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Background. Blood culture-negative endocarditis (BCNE) may account for up to 31% of all cases of endocarditis. Methods. We used a prospective, multimodal strategy incorporating serological, molecular, and histopathological assays to investigate specimens from 819 patients suspected of having BCNE. Results. Diagnosis of endocarditis was first ruled out for 60 patients. Among 759 patients with BCNE, a causative microorganism was identified in 62.7%, and a noninfective etiology in 2.5%. Blood was the most useful specimen, providing a diagnosis for 47.7% of patients by serological analysis (mainly Q fever and Bartonella infections). Broad-range polymerase chain reaction (PCR) of blood and Bartonella-specific Western blot methods diagnosed 7 additional cases. PCR of valvular biopsies identified 109 more etiologies, mostly streptococci, Tropheryma whipplei, Bartonella species, and fungi. Primer extension enrichment reaction and autoimmunohistochemistry identified a microorganism in 5 additional patients. No virus or Chlamydia species were detected. A noninfective cause of endocarditis, particularly neoplasic or autoimmune disease, was determined by histological analysis or by searching for antinuclear antibodies in 19 (2.5%) of the patients. Our diagnostic strategy proved useful and sensitive for BCNE workup. Conclusions. We highlight the major role of zoonotic agents and the underestimated role of noninfective diseases in BCNE. We propose serological analysis for Coxiella burnetii and Bartonella species, detection of antinuclear antibodies and rheumatoid factor as first-line tests, followed by specific PCR assays for T. whipplei, Bartonella species, and fungi in blood. Broad-spectrum 16S and 18S ribosomal RNA PCR may be performed on valvular biopsies, when available.

ObjectiveThe primary objective was to assess the characteristics and prognosis of pyogenic spondylodiscitis (PS) in patients with infective endocarditis (IE). The secondary objectives were to assess the factors associated with occurrence of PS.MethodsProspective case–control bi-centre study of 1755 patients with definite IE with (n=150) or without (n=1605) PS. Clinical, microbiological and prognostic variables were recorded.ResultsPatients with PS were older (mean age 69.7±18 vs 66.2±14; p=0.004) and had more arterial hypertension (48% vs 34.5%; p<0.001) and autoimmune disease (5% vs 2%; p=0.03) than patients without PS. The lumbar vertebrae were the most frequently involved (84 patients, 66%), especially L4–L5. Neurological symptoms were observed in 59% of patients. Enterococci and Streptococcus gallolyticus were more frequent (24% vs 12% and 24% vs 11%; p<0001, respectively) in the PS group. The diagnosis of PS was based on contrast-enhanced MRI in 92 patients, bone CT in 88 patients and 18F-FDG PET/CT in 56 patients. In-hospital (16% vs 13.5%, p=0.38) and 1-year (21% vs 22%, p=0.82) mortalities did not differ between patients with or without PS.ConclusionsPS is a frequent complication of IE (8.5% of IE), is observed in older hypertensive patients with enterococcal or S. gallolyticus IE, and has a similar prognosis than other forms of IE. Since PS is associated with specific management, multimodality imaging including MRI, CT and PET/CT should be used for early diagnosis of this complication of endocarditis.

ObjectiveAcute coronary syndromes (ACS) are a rare complication of infective endocarditis (IE). Only case reports and small studies have been published to date. We report the largest series of ACS in IE. The aim of our study was to describe the incidence and mechanisms of ACS associated with IE, to assess their prognostic impact and to describe their management.MethodsIn a bicentre prospective observational cohort study, all patients with a definite diagnosis of IE were prospectively included. The incidence, mechanism and prognosis of patients with ACS were studied.ResultsAmong 1210 consecutive patients with definite IE, 26 patients (2.2%) developed an ACS. Twenty-three patients (88%) had a coronary embolism. Two patients had coronary compression by an abscess or a pseudoaneurysm and one patient had an obstruction of his bioprosthesis and left coronary ostium by a large vegetation. Nineteen (73%) patients with ACS developed heart failure and this complication was 2.5 times more frequent than in patients without ACS (p<0.0001). In the ACS population, mortality rate was twice than the population without ACS.ConclusionsACS is a rare complication of IE but is associated with an increased risk of heart failure and high mortality rate.

Gut microbiota play a major role in digestion and energy conversion of nutrients. Antibiotics, such as avoparcin (a vancomycin analogue), and probiotics, such as Lactobacillus species, have been used to increase weight in farm animals. We tested the effect of antibiotics given for infective endocarditis (IE) on weight gain (WG). Forty-eight adults with a definite diagnosis of bacterial IE (antibiotic group) were compared with forty-eight age-matched controls without IE. Their body mass index (BMI) was collected at one month before the first symptoms and one year after hospital discharge. The BMI increased significantly and strongly in vancomycin-plus-gentamycin-treated patients (mean [+/-SE] kg/m(2), +2.3 [0.9], p = 0.03), but not in controls or in patients treated with other antibiotics. Seventeen patients had a BMI increase of >or=10%, and five of the antibiotic group developed obesity. The treatment by vancomycin-plus-gentamycin was an independent predictor of BMI increase of >or=10% (adjusted OR, 6.7; 95% CI, 1.37-33.0; p = 0.02), but not treatment with other antibiotics. Weight gain was particularly high in male patients older than 65 who did not undergo cardiac surgery. Indeed, all three vancomycin-treated patients with these characteristics developed obesity. A major and significant weight gain can occur after a six-week intravenous treatment by vancomycin plus gentamycin for IE with a risk of obesity, especially in males older than 65 who have not undergone surgery. We speculate on the role of the gut colonization by Lactobacillus sp, a microorganism intrinsically resistant to vancomycin, used as a growth promoter in animals, and found at a high concentration in the feces of obese patients. Thus, nutritional programs and weight follow-up should be utilized in patients under such treatment.

Mortality and morbidity associated with infective endocarditis may extend beyond successful treatment. The primary objective was to analyze rates, temporal changes, and predictors of excess mortality in patients surviving the acute phase of endocarditis. The secondary objective was to determine the rate of recurrence and the need for late cardiac surgery. An observational cohort study was conducted at a university-affiliated tertiary medical center, among 328 patients who survived the active phase of endocarditis. We used age-, sex-, and calendar year–specific mortality hazard rates of the Bouches-du-Rhone French district population to calculate expected survival and excess mortality. The risk of recurrence and late valve surgery was also assessed. Compared with expected survival, patients surviving a first episode of endocarditis had significantly worse outcomes (P = .001). The relative survival rates at 1, 3, and 5 years were 92% (95% CI, 88%-95%), 86% (95% CI, 77%-92%), and 82% (95% CI, 59%-91%), respectively. This excess mortality was observed during the entire follow-up period but was the highest during the first year after hospital discharge. Most of the recurrences and late cardiac surgeries also occurred during this period. Women exhibited a higher risk of age-adjusted excess mortality (adjusted excess hazard ratio, 2.0; 95% CI, 1.05-3.82; P = .03). Comorbidity index, recurrence of endocarditis, and history of an aortic valve endocarditis in women were independent predictors of excess mortality. These results justify close monitoring of patients after successful treatment of endocarditis, at least during the first year. Special attention should be paid to women with aortic valve damage.

ObjectiveTo assess long-term outcomes and predictors of mortality in patients treated according to current recommendations for cardiac implantable electronic device (CIED) infection.DesignTwo-group matched cohort study.SettingTertiary-care institution.PatientsConsecutive patients admitted for CIED infection between 2004 and 2008 were prospectively enrolled. Study subjects were matched to a cohort of uninfected CIED patients by age, sex and type of device.InterventionsIn all infected patients, the therapeutic approach consisted of complete hardware removal whenever possible, antimicrobial therapy, and implantation of a new device, if indicated. Patients were systematically followed, with standardised outcomes assessment.Main outcome measuresAll-cause mortality and predictors of long-term mortality.Results197 patients were included and matched 1:1 to controls. Pocket infections were present in 41.1% and definite or suspected infective endocarditis in 58.9%. Total or subtotal hardware removal was achieved in 98.5% of cases. Median follow up was 25 months (12–70). Mortality rates in the study group and controls were 14.3% vs 11.0% (NS) at 1 year and 35.4% vs 27.0% (p=NS) at 5 years. Independent predictors of long-term mortality were older age (HR=1.09, p<0.001), cardiac resynchronisation therapy (HR=3.70, p=0.001), thrombocytopenia (HR=5.10, p=0.003) and renal insufficiency (HR=2.66, p=0.006). In patients with reimplanted devices, epicardial right ventricular pacemakers were associated with higher mortality (HR=2.85, p=0.034).ConclusionIn patients with CIED infection managed by recommended therapy, long-term mortality rates are similar to comparable controls. Independent predictors include patient and disease-related factors, in addition to implantation of right ventricular epicardial pacemakers.

Background Coxiella burnetii is an intracellular and fastidious bacterium responsible of acute and persistent Q fever infection. Endocarditis and vascular infections are the most common serious complications of acute Q fever. Case report We report the case of a 63-year-old man that presented a mediastinitis associated with a prosthetic vascular infection. Serological cross-reaction was observed between Coxiella burnetii, the agent of Q fever, and Legionella pneumophila with higher antibodies titer for L. pneumophila (IgG = 1:512) than for C. burnetii (phase I IgG = 1:400). We performed western blot with cross-adsorption that supports the diagnosis of C. burnetii infection. Two weeks later, a positive qPCR and culture for C. burnetii on swab taken from the mediastinal cutaneous fistula confirmed the definitive microbiological diagnosis of Q fever mediastinitis. Conclusion Cross-reactivity between C. burnetii and Legionella spp. has long been known and should be considered in patients with persistent infections. It is important to establish the definite diagnosis because the antibiotic treatment regimens and duration are significantly different. To the best of our knowledge, we reported here the first case of mediastinitis associated to C. burnetii and we diagnosed this persistent infection despite low anti- C. burnetii phase I IgG levels.

Whipple’s disease (WD) is a chronic multisystemic infection caused by Tropheryma whipplei . If this bacterium presents an intracellular localization, associated with rare diseases and without pathognomonic signs, it is often subject to a misunderstanding of its physiopathology, often a misdiagnosis or simply an oversight. Here, we report the case of a patient treated for presumed rheumatoid arthritis. Recently, this patient presented to the hospital with infectious endocarditis. After surgery and histological analysis, we discovered the presence of T. whipplei . Electron microscopy allowed us to discover an atypical bacterial organization with a very large number of bacteria present in the extracellular medium in vegetation and valvular tissue. This atypical presentation we report here might be explained by the anti-inflammatory treatment administrated for our patient’s initial diagnosis of rheumatoid arthritis.

The burden of antibiotic resistance is currently estimated by mathematical modeling, without real count of resistance to key antibiotics. Here we report the real rate of resistance to key antibiotics in bacteria isolated from humans during a 5 years period in a large area in southeast in France. We conducted a retrospective study on antibiotic susceptibility of 539,107 clinical strains isolated from hospital and private laboratories in south of France area from January 2014 to January 2019. The resistance rate to key antibiotics as well as the proportion of bacteria classified as Difficult-to-Treat (DTR) were determined and compared with the Mann–Whitney U test, the χ 2 test or the Fisher’s exact test. Among 539,037 isolates, we did not observe any significant increase or decrease in resistance to key antibiotics for 5 years, (oxacillin resistance in Staphylococcus aureus , carbapenem resistance in enterobacteria and Pseudomonas aeruginosa and 3rd generation cephalosporin resistance in Escherichia coli and Klebsiella pneumoniae ) . However, we observed a significant decrease in imipenem resistance for Acinetobacter baumannii from 2014 to 2018 (24.19–12.27%; p  = 0.005) and a significant increase of ceftriaxone resistance in Klebsiella pneumoniae (9.9–24.03%; p  = 0.001) and Enterobacter cloacae (24.05–42.05%; p  = 0.004). Of these 539,037 isolates, 1604 (0.3%) had a DTR phenotype. Over a 5-year period, we did not observe a burden of AR in our region despite a high rate of antibiotic consumption in our country. These results highlight the need for implementation of real-time AR surveillance systems which use factual data.

Despite advances in medical, surgical, and critical care, infective endocarditis (IE) remains associated with considerable morbidity and mortality. We evaluated the performance of the Marseille score, including clinical data and biological tests obtained within 2 h, to identify patients at high risk of IE in order to initiate early antimicrobial treatment. This was secondarily confirmed using modified ESC criteria combined with molecular testing and (18)fluorodeoxyglucose-positron emission tomography/computed tomography as diagnostic tools. In a prospective cohort study, we enrolled 484 patients with cardiovascular predisposition and clinical suspicion of IE from 2011 to 2013. The final diagnosis was definite IE in 123 patients and possible IE in 107. Marseille score was calculated adding one point for each present parameter (range 0–9). This score includes clinical, epidemiological (male, fever, splenomegaly, clubbing, vascular disease and stroke) and biological criteria (Leucocytes >10,000/mm3, sedimentation rate (SR) > 50/mm or C reactive protein >10 mg/L and hemoglobin <100 g/l). A score of 2 or more performed best in predicting IE in patients with predisposing heart lesions. Sensitivity was better on left-side heart lesions (94%) than on right-side heart lesions (85%) (p = 0.04) and better for valvulopathy (94%) than intra cardiac devices (84%) (p = 0.02). The predictive positive value of prosthetic valves was greater than that of native valves (p = 0.02). Using our simple Marseille score combined with our standardized diagnostic procedures would help improve IE management by focusing on early empiric treatment within 2 h of admission for patients with cardiac predisposition factors.