International experts' practice in the antibiotic therapy of infective endocarditis is not following the guidelines.

OBJECTIVE: The management of infective endocarditis (IE) may differ from international guidelines, even in reference centres. This is probably because most recommendations are not based on hard evidence, so the consensus obtained for the guidelines does not represent actual practices. For this reason, we aimed to evaluate this question in the particular field of antibiotic therapy. METHODS: Thirteen international centres specialized in the management of IE were selected, according to their reputation, clinical results, original research publications and quotations. They were asked to detail their actual practice in terms of IE antibiotic treatment in various bacteriological and clinical situations. They were also asked to declare their IE-related in-hospital mortality for the year 2015. RESULTS: The global compliance with guidelines concerning antibiotic therapy was 58%, revealing the differences between theoretical 'consensus', local recommendations and actual practice. Some conflicts of interest were also probably expressed. The adherence to guidelines was 100% when the protocol was simple, and decreased with the seriousness of the situation (Staphylococus spp. 54%-62%) or in blood-culture-negative endocarditis (0%-15%) that requires adaptation to clinical and epidemiological data. CONCLUSION: Worldwide experts in IE management, although the majority of them were involved and co-signed the guidelines, do not follow international consensus guidelines on the particular point of the use of antibiotics.

Antiphospholipid antibodies proposed in the diagnosis of infective endocarditis.

Antiphospholipid antibodies (aPL) may occur alone or associated with other diseases. To evaluate aPL, tested as anticardiolipin antibodies (IgG aCL) in infective endocarditis (IE) diagnosis, we investigated their prevalence in a cohort of 651 patients with IE suspicion. aPL was significantly associated with definite IE versus IE-rejected patients. Their mean levels were significantly higher in patients with definite IE versus possible IE. When applied as Duke minor criterion, they were significantly more often positive, and at higher levels, in patients with definite IE than in patients with possible or rejected IE. aPL could be helpful in difficult cases of IE diagnosis.

Genome analysis of Listeria ivanovii strain G770 that caused a deadly aortic prosthesis infection.

We sequenced the genome of Listeria ivanovii strain G770, which caused a deadly infection of the thoracic aortic prosthesis of a 78-year-old man. The 2.9 Mb genome exhibited 21 specific genes among L. ivanovii strains, including five genes encoding a type I restriction modification system and one glycopeptide resistance gene.

Complementarity between targeted real-time specific PCR and conventional broad-range 16S rDNA PCR in the syndrome-driven diagnosis of infectious diseases.

Molecular tools have shown an added value in the diagnosis of infectious diseases, in particular for those caused by fastidious intracellular microorganisms, or in patients receiving antibiotics before sampling. If 16S rDNA amplification had been gradually implemented in microbiology laboratories, specific real-time polymerase chain reaction (PCR) would have permitted an increase in the sensitivity of molecular methods and a reduction of contamination. Herein, we report our experience in the diagnosis of infectious diseases over two years, during which 32,948 clinical samples from 18,056 patients were received from France and abroad. Among these samples, 81,476 PCRs were performed, of which 1,192 were positive. Molecular techniques detected intracellular microorganisms in 31.3 % of respiratory samples, 27.8 % of endocarditis samples and 51.9 % of adenitis samples. Excluding intracellular bacteria, 25 % of the positive samples in this series were sterile in culture. Conventional broad-range PCR permitted the identification of fastidious and anaerobic microorganisms, but specific real-time PCR showed a significant superiority in the diagnosis of osteoarticular infections, in particular for those caused by Kingella kingae and Staphylococcus aureus, and for endocarditis diagnosis, specifically when Streptococcus gallolyticus and Staphylococcus aureus were involved. The sensitivity of conventional broad-range PCR was 62.9 % concerning overall diagnoses for which both techniques had been performed. These findings should lead microbiologists to focus on targeted specific real-time PCR regarding the clinical syndrome. Finally, syndrome-driven diagnosis, which consists of testing a panel of microorganisms commonly involved for each syndrome, permitted the establishment of 31 incidental diagnoses.

Cardiac multidetector computed tomography in infective endocarditis: a pictorial essay.

OBJECTIVES: The goals of this pictorial essay are: (1) to set out a multislice computed tomography (MSCT) imaging protocol to assess infective endocarditis (IE); (2) to give an MSCT overview of valvular and peri-valvular involvement during IE; (3) to give a CT overview of septic embolism and infectious pseudoaneurysms during IE. METHODS: MSCT acquisition protocols to assess IE are performed in two different phases: the first acquisition, under electrocardiography (ECG) gating, covers the cardiac structures during first-pass iodine injection; the second acquisition covers the thorax, abdomen, pelvic and cerebral regions. RESULTS: Valvular and peri-valvular lesions during IE are: vegetation-a hypodense, homogeneous, irregular mass on a valve or endocardial structure; perforation-a defect in the leaflet; valvular aneurysm-loss of the homogenous curvature of the leaflet; valvular thickening; peri-valvular abscess; pseudoaneurysm; fistula and disinsertion of a prosthetic valve. Extra-cardiac location could involve all organs. CONCLUSIONS: MSCT can be considered as a useful complement in visualising the cardiac lesions of IE if echocardiography is inconclusive. MSCT is the only imaging modality that provides assessment of valvular and peri-valvular involvement, extra-cardiac lesions, and non-invasive evaluation of the coronary artery anatomy, simultaneously. MAIN MESSAGES: • MSCT provides assessment of coronary anatomy, cardiac and extra-cardiac lesions. • MSCT represents an alternative to echocardiography during IE. • Surgical valve replacement is usually required if vegetation is >10 mm. • Peri-valvular extension (abscesses, pseudoaneurysm and fistulae) required surgical treatment.

Lactobacillus reuteri and Escherichia coli in the human gut microbiota may predict weight gain associated with vancomycin treatment.

BACKGROUND: Antibiotics, used for 60 years to promote weight gain in animals, have been linked to obesity in adults and in children when administered during early infancy. Lactobacillus reuteri has been linked to obesity and weight gain in children affected with Kwashiorkor using ready-to-use therapeutic food. In contrast, Escherichia coli has been linked with the absence of obesity. Both of these bacteria are resistant to vancomycin. OBJECTIVES AND METHODS: We assessed vancomycin-associated weight and gut microbiota changes, and tested whether bacterial species previously linked with body mass index (BMI) predict weight gain at 1 year. All endocarditis patients treated with vancomycin or amoxicillin in our center were included from January 2008 to December 2010. Bacteroidetes, Firmicutes, Lactobacillus and Methanobrevibacter smithii were quantified using real-time PCR on samples obtained during the 4-6 weeks antibiotic regimen. L. reuteri, L. plantarum, L. rhamnosus, Bifidobacterium animalis and E. coli were quantified on stool samples obtained during the first week of antibiotics. RESULTS: Of the193 patients included in the study, 102 were treated with vancomycin and 91 with amoxicillin. Vancomycin was associated with a 10% BMI increase (odds ratio (OR) 14.1; 95% confidence interval (CI; 1.03-194); P=0.047) and acquired obesity (4/41 versus 0/56, P=0.01). In patients treated with vancomycin, Firmicutes, Bacteroidetes and Lactobacillus increased, whereas M. smithii decreased (P<0.05). The absence of E. coli was an independent predictor of weight gain (OR=10.7; 95% CI (1.4-82.0); P=0.02). Strikingly, a patient with an 18% BMI increase showed a dramatic increase of L. reuteri but no increase of E. coli. CONCLUSION: The acquired obesity observed in patients treated with vancomycin may be related to a modulation of the gut microbiota rather than a direct antibiotic effect. L. reuteri, which is resistant to vancomycin and produces broad bacteriocins, may have an instrumental role in this effect.

[Infective endocarditis in children without underlying heart disease: a retrospective study analyzing 11 cases]. / Endocardite infectieuse sur coeur sain chez l'enfant: étude rétrospective de 11 cas.

The aim of our study was to determine the different characteristics of infective endocarditis in children without underlying heart disease. This was a descriptive, retrospective study including all cases of infective endocarditis without underlying heart disease occurring in children under 18 years of age, hospitalized at the Timone Children's Hospital in Marseille, France, between 1997 and 2008. The clinical, microbiological, and echocardiography data; treatment; and outcome were reviewed for each case. Over an 11-year period, 26 children were hospitalized with infective endocarditis. Eleven children (7 boys) had no underlying heart disease (42 %). Their mean age was 8 years and 3 months. Underlying conditions including neoplasm, preterm birth, and central venous catheter were found in 6 cases. A heart murmur was observed in 82 % of the children. A microorganism was isolated in 10 children (91 %). Staphylococcus aureus was the most common agent (45 %), followed by fungi (18 %). Echocardiography detected cardiac complications in 7 cases (64 %). Ninety-one percent of the children received intravenous antibiotics for a mean duration of 45 days. Eighty-two percent of our patients required surgical intervention. In our series, 91 % of the patients met the modified Duke criteria defining infective endocarditis. In-hospital mortality was 11 %. Embolic complications were seen in 5 cases (45 %), patients whose cultures yielded S. aureus or fungal organisms were more likely to present complications. Infective endocarditis without heart disease has particular features that differ from those of congenital heart disease. This diagnosis must be considered when predisposing factors are present.

Clinical characteristics and outcome of infective endocarditis in adults with bicuspid aortic valves: a multicentre observational study.

OBJECTIVE: To analyse characteristics and outcomes of infective endocarditis (IE) on bicuspid aortic valves (BAV) and to compare the risk of death according to the presence or absence of BAV. DESIGN: 5-year observational study. SETTING: Population of 856 patients with definite IE according to the Duke criteria from two tertiary centres (Amiens and Marseille, France). PATIENTS: 310 consecutive patients with definite native aortic valve IE enrolled between 1991 and 2007. INTERVENTIONS: Patients underwent transthoracic and transoesophageal echocardiography during hospitalisation. Surgery was performed on a case-by-case basis according to conventional guidelines. MAIN OUTCOME MEASURES: In-hospital mortality and 5-year overall mortality. RESULTS: Patients with BAV IE (n=50, 16%) were younger, had fewer comorbidities and a higher frequency of aortic perivalvular abscess (50%). Presence of BAV (OR 3.79 (1.97-7.28); p<0.001) was independently predictive of abscess formation. Early surgery was performed in 36 BAV patients (72%) with a peri-operative mortality of 8.3%, comparable to that of patients with tricuspid aortic valve IE (p=0.89). BAV was not independently predictive of in-hospital mortality (OR 0.89 (0.28-2.85); p=0.84) or 5-year survival (HR 0.71 (0.37-1.36); p=0.30). Age, comorbidities, heart failure, Staphylococcus aureus and uncontrolled infection were associated with increased 5-year mortality in BAV patients. CONCLUSION: BAV is frequent in adults with native aortic valve IE. Patients with BAV IE incur high risk of abscess formation and require early surgery in almost three-quarters of cases. IE is a severe complication in the setting of BAV and warrants prompt diagnosis and treatment.

Evaluation of the LightCycler SeptiFast test in the rapid etiologic diagnostic of infectious endocarditis.

The SeptiFast test (Roche Diagnostics) is a new commercial molecular technique that has emerged for the detection of bacteria in blood. We compared in this study the sensitivity of blood culture to a commercially available broad-range real-time polymerase chain reaction (PCR) assay for the detection in blood of 19 bacterial species and six fungal species (SeptiFast test, Roche Diagnostics) in 63 patients with infectious endocarditis (IE). The SeptiFast test is not more sensitive for organisms such as Streptococci, Enterococci, and Staphylococcus aureus (11/29 versus 12/29 for blood culture). It has detected less commonly coagulase-negative Staphylococci (0/15 versus 3/15, P = 0.2) and significantly fewer other microorganisms (0/6 versus 4/6, P = 0.03). However, bacteria were detected from three IE treated by antibiotics, with blood culture negative on admission. The SeptiFast test may be useful in cases of IE in patients treated with antibiotics before admission.

Infective endocarditis incidentally discovered by pathological examination.

We present three patients in whom a cardiac valve replacement was needed because of degenerative and supposed non-infectious damage. The excised valves showed histological features of infective endocarditis with detection of micro-organisms. This diagnosis of infective endocarditis was confirmed by other diagnostic methods. Pathological examination of cardiac valves remains the gold standard for the diagnosis of infective endocarditis, and it should be routinely performed even without suspicion of infectious process.

Contribution of systematic serological testing in diagnosis of infective endocarditis.

Despite progress with diagnostic criteria, the type and timing of laboratory tests used to diagnose infective endocarditis (IE) have not been standardized. This is especially true with serological testing. Patients with suspected IE were evaluated by a standard diagnostic protocol. This protocol mandated an evaluation of the patients according to the modified Duke criteria and used a battery of laboratory investigations, including three sets of blood cultures and systematic serological testing for Coxiella burnetii, Bartonella spp., Aspergillus spp., Legionella pneumophila, and rheumatoid factor. In addition, cardiac valvular materials obtained at surgery were subjected to a comprehensive diagnostic evaluation, including PCR aimed at documenting the presence of fastidious organisms. The study included 1,998 suspected cases of IE seen over a 9-year period from April 1994 to December 2004 in Marseilles, France. They were evaluated prospectively. A total of 427 (21.4%) patients were diagnosed as having definite endocarditis. Possible endocarditis was diagnosed in 261 (13%) cases. The etiologic diagnosis was established in 397 (93%) cases by blood cultures, serological tests, and examination of the materials obtained from cardiac valves, respectively, in 348 (81.5%), 34 (8%), and 15 (3.5%) definite cases of IE. Concomitant infection with streptococci and C. burnetii was seen in two cases. The results of serological and rheumatoid factor evaluation reclassified 38 (8.9%) possible cases of IE as definite cases. Systematic serological testing improved the performance of the modified Duke criteria and was instrumental in establishing the etiologic diagnosis in 8% (34/427) cases of IE.

Escherichia coli endocarditis: seven new cases in adults and review of the literature.

Described here are seven new cases of infective endocarditis due to Escherichia coli, including four involving prosthetic valves, followed by a review of similar cases in the literature. The review identified cases according to the modified Duke's criteria and revealed 16 cases reported before 1960, 5 between 1960 and 1980, and 11 after 1980. Currently, patients diagnosed with E. coli endocarditis are older than the patients diagnosed before 1960 (p<0.05), and they are often diabetic with underlying heart disease. Prosthetic valves are frequently involved (p<0.05), and the principal source of infection is the urinary tract. Surgery is often necessary. The mortality rate associated with this type of infection has decreased since 1960, but it remains high, with 17% calculated for the present series of seven new cases. The data presented here suggest that elderly patients with prior valve disease or prosthetic valve and E. coli urinary tract infection should be examined for endocarditis.

Prosthetic valve endocarditis: who needs surgery? A multicentre study of 104 cases.

OBJECTIVES: To identify the prognostic markers of a bad outcome in a large population of 104 patients with prosthetic valve endocarditis (PVE), and to study the influence of medical versus surgical strategy on outcome in PVE and thus to identify patients for whom surgery may be beneficial. DESIGN: Multicentre study. METHODS AND RESULTS: Among 104 patients, 22 (21%) died in hospital. Factors associated with in-hospital death were severe co-morbidity (6% of survivors v 41% of those who died, p = 0.05), renal failure (28% v 45%, p = 0.05), moderate to severe regurgitation (22% v 54%, p = 0.006), staphylococcal infection (16% v 54%, p = 0.001), severe heart failure (22% v 64%, p = 0.001), and occurrence of any complication (60% v 90%, p = 0.05). By multivariate analysis, severe heart failure (odds ratio 5.5) and Staphylococcus aureus infection (odds ratio 6.1) were the only independent predictors of in-hospital death. Among 82 in-hospital survivors, 21 (26%) died during a 32 month follow up. A Cox proportional hazards model identified early PVE, co-morbidity, severe heart failure, staphylococcus infection, and new prosthetic dehiscence as independent predictors of long term mortality. Mortality was not significantly different between surgical and non-surgical patients (17% v 25%, respectively, not significant). However, both in-hospital and long term mortality were reduced by a surgical approach in high risk subgroups of patients with staphylococcal PVE and complicated PVE. CONCLUSIONS: Firstly, PVE not only carries a high in-hospital mortality risk but also is associated with high long term mortality and needs close follow up after the initial episode. Secondly, congestive heart failure, early PVE, staphylococcal infection, and complicated PVE are associated with a bad outcome. Thirdly, subgroups of patients could be identified for whom surgery is associated with a better outcome: patients with staphylococcal and complicated PVE. Early surgery is strongly recommended for these patients.

Causative organisms of infective endocarditis according to host status.

A prospective study of infective endocarditis (IE) was conducted between 1994 and 2000 in Marseilles, France, and included 170 definite cases diagnosed with the use of modified Duke criteria. Classification of IE based on the aetiological agent was related to epidemiological characteristics, including age, gender and the nature of the injured valve. Enterococci and Streptococcus bovis were identified more frequently in older subjects (p 0.02), and S. bovis was also associated with mitral valve infection (p 0.03). Streptococcus spp. were found to be associated with native valves (p < 10(-3)), whereas coagulase-negative staphylococci and Coxiella burnetii were associated with intracardiac prosthetic material (p < 0.05). S. bovis and Staphylococcus aureus were the predominant species associated with presumably healthy valves (p < 0.05), whereas oral streptococci caused IE exclusively in patients with previous valve damage. The basic host status of IE patients has been linked to specific microorganisms, and this may be of value when empirical treatment is needed in patients who have received previous antibiotic therapy and whose blood cultures are negative.

Actinobacillus actinomycetemcomitans endocarditis.

Among the bacteria of the HACEK group, Actinobacillus actinomycetemcomitans is the organism involved most commonly in infective endocarditis. However, the epidemiological and clinical features specifically associated with this species have not been evaluated adequately. Three patients with infective endocarditis caused by A. actinomycetemcomitans seen at the Hospital La Timone (Marseille, France) between 1994 and 2001 are reported. Of 99 cases in the literature, 75% of patients had previous heart disease before infective endocarditis, the portal of entry of which was usually the oral cavity. Among the total of 102 cases, 27 had prosthetic valves. Intermittent fever was observed in all cases, and weight loss and peripheral signs of endocarditis were noteworthy in this study. Anaemia and microscopic haematuria were frequently noted. The disease is insidious, with a mean duration of symptoms of 13 weeks before diagnosis, as confirmed by blood cultures incubated for > 5 days. The aortic valve is most commonly involved, and echocardiographic findings were non-specific. Complications occurred in 63% of patients, with emboli being the most common. The surgery rate was 23.5%. The overall mortality rate was 18%. Of the cases, 76.5% were cured with antibiotics alone, including a simple third-generation cephalosporin or a combination of ampicillin and an aminoglycoside. An antibiotic therapy duration of at least 4 weeks is recommended. Surgical therapy is usually required for haemodynamic reasons. Prophylaxis of A. actinomycetemcomitans endocarditis relies on antibiotic therapy for all cardiac patients at risk before dental procedures. Among 17 patients undergoing dental manipulations, only eight received amoxycillin before the procedure, demonstrating that prophylaxis is far from being systematically prescribed. In conclusion, A. actinomycetemcomitans endocarditis should be highly suspected in patients with previous cardiac disease and for whom symptoms have evolved over a number of weeks or even months.

Streptococcus pneumoniae endocarditis: persistence of DNA on heart valve material 7 years after infectious episode.

We amplified by PCR and sequenced Streptococcus pneumoniae rpoB from DNA of the cardiac valve of a man who had presented with pneumococcal endocarditis 7 years earlier. Histopathologically, the valve did not show evidence of endocarditis. This case raises the question of persistence of DNA without any evidence of infection.

Molecular diagnosis of Granulicatella elegans on the cardiac valve of a patient with culture-negative endocarditis.

We herein report one case of culture-negative infectious endocarditis (IE) where the organism, Granulicatella elegans, was identified by molecular analysis using broad-range PCR primers complementary to the 16S rRNA gene on the removed valve. The results and utility of this method are discussed.

Comparison of clinical and echocardiographic characteristics of Streptococcus bovis endocarditis with that caused by other pathogens.

The aim of our study was to compare the clinical, echographic, and prognostic features of Streptococcus bovis (S. bovis) endocarditis with those caused by other streptococci and pathogens in a large sample of patients with definite endocarditis by Duke criteria, using transesophageal echocardiography. Two hundred six patients (149 men, mean age 57 +/- 15 years) with a diagnosis of infective endocarditis formed the study population. All patients underwent multiplane transesophageal echocardiography and blood cultures. Cerebral, thoracoabdominal computed tomographic scan was performed in almost all patients (95%). All patients with S. bovis endocarditis underwent colonoscopy. Incidence of S. bovis endocarditis in our sample was 19%. Patients with S. bovis endocarditis were older than other groups. Multiple valve involvement, native valves, and large vegetations (>10 mm) were more frequent in patients with S. bovis. There was a significantly higher occurrence of embolism in the S. bovis group. Splenic embolism and multiple embolisms were significantly more frequent in patients with S. bovis. Gastrointestinal lesions, anemia, and spondylitis were observed more frequently with S. bovis endocarditis. In addition to the requirement for gastrointestinal examination for S. bovis endocarditis, our study underlines the need for systematic screening for vertebral and splenic localizations, and suggests the use of early surgery to prevent the high risk of embolism in these patients.