Fatal Endocarditis Research Articles

Role of lipid droplets and prostaglandinE2 in Coxiella burnetii intracellular growth.

Abstract The obligate intracellular bacterium, Coxiella burnetii, causes human Q fever. Infection with Coxiella via inhalation presents as atypical pneumonia which may relapse years later, leading to potentially fatal endocarditis. Our goal is to determine the mechanisms Coxiella employs for long-term survival in the host. While the bacterium initially infects alveolar macrophages, in endocarditis patients Coxiella is found in foamy macrophages rich in neutral lipid storage organelles, lipid droplets (LDs). Our studies show that blocking LD breakdown inhibits bacterial growth suggesting that LD-derived lipids are crucial for Coxiella’s survival. LD breakdown releases arachidonic acids, precursors for the lipid immune mediator prostaglandinE2 (PGE2) which promotes immunosuppression in alveolar macrophages. We hypothesize that Coxiella manipulates host cell LD metabolism to promote a PGE2-mediated immunosuppressive environment and survive long-term in the host. To test this, we quantified PGE2 production in Coxiella-infected cells with and without LD breakdown inhibitor, atglistatin. ELISA showed a LD breakdown-dependent increase in PGE2 levels. Fluorescence microscopy revealed PGE2 production blockade with COX-2 inhibitors significantly decreased bacterial growth which was rescued by exogenous PGE2 suggesting that PGE2 promotes Coxiella survival. Ongoing studies are identifying the correlation between LDs and PGE2 production and the role of LDs in immunosuppression.

Pathogenesis, Diagnosis, Antimicrobial Therapy, and Management of Infective Endocarditis, and Its Complications.

Infective endocarditis in the adult is life-threatening. Bacterial endocarditis is an inner infection lining the heart muscle (endocardium). The scientific study of the causes of diseases is known as etiology. The agents that cause disease fall into five groups: bacteria, viruses, protozoa, fungi, and helminths (worms). Risk factors are past heart defects, damaged or abnormal heart valves, new valves after surgery, chronic hemodialysis, and immunosuppressed state (chemotherapy, HIV, etc.). Infective endocarditis is categorized into two clinical forms: bacterial acute and subacute endocarditis. Acute bacterial endocarditis is usually caused by staphylococci (staph) and streptococci (strep). And occasionally by listeria and brucella bacterial strains. Invasive medical technology has increased the responsibility of healthcare-associated infective endocarditis (HAIE). Microscopy of the disease is the chronic aggressive cells in the deeper zone of nonspecific, composed of fibrin and platelets covering colonies of bacteria. Tuberculous valvular endocarditis due to mycobacterium tuberculosis is a rare clinical entity. Syphilitic endocarditis is pathologically the cutaneous lesions of secondary syphilis. It is caused by infection with the microorganismTreponema pallidum. Fungal endocarditis is a rare and fatal condition. They are infected with fungi such as Candida albicans, Histoplasma capsulatum, and Aspergillus species. Fatal endocarditis associated with Q fever (query fever). Q fever is a chronic or prolonged disease caused by the rickettsial-like bacillus Coxiella burnetii, a rare form of rickettsia in the endocarditis. Varicella-zoster virus (VZV) infection causes chronic and repeated febrile illness. They are followed by pharyngitis, malaise, and a vesicular rash. Chronic Q fever usually manifests as endocarditis or hepatitis. The therapy given to simplify the complications is antimicrobial therapy. The medicines prescribed are ampicillin, cefazolin, ceftazidime, gentamicin, vancomycin, metronidazole, and tobramycin. High medicinal antibiotics are used to control the spread of infective endocarditis.

Coxiella burnetii Requires Host Eukaryotic Initiation Factor 2α Activity for Efficient Intracellular Replication.

Coxiella burnetii is the causative agent of human Q fever, eliciting symptoms that range from acute fever and fatigue to chronic fatal endocarditis. C. burnetii is a Gram-negative intracellular bacterium that replicates within an acidic lysosome-like parasitophorous vacuole (PV) in human macrophages. During intracellular growth, C. burnetii delivers bacterial proteins directly into the host cytoplasm using a Dot/Icm type IV secretion system (T4SS). Multiple T4SS effectors localize to and/or disrupt the endoplasmic reticulum (ER) and secretory transport, but their role in infection is unknown. During microbial infection, unfolded nascent proteins may exceed the folding capacity of the ER, activating the unfolded protein response (UPR) and restoring the ER to its normal physiological state. A subset of intracellular pathogens manipulates the UPR to promote survival and replication in host cells. In this study, we investigated the impact of C. burnetii infection on activation of the three arms of the UPR. An inhibitor of the UPR antagonized PV expansion in macrophages, indicating this process is needed for bacterial replication niche formation. Protein kinase RNA-like ER kinase (PERK) signaling was activated during infection, leading to increased levels of phosphorylated eukaryotic initiation factor α, which was required for C. burnetii growth. Increased production and nuclear translocation of the transcription factor ATF4 also occurred, which normally drives expression of the proapoptotic C/EBP homologous protein (CHOP). CHOP protein production increased during infection; however, C. burnetii actively prevented CHOP nuclear translocation and downstream apoptosis in a T4SS-dependent manner. The results collectively demonstrate interplay between C. burnetii and specific components of the eIF2α signaling cascade to parasitize human macrophages.

Domestic sheep show average Coxiella burnetii seropositivity generations after a sheep-associated human Q fever outbreak and lack detectable shedding by placental, vaginal, and fecal routes.

Coxiella burnetii is a globally distributed zoonotic bacterial pathogen that causes abortions in ruminant livestock. In humans, an influenza-like illness results with the potential for hospitalization, chronic infection, abortion, and fatal endocarditis. Ruminant livestock, particularly small ruminants, are hypothesized to be the primary transmission source to humans. A recent Netherlands outbreak from 2007–2010 traced to dairy goats resulted in over 4,100 human cases with estimated costs of more than 300 million euros. Smaller human Q fever outbreaks of small ruminant origin have occurred in the United States, and characterizing shedding is important to understand the risk of future outbreaks. In this study, we assessed bacterial shedding and seroprevalence in 100 sheep from an Idaho location associated with a 1984 human Q fever outbreak. We observed 5% seropositivity, which was not significantly different from the national average of 2.7% for the U.S. (P>0.05). Furthermore, C. burnetii was not detected by quantitative PCR from placentas, vaginal swabs, or fecal samples. Specifically, a three-target quantitative PCR of placenta identified 0.0% shedding (exact 95% confidence interval: 0.0%-2.9%). While presence of seropositive individuals demonstrates some historical C. burnetii exposure, the placental sample confidence interval suggests 2016 shedding events were rare or absent. The location maintained the flock with little or no depopulation in 1984 and without C. burnetii vaccination during or since 1984. It is not clear how a zero-shedding rate was achieved in these sheep beyond natural immunity, and more work is required to discover and assess possible factors that may contribute towards achieving zero-shedding status. We provide the first U.S. sheep placental C. burnetii shedding update in over 60 years and demonstrate potential for C. burnetii shedding to reach undetectable levels after an outbreak event even in the absence of targeted interventions, such as vaccination.

Splenorenal Manifestations of Bartonella henselae Infection in a Pediatric Patient.

Bartonella henselae is a bacterium which can cause a wide range of clinical manifestations, ranging from fever of unknown origin to a potentially fatal endocarditis. We report a case of Bartonella henselae infection in a pediatric-aged patient following a scratch from a kitten. The patient initially presented with a prolonged fever of unknown origin which was unresponsive to antibiotic treatment. The patient was hospitalized with worsening fevers and night sweat. Subsequent ultrasound imaging demonstrated multiple hypoechoic foci within the spleen. A contrast-enhanced CT of the abdomen and pelvis was also obtained which showed hypoattenuating lesions in the spleen and bilateral kidneys. Bartonella henselae IgG and IgM titers were positive, consistent with an acute Bartonella henselae infection. The patient was discharged with a course of oral rifampin and trimethoprim-sulfamethoxazole, and all symptoms had resolved following two weeks of therapy.

Q Fever Surveillance in Ruminants, Thailand, 2012

Q Fever Surveillance in Ruminants, Thailand, 2012

NonspecificErysipelothrix rhusiopathiaeBacteremia in a Patient with Subclinical Alcoholic Liver Disease

Erysipelothrix rhusiopathiae, a pleomorphic gram-positive bacillus, is found widely in nature or as a commensal pathogen. It infects domestic animals such as swine, which may be the major reservoir of the organism. E. rhusiopathiae is primarily an occupational illness; 89% of the cases are linked to high-risk epidemiological situations. Humans that are infected by this bacillus typically present with one or a combination of the following symptoms: localized skin lesion (erysipeloid), diffuse cutaneous eruptions with systemic symptoms, or bacteremia, which is often followed by endocarditis. We report a case of E. rhusiopathiae bacteremia that was present without severe clinical illness such as endocarditis, arthritis, or skin lesions. The patient was a 64-year-old male with a complicated past medical history including subclinical alcoholic liver disease. Penicillin-G therapy completely resolved the patients bacteremia. The case presented has exceptional clinical merit due to 2 key factors: the patient does not fit the occupational demographic typically affected by this bacterium, and the patient presented with subclinical septicemia, which has a high correlation with fatal endocarditis. This case brings a new prospective to E. rhusiopathiae bacteremia.

Fatal Endocarditis Caused by Arcanobacterium haemolyticum: Case Report and Review of the Literature

© 2012 Elsevier 0196-4399/00 (see frontmatter) 13 Introduction Arcanobacterium haemolyticum (formerly Corynebacterium haemolyticum) is a gram-positive bacillus that is mainly implicated in pharyngitis and skin infections. Most of these infections occur in the adolescent age group, sometimes mixed with other pathogens. This microorganism is sometimes overlooked in the clinical microbiology laboratory because it is rare. The colonies may be dismissed as insignificant or misidentified as Streptococcus or Corynebacterium species, resulting in a missed or delayed diagnosis. Endocarditis is rarely caused by the bacterium and has been reported in only three cases in the literature. In this case report, we present a fatal case of endocarditis associated with a congenital bicuspid aortic valve. We also describe the laboratory methods used for the identification of the organism, together with a brief review of the literature on reported cases of A. haemolyticum infection.

Occurrence of genes of putative fibrinogen binding proteins and hemolysins, as well as of their phenotypic correlates in isolates of S. lugdunensis of different origins

BackgroundStaphylococcus lugdunensis is an important human pathogen that causes potentially fatal endocarditis, osteomyelitis and skin and soft tissue infections similar to diseases caused by Staphylococcus aureus. Nevertheless, in contrast to S. aureus, data on pathogenicity factors of S. lugdunensis is scarce. Two adhesins, a fibrinogen and a von Willebrand factor binding protein, and a S. lugdunensis synergistic hemolysin (SLUSH) have been previously described. Moreover, the newly sequenced genome of S. lugdunensis revealed genes of other putative fibrinogen binding adhesins and hemolysins. The aim of this study was to gain more insight into the occurrence of genes likely coding for fibrinogen binding adhesins and hemolysins using clinical strains of S. lugdunensis.FindingsMost of the putative adhesin genes and hemolysin genes investigated in this study were highly prevalent, except for the SLUSH gene cluster. In contrast to previous reports, binding to fibrinogen was detected in 29.3% of the S. lugdunensis strains. In most strains, hemolysis on blood agar plates was weak after 24 h and distinct after 48 h of incubation. The fibrinogen binding and hemolysis phenotypes were also independent of the type of clinical specimen, from which the isolates were obtained.ConclusionIn this study we described a pyrrolidonyl arylamidase negative S. lugdunensis isolate. Our data indicate that a matrix-assisted laser desorption ionisation time-of-flight MS-based identification of S. lugdunensis or species-specific PCR's should be performed in favour of pyrrolidonyl arylamidase testing. In contrast to the high occurrence of putative fibrinogen binding protein genes, 29.3% of the S. lugdunensis strains bound to fibrinogen. Putative hemolysin genes were also prevalent in most of the S. lugdunensis strains, irrespective of their hemolysis activity on Columbia blood agar plates. Similar to a previous report, hemolysis after 48 h of incubation is also indicative for S. lugdunensis. The SLUSH gene cluster was detected in an estimated 50% of the strains, indicating that this locus is different or non-prevalent in many strains.

Phase II Study of Lenalidomide in Combination with Rituximab for Patients with CD5+/CD20+ Hematologic Malignancies Who Relapse or Progress After Rituximab. Interim Analysis.

Abstract 2376Poster Board II-353 Background:Patients with relapsed or refractory CLL/SLL and patients with mantle cell lymphoma (McL) have a poor prognosis. Overall response rate (ORR) to salvage therapy for refractory patients is approximately 10-30%, and survival benefit with current treatment approaches is limited. Phase II studies of single agent lenalidomide in patients with relapsed or refractory CLL revealed an ORR of 32-58% (7-17% CR), depending on treatment dose, scheduled used and duration of treatment with lenalidomide. In patients with refractory or relapsed McL, lenalidomide treatment resulted in an ORR of 53% (CR 20%, PR 33%), and a 14-month median duration of response (Habermann et al 2009). Recent in vitro studies have shown that lenalidomide enhances the rituximab-induced killing of NHL cell lines and B-CLL cells via ADCC by restoring the defective T-cell and NK-cell mediated ability to form immune synapses to exert tumor cell cytotoxicity. Methods:Patients with relapsed or refractory CLL/SLL or McL received oral lenalidomide via dose escalation as follows, 2.5 mg on days 1-7, 5mg on day 8-14 and 10mg on day 15-21 followed by 7 days of rest in 28-day cycle; for cycle 2 and beyond 20mg was given on day 1-21 on a 28 day cycle. Rituximab was dosed at 375mg/m2 IV weekly for 4 weeks starting on day 15 of cycle 1. Treatment was continued until disease progression or toxicity. All patients were given allopurinol 300mg orally twice per day starting 3 days prior to first dose of lenalidomide. CT scans, and bone marrow biopsies were done every 2 months to assess for response. Primary objectives were overall response rate (CR+PR) and safety and tolerability of the combination regimen. Results:17 patients were enrolled on study (13 patients with CLL/SLL and 4 patients with McL). Median number of prior chemotherapies was 3 (range 1-5). Median age was 64 years (range 42-80). Among patients with CLL, the most common cytogenetic abnormalities were trisomy 12 (isolated n=3, associated with other abnormalities n=4), del11q (isolated n=1, with others n=3), isolated del13q (n=1), complex cytogenetics with 3 or more abnormalities (n=4 including 1 patient with del 17p). Responses were assessed every 2 months after initiation of therapy. Response rate for 13 evaluable patients (10 with CLL and 3 with McL) relative to months on treatment with lenalidomide are summarized in the table. Although all responses were PR, the rate of PR improved with continued therapy suggesting increased responses with a longer duration of treatment with lenalidomide. Currently, 7 patients are still receiving active treatment on study, all with CLL (3 achieved a PR and 4 have SD). Of the 4 patients with McL enrolled on study, 1 achieved a PR after 2 months of therapy; 1 achieved SD after 2 months of therapy with a sustained SD after 6 months; 1 patient achieved SD after 2 months, but progressed after 6 months on treatment.The regimen was well tolerated. Most common (>5%) toxicities include neutropenia (35% grade 3, 6% grade 4), fatigue (17% grade 1-2, 6% grade 3), tumor flare (12% grade 2, 12% grade 3), acute renal insufficiency (6% grade 1, 12% grade 3), rituximab related infusion reactions (6% grade 2, 6% grade 3), flu-like symptoms (6% grade 2, 6% grade 3), venous thromboembolic disease (6% grade 2, 6% grade 3), infections (11% including 1 patient with fatal endocarditis), and hypercalcemia (11% grade 4). Correlative studies are ongoing. Conclusions:The combination of lenalidomide with Rituximab is a promising combination regimen in CLL patients with very poor prognosis who have undergone multiple lines of therapy. This treatment combination appears tolerable with observed events consistent with the use of these two agents in other studies. Further investigation is warranted, possibly in the front line setting and in combination with other agents.Table 1Response Rates Relative to Time on LenalidomideResponse2 months4 months6 months8 months12 monthsOR1/13 (7.6%)2/11 (18.1%)4/9 (44.4%)2/6 (33.3%)2/3 (66.6%)SD11/13 (84.6%)8/11 (72.7%)4/9 (44.4%)4/6 (66.6%)1/3 (33.3%)PD1/13 (7.6%)1/11 (9.1%)1/9 (11.1%)0/6 (0%)0/3 (0%)ORR: Overall response rate; SD: stable disease; PD: progression of disease Disclosures:Lancet:Celgene: Research Funding.

Molecular Epidemiologic Evaluation of Endocarditis Due to Oerskovia turbata and CDC Group A-3 Associated with Contaminated Homograft Valves

Oerskovia turbata is an unusual bacterial cause of endocarditis and septicemia in immunocompromised patients. In this study, we compared 12 isolates from a 1975 medical center cluster, 11 originally identified as O. turbata (four from the blood of a homograft aortic valve-associated endocarditis patient and seven from contaminated homograft valves) and one CDC group A-3 strain from the blood of a second endocarditis patient with fatal outcome, with eight control strains from unrelated locations. The control strains included type and reference strains of O. turbata, Cellulomonas hominis, and CDC group A-3. The four blood isolates from the first patient and six of the valve isolates shared identical biochemical, antimicrobial susceptibility, and BglI ribotype patterns that differed from the second patient's isolate and control strains. The blood isolate from the second patient and the remaining valve isolate shared a phenotypic and genotypic profile and were phenotypically identical to, but epidemiologically different from, the CDC group A-3 reference strain with the strain-specific enzyme. Also, these isolates differed from the type strain and the other reference strains of C. hominis and O. turbata. Our results indicate that the four blood isolates from the first patient and six of the homograft valve isolates represent a single clone of O. turbata associated with endocarditis. Additionally, our results indicate that the blood isolate from the second patient and one of the homograft valve isolates differ from O. turbata and C. hominis and represent a unique clone of CDC group A-3 associated with fatal endocarditis.

Fatal mycotic endocarditis from a primary esophageal aspergilloma

Fatal mycotic endocarditis from a primary esophageal aspergilloma

Opportunistic Infection with Rhodotorula in Cancer Patients Treated by Chemotherapy: Two Case Reports

<h2>Abstract</h2> <i>Rhodotorula</i> species are commensal yeasts of variable pathogenicity. The authors report the case histories of two patients presenting with febrile neutropenia. The first was a 3-year-old girl who had been treated with combination chemotherapy for a tumour of the posterior fossa. The second was a 46-year-old man who had received chemotherapy for lymphoplasmocytic lymphoma, followed by consolidation treatment with autologous bone marrow transplantation. Investigation revealed infection caused by <i>Rhodotorula</i>. The outcome was favourable after removal of the catheter in both patients. <i>Rhodotorula</i> species have been isolated during a variety of infectious complications. Almost all published cases of fungaemia concern patients with central venous catheters that have been in place over long periods, who have also been treated with broad spectrum antibiotics. Neoplasia represents the most frequent underlying disease. The pathogenicity of <i>Rhodotorula</i> species appears to be moderate in most cases; fungal therapy or the removal of infected catheters is generally effective. Nevertheless, <i>Rhodotorula</i> has been reported to provoke fatal endocarditis or meningitis and can probably cause septic shock.

Endocarditis Caused by Multiply Resistant Bacteroides fragilis: Case Report and Review

AbstractA 78-year-old woman developed fatal endocarditis of her prosthetic aortic valve, caused by Bacteroides fragilis fragilis, and associated with ovarian carcinoma. The strain showed multiple antibiotic resistance, including resistance to beta-lactam agents and combinations with beta-lactamase inhibitors. Seventeen previously described cases of endocarditis caused by Bacteroides spp. have been found in the literature. The mean age of the 18 patients was 50.3 years, the gastro-intestinal tract was the most common site of associated disease, embolism occured in ten cases and eight patients died. Previous isolates showed the antibiotic susceptibility customarily associated with the B. fragilis group.

Fatal endocarditis due to Aerococcus urinae

Aerococcus species are Gram-positive cocci having Gram-stain characteristics of staphylococci (i.e., form clusters), but biochemical and growth characteristics resembling streptococci and enterococci (i.e., catalase-negative, α-hemolytic growth on blood agar). A case of fatal endocarditis due to Aerococcus urinae is presented. Endocarditis should be suspected and, if confirmed, treated aggressively when A. urinae is recovered from blood cultures.

Urosepticemia and Fatal Endocarditis Caused by Aerococcus-like Organisms

Two cases of invasive infections with aerococcus-like organisms (ALO) are presented: an 81-year-old man with fatal endocarditis and a 63-year-old man with urosepticemia. No antigenic relationship was found between ALO and Aerococcus viridans (NCTC 8251) in crossed immunoelectrophoretic assay.

Haemophilus aphrophilus Isolated from Blood

H. aphrophilus was isolated from 11 successively cultivated blood samples of a male (72) with a fatal atypical endocarditis. Identification and differential diagnosis from Actinobacillus (Haemophilus) actinomycetemcomitans was done on the basis of phenotypic characters of the microorganism.

Fatal Bacterial Endocarditis as a Complication of Permanent Indwelling Catheters. Report of Two Cases

Two cases of endocarditis secondary to permanent indwelling catheters are described. In both cases, the catheters were used for parenteral nutrition and became infected with Staphylococci. Secondary endocarditis developed on the tricuspid and aortic valves. Despite removal of the catheters and appropriate antibiotics, both patients died.

Endocarditis Involving a Left Ventricular Apicoaortic Valve-Bearing Conduit

Fatal infectious endocarditis involving a left ventricular apicoaortic valve-bearing conduit occurred in a 20-year-old man. Risk factors included early postoperative wound infection, broad spectrum suppressive antibiotic administration, and inadequate dental prophylaxis against infectious indocarditis. Palliative therapy included intravenous antibiotic administration and removal of the conduit. Lessons learned are discussed.

Outbreak of Serratia marcescens Infections in a Cardiothoracic Surgical Intensive Care Unit

An outbreak of infections with pigmented Serratia marcescens involving 3 patients in a cardiothoracic surgical intensive care unit is reported. A respirator is thought to have been the source of pneumonia in 2 patients, and fomite spread from 1 of these is considered responsible for the induction of fatal endocarditis in the third patient. This outbreak demonstrates the rapid dissemination of a bacterial strain within the unit, several methods of dissemination, the wide variation in apparent virulence of the organism, the alterations of antibacterial host defense which made bacterial disease possible and which determined the site of infection, and the difficulties of adequate therapy. The third patient is the seventh reported with serratia infection of a prosthetic heart valve.