Evaluating the heart valve tissue diffusion of amoxicillin in infective endocarditis: a pilot prospective observational non-comparative study.

OBJECTIVES: Treating patients with infective endocarditis (IE) due to streptococci and enterococci currently involves high-dosage antibiotics. Recent literature suggests a 30%-70% diffusion rate could be extrapolated to human heart valve tissue. The objective of this study was to evaluate the diffusion coefficient of amoxicillin in heart valve tissue of patients operated for IE. METHODS: Adult patients were prospectively included that underwent surgery at the European Hospital Georges Pompidou for IE due to streptococci and enterococci and had previous IV amoxicillin treatment. Plasma (taken 48 h preoperatively) and heart valve tissue amoxicillin concentrations were measured with a validated LC-MS/MS method. The MIC values of amoxicillin were measured for all available isolates. RESULTS: Seventeen patients were included. Eleven (64.7%) patients had native valve IE and six (35.3%) had prosthetic valve IE. Fourteen IE cases (82.4%) were due to streptococci, one (5.9%) was due to enterococci and two (11.8%) were Haemophilus spp, Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae group infections. Median (IQR) amoxicillin dose administered was 10.5 (8.0-12.0) g/day corresponding to 138.2 (112.5-160.0) mg/kg/day. The median amoxicillin plasma concentrations pre-surgery and intra-tissular weighted concentrations were 31.9 (25.9-51.9) mg/L and 19.0 (7.9-31.4) µg/g, respectively. Median tissue/plasma concentration ratio was 0.47 (0.24-0.67), with a median amoxicillin plasma/MIC ratio of 487 (179-745), and median amoxicillin tissue/MIC ratio of 42 (14-116). CONCLUSIONS: With a significant diffusion coefficient, amoxicillin dosage in heart valve tissues showed a concentration/MIC ratio well above current recommendations for bactericidal activity. Our study suggests that lower doses can be considered for susceptible bacteria.

Prevalence and risk factors of toxigenic Clostridioides difficile asymptomatic carriage in 11 French hospitals.

Clostridioides difficile infection (CDI) incidence has increased over the last 20 years. Studies suggest that asymptomatic carriers may be an important reservoir of C. difficile in healthcare settings. We conducted a point prevalence study to estimate the toxigenic C. difficile asymptomatic carriage rate and the associated risk factors in patients >3 years old. Between September 16, 2019 and January 15, 2020, all patients hospitalized in 11 healthcare facilities in the Paris urban area were included in the study. They were screened on the day of the survey for toxigenic C. difficile carriage by rectal swab and interviewed. Isolates were characterized by PCR ribotyping and multiplex PCR targeting toxin genes. A logistic regression model was used to determine the risk factors associated with toxigenic C. difficile asymptomatic carriage using uni- and multivariate analysis in the subpopulation of patients >3 years old. During the study period, 2,389 patients were included and screened. The median age was 62 years (interquartile range 35-78 years) and 1,153 were male (48.3%). Nineteen patients had a previous CDI (0.9%). Overall, 185/2389 patients were positive for C. difficile (7.7%), including 93 toxigenic strains (3.9%): 77 (82.8%) were asymptomatic (prevalence 3.2%) whereas 12 (12.9%) were diarrheic. Prevalences of toxigenic C. difficile were 3.5% in patients >3 years old and 7.0% in ≤3 years old subjects, respectively. Toxigenic strains mainly belonged to PCR ribotypes 106 (n = 14, 15.0%), 014 (n = 12, 12.9%), and 020 (n = 10, 10.8%). Among toxigenic strains, 6 (6.4%) produced the binary toxin. In multivariate analysis, two factors were positively associated with toxigenic C. difficile asymptomatic carriage in patients >3 years old: multidrug-resistant organisms co-carriage [adjusted Odd Ratio (aOR) 2.3, CI 95% 1.2-4.7, p = 0.02] and previous CDI (aOR 5.8, CI 95% 1.2-28.6, p = 0.03). Conversely, consumption of raw milk products were associated with reduced risk of toxigenic C. difficile colonization (aOR 0.5, CI 95% 0.2-0.9, p = 0.01). We showed that there was a low prevalence of asymptomatic toxigenic C. difficile carriage in hospitalized patients. Consumption of raw milk prevents toxigenic C. difficile colonization, probably due to the barrier effect of milk-associated bacteria.

Comparison of the New VITEK MS PRIME System with the Matrix-Assisted Laser Desorption Ionization Biotyper Microflex LT for the Identification of Microorganisms.

Background: Matrix-assisted laser desorption ionization (MALDI) is the cornerstone of bacterial identification. The performance of a new MALDI time-of-flight mass spectrometry VITEK MS PRIME (VMS-P) system was compared with that of the MALDI Biotyper Microflex LT (MBT) system, which is routinely used in our laboratory. Methods: Sixteen bacterial and yeast reference strains cultured in 20 different media were analyzed over 10 consecutive rounds using both systems. Bacterial and yeast isolates from the routine workflow were processed using both systems. Microcolonies were identified after a 4-hour agar subculture from positive blood culture bottles, without extraction. Results: To determine the repeatability based on the reference strains, 1,190 spots were processed using each system. Correct identification was achieved for 94.0% (MBT) and 98.4% (VMS-P; P<0.01) of spots. Among these, 83.0% (MBT) and 100.0% (VMS-P) were identified with a high degree of confidence. For 1,214 spots from routine isolates, species identification was achieved for 90.0% (MBT) and 91.4% (VMS-P; P=0.26) of spots. For 69.8% (MBT) and 87.4% (VMS-P) of the spots, identification was achieved with a high degree-of-confidence score. When identification was performed using both systems, the agreement between them was 97.9%. The identification of microcolonies from positive blood culture bottles was achieved for 55.5% (MBT) and 70.2% (VMS-P; P=0.01) of spots. Conclusions: The MBT and VMS-P systems perform similarly in routine daily practice. The new VMS-P system shows high repeatability, better confidence scores for identification, and promising ability to identify microcolonies.

Frequency and factors associated with infusion-related local complications of vancomycin on peripheral venous catheters.

BACKGROUND: Vancomycin is a reference antibiotic against methicillin-resistant staphylococci. Its administration is associated with infusion-related local complications (IRLC). To reduce this risk, it has been proposed to increase vancomycin dilution in the IV bag and to perform continuous infusion using the volumetric pump. The aim of our study was to assess the safety of peripheral infusion of vancomycin with the volumetric pump. OBJECTIVES: To compare the frequency of IRLC between patients receiving vancomycin and those receiving ß-lactam (BL) antibiotics. Our secondary objective was to assess factors associated with the occurrence of IRLC. PATIENTS AND METHODS: We conducted a prospective observational study in a French tertiary hospital. Between February 2021 and November 2021, we included all patients receiving continuous infusions of vancomycin or BL through a peripherally inserted venous catheter (PIVC). The primary endpoint was the occurrence of IRLC on Day 1 (D1). RESULTS: We included 168 patients (56 vancomycin, 112 BL). At D1, 14 patients (25%) presented IRLC in the vancomycin group versus 11 patients (10%) in the BL group (P = 0.01). There was significantly more IRLC in the group receiving vancomycin at an infused concentration above 5 mg/mL than those receiving BL (8/15, 53.3% versus 11/112, 10%, respectively, P < 0.01). However, no significant difference was observed between patients receiving infused vancomycin concentration ≤5 mg/mL and patients receiving BL (P = 0.4). CONCLUSION: Our data support safe administration of vancomycin if infused at a concentration under 5 mg/mL, through the volumetric pump on PIVC.

Clinical and biological diagnosis and follow-up of patients treated for endovascular infections due to Coxiellaburnetii.

The objective of this study was to evaluate the effectiveness of the recommended treatment for endovascular infections due to Coxiella burnetii. This single-center retrospective study was conducted in 13 patients with endovascular infection due to C. burnetii between January 2001 and December 2020 for a definite or possible endovascular infection due to C. burnetii with a minimum follow-up of 18 months post-infection. Clinical and biological data, including serology, blood and tissue PCR results, doxycycline and hydroxychloroquine assays were collected. Among the 13 patients, 11 had endocarditis (8 definite and 3 possible) and 2 had a vascular infection. At the time of diagnosis, fever was present in only 46% of cases. In case of endocarditis, 73% of patients had a pathological echocardiography. Biologically, the CRP level was low (52 mg/l ± 44). Autoimmune antibodies (antinuclear factor, neutrophil anticytoplasm) were present in 23% of patients. At the time of diagnosis, tissue PCR was very sensitive (100%) unlike blood or serum (29%). Blood levels of doxycycline and hydroxychloroquine were within expected values. Only one patient experienced treatment failure at two years, requiring surgery. For the 7 patients whose phase I IgG titres fell below 1/800, a minimum of 18 months of treatment was necessary. In the long term, the clinical and biological cure was 100% and 92% respectively, underlining the importance of monitoring the serum dosages of doxycycline and hydroxychloroquine. Given its sensitivity, tissue PCR could be added to the major Duke criteria.

Use of specific agar plates for early detection of anaerobic bacteria in surgical site infections after spinal surgery: a prospective single centre study.

To determine if additional agar plates could allow earlier detection of anaerobes in spinal surgical site infections (SSIs), we performed a prospective study (November 2017-January 2019) of patients with early spinal SSIs. In addition to routine 14-day cultures, surgical samples were inoculated onto three additional plates (CDC anaerobe agar with 5% sheep blood [CDC], CDC anaerobe laked sheep blood agar with kanamycin/vancomycin [BBL], and Bacteroides bile esculin [BBE] agar with amikacin (BD, USA)) incubated under anaerobic conditions (72 h, 37°C). The primary endpoint was detection of anaerobes by these methods, as compared to routine culture. Anaerobes were identified in 7/61 patients (11%) using the routine procedure and in one extra case with additional plates (overall detection rate 8/61, 13%). Sensitivity was greater for the CDC plate than for the BBL and BBE plates. When routine culture was positive, the CDC plate was always positive, and in three cases showed at least one additional anaerobe. Using additional agar plates, anaerobes were identified in early spinal SSI in 13% of patients. Within 3 days, CDC agar plate enabled detection of anaerobes in one extra case and at least one additional anaerobe in three other cases, compared to routine 14-day culture.

Faecal carriage of multidrug-resistant bacteria and associated risk factors: results from a point prevalence study.

OBJECTIVES: Since 2003, incidences of carbapenemase-producing Gram-negative bacilli (CP-GNB) and vancomycin-resistant Enterococcus faecium (VRE) have steadily increased in France. We therefore conducted a point prevalence study to estimate carriage rates of CP-GNB, VRE and ESBL-producing Enterobacterales (ESBL-PE) and associated risk factors. METHODS: Between September 2019 and January 2020, all inpatients hospitalized on a given day in 11 teaching hospitals in the Paris urban area were eligible. Patient interviews and rectal swab screening results were recorded by dedicated nurses. The swabs were plated onto selective chromogenic media and processed using the GeneXpert® system. RESULTS: Of 2396 patients, 364 (15.2%) yielded at least one multiresistant bacterial isolate, including 29 CP-GNB carriers (1.2%), 13 VRE carriers (0.5%) and 338 ESBL-PE carriers (14%). In 15 patients (4.4% of ESBL-PE carriers and 36.6% of CP-GNB/VRE carriers), concomitant CP-GNB/VRE and ESBL-PE carriage was observed. In 7/29 CP-GNB and 7/13 VRE carriers, carbapenemase production and vanA in the screening samples was only detected with Xpert® tests. The OXA-48 gene was predominant in 13/34 CP-GNB isolates from 29 carriers. From the 338 ESBL-PE carriers, 372 isolates were recovered, mainly Escherichia coli (61.2%). Among 379 children, 1.1% carried a CP-GNB/VRE strain, and 12.4% carried an ESBL strain. Previous hospitalization outside mainland France, previous antimicrobial treatment and previous ESBL-PE carriage were the main risk factors associated with CP-GNB and/or VRE carriage. CONCLUSIONS: The low CP-GNB and VRE prevalence likely reflects the French policy to limit intrahospital spread of CP-GNB and VRE strains.

Analysis of Microbiota and Mycobiota in Fungal Ball Rhinosinusitis: Specific Interaction between Aspergillus fumigatus and Haemophilus influenza?

Fungal ball (FB) rhinosinusitis (RS) is the main type of non-invasive fungal RS. Despite positive direct examination (DE) of biopsies, culture remains negative in more than 60% of cases. The aim of the study was to evaluate the performance/efficacy of targeted metagenomics (TM) to analyze microbiota and mycobiota in FB and find microbial associations. Forty-five sinus biopsies from patients who underwent surgery for chronic RS were included. After DE and culture, DNA was extracted, then fungal ITS1-ITS2 and bacterial V3-V4 16S rDNA loci were sequenced (MiSeqTM Illumina). Operational taxonomic units (OTUs) were defined via QIIME and assigned to SILVA (16S) and UNITE (ITS) databases. Statistical analyses were performed using SHAMAN. Thirty-eight patients had FB and seven had non-fungal rhinosinusitis (NFRS). DE and culture of FB were positive for fungi in 97.3 and 31.6% of patients, respectively. TM analysis of the 38 FB yielded more than one fungal genus in 100% of cases, with Aspergillus in 89.5% (34/38). Haemophilus was over-represented in FB with >1000 reads/sample in 47.3% (18/38) compared to NFRS (p < 0.001). TM allowed fungal identification in biopsies with negative culture. Haemophilus was associated with FB. Pathogenesis could result from fungi-bacteria interactions in a mixed biofilm-like structure.

Assessment of version 2.5 of QMAC-dRAST for rapid antimicrobial susceptibility testing with reduced sample-to-answer turnaround time and an integrated expert system.

OBJECTIVE: To assess the performance of the new rapid antimicrobial susceptibility testing (AST) QMAC-dRAST V2.5 system. METHODS: ASTs were performed using QMAC-dRAST-V2.5 and a disk diffusion method, directly from positive blood bottles with Gram-negative bacteria. Discrepancies between the results obtained using the two methods were categorized into very major errors (VME, S with dRAST vs. R with disk diffusion), major errors (ME, R vs. S, respectively), minor errors (mE, S vs. I or I vs. R, respectively), and very minor errors (Vme, I vs. S or R vs. I, respectively). For each AST, results were recorded after 4, 5, and 6h of incubation. RESULTS: From 106 bacteremia, 1416 individual AST results were obtained. Overall agreement between results using the two methods was 91%, ranging from 76.9% to 99.1% depending upon the antibiotic, with 128 errors, i.e. 14/1416 (1%) VME, 59/1416 (4.2%) ME, 25/1416 (1.8%) mE and 30/1416 (2.1%) Vme. VMEs were encountered for Klebsiellasp and Serratia marcescens isolates with low-level piperacillin and amikacin resistance, respectively. Using the integrated QMAC-dRAST-V2.5 expert system, all 14 VMEs and 3 mEs were eliminated, leading to 92.2% categorical agreement. After 45min of pre-incubation in the QMAC-dRAST-V2.5 device, 22.2% of the 1416 AST results were obtained after 4h, an additional 31.4% after 5h and a further 46.3% after 6h. CONCLUSION: QMAC-dRAST-V2.5 is an optimized version of QMAC-dRAST V2.0, particularly with respect to utilization of an expert system and reduced TAT according to the antibiotic tested.

Mitral valve granulomatosis: A paradoxical reaction complicating etanercept treatment in rheumatoid arthritis. A case report.

BACKGROUND: "Sarcoidosis-like" paradoxical reactions to Antitumor necrosis factor α (anti-TNFα) treatment have been reported. The clinical presentations are varied, most of the time, with a relatively typical picture of mediastinopulmonary involvement. More rarely, isolated granulomatous locations from various organs are described, leading to difficulties in diagnosis. CASE PRESENTATION: We report a granulomatous cardiac valve location complicating etanercept treatment in a 26-years-old caucasian male with rheumatoid arthritis. The patient received leflunomide and low-dose corticosteroids, then etanercept was introduced because of persistent disease activity. He had no history of tuberculosis infection or contact, chest CT-scan was normal. At 3 months, he showed complete remission. After 6 months of etanercept treatment, the patient suddenly complained of headache with scotomas of the right visual field and vertigo, without fever. Cerebral MRI revealed 3 recent infarcts. Cardiac ultrasonography revealed a mobile mass on the posterior mitral leaflet. C-reactive protein level was 8mg/L, and all analyses were negative for an infectious agent. Leflunomide and etanercept were discontinued, and antibiotic therapy was started. Mitral valve resection and plasty were performed 2 days later. Histology of the valve revealed large non-caseating epithelioid granulomas with a suppurative-like necrotic center. After ruling out infectious endocarditis, sarcoidosis, rheumatoid valvulitis or lupus-like reaction induced by anti-TNF therapy, the diagnosis of a paradoxical reaction to etanercept was finally retained. Tocilizumab monotherapy was introduced to treat RA flare, no antibiotic preventive treatment was added. After 2 years, the patient was in remission. CONCLUSION: This case raises for the first time the possibility of a paradoxical adverse event with an isolated granulomatous reaction on the heart valve occurring with anti-TNF treatment, namely etanercept.

Performance of 30 commercial SARS-CoV-2 serology assays in testing symptomatic COVID-19 patients.

We report evaluation of 30 assays' (17 rapid tests (RDTs) and 13 automated/manual ELISA/CLIA assay (IAs)) clinical performances with 2594 sera collected from symptomatic patients with positive SARS-CoV-2 rRT-PCR on a respiratory sample, and 1996 pre-epidemic serum samples expected to be negative. Only 4 RDT and 3 IAs fitted both specificity (> 98%) and sensitivity (> 90%) criteria according to French recommendations. Serology may offer valuable information during COVID-19 pandemic, but inconsistent performances observed among the 30 commercial assays evaluated, which underlines the importance of independent evaluation before clinical implementation.

Analytical performances of five SARS-CoV-2 whole-blood finger-stick IgG-IgM combined antibody rapid tests.

Facing the ongoing pandemic caused by SARS-CoV-2, there is an urgent need for serological assays identifying individuals previously infected by coronavirus disease 2019 (COVID-19), including rapid diagnostic tests (RDTs). We herein compared five new CE-IVD-labeled commercially available SARS-CoV-2 whole-blood finger-stick IgG/IgM combined RDTs, in parallel according to the manufacturers' instructions, with two serum panels obtained from 48 patients with confirmed COVID-19 (panel I) and from a group of 52 patients randomly selected, for whom serum samples collected before the COVID-19 epidemic (from October 1 to November 30, 2019) were negative for SARS-CoV-2 IgG (panel II). We found a sensitivity of 95.8 %, 91.6 %, 92.3 %, 97.9 % and 91.4 %, and a specificity of 98.1 %, 86.5 %, 100 %, 98.1 % and 84.6 %, for BIOSYNEX COVID-19 BSS (IgG/IgM) (Biosynex Swiss SA, Freiburg, Switzerland), Humasis COVID-19 IgG/IgM Test (Humasis Co., Ltd., Gyneonggi, Republic of Korea), LYHER COVID-19 IgM/IgG Rapid Test (Medakit Ltd, Hong Kong, China), SIENNA™ COVID-19 (IgG/IgM) Rapid Test Cassette (Salofa Oy, Salo, Finland) and NG-BIOTECH COVID-19 (IgG/IgM) (NG-Biotech, Guipry, France), respectively. Commercially available SARS-CoV-2 IgG/IgM combined RDTs have a sufficient sensitivity for identifying individuals with past SARS-CoV-2 infection, but some RDTs may lack of specificity, with risk of false positivity mainly for the IgM band.

A Case of Phage Therapy against Pandrug-Resistant Achromobacter xylosoxidans in a 12-Year-Old Lung-Transplanted Cystic Fibrosis Patient.

Bacteriophages are a promising therapeutic strategy among cystic fibrosis and lung-transplanted patients, considering the high frequency of colonization/infection caused by pandrug-resistant bacteria. However, little clinical data are available regarding the use of phages for infections with Achromobacter xylosoxidans. A 12-year-old lung-transplanted cystic fibrosis patient received two rounds of phage therapy because of persistent lung infection with pandrug-resistant A. xylosoxidans. Clinical tolerance was perfect, but initial bronchoalveolar lavage (BAL) still grew A. xylosoxidans. The patient's respiratory condition slowly improved and oxygen therapy was stopped. Low-grade airway colonization by A. xylosoxidans persisted for months before samples turned negative. No re-colonisation occurred more than two years after phage therapy was performed and imipenem treatment was stopped. Whole genome sequencing indicated that the eight A. xylosoxidans isolates, collected during phage therapy, belonged to four delineated strains, whereby one had a stop mutation in a gene for a phage receptor. The dynamics of lung colonisation were documented by means of strain-specific qPCRs on different BALs. We report the first case of phage therapy for A. xylosoxidans lung infection in a lung-transplanted patient. The dynamics of airway colonization was more complex than deduced from bacterial culture, involving phage susceptible as well as phage resistant strains.

Optimization of a Top-Down Proteomics Platform for Closely Related Pathogenic Bacterial Discrimination.

The current technique used for microbial identification in hospitals is matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). However, it suffers from important limitations, in particular, for closely related species or when the database used for the identification lacks the appropriate reference. In this work, we set up a liquid chromatography (LC)-MS/MS top-down proteomics platform, which aims at discriminating closely related pathogenic bacteria through the identification of specific proteoforms. Using Escherichia coli as a model, all steps of the workflow were optimized: protein extraction, on-line LC separation, MS method, and data analysis. Using optimized parameters, about 220 proteins, corresponding to more than 500 proteoforms, could be identified in a single run. We then used this platform for the discrimination of enterobacterial pathogens undistinguishable by MALDI-TOF, although leading to very different clinical outcomes. For each pathogen, we identified specific proteoforms that could potentially be used as biomarkers. We also improved the characterization of poorly described bacterial strains. Our results highlight the advantage of addressing proteoforms rather than peptides for accurate bacterial characterization and qualify top-down proteomics as a promising tool in clinical microbiology. Data are available via ProteomeXchange with the identifier PXD019247.

Renal abscess caused by Panton-Valentine leukocidin-producing Staphylococcus aureus: report of an unusual case and review of the literature.

BACKGROUND: Renal abscesses are rare and mainly caused by an ascending infection due to Gram-negative microorganisms. We report the first case of a renal abscess caused by Panton-Valentine leukocidin-producing Staphylococcus aureus in an immunocompetent patient, and we present a comprehensive review of the literature. CASE PRESENTATION: A 20-year-old immunocompetent woman had a 2-month history of left-sided back pain, fever and urinary symptoms. Urinalysis showed leukocyturia (19,000/mm3) without bacteriuria. Intravenous cefotaxime treatment was initiated. A computed tomographic scan showed a large abscess in the left kidney. Computed tomographic percutaneous drainage was done and cultures of abscess and blood grew methicillin-susceptible Panton-Valentine leukocidin-producing Staphylococcus aureus. Treatment was switched to cefazoline and then to clindamycin for 21 days. The patient quickly improved and the abscess was completely resolved 6 months after end of antibiotic treatment. CONCLUSION: To our knowledge, this is the first report of a renal abscess caused by Panton-Valentine leukocidin-producing Staphylococcus aureus. Treatment with percutaneous drainage and an antibiotic with toxin inhibiting effect was successful.

Role of astroglial Connexin 43 in pneumolysin cytotoxicity and during pneumococcal meningitis.

Streptococcus pneumoniae or pneumococcus (PN) is a major causative agent of bacterial meningitis with high mortality in young infants and elderly people worldwide. The mechanism underlying PN crossing of the blood brain barrier (BBB) and specifically, the role of non-endothelial cells of the neurovascular unit that control the BBB function, remains poorly understood. Here, we show that the astroglial connexin 43 (aCx43), a major gap junctional component expressed in astrocytes, plays a predominant role during PN meningitis. Following intravenous PN challenge, mice deficient for aCx43 developed milder symptoms and showed severely reduced bacterial counts in the brain. Immunofluorescence analysis of brain slices indicated that PN induces the aCx43-dependent destruction of the network of glial fibrillary acid protein (GFAP), an intermediate filament protein specifically expressed in astrocytes and up-regulated in response to brain injury. PN also induced nuclear shrinkage in astrocytes associated with the loss of BBB integrity, bacterial translocation across endothelial vessels and replication in the brain cortex. We found that aCx4-dependent astrocyte damages could be recapitulated using in vitro cultured cells upon challenge with wild-type PN but not with a ply mutant deficient for the pore-forming toxin pneumolysin (Ply). Consistently, we showed that purified Ply requires Cx43 to promote host cell plasma membrane permeabilization in a process involving the Cx43-dependent release of extracellular ATP and prolonged increase of cytosolic Ca2+ in host cells. These results point to a critical role for astrocytes during PN meningitis and suggest that the cytolytic activity of the major virulence factor Ply at concentrations relevant to bacterial infection requires co-opting of connexin plasma membrane channels.

Unexpected diagnosis of COVID-19-associated disorders by SARS-CoV-2-specific serology.

Facing the ongoing pandemic caused by SARS-CoV-2, there is an urgent need for serological assays identifying individuals with on-going infection as well as past coronavirus infectious disease 2019 (COVID-19). We herein evaluated the analytical performances of the CE IVD-labeled Abbott SARS-CoV-2 IgG assay (Des Plaines, IL, USA) carried out with the automated Abbott Architect™ i2000 platform at Hôpital Européen Georges Pompidou, Paris, France, using serum sample panels obtained from health-workers with COVID-19 history confirmed by positive nucleic acid amplification-based diagnosis and from patients randomly selected for whom serum samples were collected before the COVID-19 epidemic. The Abbott SARS-CoV-2 IgG assay showed sensitivity of 94 % and specificity of 100 %, demonstrating high analytical performances allowing convenient management of suspected on-going and past-infections. In addition, the SARS-CoV-2 IgG positivity rates were compared in COVID-19 positive and COVID-19 free areas from our hospital. Thus, the frequency of SARS-CoV-2-specific IgG was around 10-fold higher in COVID-19 areas than COVID-19 free areas (75 % versus 8%; P < 0.001). Interestingly, several inpatients hospitalized in COVID-19 free areas suffering from a wide range of unexplained clinical features including cardiac, vascular, renal, metabolic and infectious disorders, were unexpectedly found seropositive for SARS-CoV-2 IgG by systematic routine serology, suggesting possible causal involvement of SARS-CoV-2 infection. Taken together, these observations highlight the potential interest of SARS-CoV-2-specific serology in the context of COVID-19 epidemic, especially to assess past SARS-CoV-2 infection as well as possible unexpected COVID-19-associated disorders.