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The microbiology, epidemiology, diagnostics, and treatment of infective endocarditis (IE) have changed significantly since the Duke Criteria were published in 1994 and modified in 2000. The International Society for Cardiovascular Infectious Diseases (ISCVID) convened a multidisciplinary Working Group to update the diagnostic criteria for IE. The resulting 2023 Duke-ISCVID IE Criteria propose significant changes, including new microbiology diagnostics (enzyme immunoassay for Bartonella species, PCR, amplicon/metagenomic sequencing, in situ hybridization), imaging ([18F]FDG PET/CT, Cardiac Computed Tomography), and inclusion of intraoperative inspection as a new Major Clinical Criterion. The list of “typical” microorganisms causing IE was expanded and includes pathogens to be considered as typical only in the presence of intracardiac prostheses. The requirements for timing and separate venipunctures for blood cultures were removed. Last, additional predisposing conditions (transcatheter valve implants, endovascular cardiac implantable electronic devices, prior IE) were clarified. These diagnostic criteria should be updated periodically by making the ISCVID-Duke Criteria available online as a “Living Document”.

Background Virus-associated respiratory infections are in the spotlight with the emergence of SARS-CoV-2 and the expanding use of multiplex PCR (mPCR). The impact of molecular testing as a point-of-care test (POCT) in the emergency department (ED) is still unclear. Objectives To compare the impact of a syndromic test performed in the ED as a POCT and in the central laboratory on length of stay (LOS), antibiotic use and single-room assignment. Methods From 19 November 2019 to 9 March 2020, adults with acute respiratory illness seeking care in the ED of a large hospital were enrolled, with mPCR performed with a weekly alternation in the ED as a POCT (week A) or in the central laboratory (week B). Results 474 patients were analysed: 275 during A weeks and 199 during B weeks. Patient characteristics were similar. The hospital LOS (median 7 days during week A versus 7 days during week B, P = 0.29), the proportion of patients with ED-LOS Conclusions Syndromic testing performed in the ED compared with the central laboratory failed to reduce the LOS or antibiotic consumption in patients with acute respiratory illness, but was associated with an increased single-room assignment among patients in whom a significant respiratory pathogen was detected.

S10.3 The mycobiome characterization: future perspectives or just a trend?, September 24, 2022, 10:30 AM - 12:00 PM Objectives Candida albicans is both a harmless commensal intestinal yeast in healthy individuals and a harmful opportunistic pathogen in immunocompromised patients, causing life-threatening invasive candidiasis. C. albicans intestinal overgrowth is a prerequisite for intestinal translocation, which is at the root of invasive candidiasis. Therefore, to prevent invasive candidiasis in immunocompromised patients, it is necessary to curb intestinal C. albicans overgrowth. However, little is known of the role of bacterial species of the microbiota in dampening C. albicans intestinal colonization. We aimed to decipher the influence of the bacterial and fungal intestinal microbiota on C. albicans gut colonization in healthy individuals in whom their microbiota was modified or not by antibiotic treatment. Methods We studied two cohorts of healthy individuals: the first cohort included 22 volunteers for which fecal samples were collected before, during and after a 3-day regimen of third-generation cephalosporin antibiotics. The second cohort gathered 1000 healthy individuals for which a single fecal sample was collected. We quantified C. albicans carriage using a specific quantitative PCR approach. We monitored the antibiotic effect on the composition of the fungal microbiota—the so called mycobiota—in the gut of the individuals up to 180 days post-antibiotic exposure, using both the qPCR data and ITS1 targeted metagenomic. We also monitored the level of fecal β-lactamase activity, which is known to modulate the intensity of post-cephalosporin intestinal dysbiosis. Finally, to identify potential C. albicans inhibiting bacteria, we used MaAsLin2 to search for associations between C. albicans levels and bacterial species abundance, deduced from shotgun metagenomics data obtained from all individuals and annotated at the species level. Results A very high level of C. albicans carriage was observed in both cohorts, with a prevalence of 95.2% and 83.1% in the first and second cohort, respectively. Yet, the quantity of C. albicans DNA detected varied greatly between subjects. The mycobiota composition was significantly altered by antibiotics and the fungal load was increased both at short and long term. Particularly, C. albicans abundance was increased but with wide inter-subject variations. A part of these variations was explained by changes in the levels of endogenous fecal β-lactamase activity, with subjects characterized by a low increase of β-lactamase activity displaying a higher increase of C. albicans levels. Finally, using shotgun metagenomics data, we identified a first set of 50 bacterial and archaeal species whose abundance inversely correlated with C. albicans abundance. Conclusion These results (1) bring a new understanding of C. albicans overgrowth in healthy individuals, (2) lead to the identification of microbial signatures with a potential key role in controlling C. albicans gut colonization, and finally (3) show for the first time that changes in endogenous fecal β-lactamase activity is a key factor for C. albicans overgrowth in the gut after antibiotic exposure. Taken together, these results open the way for new intervention strategies to curb C. albicans intestinal overgrowth.

Background Pneumonia, skin and soft tissue infections are more frequent in obese patients and are most often treated by co-amoxiclav, using similar dosing regimens to those used for non-obese subjects. No data are available on amoxicillin pharmacokinetics among obese subjects receiving co-amoxiclav. Materials and methods Prospective, single-centre, open-label, non-randomized, crossover pharmacokinetic trial having enrolled obese otherwise healthy adult subjects. A first dose of co-amoxiclav (amoxicillin/clavulanate 1000/200 mg) was infused IV over 30 min, followed by a second dose (1000/125 mg) administered orally, separated by a washout period of ≥24 h. We assayed concentrations of amoxicillin by a validated ultra HPLC–tandem MS technique. We estimated population pharmacokinetic parameters of amoxicillin by non-linear mixed-effect modelling using the SAEM algorithm developed by Monolix. Results Twenty-seven subjects were included in the IV study, with 24 included in the oral part of the study. Median body weight and BMI were 109.3 kg and 40.6 kg/m2, respectively. Amoxicillin pharmacokinetics were best described by a two-compartment model with first-order elimination. Mean values for clearance, central volume, intercompartmental clearance and peripheral volume were, respectively, 14.6 L/h, 9.0 L, 4.2 L/h and 6.4 L for amoxicillin. Oral bioavailability of amoxicillin was 79.7%. Amoxicillin Cmax after oral administration significantly reduced with weight (P = 0.013). Dosing simulations for amoxicillin predicted that most of the population will achieve the pharmacodynamic target of fT>MIC ≥40% with the regimen of co-amoxiclav 1000/200 mg (IV) or 1000/125 mg (oral) q8h for MICs titrated up to 0.5 mg/L (IV) and 1 mg/L (oral). Conclusions Pharmacokinetic/pharmacodynamic goals for amoxicillin can be obtained in obese subjects.

Background. Calendar trends in virologic failure (VF) among human immunodeficiency virus (HIV)-infected patients can help to evaluate the performance of healthcare systems and the need for new antiretroviral therapy (ART). We examined the time trend in the rate of VF beyond 6 months of ART between 1997 and 2011 in France. Methods. We included patients from the French Hospital Database on HIV who received at least 6 months of ART. VF was defined as 2 consecutive plasma HIV-RNA values >500 copies/mL or as 1 value >500 copies/mL followed byatreatment switch. We adjusted for patients’ characteristics by fitting a multivariable generalized estimating equation logistic regression model with an exchangeable covariance matrix. Results. A total of 81738 patients were enrolled, and median follow-up was 112.4 months. Median CD4 count was 333 cells/µL, and 23% of patients had HIV infection classified as Centers for Disease Control and Prevention stage C. Overall, 29.3% of patients received single/dual-drug ART initially, and 45.4% of patients experienced at least 1 episode of VF during follow-up. The percentage of patients with VF fell from 61.5% in 1997–1998 to 9.7% in 2009–2011 (P

International audience; The French Hospital Database on HIV (FHDH) is a hospital-based multicentre open cohort with inclusions ongoing since 1989. The research objectives focus mainly on mid- and long-term clinical outcomes and therapeutic strategies, as well as severe AIDS and non-AIDS morbidities, and public health issues relative to HIV infection. FHDH also serves to describe HIV-infected patients receiving hospital care in France. FHDH includes data on more than 120,000 HIV-infected patients from 70 French general or university hospitals distributed throughout France. Patients are eligible for inclusion if they are infected by HIV-1 or HIV-2 and give their written informed consent. Standardized variables are collected at each outpatient visit or hospital admission during which a new clinical manifestation is diagnosed, a new treatment is prescribed or a change in biological markers is noted, and/or at least every 6 months. Since its inception, variables collected in FHDH include demographic characteristics, HIV-related biological markers, the date and type of AIDS and non AIDS-defining events, antiretroviral treatments and the date and causes of death, as reported in the medical records. Since 2005, data have also been collected on: co-infection with hepatitis B or C virus; alcohol and tobacco use; and non HIV-related biomarkers. Anyone can submit a research project by completing a standardized form available on the FHDH website (http://www.ccde.fr/_fold/fl-1385734776-429.pdf) or from the corresponding author, describing the context and objectives of the study. All projects are reviewed by the scientific committee.

Elderly individuals are at increased risk of morbidity and mortality due to microbial infections because of coexisting chronic disease and immune senescence [1]. The contribution of noninfluenza viral infections to acute respiratory illness in the elderly has not been well studied, partly due to difficulties in diagnosis due to atypical presentations and low viral loads [2–5]. However, identification of respiratory viruses is now possible with the advent of sensitive molecular detection methods, including polymerase chain reaction (PCR) [6, 7]. Respiratory syncytial virus (RSV) is increasingly recognized as an important cause of respiratory infections in adults, particularly affecting the elderly, immunocompromised, and those with underlying chronic cardiopulmonary disease [8]. RSV appears to be a predictable cause of wintertime respiratory illnesses among older adults living in congregate settings such as long-term care or attending daycare and is estimated to infect 5%–10% of nursing home residents per year, with rates of pneumonia and death of 10%–20% and 2%–5%, respectively [9]. Few studies have prospectively assessed etiologies of acute respiratory infections in community-based elderly individuals [8, 10]. Much of the available data describing RSV and other viral infections in the elderly come from a limited number of geographic locations, primarily the United States (US). Different cultures, climates, and intergenerational household members might influence infection rates; thus, global data on RSV and other respiratory viral infections in this population are needed. We used multiplex reverse transcriptase PCR (RT-PCR) to identify viral respiratory pathogens in nasal and throat swabs from episodes of moderate-to-severe influenza-like illness (ILI) in influenza-vaccinated elderly individuals.

Aims In patients with a suspicion of prosthetic valve endocarditis (PVE), detection of perivalvular infection can be difficult based only on echocardiography. The aim of this retrospective study was to test the interest of radiolabelled leucocyte scintigraphy (LS) for the detection of perivalvular infection in patients with a suspicion of PVE and inconclusive transoesophageal echocardiography (TEE). Methods and results LS was performed in 42 patients. The results of LS were classified as positive in the cardiac area (intense or mild), or negative. Macroscopical aspects and bacteriology were obtained from patients who underwent cardiac surgery ( n = 10). Clinical outcome was collected in patients treated medically ( n = 32). Among patients with intense signal with LS who underwent surgery ( n = 6), five had an abscess confirmed during intervention and one, post-operatively. Patients with intense accumulation of radiolabelled leucocytes with scintigraphy and treated medically ( n = 3) had a poor outcome: death ( n = 1); prosthetic valve dehiscence ( n = 1); and recurrent endocarditis ( n = 1). Among patients with mild activity with LS ( n = 5), one patient developed a large prosthetic valve dehiscence during the follow-up. The remaining four patients were treated medically and did not present any recurrent endocarditis after a median follow-up of 14 months. No abscess was detected in patients with negative LS who underwent surgery ( n = 4). Among the patients with negative LS treated medically ( n = 24), none presented recurrent endocarditis after a mean follow-up of 15 ± 16 months. Patient management was influenced by the results of LS in 12 out of 42 patients (29%). Conclusion This study suggests that LS is useful for the identification of perivalvular infection in patients with a suspicion of PVE and inconclusive TEE.

There is currently no medical therapy that can prevent the progression of aortic valve stenosis (AS). Recent data highlight a possible relationship between bone metabolism and AS progression but prospective data are lacking.Serum levels of calcium, phosphorus, creatinine, 25-OH vitamin D, intact parathyroid hormon (iPTH), C-terminal-telopeptide of type-1-collagen (CTX) and osteocalcin were assessed at baseline in 110 elderly patients (age ≥70 years) with at least mild AS. CTX/osteocalcin ratio was calculated as a marker of bone remodelling balance. AS severity was assessed at baseline and 1-year based on the mean gradient. Two-thirds of patients had low 25-OH vitamin D and 20% had secondary hyperparathyroidism. AS progression was not associated with age, glomerular filtration rate (GFR), calcium and phosphorus levels, calcium-phosphorus product, but significantly with iPTH, CTX/osteocalcin and vitamin D status (all P0.01). There was no correlation between iPTH and CTX/osteocalcin (R = 0.04, P = 0.70) and AS progression was associated with CTX/osteocalcin (R = 0.42, P = 0.009), but not with iPTH (R = 0.10, P = 0.55) in patients with normal vitamin D levels, whereas it was associated with iPTH (R = 0.47, P0.001) and not with CTX/osteocalcin (R = 0.04, P = 0.73) in those with low vitamin D levels, especially if mild renal insufficiency was present (R = 0.61, P0.001).In elderly patients with AS, we observed an association between AS progression and vitamin D, iPTH and CTX/osteocalcin ratio and their respective influence varied according to the vitamin D status. In patients with normal vitamin D levels, AS progression was associated with a bone resorptive balance, whereas in patients with low vitamin D levels, AS progression was associated with iPTH and secondary hyperparathyroidism, especially if mild renal insufficiency was present. These findings may have important prognostic and therapeutic implications. Trial registration information: Clinicaltrials.gov identifier number: NCT00338676, funded by AP-HP, the COFRASA study.

International audience; BACKGROUND: Human immunodeficiency virus (HIV)-infected patients have decreased immune response to vaccines. Few data are available about pandemic flu vaccination in this population. METHODS: We conducted a multicenter, patient-blinded, randomized trial in a cohort of HIV-infected adults. Patients received 2 injections 21 days apart of a AS03(A)-adjuvanted H1N1v vaccine containing 3.75 μg hemagglutinin (HA) or a nonadjuvanted H1N1v vaccine containing 15 μg HA to assess hemagglutination inhibition (HI) response and safety. RESULTS: A total of 309 patients were randomized, and 306 were vaccinated. After the first vaccine dose, HI titers ≥1:40 were observed in 93.4% of the patients in the adjuvanted group (A group) (n = 155) and in 75.5% in the nonadjuvanted group (B group) (n = 151) (P < .001); seroconversion rates were 88.8% and 71.2%, and factor increases in geometric mean titers (GMT) of 21.9 and 15.1, respectively. After 2 injections, 98.6% of patients of the A group and 92.1% of the B group demonstrated HI titers ≥1:40 (P = .018); seroconversion rates were 96.5% and 87.1%, respectively, and factor increases in GMT were 45.5 and 21.2, respectively. The majority of adverse events were mild to moderate in severity; no impact on CD4+ cell count or viral load has been detected. CONCLUSIONS: In HIV-1-infected adults, the AS03(A)-adjuvanted H1N1v vaccine yielded a higher immune response than did the nonadjuvanted one, with no impact on HIV infection.

Immune reconstitution inflammatory syndrome (IRIS) occurred in 16 of 37 antiretroviral-naive patients who were treated subsequently for tuberculosis and human immunodeficiency virus (HIV) type 1 infection. IRIS was related to increases in the CD4 cell percentage and in the ratio of CD4 cells to CD8 cells after 1 month of antiretroviral therapy and to dissemination of tuberculosis. These results have implications for the diagnosis of IRIS and the understanding of its pathogenesis.

8 Unite ´ de Maladies Infectieuses et Tropicales, Hotel-Dieu, Nantes, France Risk factors associated with the occurrence of protease inhibitor (PI)-related severe and serious adverse drug reactions (SADRs) were analyzed in a prospective cohort of 1155 patients who initiated PI-containing therapy. During a total follow-up of 2037 patient-years, 169 SADRs were reported, yielding a rate of 8 incidents per 100 patient-years (95% confidence interval (CI), 6.8-8.6). The most frequent SADRs were elevated transaminase levels (in 49 events); renal colic (27); abnormal hematological findings (23); and metabolic (18), neuromuscular (7), pancreatic (6), cutaneous (6), cardiovascular (5), and psychiatric disorders (5). Among baseline charac- teristics, plasma human immunodeficiency virus RNA levels of 5l og 10 copies/mL (hazard ratio (HR), 1.5; 95% CI, 1.1-2.2), elevated aspartate aminotransferase levels (HR, 1.1 for each 20 IU of elevation; 95% CI, 1.1- 1.2), creatinine clearance levels of !70 mL/min (HR, 2.1; 95% CI, 1.2-3.7), test results positive for hepatitis C virus antibodies or hepatitis B surface antigenemia (HR, 2.6; 95% CI, 1.8-3.7), and receipt of indinavir (HR, 1.7; 95% CI, 1.2-2.4) were independently predictive of a SADR. SADRs were frequent in the first 4 months after initiation of highly active antiretroviral therapy but continued to occur after that time period.

To describe characteristics of infective endocarditis (IE) in pacemaker (PM) recipients, including the annual incidence and exact localization of IE on PM leads, cardiac valves, or both, we prospectively analyzed 45 PM recipients from a group of 559 patients with definite IE who responded to a population-based survey conducted in France in 1999. Thirty-three patients had definite PM-lead IE (group I), and 12 had valvular IE without evidence of PM involvement (group II). The valvular structure was involved in almost two-thirds of IE cases among PM recipients. Of the 28 patients (62%) with valvular IE, 10 group I patients had tricuspid involvement, and 6 group I patients had left heart-valve involvement. The most frequent causative organisms in groups I and II were staphylococci (82%) and streptococci (50%), respectively. The incidence of age- and sex-standardized IE was 550 cases/million PM recipients per year. The incidence of IE with PM involvement is between that of valvular IE in the general population and prosthetic valve IE.

To evaluate factors associated with durable viral suppression (DVS), low viral rebound (virus load of 500-5000 copies/mL), and high viral rebound (virus load above 5000 copies/mL), we studied 3736 patients who achieved an undetectable virus load (i.e.