Proposal for the use of echocardiography in bloodstream infections due to different streptococcal species.

BACKGROUND: Infective endocarditis (IE) is diagnosed in 7-8% of streptococcal bloodstream infections (BSIs), yet it is unclear when to perform transthoracic (TTE) and transoesophageal echocardiography (TOE) according to different streptococcal species. The aim of this sub-study was to propose a flowchart for the use of echocardiography in streptococcal BSIs. METHODS: In a population-based setup, we investigated all patients admitted with streptococcal BSIs and crosslinked data with nationwide registries to identify comorbidities and concomitant hospitalization with IE. Streptococcal species were divided in four groups based on the crude risk of being diagnosed with IE (low-risk < 3%, moderate-risk 3-10%, high-risk 10-30% and very high-risk > 30%). Based on number of positive blood culture (BC) bottles and IE risk factors (prosthetic valve, previous IE, native valve disease, and cardiac device), we further stratified cases according to probability of concomitant IE diagnosis to create a flowchart suggesting TTE plus TOE (IE > 10%), TTE (IE 3-10%), or "wait & see" (IE < 3%). RESULTS: We included 6393 cases with streptococcal BSIs (mean age 68.1 years [SD 16.2], 52.8% men). BSIs with low-risk streptococci (S. pneumoniae, S. pyogenes, S. intermedius) are not initially recommended echocardiography, unless they have ≥3 positive BC bottles and an IE risk factor. Moderate-risk streptococci (S. agalactiae, S. anginosus, S. constellatus, S. dysgalactiae, S. salivarius, S. thermophilus) are guided to "wait & see" strategy if they neither have a risk factor nor ≥3 positive BC bottles, while a TTE is recommended if they have either ≥3 positive BC bottles or a risk factor. Further, a TTE and TOE are recommended if they present with both. High-risk streptococci (S. mitis/oralis, S. parasanguinis, G. adiacens) are directed to a TTE if they neither have a risk factor nor ≥3 positive BC bottles, but to TTE and TOE if they have either ≥3 positive BC bottles or a risk factor. Very high-risk streptococci (S. gordonii, S. gallolyticus, S. mutans, S. sanguinis) are guided directly to TTE and TOE due to a high baseline IE prevalence. CONCLUSION: In addition to the clinical picture, this flowchart based on streptococcal species, number of positive blood culture bottles, and risk factors, can help guide the use of echocardiography in streptococcal bloodstream infections. Since echocardiography results are not available the findings should be confirmed prospectively with the use of systematic echocardiography.

Comparison of Demographic Profile, Laboratory, Epidemiology and Clinical Outcomes in Patients with Native Valve and Prosthetic Valve Endocarditis.

BACKGROUND: Infective endocarditis (IE) is a heterogenous infection that affects the endothelial surface of the intracardiac structures and other implanted intracardiac devices. We aimed to compare demographical characteristics, causative microorganisms, treatment, and prognosis of prosthetic and native valve endocarditis diagnosed in two separate hospitals. MATERIAL AND METHODS: Between 2010 and 2020, patients admitted with the diagnosis of IE were retrospectively included in our multicenter study. Patients' demographic and epidemiological data, clinical characteristics, infected intracardiac structure and sort of valve, culprit microorganisms, laboratory findings, treatment manifestations and in-hospital outcomes with a period of 6 months were obtained from an electronic medical record system. RESULTS: A total of 173 consecutive patients had diagnosed IE, 60.1% (104 patients) of them native valve endocarditis (NVE) and 39.8 % (69 patients) of them prosthetic valve endocarditis (PVE).  Baseline demographic properties were not different except hypertension and atrial fibrillation. Patients with prior hypertension were 25% (26 patients) in NVE; 39.1% (27 patients) in PVE and the difference was statistically significant. Septic shock was significantly higher in the PVE group than the NVE group (7.4% versus 1%; P = .036), and also recurrent endocarditis occurred more frequently in the PVE group than the NVE group (8.8% versus 1%; P = .016). CONCLUSION: In our study, although we detected higher mean age, HT, RDW and atrial fibrillation rates compared with NVE, we did not detect a significant difference in mortality and morbidity.

Short time to blood culture positivity in Enterococcus faecalis infective endocarditis.

Time to blood culture positivity (TTP) is an indirect measure of bacterial concentration in blood. A short TTP has been linked to the presence of infective endocarditis (IE) and to poor prognosis in Staphylococcus aureus bacteremia. We analyze factors influencing TTP in bacteremia with Enterococcus faecalis. This retrospective observational study of medical records included adults diagnosed with monomicrobial E. faecalis bacteremia between 2015 and 2018 in the Skåne region (Sweden). For each episode, the shortest TTP was recorded. Median TTP was compared between patients grouped based on age, sex, comorbidity, site of acquisition, and focus of infection. Using a dichotomized TTP (shorter or longer than 12 h), a multivariable logistic regression for factors associated to TTP was performed. The association between TTP and IE or mortality was evaluated. Three hundred sixty-seven episodes with monomicrobial E. faecalis bacteremia with the corresponding TTP were identified. Median TTP for the entire cohort was 11.6 (IQR 9.9-14.1) h and a significantly shorter TTP was noted for episodes which represented IE (n = 55, 9.4 (IQR 6.4-10.6) h). Only IE remained associated with a short TTP (≤ 12 h) in binary logistic regression analysis. Factors associated with IE were investigated and TTP was associated with IE also when adjusted for age, gender, comorbidity, and nosocomial acquisition. There was no association between TTP and mortality. A low TTP is associated with IE in E. faecalis bacteremia and could be used as a help in determining the need for echocardiography in patients with this condition.

Prognostic value of pro-adrenomedullin and copeptin in acute infective endocarditis.

BACKGROUND: Infective endocarditis (IE) is a life-threatening disease whose prognosis is often difficult to predict based on clinical data. Biomarkers have been shown to favorably affect disease management in a number of cardiac disorders. Aims of this retrospective study were to assess the prognostic role of procalcitonin (PCT), pro-adrenomedullin (pro-ADM) and copeptin in IE and their relation with disease characteristics and the traditional biomarker C-reactive protein (CRP). METHODS: We studied 196 patients with definite IE. Clinical, laboratory and echocardiography parameters were analyzed, with a focus on co-morbidities. PCT, pro-ADM and copeptin were measured on stored plasma samples obtained on admission during the acute phase of the disease. RESULTS: Pro-ADM and copeptin were significantly higher in older patients and associated with prior chronic kidney disease. Pro-ADM was an independent predictor of hospital mortality (OR 3.29 [95%C.I. 1.04-11.5]; p = 0.042) whilst copeptin independently predicted 1-year mortality (OR 2.55 [95%C.I. 1.18-5.54]; p = 0.017). A high PCT value was strictly tied with S. aureus etiology (p = 0.001). CRP was the only biomarker associated with embolic events (p = 0.003). CONCLUSIONS: Different biomarkers correlate with distinct IE outcomes. Pro-ADM and copeptin may signal a worse prognosis of IE on admission to the hospital and could be used to identify patients who need more aggressive treatment. CRP remains a low-cost marker of embolic risk. A high PCT value should suggest S. aureus etiology.

Ultrastructure of a late-stage bacterial endocarditis valve vegetation.

Infective endocarditis (IE) remains a severe illness with high mortality rate, despite advances in antibiotic therapy and cardiac surgery. If infectious bacteria and platelets are two key players of human IE vegetation developmental process, their interactions and respective roles in fully developed late-stage IE vegetations remain obscure. The objective of this study was to better understand the organization of the different components of the IE vegetation and to provide a detailed description of this vegetation ultrastructure. A late stage Staphylococcal endocarditic vegetation was provided from a 13 years teenager patient. After reception of the surgical piece, we carried out a histological study using routine methods, notably the hematoxylin-eosin-saffron staining. Labeling with the anti-CD 61 antibody was also carried out. In a second step, we used transmission electron microscopy to describe the different regions making up the vegetation. Our ultrastructural study revealed vegetation was clearly composed by three different regions and identified the specific location of the bacteria and platelets in the vegetation tissues. Histological analysis showed that platelets and Staphylococcus aureus were not co-localized. Electron microscopy study confirmed that S. aureus were found at distance from platelets, as well from immune cells, embedded in a biofilm and/or a necrotic area. These results reveal a development of a deep bacteria-only niche in vegetation, raising questions about medication access to these microorganisms. Vegetation composed of three regions: a region rich in bacteria incorporated into the necrotic tissue, the second region composed of fibrin filaments and the third region rich in platelets and free of bacteria.

First Danish case of infective endocarditis caused by Enterococcus hirae.

Enterococcus hirae, a member of the Enterococcus genus, is known to cause infections, including infective endocarditis (IE), in animal species. In humans, E. hirae is an uncommon pathogen, but has been associated with severe and recurrent disease. Here, we report the first Danish case of E. hirae native aortic valve IE in a 62-year-old woman with no history of heart disease. She presented to the hospital with symptoms of gastroenteritis but no signs of heart disease. Nevertheless, blood culture revealed growth of E. hirae, and a transoesophageal echocardiography demonstrated a mobile mass adherent to the aortic valve, compatible with a vegetation. The patient was successfully treated for E. hirae native aortic valve IE with 4 weeks of intravenous benzylpenicillin in combination with gentamicin for the initial 2 weeks. To the best of our knowledge, this is the first documented case of E. hirae IE in Denmark and the sixth documented case worldwide.

Infective endocarditis due to Erysipelothrix rhusiopathiae in a dog - a case report.

BACKGROUND: Infective endocarditis is a rare but severe condition associated with a high mortality rate in small animal patients. This condition is caused by a microbial (most often bacterial) infection of the valvular portion of the endocardium, from which proliferative and/or erosive lesions on the cardiac valves or immediately adjacent structures develop. The two most commonly affected cardiac valves are the aortic and mitral valves. CASE PRESENTATION: We report the clinical case of a 4-year old male neutered Bull terrier, 27.6 kg, body condition score 4/9, that presented with a 3-months history of pyrexia and general weakness. The patient history also revealed a transient left hind limb lameness (grade 2/4), which coincided with the onset of clinical signs about 3 months before presentation. On physical examination, a left-sided systolic heart murmur (grade 3/6) with the same intensity at the left heart base and apex, and an irregularly irregular heart rhythm were noted. Electrocardiography showed ventricular premature complexes, and echocardiography revealed lesions consistent with endocarditis involving the aortic and mitral valve. Bacterial culture of blood yielded a positive result, and the organism isolated was identified as Erysipelothrix rhusiopathiae. The extended patient history revealed that the dog lived close to a farm housing pigs and other livestock. CONCLUSION: We report a rare case of the premortal diagnosis of infective bacterial endocarditis in a dog due to E. rhusiopathiae infection. Most reports about this condition are from necropsy series. This clinical case report emphasizes that E. rhusiopathiae infection and bacteremia should be considered as a differential diagnosis in dogs with suspected infective endocarditis, especially in dogs living in rural areas with access to livestock and particularly farm pigs. Also, particular emphasis should be placed on the zoonotic potential of this infectious disease.

Precise diagnosis of Neisseria macacae infective endocarditis assisted by nanopore sequencing.

Infective endocarditis caused by Neisseria macacae in humans is extremely rare. We presented here a case of N. macacae infective endocarditis in a 61-year-old man with a native aortic valve infection. N. macacae was isolated from blood culture and was detected by nanopore-based metagenomic sequencing in the vegetations. Finally, the patient recovered completely after surgery and antibiotic therapy.

Culture-negative endocarditis with neurologic presentations and dramatic response to heparin: a case report.

BACKGROUND: Blood culture-negative endocarditis (BCNE) is diagnosed in 2-7% of patients with infective endocarditis (IE) and recent antibiotic use is a known risk factor. Altered mental status may be a presenting symptom. Besides empiric antibiotics, intravenous anticoagulation using heparin may have a role in the management of such patients. CASE PRESENTATION: A 23-year-old male patient was referred to our center with fever, altered mental status and abnormal gait. Neurologic examination revealed Wernicke's aphasia. Cardiac auscultation revealed systolic murmur at the left sternal border. ECG (electrocardiogram) was unremarkable. Brain MRI showed multiple cerebellar lesions. Transthoracic echocardiography (TTE) demonstrated three large masses on the right ventricle (RV), tricuspid valve (TV), and anterior mitral valve (MV) leaflet. Blood cultures (three sets) were negative. Intravenous heparin therapy was administered. After 48 h, the second TTE demonstrated that one valvular lesion disappeared and the other two lesions showed a significant decrease in size. The patient's neurological symptoms resolved gradually. Further workup for collagen vascular disorders did not show any abnormality. CONCLUSION: BCNE should be considered in patients with fever and neurologic manifestations. TTE should be performed to detect valvular abnormalities. Intravenous heparin could be used in such patients when TTE demonstrate valvular vegetations.

Exebacase for patients with Staphylococcus aureus bloodstream infection and endocarditis.

BACKGROUNDNovel therapeutic approaches are critically needed for Staphylococcus aureus bloodstream infections (BSIs), particularly for methicillin-resistant S. aureus (MRSA). Exebacase, a first-in-class antistaphylococcal lysin, is a direct lytic agent that is rapidly bacteriolytic, eradicates biofilms, and synergizes with antibiotics.METHODSIn this superiority-design study, we randomly assigned 121 patients with S. aureus BSI/endocarditis to receive a single dose of exebacase or placebo. All patients received standard-of-care antibiotics. The primary efficacy endpoint was clinical outcome (responder rate) on day 14.RESULTSClinical responder rates on day 14 were 70.4% and 60.0% in the exebacase + antibiotics and antibiotics-alone groups, respectively (difference = 10.4, 90% CI [-6.3, 27.2], P = 0.31), and were 42.8 percentage points higher in the prespecified exploratory MRSA subgroup (74.1% vs. 31.3%, difference = 42.8, 90% CI [14.3, 71.4], ad hoc P = 0.01). Rates of adverse events (AEs) were similar in both groups. No AEs of hypersensitivity to exebacase were reported. Thirty-day all-cause mortality rates were 9.7% and 12.8% in the exebacase + antibiotics and antibiotics-alone groups, respectively, with a notable difference in MRSA patients (3.7% vs. 25.0%, difference = -21.3, 90% CI [-45.1, 2.5], ad hoc P = 0.06). Among MRSA patients in the United States, median length of stay was 4 days shorter and 30-day hospital readmission rates were 48% lower in the exebacase-treated group compared with antibiotics alone.CONCLUSIONThis study establishes proof of concept for exebacase and direct lytic agents as potential therapeutics and supports conduct of a confirmatory study focused on exebacase to treat MRSA BSIs.TRIAL REGISTRATIONClinicaltrials.gov NCT03163446.FUNDINGContraFect Corporation.

Incidental detection of Corynebacterium jeikeium endocarditis via regular blood examination in an afebrile hemodialysis patient.

Herein, we describe a rare case of Corynebacterium jeikeium endocarditis that silently progressed in a 65-year-old man undergoing hemodialysis. Because routine monthly blood examination revealed high C-reactive protein levels, blood cultures were collected, although he had no symptom and was afebrile. After 2 days, a Gram-positive rod was detected in one set of the blood culture. Furthermore, transthoracic echocardiography revealed new aortic regurgitation (AR) and vegetations, and, therefore, infective endocarditis was suspected. Transesophageal echocardiography showed vegetations with a maximum diameter of 8 mm on his aortic valve, with some valve destruction. C. jeikeium was identified in three sets of blood cultures. Administration of daptomycin was started because he had vancomycin allergy. Judging from the high risk of embolization due to vegetations, emergency aortic valve replacement was performed on the second day. C. jeikeium was detected in a resected cardiac valve specimen and blood. This case emphasizes that physicians should always consider the possibility of infective endocarditis even in hemodialysis patients without any symptoms.

Pulmonary Valve Endocarditis: The Potential Utility of Multimodal Imaging Prior to Surgery.

BACKGROUND: The presence of echocardiographic (echo) evidence is a major criterion for the diagnosis of infective endocarditis (IE) by modified Duke criteria. Pulmonary valve (PV) IE, however, can be challenging to identify by echo. We sought to evaluate the added utility of multimodal imaging in PV IE. METHODS: This is a single-center case series. We retrospectively analyzed demographic, laboratory, imaging, clinical, and surgical data from patients diagnosed with PV IE from 2008 to 2018. RESULTS: A total of 23 patients were identified with definite PV IE by Duke criteria (83% male and ages 2 months to 70 years). Twenty-two patients had congenital heart disease, with 21 involving the right ventricular outflow tract (including three with transcatheter PV implant). Overall, 20 (87%) of 23 had positive blood cultures. A total of 17 (74%) of 23 patients demonstrated echo evidence of PV IE. In three cases, echo was negative (did not show vegetations) but showed new PV obstruction. In four cases with negative transthoracic echocardiogram and transesophageal echocardiogram, evidence of PV IE was subsequently seen by positron emission tomography/computed tomography (n = 2) or cardiac magnetic resonance imaging (n = 2). Pulmonary valve IE was confirmed at surgery by evaluation of pathologic samples in 20 cases. CONCLUSIONS: Multimodal imaging improves the ability to preoperatively identify endocardial involvement in PV IE in cases where echo is negative. Consideration should be given to revise Duke criteria to include new obstruction and endocardial involvement by multimodal imaging for PV IE.

Intraoperative Hemoadsorption in Patients With Native Mitral Valve Infective Endocarditis.

BACKGROUND: Cardiac surgery in patients with infective endocarditis is associated with high mortality owing to postoperative septic multiorgan failure. Hemoadsorption therapy may improve surgical outcomes by reducing the circulating cytokines. We aimed to evaluate the clinical effects of intraoperative hemoadsorption in patients with mitral valve endocarditis. METHODS: Eligible candidates were patients with infective endocarditis of the native mitral valve undergoing cardiac surgery between January 2014 and July 2018. Patients with intraoperative hemoadsorption (hemoadsorption) were compared with surgery without hemoadsorption (control). The end points were the incidence of postoperative sepsis, sepsis-associated death, and 30-day mortality. Furthermore, postoperative need for epinephrine and norepinephrine and systemic vascular resistance were evaluated. RESULTS: A total of 58 consecutive patients were included: 30 in the hemoadsorption group and 28 in the control group. Postoperative sepsis occurred in 5 patients in the hemoadsorption group and in 11 in the control group (P = .05). No sepsis-associated death occurred in the hemoadsorption group, whereas five septic patients in the control group died (P = .02). Thirty-day mortality was 10% in the hemoadsorption group versus 18% in the control group (P = .39). On intensive care unit admission, the cumulative need for epinephrine and norepinephrine was 0.15 versus 0.24 µg/kg body weight/min (P = .01) and the median systemic vascular resistance was 1413 versus 1010 dyn·s·cm-5 (P = .02) in the hemoadsorption versus control group, respectively. CONCLUSIONS: Intraoperative hemoadsorption might reduce the incidence of postoperative sepsis and sepsis-related death. In addition, patients with intraoperative hemoadsorption showed greater hemodynamic stability. These data suggest that intraoperative hemoadsorption may improve surgical outcome in patients with mitral valve endocarditis.

Procalcitonin, white blood cell count and C-reactive protein as predictors of S. aureus infection and mortality in infective endocarditis.

BACKGROUND: Infective endocarditis (IE) is characterized by high rates of in-hospital death, and Staphylococcus aureus infection predicts a worse prognosis. We aimed to assess if admission inflammatory biomarkers (white blood cell - WBC - count, C-reactive protein - CRP, and procalcitonin) are informative on microbiological etiology and short-term outcomes. METHODS: Data from 236 patients admitted for IE from January 2013 to June 2018 were retrieved from a multicenter registry. RESULTS: Fifty-two patients (22%) were infected by S. aureus. WBC, CRP and procalcitonin had area under the curve (AUC) values for S. aureus infection of 0.595, 0.675, and 0.727, respectively. Adding procalcitonin to WBC improved discrimination over WBC alone (p = 0.045), and procalcitonin predicted S. aureus infection independently from the other inflammatory biomarkers and patient characteristics. Patients with WBC ≥ 12,800/mm3, CRP ≥ 130 mg/L, and procalcitonin ≥ 1.7 ng/mL had an almost 20-fold higher risk of S. aureus infection than patients with all biomarkers < cut-offs. AUC values for in-hospital death were 0.702, 0.725 and 0.727 for the WBC, CRP, and procalcitonin, respectively. Among inflammatory biomarkers, WBC and procalcitonin independently predicted in-hospital death. Procalcitonin refined risk stratification when added to WBC, and to the combination of WBC and CRP. Patients with WBC ≥ 10,535/mm3, CRP ≥ 85 mg/dL, and procalcitonin ≥ 0.4 ng/mL had a 27-fold higher risk of in-hospital death than patients with all biomarkers < cut-offs. CONCLUSIONS: Among patients with IE, high levels of inflammatory biomarkers on admission, particularly procalcitonin, are associated with a higher likelihood of S. aureus infection, and a higher risk of in-hospital mortality.

The Utility of Echocardiography in Pediatric Patients with Structurally Normal Hearts and Suspected Endocarditis.

The objective of this study was to evaluate the utility of transthoracic echocardiography (TTE) in children with structurally normal hearts suspected of having infective endocarditis (IE). We hypothesized that the diagnostic yield of TTE is minimal in low-risk patients with normal hearts. We performed a retrospective chart review of TTEs performed for concern for endocarditis at a pediatric tertiary care referral center in Portland, Oregon. Three hundred patients met inclusion criteria (< 21 years old, completed TTE for IE from 2005 to 2015, no history of congenital heart disease or endocarditis). We recorded findings that met the modified Duke criteria (MDC) including fever, positive blood culture, and vascular/immunologic findings; presence of a central line; whether or not patients were diagnosed with IE clinically; and if any changes to antibiotic regimens were made based on TTE. Ten patients (3%) had echocardiograms consistent with IE. When compared to the clinical diagnosis of IE, the positive predictive value (PPV) of one positive blood culture without other major/minor MDC was 0. Similarly, the PPV of two positive blood cultures without other major/minor criteria was 0.071. Patients should be evaluated using the MDC to assess the clinical probability of IE prior to performing a TTE. Patients with a low probability for IE should not undergo TTE as it has a low diagnostic yield and patients are unlikely to be diagnosed with disease.

Associations between echocardiographic manifestations and bacterial species in patients with infective endocarditis: a cohort study.

BACKGROUND: The diagnosis of infective endocarditis (IE) is based on microbiological analyses and diagnostic imaging of cardiac manifestations. Echocardiography (ECHO) is preferred for visualization of IE-induced cardiac manifestations. We investigated associations between bacterial infections and IE manifestations diagnosed by ECHO. METHODS: In this cohort study, data from patients aged 18 years or above, with definite IE admitted at the Karolinska University Hospital between 2008 and 2017 were obtained from Swedish National Registry of Endocarditis. Bacteria registered as pathogen were primarily selected from positive blood culture and for patients with negative blood culture, bacteria found in culture or PCR from postoperative material was registered as pathogen. Patients with negative results from culture or PCR, and patients who did not undergo ECHO during hospital stay, were excluded. IE manifestations diagnosed by ECHO were obtained from the registry. Chi-squared test and two-sided Fisher's exact test was used for comparisons between categorical variables, and student's t test was used for continuous numerical variables. Multivariable analyses were performed using logistic regression. Secular trend analyses were performed using linear regression. Associations and the strength between the variables were estimated using odds ratios (ORs) with 95% confidence intervals (CIs). P < 0.05 was considered significant. RESULTS: The most common bacteria were Staphylococcus aureus (n = 239, 49%) and viridans group streptococci (n = 102, 21%). The most common manifestations were vegetation in the mitral (n = 195, 40%), aortic (n = 190, 39%), and tricuspid valves (n = 108, 22%). Associations were seen between aortic valve vegetations and Enterococcus faecalis among patients with native aortic valves, between mitral valve vegetations and streptococci of group B or viridans group, between tricuspid valve vegetations and S. aureus among patients with intravenous drug abuse, and between perivalvular abscesses as well as cardiovascular implantable electronic device (CIED)-associated IE and coagulase negative staphylococci (all P < 0.05). CONCLUSIONS: Associations were found between certain bacterial species and specific ECHO manifestations. Our study contributes to a better understanding of IE manifestations and their underlying bacterial etiology, which pathogens can cause severe infections and might require close follow-up and surgical treatment.

IgM ANCA in healthy individuals and in patients with ANCA-associated vasculitis.

Low levels of IgM auto-antibodies have been reported in health and disease. IgM anti-neutrophil cytoplasmic antibodies (ANCA) have been reported in patients with ANCA-associated vasculitis (AAV). We sought to investigate if healthy individuals may have IgM ANCA in their sera. The first aim of the study was to determine whether IgM ANCA was present in healthy individuals and in patients with ANCA-associated vasculitis. The second aim was to determine what happens to IgM ANCA levels over time. The third aim was to determine whether bacterial infections affected IgM ANCA levels in non-AAV patients. Sera from healthy individuals and patients with AAV were tested for IgM ANCA by immunofluorescence on fixed neutrophils, immunoprecipitation, Western blot and ELISA. Peripheral blood mononuclear cells were isolated and tested by ELISpot for circulating IgM ANCA B cells. To determine whether infection affected IgM ANCA levels, we studied non-AAV patients with bacterial endocarditis or Staphylococcus aureus bacteraemia and measured IgM ANCA levels over time. IgM ANCA is detectable in both healthy individuals and patients with AAV and the titres decreased with increasing age. Circulating IgM ANCA B cells were identified by ELISpot. In the presence of infection, we could not find a significant change in IgM ANCA levels. We report the presence of low-level specific IgM ANCA in the sera of healthy individuals and in patients with ANCA-associated vasculitis. Bacterial infection did not affect the level of IgM ANCA in this small study.

Infective endocarditis without biological inflammatory syndrome: Description of a particular entity.

BACKGROUND: Bacterial infective endocarditis (IE) is rarely suspected in patients with a low C-reactive protein (CRP) concentration. AIMS: To address the incidence, characteristics and outcome of left-sided valvular IE with low CRP concentration. METHODS: This was a retrospective analysis of cases of IE discharged from our institution between January 2009 and May 2017. The 10% lowest CRP concentration (<20mg/L) was used to define low CRP concentration. Right-sided cardiac device-related IE, non-bacterial IE, sequelar IE and IE previously treated by antibiotics were excluded. RESULTS: Of the 469 patients, 13 (2.8%; median age 68 [61-76] years) had definite (n=8) or possible (n=5) left-sided valvular IE with CRP<20mg/L (median 9.3 [4.7-14.2] mg/L). The median white blood cell count was 6.3 (5.3-7.5) G/L. The main presentations were heart failure (n=7; 54%) and stroke (n=3; 23%). Transthoracic echocardiography (TTE) showed vegetations (n=5) or isolated valvular regurgitation (n=4). Overall, eight patients (62%) had severe valvular lesions on transoesophageal echocardiography (TOE), and nine patients (69%) underwent cardiac surgery. All patients survived at 1-year follow-up. Bacterial pathogens were documented in eight patients (streptococci, coagulase-negative Staphylococcus, Corynebacteriumjeikeium, HACEK group, Coxiella burnetii, Bartonella henselae) using blood cultures, serology or valve culture and/or polymerase chain reaction analysis. CONCLUSIONS: Left-sided valvular IE with limited or no biological syndrome is rare, but is often associated with severe valvular and paravalvular lesions. TOE should be performed in presence of unexplained heart failure, new valvular regurgitation or cardioembolic stroke when TTE is insufficient to rule out endocarditis, even in patients with a low CRP concentration.