bartonella mcfDNA signal ranged from 22–42 days (30.7, +/- 10.3). Conclusion Open-ended, plasma-based NGS for mcfDNA provides a rapid, non-invasive method to diagnose diverse clinical manifestations of invasive pediatric Bartonella infection against a competing broad differential diagnosis. The quantification of mcfDNA may further help in differentiating the various clinical syndromes caused by Bartonella. Finally, serial monitoring to trend MPMs may serve as an indicator of burden of infection, provide a means to monitor treatment efficacy and ultimately help define the length of therapy for optimal outcomes. All detections are Bartonella henselae except for one case of *Bartonella quintana (prosthetic valve endocarditis). MPM=molecules/μL; GN=glomerulonephritis, LN=lymph node involvement, FUO=fever of unknown origin, CSD=cat scratch disease

Laboratory Diagnosis of 37 Cases of Bartonella Endocarditis Based on Enzyme Immunoassay and Real-Time PCR.

Bartonella spp., mostly Bartonella quintana and B. henselae, are a common cause of culture-negative endocarditis. Serology using immunofluorescence assay (IFA) and PCR performed on cardiac tissues are the mainstays of diagnosis. We developed an enzyme immunoassay (EIA) and a novel multiplex real-time PCR assay, utilizing Bartonella genus-specific, B. henselae-specific, and B. quintana-specific SimpleProbe probes, for diagnosis of Bartonella endocarditis. We aimed to evaluate the performance of these assays. Thirty-seven patients with definite endocarditis, 18 with B. henselae, 18 with B. quintana, and 1 with B. koehlerae, were studied. Diagnosis was confirmed by conventional PCR and DNA sequencing of surgical cardiac specimens. Similar to the case with IFA, anti-Bartonella IgG titers of ≥1:800 were found in 94% of patients by EIA; cross-reactivity between B. henselae and B. quintana precluded species-specific serodiagnosis, and frequent (41%) but low-titer cross-reactivity between Coxiella burnetii antibodies and B. henselae antigen was found in patients with Q fever endocarditis. Low-titer (1:100) cross-reactivity was uncommonly found also in patients with brucellosis and culture-positive endocarditis, particularly Enterococcus faecalis endocarditis. Real-time PCR performed on explanted heart valves/vegetations was in complete agreement with results of sequence-based diagnosis with characteristic melting curves. The genus-specific probe identified five additional endocarditis-associated Bartonella spp. at the genus level. In conclusion, EIA coupled with a novel real-time PCR assay can play an important role in Bartonella endocarditis diagnosis and expand the diagnostic arsenal at the disposal of the clinical microbiologist. Since serology remains a major diagnostic tool, recognizing its pitfalls is essential to avoid incorrect diagnosis.

Bartonella species as a cause of culture-negative endocarditis in South Africa.

Previous reports have highlighted the high prevalence of blood culture negative endocarditis (BCNE) in South Africa. The Tygerberg Endocarditis Cohort (TEC) study is an ongoing prospective cohort study of patients with confirmed or suspected IE presenting to Tygerberg Academic Hospital, Cape Town, South Africa. Current analysis includes patients that presented between November 2019 and August 2020. Forty four (44) patients have been included in this ongoing study. Fourteen of the 44 patients (31.8%) had BCNE. Further analysis of the patients with BCNE identified Bartonella species as the most common causative organism (n=6; 43%). Other causes included Mycoplasma species (n=2). No cause could be identified in 4 of the 44 patients (9%). Bartonella quintana was identified with PCR of valvular tissue as the causative organism in 4 of the 5 patients that underwent urgent surgery. The patients with Bartonella IE (n=6) had an average age of 39 years with equal gender distribution. The common clinical features were clubbing (n=5; 83%), anemia (n=4; 66.6%), haematuria (n=3; 50%), acute on chronic severe regurgitant lesion (n=3; 50%) and acute severe regurgitant lesion (n=2; 33.3%).The aortic valve was involved in 5 of 6 patients. During a mean follow-up period of 251 days after diagnosis, no major adverse events occurred. Bartonella-associated IE is an important cause of BCNE in the Western Cape of South Africa. Imaging findings (in patients with BCNE) of significant valvular destruction with large vegetations on the aortic valve not affected by congenital or rheumatic valve disease should raise the suspicion of Bartonella-associated IE.

Molecular diagnosis of Coxiella burnetii in culture negative endocarditis and vascular infection in South Korea

Background Q fever endocarditis is a major cause of culture-negative endocarditis. The role of Coxellia burnetii is underestimated because it is difficult to diagnose. We investigated the significance of C. burnetii as the cause of culture-negative endocarditis and vascular infection by examining blood and tissue specimens using serological testing and polymerase chain reaction (PCR). Methods All patients with infective endocarditis or large vessel vasculitis were prospectively enrolled at a tertiary-care hospital from May 2016 through September 2020. Q fever endocarditis and vascular infection were diagnosed based on: (1) positive PCR for a cardiac valve or vascular tissue, (2) positive PCR for blood or phase I immunoglobulin G (IgG) ≥ 6400, or (3) phase I IgG ≥ 800 and < 6400 with morphologic abnormality. PCR targeted C. burnetii transposase gene insertion element IS1111a. Results Of the 163 patients, 40 (25%) had culture-negative endocarditis (n = 35) or vascular infection (n = 5). Of the 40 patients, 24 (60%) were enrolled. Eight (33%) were diagnosed with Q fever endocarditis or vascular infection. Of these 8 patients, 6 had suspected acute Q fever endocarditis or vascular infection with negative phase I IgG. Six patients were not treated for C. burnetii, 4 were stable after surgery. One patient died due to surgical site infection after 5 months post-operatively and one died due to worsening underlying disease. Conclusions Approximately one-third of patients with culture-negative endocarditis and vascular infection was diagnosed as Q fever. Q fever endocarditis and vascular infection may be underestimated in routine clinical practice in South Korea. KEY MESSAGE Q fever endocarditis and vascular infection may be underestimated in routine clinical practice, thus, try to find evidence of C. burnetti infection in suspected patients by all available diagnostic tests including PCR.

710. Non-invasive Diagnosis of Whipple Endocarditis Using Next-Generation Sequencing for Microbial Cell-free DNA in Plasma

Background Tropheryma whipplei is a gram-positive bacillus that causes Whipple’s disease, a protean multisystemic syndrome classically characterized by arthralgias, chronic diarrhea, malabsorption, and weight loss. T. whipplei infection has a wide spectrum of clinical manifestations including pleuropulmonary disease, skin hyperpigmentation and cardiac infection. Endocarditis has been diagnosed in a small number of patients and may represent an atypical presentation of T. whipplei infection. Diagnosis can be challenging and has typically been accomplished with histopathology on resected valvular tissue or GI tract biopsy. Next-generation sequencing (NGS) of microbial cell-free DNA (mcfDNA) in plasma offers a rapid, non-invasive means of diagnosis of this rare cause of culture-negative endocarditis and challenging clinical entity.MethodsMcfDNA analysis was performed in a patient with culture negative endocarditis. McDNA was extracted from plasma and NGS was performed by Karius, Inc. (Redwood City, California). Human sequences were removed and remaining sequences were aligned to a curated database of over 1,400 pathogens. Organisms present above a predefined statistical significance threshold were reported and quantified in DNA molecules per microliter (MPM). Chart review was performed for clinical correlation.ResultsA 64 year-old male with history of valve replacement presented with significant deterioration of the mitral valve. An exhaustive infectious workup including blood cultures was negative. Karius testing detected T. whipplei at 766 MPM within two days of sample receipt. The normal range for T. whipplei is 0 MPM based on a cohort of 684 healthy individuals. Blood PCR for T. whipplei was confirmatory.Table 1: Clinical Parameters of Case ConclusionNGS for mcfDNA in plasma offers a rapid, non-invasive method for identifying T. whipplei and, to our knowledge, the first diagnosis of Whipple disease using NGS of plasma mcfDNA.DisclosuresChristiaan R. de Vries, MD, PhD, Karius (Consultant, Independent Contractor)Stanford University (Employee) Ann Macintyre, DO, Karius (Employee)

Silent but Deadly

Abstract Legionella species are a rare cause of culture-negative endocarditis. We report the first case of bioprosthetic valve endocarditis due to Legionella maceachernii. This case highlights the importance of the use of DNA target sequencing to identify the cause of culture-negative endocarditis, as standard empiric therapy would not have covered the identified organism.

P30 A ‘cat’-astrophic case of Bartonella infective endocarditis causing a secondary cryoglobulinemia

Abstract Background A 17-year-old college student presented with a year long history of weight loss and poor appetite. She had a background of pulmonary atresia with a ventricular septal defect, treated with a contegra conduit in childhood. She was initially treated for depression. Subsequently she developed a vasculitic rash on her legs with urinalysis demonstrating haemoproteinuria (urine PCR=116) resulting in renal referral and hospital admission. On examination, the patient had a BMI of 15 and was found to have massive splenomegaly. Methods Her initial creatinine was 128 (eGFR 58), although cystatin C (which accounts for low muscle mass) estimated her eGFR at 16. Renal biopsy showed focal necrotizing glomerulonephritis with no acute tubular necrosis or chronic change. Haematological work up was normal with bone marrow revealing reactive changes. Bloods revealed a weakly positive PR3 antibody and a provisional diagnosis of ANCA associated vasculitis was made for which prednisolone was commenced. A rheumatology review was sought. Review of systems was relevant for intermittent joint pains and ocular dryness. Additional bloods showed a low C4, positive RhF, negative anti-CCP, elevated immunoglobulins (IgG 45) and normal ENA profile. Results The provisional diagnosis was altered to cryoglobulinaemic vasculitis which was confirmed as a Type 3 cryoglobulin. Initial investigations for an infectious cause were negative however an echocardiogram showed vegetations on her conduit and treatment was commenced for endocarditis. Blood cultures were negative. Inflammatory markers failed to settle following two weeks of intravenous antibiotics and accordingly the patient was referred for surgical revision of her conduit. Tissue samples ultimately grew Bartonella and aspergillus species. Antibiotic therapy was altered to doxycycline and anti-fungal therapy whilst steroids were continued. Following completion of antibiotic treatment, she has had resolution of her cryoglobulinaemia, normalization of RhF/C4, creatinine is 58 with no proteinuria and IgG is 13. The diagnosis was therefore confirmed as a Type 3 Cryoglobulinaemia secondary to Bartonella endocarditis +/- fungal infection of conduit. The patient’s mother revealed she had adopted several stray cats in the preceding year which was identified as the likely cause of the Bartonella infection. Conclusion In summary, this is a case of Bartonella endocarditis causing a secondary cryoglobulinemia; the exact mechanisms of this is not fully understood but is thought to be due to B cell hyperactivity. Culture-negative infective endocarditis constitutes approximately 10% of the total number of cases of infective endocarditis. Bartonella endocarditis is one of the most common causes of culture-negative endocarditis and is associated with a high mortality rate. Contact with animals, particularly cats, is a key risk factor. It is, therefore, important to enquire about such exposure especially when culture-negative endocarditis is suspected. Disclosures A. Vivekanantham None. E. McCarthy None.

Tropheryma whipplei—A rare and diagnostically challenging cause of culture-negative endocarditis

Keywords: Culture-negative endocarditis, Tropheryma whipplei, Whipple’s disease, Whipple’s endocarditis

Bartonella henselae Endocarditis: An Usual Presentation of an Unusual Disease.

Bartonella species are an emerging cause of culture-negative endocarditis with more cases being diagnosed now than 25 years ago when Bartonella quintana endocarditis was first described in a patient infected with human immunodeficiency virus (HIV). Despite the disease being increasingly reported, the exact epidemiological features are not clear, with prevalence rates ranging between 2% and 10% of all cases of culture-negative endocarditis. Moreover, the mortality rate is still high, presumably because of the subacute nature and relative rareness of the disease. Bartonella endocarditis occurs more often in men, and previous valvular surgery is a major risk factor. There is insufficient data to guide definitive treatment due to the paucity of literature. A previous study demonstrated that effective antibiotic therapy for Bartonella endocarditis should include an aminoglycoside prescribed for a minimum of 2 weeks. However, the treatment strategy is a matter of expert opinion.LEARNING POINTSBartonella endocarditis is considered one of the most common causes of culture-negative endocarditis, yet tardy diagnosis of the disease is usually made, thus carrying a high mortality rate.Awareness of the unusual presentation of Bartonella endocarditis could potentially decrease complications and mortality rates.Contact with animals, and cats in particular, is a prominent risk factor for Bartonella henselae infection. Physicians should therefore routinely enquire about such exposure when endocarditis and especially culture-negative endocarditis is suspected.Empirical therapy should be started when culture-negative endocarditis is suspected and even when Duke criteria are not met; watchful waiting for final serological tests might be harmful, as recommended by some international authors.Most organisms causing culture-negative endocarditis are not covered in the initial treatment of infective endocarditis before or without pathogen identification recommended by the European Society of Cardiology.

Tropheryma whipplei Endocarditis: Case Presentation and Review of the Literature.

Whipple’s disease is a rare infective condition, classically presenting with gastrointestinal manifestations. It is increasingly recognized as an important cause of culture-negative endocarditis. We present a case of Whipple’s endocarditis presenting with heart failure. A literature review identified 44 publications documenting 169 patients with Whipple’s endocarditis. The average age was 57.1 years. There is a clear sex predominance, with 85% of cases being male. Presenting symptoms were primarily articular involvement (52%) and heart failure (41%). In the majority of cases, the diagnosis was made on examination of valvular tissue. Preexisting valvular abnormalities were reported in 21%. The aortic valve was most commonly involved, and multiple valves were involved in 64% and 23% of cases, respectively. Antibiotic therapy was widely varied and included a ceftriaxone, trimethoprim, and sulfamethoxazole combination. The average follow-up was 20 months, and mortality was approximately 24%. Physician awareness is paramount in the diagnosis and management of this rare condition.

MORE THAN MEETS THE EYE: BARTONELLA HENSELAE ENDOCARDITIS PRESENTING AS ACUTE KIDNEY INJURY

Bartonella Henselae, a common cause of culture-negative endocarditis, may be challenging to diagnose increasing the mortality and morbidity risk. A 54-year old male with past medical history of paroxysmal atrial fibrillation (controlled on sotalol), hypertension (medically managed), rheumatic fever

TROPHERYMA WHIPPLEI: AN UNUSUAL CAUSE OF MITRAL AND AORTIC VALVE ENDOCARDITIS

Whipple's disease is an uncommon, chronic systemic illness characterized by abdominal discomfort, weight loss and arthralgia, caused by Tropheryma whipplei. While cardiac involvement occurs less commonly, it has become apparent that some causes of culture-negative endocarditis may be attributed to

Elevated Cholesterol in the Coxiella burnetii Intracellular Niche Is Bacteriolytic.

ABSTRACTCoxiella burnetii is an intracellular bacterial pathogen and a significant cause of culture-negative endocarditis in the United States. Upon infection, the nascent Coxiella phagosome fuses with the host endocytic pathway to form a large lysosome-like vacuole called the parasitophorous vacuole (PV). The PV membrane is rich in sterols, and drugs perturbing host cell cholesterol homeostasis inhibit PV formation and bacterial growth. Using cholesterol supplementation of a cholesterol-free cell model system, we found smaller PVs and reduced Coxiella growth as cellular cholesterol concentration increased. Further, we observed in cells with cholesterol a significant number of nonfusogenic PVs that contained degraded bacteria, a phenotype not observed in cholesterol-free cells. Cholesterol had no effect on axenic Coxiella cultures, indicating that only intracellular bacteria are sensitive to cholesterol. Live-cell microscopy revealed that both plasma membrane-derived cholesterol and the exogenous cholesterol carrier protein low-density lipoprotein (LDL) traffic to the PV. To test the possibility that increasing PV cholesterol levels affects bacterial survival, infected cells were treated with U18666A, a drug that traps cholesterol in lysosomes and PVs. U18666A treatment led to PVs containing degraded bacteria and a significant loss in bacterial viability. The PV pH was significantly more acidic in cells with cholesterol or cells treated with U18666A, and the vacuolar ATPase inhibitor bafilomycin blocked cholesterol-induced PV acidification and bacterial death. Additionally, treatment of infected HeLa cells with several FDA-approved cholesterol-altering drugs led to a loss of bacterial viability, a phenotype also rescued by bafilomycin. Collectively, these data suggest that increasing PV cholesterol further acidifies the PV, leading to Coxiella death.