Unsupervised machine learning predicts future sexual behaviour and sexually transmitted infections among HIV-positive men who have sex with men.

Machine learning is increasingly introduced into medical fields, yet there is limited evidence for its benefit over more commonly used statistical methods in epidemiological studies. We introduce an unsupervised machine learning framework for longitudinal features and evaluate it using sexual behaviour data from the last 20 years from over 3'700 participants in the Swiss HIV Cohort Study (SHCS). We use hierarchical clustering to find subgroups of men who have sex with men in the SHCS with similar sexual behaviour up to May 2017, and apply regression to test whether these clusters enhance predictions of sexual behaviour or sexually transmitted diseases (STIs) after May 2017 beyond what can be predicted with conventional parameters. We find that behavioural clusters enhance model performance according to likelihood ratio test, Akaike information criterion and area under the receiver operator characteristic curve for all outcomes studied, and according to Bayesian information criterion for five out of ten outcomes, with particularly good performance for predicting future sexual behaviour and recurrent STIs. We thus assess a methodology that can be used as an alternative means for creating exposure categories from longitudinal data in epidemiological models, and can contribute to the understanding of time-varying risk factors.

[Urethritis in the context of risk of sexually transmitted infections : update!] / Urétrites en contexte de risque d'infections sexuellement transmises : actualités.

Urethritis of infectious origin are part of the sexually transmitted diseases (STD) that represent a major public health problem in terms of costs and morbidity. The incidence of urethritis has been increasing for several years and the diagnosis and management must be carried out as soon as possible to avoid complications that may arise and that are sometimes irreversible, but also to limit contamination chains. The difficulties of diagnosis lie in the numerous asymptomatic cases and the management of sexual partners who may be multiple and difficult to identify. The constantly changing epidemiology and resistance to antibiotics guide new developments in their management.

Les urétrites d'origine infectieuse font partie des IST et représentent un problème majeur de santé publique en termes de coûts et de morbidités. Depuis plusieurs années, leur incidence ne cesse d'augmenter et le diagnostic ainsi que la prise en charge doivent être réalisés dans les meilleurs délais afin d'éviter des complications parfois irréversibles, mais aussi de limiter la chaîne de contamination. Les difficultés du diagnostic résident dans les nombreux cas asymptomatiques et la prise en charge des partenaires sexuels qui peuvent être multiples et difficiles à identifier. L'épidémiologie et la résistance aux antibiotiques en constante évolution guident les nouveautés de leur prise en charge.

Antiretroviral Drugs Associated With Subclinical Coronary Artery Disease in the Swiss Human Immunodeficiency Virus Cohort Study.

BACKGROUND: Coronary artery disease (CAD) events have been associated with certain antiretroviral therapy (ART) agents. In contrast, the influence of ART on subclinical atherosclerosis is not clear. The study objective was to assess the association between individual ART agents and the prevalence and extent of subclinical CAD. METHODS: Coronary artery calcium (CAC) scoring and coronary computed tomography angiography (CCTA) were performed in ≥45-year-old Swiss Human Immunodeficiency Virus Cohort Study participants. The following subclinical CAD endpoints were analyzed separately: CAC score >0, any plaque, calcified plaque, noncalcified/mixed plaque, segment involvement score (SIS), and segment severity score (SSS). Logistic regression models calculated by inverse probability of treatment weights (IPTW) were used to explore associations between subclinical CAD and cumulative exposure to the 10 most frequently used drugs. RESULTS: There were 403 patients who underwent CCTA. A CAC score >0 was recorded in 188 (47%), any plaque in 214 (53%), calcified plaque in 151 (38%), and noncalcified/mixed plaque in 150 (37%) participants. A CAC score >0 was negatively associated with efavirenz (IPTW adjusted odds ratio per 5 years 0.73, 95% confidence interval [CI] 0.56-0.96), tenofovir disoproxil fumarate (0.68, 95% CI 0.49-0.95), and lopinavir (0.64, 95% CI 0.43-0.96). Any plaque was negatively associated with tenofovir disoproxil fumarate (0.71, 95% CI 0.51-0.99). Calcified plaque was negatively associated with efavirenz (0.7, 95% CI 0.57-0.97). Noncalcified/mixed plaque was positively associated with abacavir (1.46, 95% CI 1.08-1.98) and negatively associated with emtricitabine (0.67, 95% CI 0.46-0.99). For SSS and SIS, we found no association with any drug. CONCLUSIONS: An increased risk of noncalcified/mixed plaque was only found in patients exposed to abacavir. Emtricitabine was negatively associated with noncalcified/mixed plaque, while tenofovir disoproxil fumarate and efavirenz were negatively associated with any plaque and calcified plaque, respectively.

Self-reported Neurocognitive Impairment in People Living With Human Immunodeficiency Virus (HIV): Characterizing Clusters of Patients With Similar Changes in Self-reported Neurocognitive Impairment, 2013-2017, in the Swiss HIV Cohort Study.

BACKGROUND: Self-reported neurocognitive impairment (SRNI) in people living with human immunodeficiency virus type 1 (HIV-1) infection is frequent. We use longitudinal information on SRNI in the Swiss HIV Cohort Study (SHCS) to identify and characterize groups of patients with persisting SRNI over time. METHODS: We included all SHCS patients who were assessed for SRNI during at least 5 visits spanning at least 2.5 years in 2013-2017. We first compared patients with SRNI to those without SRNI over the whole study period. Second, we used a hierarchical cluster algorithm to identify groups of patients with similar changes of SRNI over time. In both analyses, we studied clinical and demographic factors potentially influencing SRNI. RESULTS: In total, 79 683 questionnaires of 11 029 patients contained information about SRNI, and 8545 of 11 029 (77.5%) patients had longitudinal information. The overall percentage of patients with SRNI decreased from 19.6% in 2013 to 10.7% in 2017. Compared to patients in the cluster with low-level SRNI over time, patients in the cluster with high-level persisting SRNI more often had a prior opportunistic infection of the central nervous system (CNS) (odds ratio [OR], 3.7; P < .001), imperfect adherence to antiretroviral therapy (ART) (OR, 2.8; P < .001), and depression (OR, 1.9; P < .001). CONCLUSIONS: Although overall SRNI is decreasing in the SHCS, there is a group of patients with persisting SRNI over time. Past opportunistic infections of the CNS, imperfect adherence to ART, and depression were associated most with persisting SRNI. Patients with these characteristics should be preferentially tested for neurocognitive impairment.Although overall self-reported neurocognitive impairment (SRNI) is decreasing in the Swiss HIV Cohort Study, there is a group of patients with persisting SRNI over time, characterized by more past opportunistic infections of the central nervous system, imperfect adherence to antiretroviral therapy, and depression.

Subclinical coronary artery disease in Swiss HIV-positive and HIV-negative persons.

Aims: HIV-positive persons have increased cardiovascular event rates but data on the prevalence of subclinical atherosclerosis compared with HIV-negative persons are not uniform. We assessed subclinical atherosclerosis utilizing coronary artery calcium (CAC) scoring and coronary computed tomography angiography (CCTA) in 428 HIV-positive participants of the Swiss HIV Cohort Study and 276 HIV-negative controls concurrently referred for clinically indicated CCTA. Methods and results: We assessed the association of HIV infection, cardiovascular risk profile, and HIV-related factors with subclinical atherosclerosis in univariable and multivariable analyses. HIV-positive participants (median duration of HIV infection, 15 years) were younger than HIV-negative participants (median age 52 vs. 56 years; P < 0.01) but had similar median 10-year Framingham risk scores (9.0% vs. 9.7%; P = 0.40). The prevalence of CAC score >0 (53% vs. 56.2%; P = 0.42) and median CAC scores (47 vs. 47; P = 0.80) were similar, as was the prevalence of any, non-calcified/mixed, and high-risk plaque. In multivariable adjusted analysis, HIV-positive participants had a lower prevalence of calcified plaque than HIV-negative participants [36.9% vs. 48.6%, P < 0.01; adjusted odds ratio (aOR) 0.57; 95% confidence interval (CI) 0.40-0.82; P < 0.01], lower coronary segment severity score (aOR 0.72; 95% CI 0.53-0.99; P = 0.04), and lower segment involvement score (aOR 0.71, 95% CI 0.52-0.97; P = 0.03). Advanced immunosuppression was associated with non-calcified/mixed plaque (aOR 1.97; 95% CI 1.09-3.56; P = 0.02). Conclusion: HIV-positive persons in Switzerland had a similar degree of non-calcified/mixed plaque and high-risk plaque, and may have less calcified coronary plaque, and lower coronary atherosclerosis involvement and severity scores than HIV-negative persons with similar Framingham risk scores.

Cardiac surgery during the acute phase of infective endocarditis: discrepancies between European Society of Cardiology guidelines and practices.

AIMS: Indications for surgery in acute infective endocarditis (IE) are detailed in guidelines, but their application is not well known. We analysed the agreement between the patient's attending physicians and European Society of Cardiology guidelines regarding indications for surgery. We also assessed whether surgery was performed in patients who had an indication. METHODS AND RESULTS: From the 2008 prospective population-based French survey on IE, 303 patients with definite left-sided native IE were identified. For each case, we prospectively recorded (i) indication for surgery according to the attending physicians and (ii) indication for surgery according to guidelines. Surgery was indicated in 194 (65%) patients according to attending physicians and in 221 (73%) according to guidelines, while 139 (46%) underwent surgery. Agreement was moderate between attending physicians and guidelines (kappa 0.41-0.59) and between indication according to guidelines and the performance of surgery (kappa 0.38). Of the 90 (30%) patients not operated despite indication, contraindication to surgery was reported by the attending physicians in 42 (47%), and indication was not identified in 48 (53%). One-year survival was 76% in patients with indication and surgery performed (n = 131), 69% in patients without indication and no surgery (n = 74), 56% in patients with identified indication and contraindication to surgery (n = 42), and 60% in patients with no identified indication (n = 48; P = 0.059). CONCLUSION: Cardiac surgery during acute IE was recommended in almost three out of four patients, although fewer than half were actually operated. Indication was not acknowledged by the attending physicians in one out of six patients.

Privacy-preserving genomic testing in the clinic: a model using HIV treatment.

PURPOSE: The implementation of genomic-based medicine is hindered by unresolved questions regarding data privacy and delivery of interpreted results to health-care practitioners. We used DNA-based prediction of HIV-related outcomes as a model to explore critical issues in clinical genomics. METHODS: We genotyped 4,149 markers in HIV-positive individuals. Variants allowed for prediction of 17 traits relevant to HIV medical care, inference of patient ancestry, and imputation of human leukocyte antigen (HLA) types. Genetic data were processed under a privacy-preserving framework using homomorphic encryption, and clinical reports describing potentially actionable results were delivered to health-care providers. RESULTS: A total of 230 patients were included in the study. We demonstrated the feasibility of encrypting a large number of genetic markers, inferring patient ancestry, computing monogenic and polygenic trait risks, and reporting results under privacy-preserving conditions. The average execution time of a multimarker test on encrypted data was 865 ms on a standard computer. The proportion of tests returning potentially actionable genetic results ranged from 0 to 54%. CONCLUSIONS: The model of implementation presented herein informs on strategies to deliver genomic test results for clinical care. Data encryption to ensure privacy helps to build patient trust, a key requirement on the road to genomic-based medicine.Genet Med 18 8, 814-822.

Preeminence of Staphylococcus aureus in infective endocarditis: a 1-year population-based survey.

BACKGROUND: Observational studies showed that the profile of infective endocarditis (IE) significantly changed over the past decades. However, most studies involved referral centers. We conducted a population-based study to control for this referral bias. The objective was to update the description of characteristics of IE in France and to compare the profile of community-acquired versus healthcare-associated IE. METHODS: A prospective population-based observational study conducted in all medical facilities from 7 French regions (32% of French individuals aged ≥18 years) identified 497 adults with Duke-Li-definite IE who were first admitted to the hospital in 2008. Main measures included age-standardized and sex-standardized incidence of IE and multivariate Cox regression analysis for risk factors of in-hospital death. RESULTS: The age-standardized and sex-standardized annual incidence of IE was 33.8 (95% confidence interval [CI], 30.8-36.9) cases per million inhabitants. The incidence was highest in men aged 75-79 years. A majority of patients had no previously known heart disease. Staphylococci were the most common causal agents, accounting for 36.2% of cases (Staphylococcus aureus, 26.6%; coagulase-negative staphylococci, 9.7%). Healthcare-associated IE represented 26.7% of all cases and exhibited a clinical pattern significantly different from that of community-acquired IE. S. aureus as the causal agent of IE was the most important factor associated with in-hospital death in community-acquired IE (hazard ratio [HR], 2.82 [95% CI, 1.72-4.61]) and the single factor in healthcare-associated IE (HR, 2.54 [95% CI, 1.33-4.85]). CONCLUSIONS: S. aureus became both the leading cause and the most important prognostic factor of IE, and healthcare-associated IE appeared as a major subgroup of the disease.

Relevance of fluoroquinolone use in hospitals in the Lorraine region of France before and after corrective measures: an investigation by the Antibiolor Network.

OBJECTIVES: This study of fluoroquinolone use was carried out before and after an educational intervention run by Antibiolor, a regional network to all hospitals in the Lorraine region of France. METHODS: The relevance of fluoroquinolone prescription according to regional guidelines was assessed using a standard card filled out by physicians and pharmacists at the voluntarily participating hospitals. A therapeutic index of adequacy was established for each card. The initial survey took place in January 2008, with feedback and proposals for corrective measures in January 2009. The second survey was organized in June 2009. The results of the 2 surveys were compared. RESULTS: Twenty-four hospitals completed a total of 1336 cards in the first survey (S1) and 944 cards in the second (S2). The appropriateness of indications for fluoroquinolone use improved by 57% between the 2 surveys. All the criteria analyzed (choice of drug, dosage, treatment duration) were significantly improved in S2 compared to S1, as was the adequacy index (70% improvement). CONCLUSIONS: In view of the consequences of fluoroquinolone use, many hospitals in Lorraine were keen to participate in this study, confirming its feasibility over a large area. In view of the study results, the book of guidelines was re-examined and republished at the conclusion of S2. Greater adherence to guidelines was noted in S2, demonstrating the benefit of assessing the situation thoroughly before proposing corrective measures and evaluating their impact.

Fatal Histoplasma capsulatum mitral endocarditis in a French patient treated for rheumatoid arthritis.

Histoplasmosis is an infectious disease caused by the inhalation of Histoplasma capsulatum spores, a fungus encountered in many diverse areas around the world. Although this infection is often asymptomatic, it may become dramatic in immunocompromised patients. In November 2005, an endocarditis due to Histoplasma capsulatum was diagnosed in a French woman treated for rheumatoid arthritis and who had traveled to South America 2 years earlier. We confirmed the biological diagnosis by mycological, serological, and histological methods. In spite of receiving the appropriate treatment, the patient died 3 months later of cardiac insufficiency. We report here this additional case of Histoplasma endocarditis, by hoping to help rapid and accurate diagnosis of such infections in their early stages of development, in non-endemic areas.

Methicillin-susceptible Staphylococcus aureus endocarditis isolates are associated with clonal complex 30 genotype and a distinct repertoire of enterotoxins and adhesins.

BACKGROUND: Using multinational collections of methicillin-susceptible Staphylococcus aureus (MSSA) isolates from infective endocarditis (IE) and soft tissue infections (STIs), we sought to (1) validate the finding that S. aureus in clonal complex (CC) 30 is associated with hematogenous complications and (2) test the hypothesis that specific genetic characteristics in S. aureus are associated with infection severity. METHODS: IE and STI isolates from 2 cohorts were frequency matched by geographic origin. Isolates underwent spa typing to infer CC and multiplex polymerase chain reaction for presence of virulence genes. RESULTS: 114 isolate pairs were genotyped. IE isolates were more likely to be CC30 (19.5% vs 6.2%; P = .005) and to contain 3 adhesins (clfB, cna, map/eap; P < .0001 for all) and 5 enterotoxins (tst, sea, sed, see, and sei; P ≤ .005 for all). CC30 isolates were more likely to contain cna, tst, sea, see, seg, and chp (P < .05 for all). CONCLUSIONS: MSSA IE isolates were significantly more likely to be CC30 and to possess a distinct repertoire of virulence genes than MSSA STI isolates from the same region. The genetic basis of this association requires further study.

Clinical and microbiologic features of multivalvular endocarditis.

Multivalvular endocarditis accounts for 15% of all endocarditis. The mechanisms of spread of the infection differs whether endocarditis is only left-sided (involving both the mitral and aortic valves) or bilateral. In left-sided bivalvular endocarditis, it is often a secondary mitral lesion following a primary aortic endocarditis. Multivalvular endocarditis often results in severe and extensive cardiac lesions, well described at echocardiography and frequently responsible for severe heart failure. Patients often need surgery, which consists of radical debridement of all the infected tissue with reconstruction using different types of prostheses; therefore, the surgery may be very complex. The goal should be an early diagnosis of endocarditis to avoid spread of the infection to more than one valve, to improve the prognosis for those patients.

An Adherence-Enhancing Program Increases Retention in Care in the Swiss HIV Cohort.

BACKGROUND: This study tested a theory-based adherence-enhancing intervention: the "Interprofessional Medication Adherence Program" (IMAP) to increase human immunodeficiency virus (HIV) retention in care. METHODS: We retrospectively compared our intervention center (intervention group [IG]) with a standard of care center (control group [CG]) both participating in the Swiss HIV Cohort Study between 2004 and 2012. Endpoints were defined as >6-month and >12-month gaps in care for intervals of care longer than 6 and 12 months without any blood draw. Inverse probability of treatment weights was used to adjust for differences between patients at the 2 centers. Viral failure was defined as ribonucleic acid ≥50 copies/mL after 24+ weeks on antiretrovirals. RESULTS: The IG included 451 patients, CG 311. In the IG, 179 (40%) patients took part in the IMAP for a median of 27 months (interquartile range, 12-45). Gaps in care of ≥6 months were significantly more likely to happen in the CG versus IG (74.6% vs 57%, P < .001). The median time until the first treatment gap was longer in the IG vs CG (120 vs 84 weeks, P < .001). Gaps in care of ≥12 months evaluated in 709 (93%) patients were significantly more likely to occur in the CG compared with the IG (22.6% vs 12.5%, P < .001). The rate of viral failure was significantly lower in the IG (8.3% vs 15.1%, P = .003). CONCLUSIONS: This study, in a real-world setting, shows the effectiveness of the IMAP to reduce 6- and 12-month gaps in follow up among people with HIV. These results should be confirmed by studies in other settings.

Brief Report: Switching From TDF to TAF in HIV/HBV-Coinfected Individuals With Renal Dysfunction-A Prospective Cohort Study.

BACKGROUND: Whereas tenofovir disoproxil fumarate (TDF) can lead to renal adverse events, tenofovir alafenamide (TAF) has a more favorable renal safety profile. However, the impact of replacing TDF with TAF on renal function and liver parameters among HIV/hepatitis B virus (HBV)-coinfected individuals with renal dysfunction remains unclear. METHODS: We included all participants from the Swiss HIV Cohort Study with an HIV/HBV coinfection who switched from TDF to TAF and had an estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m and a suppressed HIV viral load (<200 cp/mL). We assessed changes in eGFR, urine protein-to-creatinine ratio, and alanine aminotransferase (ALT) after 1 year using mixed-effect models with interrupted time series. RESULTS: Among 106 participants (15.1% women, median age 53 years), eGFR was 60-89 mL/min/1.73 m in 84 (79.2%) and <60 mL/min/1.73 m in 22 (20.8%) individuals at the time of switch. One year after the switch from TDF to TAF, individuals with an eGFR between 60 and 89 mL/min/1.73 m experienced increases in eGFR of 3.2 mL/min/1.73 m (95% confidence interval [CI] 1.2 to 5.2), whereas those with an eGFR <60 mL/min/1.73 m experienced improvements of 6.2 mL/min/1.73 m (95% CI 2.4 to 10.0). Urine protein-to-creatinine ratio decreased overall (-6.3 mg/mmol, 95% CI -10.0 to -2.7), and ALT levels declined in patients with elevated baseline levels (-11.8 IU/L, 95% CI -17.3 to -6.4) 1 year after replacing TDF with TAF. CONCLUSIONS: Switching from TDF to TAF among HIV/HBV-coinfected individuals with renal impairment led to improvements in eGFR, a decline in proteinuria, and to ALT normalization in those with elevated ALT levels.

Longitudinal Progression of Subclinical Coronary Atherosclerosis in Swiss HIV-Positive Compared With HIV-Negative Persons Undergoing Coronary Calcium Score Scan and CT Angiography.

BACKGROUND: People with HIV (HIV+) may have increased cardiovascular event rates compared with HIV-negative (HIV-) persons. Cross-sectional data from the United States and Switzerland, based on coronary artery calcium scan (CAC) and coronary computed tomography angiography (CCTA), suggest, respectively, increased and similar prevalence of subclinical atherosclerosis in HIV+ vs HIV- persons. METHODS: We repeated CAC/CCTA in 340 HIV+ and 90 HIV- study participants >2 years after baseline CAC/CCTA. We assessed the association of HIV infection, Framingham risk score (FRS), and HIV-related factors with the progression of subclinical atherosclerosis. RESULTS: HIV+ were younger than HIV- participants (median age, 52 vs 56 years; P < .01) but had similar median 10-year FRS (8.9% vs 9.0%; P = .82); 94% had suppressed HIV viral load. In univariable and multivariable analyses, FRS was associated with the incidence rate ratio (IRR) of new subclinical atherosclerosis at the follow-up CAC/CCTA, but HIV infection was not: any plaque (adjusted IRR for HIV+ vs HIV- participants, 1.21; 95% CI, 0.62-2.35), calcified plaque (adjusted IRR for HIV+ vs HIV- participants, 1.06; 95% CI, 0.56-2), noncalcified/mixed plaque (adjusted IRR for HIV+ vs HIV- participants, 1.24; 95% CI, 0.69-2.21), and high-risk plaque (adjusted IRR for HIV+ vs HIV- participants, 1.46; 95% CI, 0.66-3.20). Progression of CAC score between baseline and follow-up CAC/CCTA was similar in HIV+ (median annualized change [interquartile range {IQR}], 0.41 [0-10.19]) and HIV- participants (median annualized change [IQR], 2.38 [0-16.29]; P = .11), as was progression of coronary segment severity score (HIV+: median annualized change [IQR], 0 [0-0.47]; HIV-: median annualized change [IQR], 0 [0-0.52]; P = .10) and coronary segment involvement score (HIV+: median annualized change [IQR], 0 [0-0.45]; HIV-: median annualized change [IQR], 0 [0-0.41]; P = .25). CONCLUSIONS: In this longitudinal CAC/CCTA study from Switzerland, Framingham risk score was associated with progression of subclinical atherosclerosis, but HIV infection was not.

Beta-Hemolytic Streptococcal Infective Endocarditis: Characteristics and Outcomes From a Large, Multinational Cohort.

BACKGROUND: Beta-hemolytic streptococci (BHS) are an uncommon cause of infective endocarditis (IE). The aim of this study was to describe the clinical features and outcomes of patients with BHS IE in a large multinational cohort and compare them with patients with viridans streptococcal IE. METHODS: The International Collaboration on Endocarditis Prospective Cohort Study (ICE-PCS) is a large multinational database that recruited patients with IE prospectively using a standardized data set. Sixty-four sites in 28 countries reported patients prospectively using a standard case report form developed by ICE collaborators. RESULTS: Among 1336 definite cases of streptococcal IE, 823 were caused by VGS and 147 by BHS. Patients with BHS IE had a lower prevalence of native valve (P < .005) and congenital heart disease predisposition (P = .002), but higher prevalence of implantable cardiac device predisposition (P < .005). Clinically, they were more likely to present acutely (P < .005) and with fever (P = .024). BHS IE was more likely to be complicated by stroke and other systemic emboli (P < .005). The overall in-hospital mortality of BHS IE was significantly higher than that of VGS IE (P = .001). In univariate analysis, variables associated with in-hospital mortality for BHS IE were age (odds ratio [OR], 1.044; P = .004), prosthetic valve IE (OR, 3.029; P = .022), congestive heart failure (OR, 2.513; P = .034), and stroke (OR, 3.198; P = .009). CONCLUSIONS: BHS IE is characterized by an acute presentation and higher rate of stroke, systemic emboli, and in-hospital mortality than VGS IE. Implantable cardiac devices as a predisposing factor were more often found in BHS IE compared with VGS IE.

Phylogenetic analysis of viridans group streptococci causing endocarditis.

Identification of viridans group streptococci (VGS) to the species level is difficult because VGS exchange genetic material. We performed multilocus DNA target sequencing to assess phylogenetic concordance of VGS for a well-defined clinical syndrome. The hierarchy of sequence data was often discordant, underscoring the importance of establishing biological relevance for finer phylogenetic distinctions.

Genotypic diversity of coagulase-negative staphylococci causing endocarditis: a global perspective.

Coagulase-negative staphylococci (CNS) are important causes of infective endocarditis (IE), but their microbiological profiles are poorly described. We performed DNA target sequencing and susceptibility testing for 91 patients with definite CNS IE who were identified from the International Collaboration on Endocarditis-Microbiology, a large, multicenter, multinational consortium. A hierarchy of gene sequences demonstrated great genetic diversity within CNS from patients with definite endocarditis that represented diverse geographic regions. In particular, rpoB sequence data demonstrated unique genetic signatures with the potential to serve as an important tool for global surveillance.

Possible relationship between antiphospholipid antibodies and embolic events in infective endocarditis.

OBJECTIVE: Antiphospholipid (aPL) antibodies may activate platelets and contribute to vegetation growth and embolisation in infective endocarditis (IE). We aimed to determine the value of aPL as predictors of embolic events (EE) in IE. METHODS: We studied 186 patients with definite IE (Duke-Li criteria, all types of IE) from the Nanc-IE prospective registry (2007-2012) who all had a frozen blood sample and at least one imaging procedure to detect asymptomatic or confirm symptomatic EE. Anticardiolipin (aCL) and anti-ß2-glycoprotein I (ß2GPI) antibodies (IgG and IgM) were assessed after the end of patients' inclusion. The relationship between antibodies and the detection of EE after IE diagnosis were studied with Kaplan-Meier and Cox multivariate analyses. RESULTS: At least one EE was detected in 118 (63%) patients (52 cerebral, 95 other locations) after IE diagnosis in 80 (time interval between IE and EE diagnosis: 5.9±11.3 days). At least one aPL antibody was found in 31 patients (17%).Detection of EE over time after IE diagnosis was more frequent among patients with anti-ß2GPI IgM (log-rank P=0.0036) and that of cerebral embolisms, among patients with aCL IgM and anti-ß2GPI IgM (log-rank P=0.002 and P<0.0001, respectively).Factors predictive of EE were anti-ß2GPI IgM (HR=3.45 (1.47-8.08), P=0.0045), creatinine (2.74 (1.55-4.84), P=0.0005) and vegetation size (2.41 (1.41-4.12), P=0.0014). Those of cerebral embolism were aCL IgM (2.84 (1.22-6.62), P=0.016) and anti-ß2GPI IgM (4.77 (1.79-12.74), P=0.0018). CONCLUSION: The presence of aCL and anti-ß2GPI IgM was associated with EE, particularly cerebral ones, and could contribute to assess the embolic risk of IE.

The relationship between the initiation of antimicrobial therapy and the incidence of stroke in infective endocarditis: an analysis from the ICE Prospective Cohort Study (ICE-PCS).

BACKGROUND: Embolic events to the central nervous system are a major cause of morbidity and mortality in patients with infective endocarditis (IE). The appropriate role of valvular surgery in reducing such embolic events is unclear. The purpose of this study was to determine the relationship between the initiation of antimicrobial therapy and the temporal incidence of stroke in patients with IE and to determine if this time course differs from that shown for embolic events in previous studies. METHODS: Prospective incidence cohort study involving 61 tertiary referral centers in 28 countries. Case report forms were analyzed from 1437 consecutive patients with left-sided endocarditis admitted directly to participating centers. RESULTS: The crude incidence of stroke in patients receiving appropriate antimicrobial therapy was 4.82/1000 patient days in the first week of therapy and fell to 1.71/1000 patient days in the second week. This rate continued to decline with further therapy. Stroke rates fell similarly regardless of the valve or organism involved. After 1 week of antimicrobial therapy, only 3.1% of the cohort experienced a stroke. CONCLUSIONS: The risk of stroke in IE falls dramatically after the initiation of effective antimicrobial therapy. The falling risk of stroke in patients with IE as a whole precludes stroke prevention as the sole indication for valvular surgery after 1 week of therapy.