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Intravesical instillation of Bacilli Calmette Guérin (BCG) as a superficial bladder cancer treatment is generally well tolerated, but local or systemic complications may occur, some of which may be life-threatening. Following the suspicion of post-BCG cystitis in a 72-year-old man with a history of urothelial carcinoma treated by intravesical BCG instillation, we used fluorescence in situ hybridization (FISH) targeting the rpoB gene of the Mycobacterium tuberculosis complex to detect Mycobacterium bovis BCG in paraffin-embedded bladder biopsy sections. FISH yielded specific detection of BCG mycobacteria in the bladder biopsy section, appearing as red-fluorescent bacilli. Treatment with rifampicin, ethambutol and isoniazid is then initiated in combination with corticosteroid therapy.

Background: Blood culture-negative endocarditis (BCNE) is a diagnostic challenge, therefore our objective was to pinpoint high-risk cohorts for BCNE., Methods: The study included adult patients with definite endocarditis. Data were collected via the Infectious Diseases International Research Initiative (ID-IRI). The study analysing one of the largest case series ever reported was conducted across 41 centers in 13 countries. We analysed the database to determine the predictors of BCNE using univariate and logistic regression analyses., Results: Blood cultures were negative in 101 (11.65 %) of 867 patients. We disclosed that as patients age, the likelihood of a negative blood culture significantly decreases (OR 0.975, 95 % CI 0.963-0.987, p < 0.001). Additionally, factors such as rheumatic heart disease (OR 2.036, 95 % CI 0.970-4.276, p = 0.049), aortic stenosis (OR 3.066, 95 % CI 1.564-6.010, p = 0.001), mitral regurgitation (OR 1.693, 95 % CI 1.012-2.833, p = 0.045), and prosthetic valves (OR 2.539, 95 % CI 1.599-4.031, p < 0.001) are associated with higher likelihoods of negative blood cultures. Our model can predict whether a patient falls into the culture-negative or culture-positive groups with a threshold of 0.104 (AUC±SE = 0.707 ± 0.027). The final model demonstrates a sensitivity of 70.3 % and a specificity of 57.0 %., Conclusion: Caution should be exercised when diagnosing endocarditis in patients with concurrent cardiac disorders, particularly in younger cases., Competing Interests: None to declare., (© 2024 Published by Elsevier Ltd.)

Context: In 2007, we performed a nationwide prospective study to assess the epidemiology of encephalitis in France. We aimed to evaluate epidemiological changes 10years later., Methods: We performed a 4-year prospective cohort study in France (ENCEIF) from 2016 to 2019. Medical history, comorbidities, as well as clinical, biological, imaging, and demographic data were collected. For the comparison analysis, we selected similar data from adult patients enrolled in the 2007 study. We used Stata statistical software, version 15 (Stata Corp). Indicative variable distributions were compared using Pearson's Chi 2 test, and means were compared using Student's t-test for continuous variables., Results: We analyzed 494 cases from 62 hospitals. A causative agent was identified in 65.7% of cases. Viruses represented 81.8% of causative agents, Herpesviridae being the most frequent (63.6%). Arboviruses accounted for 10.8%. Bacteria and parasites were responsible for respectively 14.8% and 1.2% of documented cases. Zoonotic infections represented 21% of cases. When comparing ENCEIF with the 2007 cohort (222 adults patients from 59 hospitals), a higher proportion of etiologies were obtained in 2016-2019 (66% vs. 53%). Between 2007 and 2016-2019, the proportions of Herpes simplex virus and Listeria encephalitis cases remained similar, but the proportion of tuberculosis cases decreased (P=0.0001), while tick-borne encephalitis virus (P=0.01) and VZV cases (P=0.03) increased. In the 2016-2019 study, 32 causative agents were identified, whereas only 17 were identified in the 2007 study., Conclusion: Our results emphasize the need to regularly perform such studies to monitor the evolution of infectious encephalitis and to adapt guidelines., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: PCRs targeting 16S ribosomal DNA (16S PCR) followed by Sanger's sequencing can identify bacteria from normally sterile sites and complement standard analyzes, but they are expensive. We conducted a retrospective study in the Strasbourg University Hospital to assess the clinical impact of 16S PCR sequencing on patients' treatments according to different sample types., Methods: From 2014 to 2018, 806 16S PCR samples were processed, and 191 of those were positive., Results: Overall, the test impacted the treatment of 62 of the 191 patients (32%). The antibiotic treatment was rationalized in 31 patients (50%) and extended in 24 patients (39%), and an invasive procedure was chosen for 7 patients (11%) due to the 16S PCR sequencing results. Positive 16S PCR sequencing results on cerebrospinal fluid (CSF) had a greater impact on patients' management than positive ones on cardiac valves (p = 0.044). The clinical impact of positive 16S PCR sequencing results were significantly higher when blood cultures were negative (p < 0.001), and this difference appeared larger when both blood and sample cultures were negative (p < 0.001). The diagnostic contribution of 16S PCR was higher in patients with previous antibiotic treatment (p < 0.001)., Conclusion: In all, 16S PCR analysis has a significant clinical impact on patient management, particularly for suspected CSF infections, for patients with culture-negative samples and for those with previous antibiotic treatments.

JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML) in immunosuppressed patients. There is currently no effective specific antiviral treatment and PML management relies on immune restoration. Prognosis markers are crucially needed in this disease because of its high mortality rate. In this work, we investigated the compartmentalization of JCV strains as well as the humoral neutralizing response in various matrices to further understand the pathophysiology of PML and define markers of survival. Four patients were included, of which three died in the few months following PML onset. Cerebrospinal fluid (CSF) viral loads were the highest, with plasma samples having lower viral loads and urine samples being mostly negative. Whether at PML onset or during follow-up, neutralizing antibody (NAb) titers directed against the same autologous strain (genotype or mutant) were the highest in plasma, with CSF titers being on average 430-fold lower and urine titers 500-fold lower at the same timepoint. Plasma NAb titers against autologous genotype or mutant were lower in non-survivor patients, though no neutralization "blind spot" was observed. The surviving patient was followed up until nine months after PML onset and presented, at that time, an increase in neutralizing titers, from 38-fold against the autologous genotype to around 200-fold against PML mutants. Our results suggest that patients' humoral neutralizing response against their autologous strain may play a role in PML outcome, with survivors developing high NAb titers in both plasma and CSF.

Objective: Risk factors associated with treatment failure after the infectious disease specialist's (IDS) advice remain unknown. We aimed to identify these risk factors., Methods: We included patients hospitalized in our tertiary care center who consulted an infectious disease specialist between January 2013 and April 2015. Treatment failure was defined by a composite criterion: signs of sepsis beyond Day 3, ICU admission, or death. Treatment success was defined by the patient's sustained clinical improvement., Results: A total of 240 IDS recommendations were made. Diagnosis was changed for 64 patients (26.7%) and 50 patients experienced treatment failure after the IDS advice. In multivariate analysis, compliance with the IDS advice was associated with a higher rate of success (OR=0.09, 95%CI [0.01-0.67]). Variables associated with treatment failure in the multivariate analysis were Charlson comorbidity score at admission (OR=1.24, 95%CI [1.03-1.50]), a history of infection or colonization with multidrug-resistant bacteria (OR=8.27, 95%CI [1.37-49.80]), and deterioration of the patient's status three days after the IDS advice (OR=12.50, 95%CI [3.16-49.46])., Conclusion: Reassessing IDS recommendations could be interesting for specific patients to further adapt and improve them., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

We aimed to develop a scoring system for predicting in-hospital mortality of community-acquired (CA) sepsis patients. This was a prospective, observational multicenter study performed to analyze CA sepsis among adult patients through ID-IRI (Infectious Diseases International Research Initiative) at 32 centers in 10 countries between December 1, 2015, and May 15, 2016. After baseline evaluation, we used univariate analysis at the second and logistic regression analysis at the third phase. In this prospective observational study, data of 373 cases with CA sepsis or septic shock were submitted from 32 referral centers in 10 countries. The median age was 68 (51-77) years, and 174 (46,6%) of the patients were females. The median hospitalization time of the patients was 15 (10-21) days. Overall mortality rate due to CA sepsis was 17.7% (n = 66). The possible predictors which have strong correlation and the variables that cause collinearity are acute oliguria, altered consciousness, persistent hypotension, fever, serum creatinine, age, and serum total protein. CAS (%) is a new scoring system and works in accordance with the parameters in third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). The system has yielded successful results in terms of predicting mortality in CA sepsis patients.

Background: Streptococci involved in infective endocarditis (IE) primarily comprise alpha- or non-hemolytic streptococci (ANHS). Moreover, beta-hemolytic streptococci (BHS) can be involved, and guidelines recommend the addition of gentamicin for the first 2 weeks of treatment and the consideration of early surgery in such cases. This study compared the morbidity and mortality associated with IE depending on the microorganisms involved (BHS, ANHS, staphylococci, and enterococci)., Methods: We conducted a retrospective observational study between 2012 and 2017 in a single hospital in France. The endpoints were overall in-hospital mortality, 1-year mortality and the occurrence of complications., Results: We analyzed 316 episodes of definite IE including 150 (38%), 96 (25%), 46 (12%), and 24 cases (6%) of staphylococcal, ANHS, enterococcal, and BHS IE, respectively. In-hospital mortality was significantly higher in the staphylococcal (n = 40; 26.7%) and BHS groups (n = 6; 25.0%) than in the ANHS (n = 9; 9.4%) and enterococcal groups (n = 5; 10.9%) (all p < 0.01). The rates of septic shock and cerebral emboli were also higher in the BHS group than in the ANHS group [n = 7 (29.2%) vs. n = 3 (3.1%), p < 0.001; n = 7 (29.2%) vs. n = 12 (12.5%); p = 0.05, respectively]., Conclusion: This study confirmed that BHS IE has a more severe prognosis than ANHS IE. The virulence of BHS may be similar to that of staphylococci, justifying increased monitoring of these patients and more 'aggressive' treatments such as early surgery.

Introduction: Multidrug-resistant tuberculosis (MDR-TB) is a major public health problem with great regional disparities. The aim of this study was to describe the epidemiological, clinical, and therapeutics aspects of MDR-TB in Alsace, France., Patients and Methods: A 10 years retrospective study, conducted for the years 2006 to 2016, of all MDR-TB cases diagnosed in Alsace and particularly in Strasbourg University Hospitals., Results: We included 22 patients with MDR-TB of whom 90% originated from Eastern Europe, 13.6% had extensively-resistant strains, and 41% reported previously treated tuberculosis. Clinically, 86,4% had a pulmonary form of tuberculosis. The mean length of antibiotic treatment was 21 months with several changes of drugs because of severe side effects. The mean follow-up was 48 months, during which time 2 patients were lost from contact and the 20 remaining patients were cured., Conclusions: Management of MDR-TB is a real social and medical challenge. Our study shows that the therapeutic protocols used in the management of these patients lead to an unusually high rate of success despite the occurrence of several, sometimes severe, side effects., (Copyright © 2019 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Staphylococcus lugdunensis is a commensal bacterium of human skin that has emerged as a virulent Coagulase-Negative Staphylococcus in both community-acquired and healthcare associated infections. Genotyping methods have shown a clonal population structure of this pathogen but failed to identify hypervirulent lineages. Here, complete genomes of three pathogenic and three carriage S. lugdunensis strains were obtained by Single-Molecule sequencing (PacBio) and compared to 15 complete genomes available in GenBank database. The aim was to identify (i) genetic determinants specific to pathogenic or carriage strains or specific to clonal complexes (CCs) defined by MultiLocus Sequence Typing, and (ii) antibiotic resistance genes and new putative virulence factors encoded or not by mobile genetic elements (MGE). Comparative genomic analysis did not show a strict correlation between gene content and the ability of the six strains to cause infections in humans and in a Galleria mellonella infection model. However, this study identified new MGEs (five prophages, two genomic islands and one plasmid) and genetic variations of some putative virulence-associated loci , especially in CC3 strains. For a clonal population, high variability and eight CC-dependent genetic organizations were observed for the ess locus , which encodes a putative type VII secretion system (T7SS) homologous to that of S. aureus . Further phenotypic and functional studies are needed to characterize this particular CC3 and to evaluate the role of T7SS in the virulence of S. lugdunensis ., (Copyright © 2019 Lebeurre, Dahyot, Diene, Paulay, Aubourg, Argemi, Giard, Tournier, François and Pestel-Caron.)

Infective endocarditis is a growing problem with many shifts due to ever-increasing comorbid illnesses, invasive procedures, and increase in the elderly. We performed this multinational study to depict definite infective endocarditis. Adult patients with definite endocarditis hospitalized between January 1, 2015, and October 1, 2018, were included from 41 hospitals in 13 countries. We included microbiological features, types and severity of the disease, complications, but excluded therapeutic parameters. A total of 867 patients were included. A total of 631 (72.8%) patients had native valve endocarditis (NVE), 214 (24.7%) patients had prosthetic valve endocarditis (PVE), 21 (2.4%) patients had pacemaker lead endocarditis, and 1 patient had catheter port endocarditis. Eighteen percent of NVE patients were hospital-acquired. PVE patients were classified as early-onset in 24.9%. A total of 385 (44.4%) patients had major embolic events, most frequently to the brain (n = 227, 26.3%). Blood cultures yielded pathogens in 766 (88.4%). In 101 (11.6%) patients, blood cultures were negative. Molecular testing of vegetations disclosed pathogens in 65 cases. Overall, 795 (91.7%) endocarditis patients had any identified pathogen. Leading pathogens (Staphylococcus aureus (n = 267, 33.6%), Streptococcus viridans (n = 149, 18.7%), enterococci (n = 128, 16.1%), coagulase-negative staphylococci (n = 92, 11.6%)) displayed substantial resistance profiles. A total of 132 (15.2%) patients had cardiac abscesses; 693 (79.9%) patients had left-sided endocarditis. Aortic (n = 394, 45.4%) and mitral valves (n = 369, 42.5%) were most frequently involved. Mortality was more common in PVE than NVE (NVE (n = 101, 16%), PVE (n = 49, 22.9%), p = 0.042).

We report an unusual case of a 53-year-old woman who presented with multiple lung cystic lesions presumed to be related to pulmonary hydatidosis, treated and followed for 3 years before surgical removal was decided. Unexpectedly, pathologic findings showed benign spindle cell proliferation. Immunohistochemical staining confirmed the smooth-muscle nature of the spindle cells, which were also positive for hormonal receptors and corresponded to multiple cystic pulmonary hamartomas., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: Daptomycin has shown clinical efficacy in diabetic foot infections (DFI). However, only limited data are available on its bone penetration in this particular population. The aim of this study was to determine daptomycin bone concentrations in patients with DFI undergoing surgery after multiple daptomycin infusions and to determine bone daptomycin inhibitory quotients (IQs) for the predominant gram-positive species involved in DFI., Methods: Fourteen adult patients hospitalized with DFI treated with daptomycin and requiring surgical bone debridement and amputation were included in this single-centre prospective study. Daptomycin concentrations in serum and bone were determined by HPLC at steady state. Bone IQs were then calculated according to different minimum inhibitory concentrations (MICs; range 0.25-4mg/l) that are representative of the main MICs for Staphylococcus aureus, coagulase-negative staphylococci (CoNS), and Enterococcus sp populations., Results: Residual and peak concentrations varied from 4.5mg/l to 39.9mg/l and from 31.8mg/l to 110.9mg/l, respectively. Bone daptomycin concentrations at the moment of surgery varied from 1.2mg/l to 17mg/l. Up to a MIC of 1mg/l, which is the epidemiological cut-off value (ECOFF) and breakpoint value for S. aureus and CoNS, all bone daptomycin IQs were positive. The highest bone IQs were observed with Staphylococcus species. Calculated bone IQs for Enterococcus species were often weak at MIC values near the ECOFF., Conclusions: Daptomycin penetrates bone well in patients treated for DFI. At an initially recommended dosage of 6mg/kg, bone concentrations are likely to be effective against staphylococcal infections and infections due to low-MIC Enterococcus., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Intravesical BCG is the standard treatment of non-muscle invasive bladder cancer. No difference has yet been reported in the safety profiles of the various BCG strains., Methods: A nationwide multidisciplinary retrospective survey was conducted between January 2013 and December 2016 to identify cases of BCG infection and differentiate them based on the type of BCG strain used., Results: Forty patients were identified (BCG RIVM 28; other strains 8; unknown 4). Patients treated with BCG RIVM were less severely ill, with fewer occurrences of septic shock (3.6% vs. 50%, P=0.003) and ICU admission (7.1% vs. 62.5%, P=0.003). A higher frequency of pulmonary miliaries (71.4% vs. 12.5%, P=0.005) but lower transaminase levels (mean AST 65 vs. 264 U/L, P=0.001) were observed in these patients. No difference in terms of recovery was reported., Conclusion: The type of BCG strain could correlate with the frequency and severity of subsequent BCG infections., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Introduction: Mesenteric lymph node cavitation is an exceptional complication of celiac disease. We report four original observations of this syndrome, completed by a literature review., Discussion: The analysis of 38 cases showed that this complication occurred exclusively in adults, with a mean age at diagnosis of 54 years. It revealed the celiac disease in the majority of cases. Hyposplenism was almost systematically associated. The risk of lymphoma appeared higher, especially enteropathy-associated T-cell lymphoma. The prognosis was poor with nearly 50% mortality and seemed related to the clinical response to the gluten-free diet., Conclusion: The severity of this complication deserves to be known and should lead to its research in celiac patients, especially in cases diagnosed in adulthood or in case of refractory disease., (Copyright © 2019 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Tick-borne encephalitis virus (TBEV) is a zoonotic agent causing severe encephalitis. The transmission cycle involves the virus, the Ixodes tick vector, and a vertebrate reservoir, such as small mammals (rodents, or shrews). Humans are accidentally involved in this transmission cycle. Tick-borne encephalitis (TBE) has been a growing public health problem in Europe and Asia over the past 30 years. The mechanisms involved in the development of TBE are very complex and likely multifactorial, involving both host and viral factors. The purpose of this review is to provide an overview of the current literature on TBE neuropathogenesis in the human host and to demonstrate the emergence of common themes in the molecular pathogenesis of TBE in humans. We discuss and review data on experimental study models and on both viral (molecular genetics of TBEV) and host (immune response, and genetic background) factors involved in TBE neuropathogenesis in the context of human infection.

Background: Infective endocarditis (IE) remains a severe disease with a high mortality rate. Therefore, guidelines encourage the setup of a multidisciplinary group in reference centers. The present study evaluated the impact of this "Endocarditis Team" (ET)., Methods: We conducted a monocentric observational study at Strasbourg University Hospital, Strasbourg, France, between 2012 and 2017. The primary end point was in-hospital mortality. Secondary end points were 6-month and 1-year mortality, surgery rate, time to surgical procedure, duration of effective antibiotic therapy, length of in-hospital stay, and sequelae. We also assessed predictors of in-hospital mortality., Results: We analyzed 391 episodes of IE. In the post-ET period, there was a nonsignificant decrease in in-hospital mortality (20.3% vs 14.7%, respectively; P = .27) and sequelae, along with a significant reduction in time to surgery (16.4 vs 10.3 days, respectively; P = .049), duration of antibiotic therapy (55.2 vs 47.2 days, respectively; P < .001), and length of in-hospital stay (40.6 vs 31.9 days, respectively; P < .01). In a multivariate analysis, the post-ET period was positively associated with survival (odds ratio, 0.45; 95% confidence interval, 0.20-0.96; P = .048)., Conclusions: This multidisciplinary approach exerted a positive impact on the management of IE and should be considered in all hospitals managing IE., (© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Staphylococcus lugdunensis is increasingly recognized as a potent pathogen, responsible for severe infections with an outcome resembling that of Staphylococcus aureus . Here, we developed and evaluated a tool for S. lugdunensis typing, using DNA sequence analysis of the repeat-encoding region (R-domain) in the gene encoding the fibrinogen (Fg)-binding protein Fbl ( fbl -typing). We typed 240 S. lugdunensis isolates from various clinical and geographical origins. The length of the R-domain ranged from 9 to 52 repeats. fbl -typing identified 54 unique 18-bp repeat sequences and 92 distinct fbl -types. The discriminatory power of fbl -typing was higher than that of multilocus sequence typing (MLST) and equivalent to that of tandem repeat sequence typing. fbl -types could assign isolates to MLST clonal complexes with excellent predictive power. The ability to promote adherence to immobilized human Fg was evaluated for 55 isolates chosen to reflect the genetic diversity of the fbl gene. We observed no direct correlation between Fg binding ability and fbl -types. However, the lowest percentage of Fg binding was observed for isolates carrying a 5'-end frameshift mutation of the fbl gene and for those harboring fewer than 43 repeats in the R-domain. qRT-PCR assays for some isolates revealed no correlation between fbl gene expression and Fg binding capacity. In conclusion, this study shows that fbl -typing is a useful tool in S. lugdunensis epidemiology, especially because it is an easy, cost-effective, rapid and portable method (http://fbl-typing.univ-rouen.fr/). The impact of fbl polymorphism on the structure of the protein, its expression on the cell surface and in virulence remains to be determined.

We prospectively examined the effectiveness of diagnostic tests for anaplasmosis using patients with suspected diagnoses in France. PCR (sensitivity 0.74, specificity 1) was the best-suited test. Serology had a lower specificity but higher sensitivity when testing acute and convalescent samples. PCR and serology should be used in combination for anaplasmosis diagnosis.

Coagulase-negative Staphylococci (CoNS) are skin commensal bacteria. Besides their role in maintaining homeostasis, CoNS have emerged as major pathogens in nosocomial settings. Several studies have investigated the molecular basis for this emergence and identified multiple putative virulence factors with regards to Staphylococcus aureus pathogenicity. In the last decade, numerous CoNS whole-genome sequences have been released, leading to the identification of numerous putative virulence factors. Koch's postulates and the molecular rendition of these postulates, established by Stanley Falkow in 1988, do not explain the microbial pathogenicity of CoNS. However, whole-genome sequence data has shed new light on CoNS pathogenicity. In this review, we analyzed the contribution of genomics in defining CoNS virulence, focusing on the most frequent and pathogenic CoNS species: S. epidermidis , S. haemolyticus, S. saprophyticus , S. capitis , and S. lugdunensis .

Neurosyphilis (NS) has different clinical manifestations and can appear during any stage of syphilis. We aimed to identify the factors affecting poor outcome in NS patients. Patients with positive cerebrospinal fluid Venereal Disease Research Laboratory test, and positive serological serum treponemal or nontreponemal tests were classified as definite NS. The data of 141 patients with definite NS were submitted from 22 referral centers. Asymptomatic NS, syphilitic meningitis, meningovascular syphilis, tabes dorsalis, general paresis, and taboparesis were detected in 22 (15.6%), 67 (47.5%), 13 (9.2%), 10 (7%), 13 (9.2%), and 16 patients (11.3%), respectively. The number of HIV-positive patients was 43 (30.4%). The most common symptoms were headache (n = 55, 39%), fatigue (n = 52, 36.8%), and altered consciousness (50, 35.4%). Tabetic symptoms were detected in 28 (19.8%), paretic symptoms in 32 (22.6%), and vascular symptoms in 39 patients (27.6%). Eye involvement was detected in 19 of 80 patients (23.7%) who underwent eye examination and ear involvement was detected in eight of 25 patients (32%) who underwent ear examination. Crystallized penicillin was used in 109 (77.3%), procaine penicillin in seven (4.9%), ceftriaxone in 31 (21.9%), and doxycycline in five patients (3.5%). According to multivariate regression analysis, while headache was a protective factor in NS patients, double vision was significantly associated to poor outcome. We concluded that double vision indicated unfavorable outcome among NS patients. A high clinical suspicion is needed for the diagnosis NS. As determined in our study, the presence of headache in syphilitic patients can help in early diagnosis of central nervous system disease.

Background: Opportunistic invasive fungal infections (IFIs) comprise a heterogeneous spectrum of pathogens, whose early diagnosis remains challenging. Candida spp. and Aspergillus spp, the most frequent pathogens in immunocompromised patients, frequently affect lungs, liver, bone and skin., Aim: To evaluate the impact of 18F-FDG PET/CT in the management of immunocompromised patients with IFI., Design: A single-center retrospective study included 51 immunocompromised patients with IFI diagnosis undergoing 83 18F-FDG PET/CTs., Methods: Twenty-nine 18F-FDG PET/CTs were performed for primary work-up in 29 treatment-naïve patients. Fifty-four PET/CTs were performed during follow-up to confirm IFI suspicion in 22 patients who had anti-fungal drug therapy before PET/CT. When available, histological and/or microbiological criteria were used to assess IFI diagnosis., Results: Aspergillus spp. and Candida spp. were the most frequent microorganisms responsible for IFI in our population. 18F-FDG PET/CT sensitivity, specificity, positive and negative predictive values, and global accuracy were 93%, 81%, 95%, 72% and 90%, respectively. 18F-FDG PET/CT influenced the diagnostic work-up at primary staging in 16/29 patients (55%) by assessing the extent of infection and targeting the diagnostic procedure. 18F-FDG PET/CT results during treatment induced anti-fungal drugs dosage increase and/or new drugs addition in 8/54 cases (15%) and contributed to the reduction of anti-fungal drugs dosage or treatment withdraws in 17 cases (31%)., Conclusions: We recommend the utilization of 18F-FDG PET/CT to improve the primary staging work-up of immunocompromised patients with IFI and to assess treatment effectiveness or disease relapse. Both 18F-FDG PET/CT and conventional imaging should be integrated into a well-defined imaging diagnostic algorithm considering the clinical context and both strengths and limitations of each diagnostic modality.

Background: Coagulase negative staphylococci (CoNS) are commensal bacteria on human skin. Staphylococcus lugdunensis is a unique CoNS which produces various virulence factors and may, like S. aureus, cause severe infections, particularly in hospital settings. Unlike other staphylococci, it remains highly susceptible to antimicrobials, and genome-based phylogenetic studies have evidenced a highly conserved genome that distinguishes it from all other staphylococci., Results: We demonstrate that S. lugdunensis possesses a closed pan-genome with a very limited number of new genes, in contrast to other staphylococci that have an open pan-genome. Whole-genome nucleotide and amino acid identity levels are also higher than in other staphylococci. We identified numerous genetic barriers to horizontal gene transfer that might explain this result. The S. lugdunensis genome has multiple operons encoding for restriction-modification, CRISPR/Cas and toxin/antitoxin systems. We also identified a new PIN-like domain-associated protein that might belong to a larger operon, comprising a metalloprotease, that could function as a new toxin/antitoxin or detoxification system., Conclusion: We show that S. lugdunensis has a unique genome profile within staphylococci, with a closed pan-genome and several systems to prevent horizontal gene transfer. Its virulence in clinical settings does not rely on its ability to acquire and exchange antibiotic resistance genes or other virulence factors as shown for other staphylococci.

Staphylococcus lugdunensis is an emergent virulent coagulase-negative Staphylococcus that is increasingly responsible for severe infections. In an attempt to generate informative sequence data for subtyping S. lugdunensis, we selected and sequenced seven polymorphic variable number of tandem repeats (VNTRs) to develop two new methods: a classic length-based multiple-locus VNTR analysis (MLVA) method and a tandem repeat sequence typing (TRST) method. We assessed their performances compared to two existing methods, multilocus sequence typing (MLST) and multivirulence-locus sequence typing (MVLST) for 128 isolates from diverse clinical settings and geographical origins. The clustering achieved by the four methods was highly congruent, with MLVA discriminating within clonal complexes as defined by MLST. Indeed, MLVA was highly discriminant compared to MLST and MVLST in terms of number of genotypes as well as diversity indexes. Sequencing of the seven VNTRs showed that they were stable, and analysis of sequence polymorphisms provided superior discriminatory power. The typeability, reproducibility, and epidemiological concordance of these new methods were excellent. Of note, no link between clustering and clinical settings was identified. This study demonstrates that MLVA and TRST provide valuable information for molecular epidemiological study of S. lugdunensis, and represent promising tools to distinguish between strains of homogenous lineages in this clonal species.

Cryptococcal meningitis (CM) is mostly seen in immunocompromised patients, particularly human immunodeficiency virus (HIV)-positive patients, but CM may also occur in apparently immunocompetent individuals. Outcome analyses have been performed in such patients but, due to the high prevalence of HIV infection worldwide, CM patients today may be admitted to hospitals with unknown HIV status, particularly in underdeveloped countries. The objective of this multicenter study was to analyze all types of CM cases in an aggregate cohort to disclose unfavorable outcomes. We retrospectively reviewed the hospitalized CM patients from 2000 to 2015 in 26 medical centers from 11 countries. Demographics, clinical, microbiological, radiological, therapeutic data, and outcomes were included. Death, neurological sequelae, or relapse were unfavorable outcomes. Seventy (43.8%) out of 160 study cases were identified as unfavorable and 104 (65%) were HIV infected. On multivariate analysis, the higher Glasgow Coma Scale (GCS) scores (p = 0.021), cerebrospinal fluid (CSF) leukocyte counts > 20 (p = 0.038), and higher CSF glucose levels (p = 0.048) were associated with favorable outcomes. On the other hand, malignancy (p = 0.026) was associated with poor outcomes. Although all CM patients require prompt and rational fungal management, those with significant risks for poor outcomes need to be closely monitored.

In the original version of this article, Mustafa Sunbul was not included in the list of authors for this article. The name has been added accordingly.

Introduction: Aerococccus urinae (AU) is a pathogen mainly identified in male urinary tract infections and responsible for bacteremia and endocarditis. To the best of our knowledge, there are only five patients with osteomyelitis due to AU described in the literature. All of them had urinary tract disease or systemic conditions such as diabetes, and two were associated with an endocarditis., Case Report: We described the first case of isolated spondylodiscitis without general or local predisposing condition, excepted age > 65 years.

Staphylococcus epidermidis is a leading cause of nosocomial infections, majorly resistant to beta-lactam antibiotics, and may transfer several mobile genetic elements among the members of its own species, as well as to Staphylococcus aureus ; however, a genetic exchange from S. aureus to S. epidermidis remains controversial. We recently identified two pathogenic clinical strains of S. epidermidis that produce a staphylococcal enterotoxin C3-like (SEC) similar to that by S. aureus pathogenicity islands. This study aimed to determine the genetic environment of the SEC-coding sequence and to identify the mobile genetic elements. Whole-genome sequencing and annotation of the S. epidermidis strains were performed using Illumina technology and a bioinformatics pipeline for assembly, which provided evidence that the SEC-coding sequences were located in a composite pathogenicity island that was previously described in the S. epidermidis strain FRI909, called SePI-1/SeCI-1, with 83.8-89.7% nucleotide similarity. Various other plasmids were identified, particularly p&#95;3&#95;95 and p&#95;4&#95;95, which carry antibiotic resistance genes ( hsrA and dfrG , respectively), and share homologies with SAP085A and pUSA04-2-SUR11, two plasmids described in S. aureus . Eventually, one complete prophage was identified, ΦSE90, sharing 30 out of 52 coding sequences with the Acinetobacter phage vB&#95;AbaM&#95;IME200. Thus, the SePI-1/SeCI-1 pathogenicity island was identified in two pathogenic strains of S. epidermidis that produced a SEC enterotoxin causing septic shock. These findings suggest the existence of in vivo genetic exchange from S. aureus to S. epidermidis ., Competing Interests: The authors declare no conflict of interest.

Objectives: Tick-borne encephalitis virus (TBEV) is a zoonotic agent causing severe encephalitis. In 2016, in Northeastern France, we faced a TBEV infection increase, leading to a warning from the Regional Health Agency. Here, we report the confirmed TBE cases diagnosed between January 2013 and December 2016, with particular emphasis on the year 2016., Methods: A total of 1643 blood and cerebrospinal fluid (CSF) samples from everywhere in France, corresponding to 1460 patients, were prospectively tested for anti-TBEV-specific IgM and IgG antibodies by ELISA. Additional 39 blood and CSF samples from patients with suspected Lyme neuroborreliosis were retrospectively investigated., Results: The TBEV seropositivity rate was estimated to 5.89% and 54 patients were diagnosed as TBE-confirmed cases. A significant increase in TBE cases was observed during the year 2016 with 29 confirmed cases, instead of a mean of eight cases during the three previous years (p=0.0006). Six imported cases and 48 autochthonous cases, located in the Alsace region (n=43) and in the Alpine region (n=5) were reported. Forty-six patients experienced neurological impairment. Nine patients showed an incomplete recovery at last follow-up (from 15days to eight months post-infection). TBE diagnosis was performed earlier for patients taken in charge in the Alsace region than those hospitalized elsewhere in France (p=0.0087). Among the 39 patients with suspected Lyme neuroborreliosis retrospectively investigated, one showed a TBEV recent infection., Conclusion: The TBE increase that occurred in France in 2016 highlights the need to improve our knowledge about the true burden of TBEV infection and subsequent long-term outcomes., (Copyright © 2017 Elsevier GmbH. All rights reserved.)