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.

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.

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.

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.

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.

Echocardiography predicts embolic events in infective endocarditis.

OBJECTIVES: The aim of our study was to assess the value of transesophageal echocardiography (TEE) in predicting embolic events (EEs) in a large group of patients with definite endocarditis according to the Duke criteria, including silent embolism. BACKGROUND: The value of echocardiography in predicting embolism in patients with endocarditis remains controversial. Some studies reported an increased risk of embolism in patients with large and mobile vegetations, whereas other studies failed to demonstrate such a relationship. METHODS: Multiplane transesophageal echocardiograms of 178 consecutive patients with definite infective endocarditis (IE) were analyzed. The incidence of embolism was compared with the echocardiographic characteristics (localization, size and mobility) of the vegetations. To detect silent embolism, cerebral and thoraco-abdominal scans were performed in 95% of patients. RESULTS: Among 178 patients, 66 (37%) had one or more EEs. There was no difference between patients with and without embolism in terms of age, gender and left valve involved. On univariate analysis, Staphylococcus infection, right-side valve endocarditis and vegetation length and mobility were significantly related to EEs. A significant higher incidence of embolism was present in patients with vegetation length >10 mm (60%, p < 0.001) and in patients with mobile vegetations (62%, p < 0.001). Embolism was particularly frequent among 30 patients with both severely mobile and large vegetations (> 15 mm) (83%, p < 0.001). On multivariate analysis, the only predictors of embolism were vegetation length (p = 0.03) and mobility (p = 0.01). CONCLUSIONS: Our study shows that the presence of vegetations on TEE is predictive of embolism and that the morphologic characteristics of vegetations are helpful in predicting EEs in both mitral and aortic valve IE. It also suggests that early operation may be recommended in patients with vegetations > 15 mm and high mobility, irrespective of the degree of valve destruction, heart failure and response to antibiotic therapy.

Value and limitations of the Duke criteria for the diagnosis of infective endocarditis.

OBJECTIVES: The purpose of this study was to assess the value and limitations of Duke criteria for the diagnosis of infective endocarditis (IE). BACKGROUND: Duke criteria have been shown to be more sensitive in diagnosing IE than the von Reyn criteria, but the diagnosis of IE remains difficult in some patients. METHODS: Both classifications were applied in 93 consecutive patients with pathologically proven IE. Blood cultures, and transthoracic and transesophageal echocardiography were performed in all patients. RESULTS: Sensitivities for the diagnosis of IE were 56% and 76% for von Reyn and Duke criteria, respectively. Fifty-two patients were correctly classified as "probable IE" by von Reyn and "definite IE" by Duke criteria (group 1). However, discrepancies were observed in 41 patients. Eleven patients (group 2) were misclassified as "rejected" by von Reyn, but were "definite IE" by Duke criteria; this difference could be explained by negative blood cultures and positive echocardiogram in all patients. In eight patients (group 3), the diagnosis of IE was "possible" by von Reyn but "definite" by Duke criteria. This difference was essentially explained by the failure of the von Reyn classification to consider echocardiographic abnormalities as major criteria. Twenty-two patients (group 4) were misclassified as possible IE using Duke criteria, being false negative of this classification. Echocardiographic major criteria were present in 19 patients, but blood cultures were negative in 21 patients. The cause of negative blood cultures was prior antibiotic therapy in 11 patients and Q-fever endocarditis diagnosed by positive serology in three cases. CONCLUSIONS: Twenty-four percent of patients with proved IE remain misclassified as "possible IE" despite the use of Duke criteria, especially in cases of culture-negative and Q-fever IE. Increasing the diagnostic value of echographic criteria in patients with prior antibiotic therapy and typical echocardiographic findings and considering the serologic diagnosis of Q fever as a major criterion would further improve the clinical diagnosis of IE.

Mycoplasma pneumoniae pneumonia following assisted ventilation.

BACKGROUND: Mycoplasma pneumoniae pneumonia is regarded as a community-acquired pneumonia, rarely requiring hospitalization, with sporadic cases or limited outbreaks occurring after close contacts with an infected patient. Few reports mention M pneumoniae pneumonia acquired during hospitalization. PATIENTS AND METHODS: M pneumoniae was diagnosed in patients who developed pneumonia following perioperative and postoperative assisted ventilation by the isolation of M pneumoniae from bronchial washing, the detection of M pneumoniae DNA from bronchial washing, and serologic testing for the presence of specific immunoglobulin M (IgM) antibodies. RESULTS: Four patients were diagnosed as having M pneumoniae pneumonia following mechanical ventilation over a 1 1/2-year period. They were men, older than 50 years, and were hospitalized for vascular surgery. They developed febrile hypoxemia and intersticial pneumonia. Isolation of M pneumoniae and detection of M pneumoniae DNA were positive in 1 case; specific IgM antibodies were present in 4 cases. CONCLUSIONS: These observations allow the description of a new clinical entity and highlight the role of M pneumoniae as an agent of nosocomial infections. This diagnosis should be considered in any patient with precocious post-assisted ventilation febrile hypoxemia and diffuse interstitial pneumonia, and empiric treatment protocols may include M pneumoniae in their spectrum.

Modification of the diagnostic criteria proposed by the Duke Endocarditis Service to permit improved diagnosis of Q fever endocarditis.

BACKGROUND: Q fever endocarditis is a life-threatening disease for which the diagnosis is usually based on serology. The major microbiologic criterion for the diagnosis of infectious endocarditis (two separate positive blood cultures) cannot be achieved in most routine laboratories because of the biohazard associated with the culture of Coxiella burnetii, the etiological agent of Q fever. PURPOSE: Recently, new criteria for the diagnosis of infectious endocarditis have been proposed, and in this study we attempted to assess the suitability of these criteria specifically for the diagnosis of Q fever endocarditis. PATIENTS AND METHODS: To achieve this aim, we first selected from our series 20 recent cases in whom endocarditis had been confirmed following valvular pathological examination, and for whom microbiological evidence for the involvement of C burnetii was available. Then, we applied the criteria proposed by the Duke Endocarditis Service (ie, C burnetii positive serology being considered a minor criterion) to this cohort of patients but excluding pathological findings. Although the Duke Endocarditis Service criteria confirmed diagnosis in 16 of the patients, 4 were misclassified as "possible" cases (20%). However, when the Q fever serological results (using an 1/800 antiphase I immunoglobulin G cut off) and single blood culture results were changed from minor to major diagnostic criteria, endocarditis was confirmed in them all. A second time, prospectively, we applied the Duke Endocarditis Service criteria to a further 5 patients affected with Q fever endocarditis. Strict application of these criteria resulted in 1 of the 5 being misdiagnosed. Applying the suggested modification for C burnetii results, all 5 were confirmed as having infectious endocarditis. CONCLUSION: We propose that the modifications discussed in this study be applied to the Duke Endocarditis Service criteria in order that the diagnosis of C burnetii induced endocarditis is improved.

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.

Detection of fastidious bacteria in cardiac valves in cases of blood culture negative endocarditis.

The diagnosis of blood culture negative endocarditis is still a problem. Fastidious bacteria such as bartonella and coxiella are responsible for cases of blood culture negative endocarditis, the identification of which is mainly based on serological and DNA studies only available in specialised centres. Therefore, a routine technique is needed in surgical pathology laboratories to detect these bacteria in cardiac valve tissue sections. This report describes a staining technique, the Gimenez stain, feasible and sensitive in detecting bartonella and coxiella in two cases of blood culture negative endocarditis.

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.

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.

Aortoabdominal aneurysm infected by Yersinia enterocolitica serotype O:9.

A 78-year-old-man was hospitalized for surgical treatment of a Yersinia enterocolitica serotype O:9 infected primary aortoabdominal aneurysm which ruptured soon after admission. Infection of aneurysm is an unusual manifestation of yersiniosis, especially in patients with no predisposing underlying condition. This case, and review of the literature, highlights that serotype O:9 has a predilection for vascular tissue. Cross reaction with Brucella spp. may be responsible for misdiagnosis of Y. enterocolitica O:9 infected aneurysms.

[Non bacterial thrombotic endocarditis (marantic endocarditis). Apropos of a case and value of transoesophageal echocardiography]. / Endocardite thrombotique abactérienne (endocardite marastique). A propos d'un cas et de l'intérêt de l'échographie transoesophagienne.

Marantic or non-bacterial thrombotic endocarditis is a common complication of terminal malignancy, usually discovered at autopsy. The authors report a case of marantic endocarditis as a presenting sign of pancreatic carcinoma in which the diagnosis was made ante-mortem by transoesophageal echocardiography.

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.

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.