Publications by authors named "Nicolas Lefebvre"

33 Publications

Revised version (INFD-D-20-00242): impact of 16S rDNA sequencing on clinical treatment decisions: a single center retrospective study.

BMC Infect Dis 2021 Feb 18;21(1):190. Epub 2021 Feb 18.

Maladies Infectieuses et Tropicales, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

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.
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http://dx.doi.org/10.1186/s12879-021-05892-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890971PMC
February 2021

The BASIC Score: A Useful Tool to Identify Patients at High Risk of Early Progression to Severe Coronavirus Disease 2019.

Open Forum Infect Dis 2020 Oct 1;7(10):ofaa405. Epub 2020 Sep 1.

CHU de Strasbourg, Department of Infectious and Tropical Diseases, Strasbourg, France.

We developed a score, with easily accessible data (age, sex, body mass index, dyspnea, inflammatory parameters), to predict the risk of rapid progression to severe coronavirus disease 2019. Using a cutoff of >6 points, the negative predictive value was 87%.
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http://dx.doi.org/10.1093/ofid/ofaa405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499730PMC
October 2020

Clinical characteristics and risk factors associated with severe COVID-19: prospective analysis of 1,045 hospitalised cases in North-Eastern France, March 2020.

Euro Surveill 2020 12;25(48)

CHU de Strasbourg, Department of Infectious and Tropical Diseases; Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Strasbourg, France.

BackgroundIn March 2020, the COVID-19 outbreak was declared a pandemic by the World Health Organization.AimOur objective was to identify risk factors predictive of severe disease and death in France.MethodsIn this prospective cohort study, we included patients ≥ 18 years old with confirmed COVID-19, hospitalised in Strasbourg and Mulhouse hospitals (France), in March 2020. We respectively compared patients who developed severe disease (admission to an intensive care unit (ICU) or death) and patients who died, to those who did not, by day 7 after hospitalisation.ResultsAmong 1,045 patients, 424 (41%) had severe disease, including 335 (32%) who were admitted to ICU, and 115 (11%) who died. Mean age was 66 years (range: 20-100), and 612 (59%) were men. Almost 75% of patients with body mass index (BMI) data (n = 897) had a BMI ≥ 25 kg/m2 (n = 661). Independent risk factors associated with severe disease were advanced age (odds ratio (OR): 1.1 per 10-year increase; 95% CrI (credible interval): 1.0-1.2), male sex (OR: 2.1; 95% CrI: 1.5-2.8), BMI of 25-29.9 kg/m2 (OR: 1.8; 95% CrI: 1.2-2.7) or ≥ 30 (OR: 2.2; 95% CrI: 1.5-3.3), dyspnoea (OR: 2.5; 95% CrI: 1.8-3.4) and inflammatory parameters (elevated C-reactive protein and neutrophil count, low lymphocyte count). Risk factors associated with death were advanced age (OR: 2.7 per 10-year increase; 95% CrI: 2.1-3.4), male sex (OR: 1.7; 95% CrI: 1.1-2.7), immunosuppression (OR: 3.8; 95% CrI: 1.6-7.7), diabetes (OR: 1.7; 95% CrI: 1.0-2.7), chronic kidney disease (OR: 2.3; 95% CrI: 1.3-3.9), dyspnoea (OR: 2.1; 95% CrI: 1.2-3.4) and inflammatory parameters.ConclusionsOverweightedness, obesity, advanced age, male sex, comorbidities, dyspnoea and inflammation are risk factors for severe COVID-19 or death in hospitalised patients. Identifying these features among patients in routine clinical practice might improve COVID-19 management.
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http://dx.doi.org/10.2807/1560-7917.ES.2020.25.48.2000895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716399PMC
December 2020

Cerebrospinal Fluid Features in Patients With Coronavirus Disease 2019 and Neurological Manifestations: Correlation with Brain Magnetic Resonance Imaging Findings in 58 Patients.

J Infect Dis 2021 02;223(4):600-609

Service d'Imagerie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Background: Neurological manifestations are common in patients with coronavirus disease 2019 (COVID-19), but little is known about pathophysiological mechanisms. In this single-center study, we examined neurological manifestations in 58 patients, including cerebrospinal fluid (CSF) analysis and neuroimaging findings.

Methods: The study included 58 patients with COVID-19 and neurological manifestations in whom severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction screening and on CSF analysis were performed. Clinical, laboratory, and brain magnetic resonance (MR) imaging data were retrospectively collected and analyzed.

Results: Patients were mostly men (66%), with a median age of 62 years. Encephalopathy was frequent (81%), followed by pyramidal dysfunction (16%), seizures (10%), and headaches (5%). CSF protein and albumin levels were increased in 38% and 23%, respectively. A total of 40% of patients displayed an elevated albumin quotient, suggesting impaired blood-brain barrier integrity. CSF-specific immunoglobulin G oligoclonal band was found in 5 patients (11%), suggesting an intrathecal synthesis of immunoglobulin G, and 26 patients (55%) presented identical oligoclonal bands in serum and CSF. Four patients (7%) had a positive CSF SARS-CoV-2 reverse-transcription polymerase chain reaction. Leptomeningeal enhancement was present on brain MR images in 20 patients (38%).

Conclusions: Brain MR imaging abnormalities, especially leptomeningeal enhancement, and increased inflammatory markers in CSF are frequent in patients with neurological manifestations related to COVID-19, whereas SARS-CoV-2 detection in CSF remained scanty.
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http://dx.doi.org/10.1093/infdis/jiaa745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798956PMC
February 2021

3D-printed simulator for nasopharyngeal swab collection for COVID-19.

Eur Arch Otorhinolaryngol 2020 Nov 6. Epub 2020 Nov 6.

INSERM UMR-S 1121 'Biomaterials and Bioengineering', Strasbourg University, Strasbourg, France.

Introduction: Testing for COVID-19 is a cornerstone of pandemic control. If conducted inappropriately, nasopharyngeal swab collection can be painful and preanalytical sample collection errors may lead to false negative results. Our objective was to develop a realistic and easily available synthetic simulator for nasopharyngeal swab collection.

Materials And Methods: The nasopharyngeal swab collection simulator was designed through different development steps: segmentation, computer-aided design (CAD), and 3D printing. The model was 3D printed using PolyJet technology, which allows multi-material printing using hard and soft materials.

Results: The simulator splits in the parasagittal plane close to the septum to allow better visualization and understanding of nasal cavity landmarks. The model is able to simulate the softness and texture of different structural elements. The simulator allows the user to conduct realistic nasopharyngeal swab collection. A colored pad on the posterior wall of the nasopharynx provides real-time feedback to the user. The simulator also permits incorrect swab insertion, which is of obvious benefit from a training perspective. Comprehensive 3D files for printing and full instructions for manufacturing the simulator is freely available online via an open access link.

Conclusion: In the context of the COVID-19 pandemic, we developed a nasopharyngeal swab collection simulator which can be produced by 3D printing via an open access link, which offers complete operating instructions.
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http://dx.doi.org/10.1007/s00405-020-06454-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645909PMC
November 2020

Serologic responses to SARS-CoV-2 infection among hospital staff with mild disease in eastern France.

EBioMedicine 2020 Sep 31;59:102915. Epub 2020 Jul 31.

Institut Pasteur, Emerging Diseases Epidemiology Unit, Paris, France; Conservatoire National des Arts et Métiers, PACRI Unit, Paris, France.

Background: The serologic response of individuals with mild forms of SARS-CoV-2 infection is poorly characterized.

Methods: Hospital staff who had recovered from mild forms of PCR-confirmed SARS-CoV-2 infection were tested for anti-SARS-CoV-2 antibodies using two assays: a rapid immunodiagnostic test (99.4% specificity) and the S-Flow assay (~99% specificity). The neutralizing activity of the sera was tested with a pseudovirus-based assay.

Findings: Of 162 hospital staff who participated in the investigation, 160 reported SARS-CoV-2 infection that had not required hospital admission and were included in these analyses. The median time from symptom onset to blood sample collection was 24 days (IQR: 21-28, range 13-39). The rapid immunodiagnostic test detected antibodies in 153 (95.6%) of the samples and the S-Flow assay in 159 (99.4%), failing to detect antibodies in one sample collected 18 days after symptom onset (the rapid test did not detect antibodies in that patient). Neutralizing antibodies (NAbs) were detected in 79%, 92% and 98% of samples collected 13-20, 21-27 and 28-41 days after symptom onset, respectively (P = 0.02).

Interpretation: Antibodies against SARS-CoV-2 were detected in virtually all hospital staff sampled from 13 days after the onset of COVID-19 symptoms. This finding supports the use of serologic testing for the diagnosis of individuals who have recovered from SARS-CoV-2 infection. The neutralizing activity of the antibodies increased overtime. Future studies will help assess the persistence of the humoral response and its associated neutralization capacity in recovered patients.

Fundings: The funders had no role in study design, data collection, interpretation, or the decision to submit the work for publication.
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http://dx.doi.org/10.1016/j.ebiom.2020.102915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502660PMC
September 2020

CT lung lesions as predictors of early death or ICU admission in COVID-19 patients.

Clin Microbiol Infect 2020 Oct 24;26(10):1417.e5-1417.e8. Epub 2020 Jul 24.

Department of Infectious Disease, Strasbourg University Hospital, Strasbourg, France.

Objective: The main objective of this study was to investigate the prognostic value of early systematic chest computed tomography (CT) with quantification of lung lesions in coronavirus disease 2019 (COVID-19) patients.

Methods: We studied 572 patients diagnosed with COVID-19 (confirmed using polymerase chain reaction) for whom a chest CT was performed at hospital admission. Visual quantification was used to classify patients as per the percentage of lung parenchyma affected by COVID-19 lesions: normal CT, 0-10%, 11-25%, 26-50%, 51-75% and >75%. The primary endpoint was severe disease, defined by death or admission to the intensive care unit in the 7 days following first admission.

Results: The mean patient age was 66.0 ± 16.0 years, and 343/572 (60.0%) were men. The primary endpoint occurred in 206/572 patients (36.0%). The extent of lesions on initial CT was independently associated with prognosis (odds ratio = 2.35, 95% confidence interval 1.24-4.46; p < 0.01). Most patients with lung involvement >50% (66/95, 69.5%) developed severe disease compared to patients with lung involvement of 26-50% (70/171, 40.9%) and ≤25% (70/306, 22.9%) (p < 0.01 and p < 0.01, respectively). None of the patients with normal CT (0/14) had severe disease.

Conclusion: Chest CT findings at admission are associated with outcome in COVID-19 patients.
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http://dx.doi.org/10.1016/j.cmi.2020.07.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378475PMC
October 2020

Rapid Radiological Worsening and Cytokine Storm Syndrome in COVID-19 Pneumonia.

Eur J Case Rep Intern Med 2020 2;7(7):001822. Epub 2020 Jul 2.

Department of Infectious Diseases, Strasbourg University Hospital, Strasbourg, France.

Background: In June 2020, a large randomised controlled clinical trial in the UK found that dexamethasone was effective in reducing the number of deaths in patients with severe coronavirus disease 2019 (COVID-19).

Case Description: We describe a patient with rapid worsening of COVID-19 pneumonia and its dramatic improvement under corticosteroids.

Discussion: Corticosteroids could be useful in patients with an inflammatory profile, considering that acute respiratory distress syndrome may be the consequence of cytokine storm syndrome.

Learning Points: One of the main pathophysiological hypotheses for severe COVID-19 pneumonia is inappropriate immunological hyperactivation.Corticosteroid therapy may be useful in these patients.
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http://dx.doi.org/10.12890/2020_001822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350974PMC
July 2020

Brain MRI Findings in Severe COVID-19: A Retrospective Observational Study.

Radiology 2020 11 16;297(2):E242-E251. Epub 2020 Jun 16.

From the Hôpitaux Universitaires de Strasbourg, Service d'Imagerie 2, Hôpital de Hautepierre, Strasbourg, France (S.K.).

Background Brain MRI parenchymal signal abnormalities have been associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Purpose To describe the neuroimaging findings (excluding ischemic infarcts) in patients with severe coronavirus disease 2019 (COVID-19) infection. Materials and Methods This was a retrospective study of patients evaluated from March 23, 2020, to April 27, 2020, at 16 hospitals. Inclusion criteria were () positive nasopharyngeal or lower respiratory tract reverse transcriptase polymerase chain reaction assays, () severe COVID-19 infection defined as a requirement for hospitalization and oxygen therapy, () neurologic manifestations, and () abnormal brain MRI findings. Exclusion criteria were patients with missing or noncontributory data regarding brain MRI or brain MRI showing ischemic infarcts, cerebral venous thrombosis, or chronic lesions unrelated to the current event. Categorical data were compared using the Fisher exact test. Quantitative data were compared using the Student test or Wilcoxon test. < .05 represented a significant difference. Results Thirty men (81%) and seven women (19%) met the inclusion criteria, with a mean age of 61 years ± 12 (standard deviation) (age range, 8-78 years). The most common neurologic manifestations were alteration of consciousness (27 of 37, 73%), abnormal wakefulness when sedation was stopped (15 of 37, 41%), confusion (12 of 37, 32%), and agitation (seven of 37, 19%). The most frequent MRI findings were signal abnormalities located in the medial temporal lobe in 16 of 37 patients (43%; 95% confidence interval [CI]: 27%, 59%), nonconfluent multifocal white matter hyperintense lesions seen with fluid-attenuated inversion recovery and diffusion-weighted sequences with variable enhancement, with associated hemorrhagic lesions in 11 of 37 patients (30%; 95% CI: 15%, 45%), and extensive and isolated white matter microhemorrhages in nine of 37 patients (24%; 95% CI: 10%, 38%). A majority of patients (20 of 37, 54%) had intracerebral hemorrhagic lesions with a more severe clinical presentation and a higher admission rate in intensive care units (20 of 20 patients [100%] vs 12 of 17 patients without hemorrhage [71%], = .01) and development of the acute respiratory distress syndrome (20 of 20 patients [100%] vs 11 of 17 patients [65%], = .005). Only one patient had SARS-CoV-2 RNA in the cerebrospinal fluid. Conclusion Patients with severe coronavirus disease 2019 and without ischemic infarcts had a wide range of neurologic manifestations that were associated with abnormal brain MRI scans. Eight distinctive neuroradiologic patterns were described. © RSNA, 2020.
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http://dx.doi.org/10.1148/radiol.2020202222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301613PMC
November 2020

The Good, the Bad, and the Hoax: When Publication Instantaneously Impacts Treatment Strategies for COVID-19.

Antimicrob Agents Chemother 2020 07 22;64(8). Epub 2020 Jul 22.

CHU de Strasbourg, Service de Maladies Infectieuses et Tropicales, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Strasbourg, France.

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http://dx.doi.org/10.1128/AAC.01127-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526849PMC
July 2020

Rat Bite Fever.

N Engl J Med 2019 Oct;381(18):1762

Nouvel Hôpital Civil, Strasbourg, France

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http://dx.doi.org/10.1056/NEJMicm1905921DOI Listing
October 2019

Impact of Setting up an "Endocarditis Team" on the Management of Infective Endocarditis.

Open Forum Infect Dis 2019 Sep 16;6(9):ofz308. Epub 2019 Jul 16.

Department of Infectious Disease, Strasbourg University Hospital, Strasbourg, France.

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; = .27) and sequelae, along with a significant reduction in time to surgery (16.4 vs 10.3 days, respectively; = .049), duration of antibiotic therapy (55.2 vs 47.2 days, respectively; < .001), and length of in-hospital stay (40.6 vs 31.9 days, respectively; < .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; = .048).

Conclusions: This multidisciplinary approach exerted a positive impact on the management of IE and should be considered in all hospitals managing IE.
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http://dx.doi.org/10.1093/ofid/ofz308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735925PMC
September 2019

Virulence of beta-hemolytic streptococci in infective endocarditis.

Infection 2020 Feb 13;48(1):91-97. Epub 2019 Sep 13.

Department of Infectious Disease, Strasbourg University Hospital, Strasbourg, France.

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.
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http://dx.doi.org/10.1007/s15010-019-01358-7DOI Listing
February 2020

Safety and efficacy of percutaneous instrumentation combined with antibiotic treatment in spondylodiscitis.

Orthop Traumatol Surg Res 2019 10 27;105(6):1165-1170. Epub 2019 Aug 27.

Service de chirurgie du Rachis, hôpitaux universitaires de Strasbourg, 67200 Strasbourg, France.

Background: Patients with spondylodiscitis are treated with antibiotics and braces for 6 to 12 weeks. Braces aim to decrease pain and prevent kyphotic deformity due to vertebral body collapse. Percutaneous instrumentation could be an alternative to influence pain and patient's autonomy.

Purpose: The purpose of this study was to analyze back pain, quality of life, sagittal deformity, and complications after percutaneous instrumentation in spondylodiscitis.

Patients And Methods: VAS for back pain, EQ-5D, radiographic sagittal index were assessed retrospectively for 28 patients who had a standardized follow-up at 5 days, 6 weeks, 3 months, 1 and 2 years. Probabilities>0.95 indicated significant changes (Bayesian model).

Results: VAS was 7.0 preoperatively, 3.2 (day 5), 2.2 (6 weeks), 1.9 (3 months), 1.6 (1 year), 1.4 (2 years): probabilities>0.95 within 6 weeks. EQ-5D was 0.229 preoperatively, 0.563 (6 weeks), 0.687 (3 months), 0.755 (1 year), 0.787 (2 years): probabilities>0.95 within 1 year. Sagittal index was 15.1° preoperatively, 9.6° postoperatively: probability>0.95. Inter-body fusion was: complete 60.7%, partial 17.9%, and nonunion 21.4%. Antibiotic treatment was stopped at 6 weeks in 82.1%, at 3 months in 17.9%, without septic complication.

Conclusion: Percutaneous instrumentation improved pain control, quality of life and prevented kyphosis. Antibiotic treatment was not influenced. Septic complications were not observed.

Level Of Evidence: IV.
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http://dx.doi.org/10.1016/j.otsr.2019.05.016DOI Listing
October 2019

Evaluation of the reverse transcription strand invasion based amplification (RT-SIBA) RSV assay, a rapid molecular assay for the detection of respiratory syncytial virus.

Diagn Microbiol Infect Dis 2019 Sep 26;95(1):55-58. Epub 2019 Apr 26.

Univ Lille, Faculté de Médecine, CHU Lille, Laboratoire de Virologie EA3610, F-59000 Lille, France. Electronic address:

Respiratory syncytial virus (RSV) causes acute respiratory infections. Rapid RSV diagnosis has an impact on patient management. In a newly developed molecular assay, named reverse transcription strand invasion based amplification (RT-SIBA) RSV assay, RSV RNA is reverse transcribed to cDNA and amplified and detected under isothermal reaction conditions. The performance of this assay was evaluated. Respiratory samples that tested positive (n = 81) or negative (n = 61) for RSV with the multiplex RT-PCR Anyplex II RV16 Detection Kit (Anyplex) were analyzed with the RT-SIBA assay. Discordant samples were tested with the GeneXpert Flu/RSV XC assay. Consistent results in at least 2 of the 3 methods were defined as reference standard. The RT-SIBA assay yielded a negative result for the 61 negative samples and a positive result in 71/81 (85.5%) of the Anyplex positive samples. After a resolution of discordant samples, the positive and negative percent agreement of the RT-SIBA assay were 92% and 100%, respectively. The RT-SIBA assay is a rapid molecular assay for the detection of RSV with good performance in clinical specimens.
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http://dx.doi.org/10.1016/j.diagmicrobio.2019.04.006DOI Listing
September 2019

Bone penetration of daptomycin in diabetic patients with bacterial foot infections.

Int J Infect Dis 2019 Aug 13;85:127-131. Epub 2019 May 13.

Hôpitaux Universitaires, Institut de Bactériologie, Strasbourg, France.

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.
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http://dx.doi.org/10.1016/j.ijid.2019.05.011DOI Listing
August 2019

Value of PCR, Serology, and Blood Smears for Human Granulocytic Anaplasmosis Diagnosis, France.

Emerg Infect Dis 2019 05;25(5):996-998

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.
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http://dx.doi.org/10.3201/eid2505.171751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478229PMC
May 2019

Spondylodiscitis due to Aerococcus urinae and literature review.

Infection 2018 Jun 16;46(3):419-421. Epub 2018 Feb 16.

Service des Maladies infectieuses et Tropicales, Hopitaux Universitaires de Strasbourg, 1 place de l'hôpital, 67000, Strasbourg, France.

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.
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http://dx.doi.org/10.1007/s15010-017-1106-0DOI Listing
June 2018

Determinants of site of tuberculosis disease: An analysis of European surveillance data from 2003 to 2014.

PLoS One 2017 20;12(11):e0186499. Epub 2017 Nov 20.

European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden.

Background: We explored host-related factors associated with the site of tuberculosis (TB) disease using variables routinely collected by the 31 EU/EEA countries for national surveillance.

Methods: Logistic regression models were fitted to case-based surveillance data reported to the European Centre for Disease Prevention and Control for TB cases notified from 2003 to 2014. Missing data on HIV infection and on susceptibility to isoniazid and rifampicin for many patients precluded the inclusion of these variables in the analysis. Records from Finland, Lithuania, Spain and the United Kingdom were excluded for lack of exact details of disease localisation; other records without one or more variable (e.g. previous treatment history, geographical origin) or who had mixed pulmonary and extrapulmonary disease or more than one form of extrapulmonary disease were also removed (total exclusion = 38% of 913,637 notifications).

Results: 564,916 TB cases reported by 27 EU/EEA countries had exclusive pulmonary (PTB; 83%) or extrapulmonary (EPTB; 17%) disease. EPTB was associated with age <15 years (aOR: 5.50), female sex (aOR: 1.60), no previous TB treatment (aOR: 3.10), and geographic origin (aOR range: 0.52-3.74). Origin from the Indian subcontinent or Africa was most strongly associated with lymphatic, osteo-articular and peritoneal/digestive localization (aOR>3.7), and age <15 years with lymphatic (aOR: 17.96) and central nervous system disease (aOR: 11.41).

Conclusions: Awareness of host-related determinants of site of TB is useful for diagnosis. The predilection for EPTB among patients originating from countries outside Europe may reflect strain preferences for disease localization, geographic/ethnic differences in disease manifestation and other factors, like HIV.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186499PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695811PMC
December 2017

Pulmonary Cystic Echinococcosis.

Am J Trop Med Hyg 2017 09;97(3):641-642

Hôpitaux Universitaires, Maladies Infectieuses et Tropicales, Strasbourg, France.

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http://dx.doi.org/10.4269/ajtmh.17-0298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5590611PMC
September 2017

Clinical usefulness of F-FDG PET/CT for initial staging and assessment of treatment efficacy in patients with lymph node tuberculosis.

Nucl Med Biol 2017 Jul 8;50:17-24. Epub 2017 Apr 8.

Department of Biophysic and Nuclear Medicine, University Hospital of Strasbourg And University of Strasbourg, Strasbourg, France.

Introduction: Few studies have evaluated the promising role of F-fluoro-2-deoxy-D-glucose positron emission tomography (PET) and PET/computed tomography FDG PET/CT in evaluating and monitoring treatment response in patients with lymph node tuberculosis (LNTB). The aim of this clinical investigation was to assess the clinical usefulness of FDG PET/CT for initial tuberculosis staging and to determine the prognostic value of the decrease of F-FDG uptake during antibiotic treatment in LNTB patients.

Methods: We retrospectively reviewed 18 cases of LNTB admitted at a single center from 2004 to 2014. Medical records of patients who underwent two FDG PET/CT (>6 months interval), at initial staging and at the end of therapy were reviewed to determine the impact of FDG PET/CT on initial management of LNTB and response to therapy. Statistical analysis was performed using linear mixed-effects model.

Results: Thirteen cases of disseminated LNTB and five cases of localized LNTB were included in the study. Initial FDG PET/CT allowed guided biopsy for initial diagnosis in 5 patients and identified unknown extra-LN TB sites in 9 patients. Visual analysis follow-up of FDG PET/CT showed a complete metabolic response in 9/18 patients (all of whom were cured), a partial response in 7/18 (5 of whom were cured) and no response in 2/18 (all of whom were not cured). The semi-quantitative evaluation of 18F-FDG intensity decrease based on the maximum standardized uptake value (SUVmax), compared to targeted estimated decrease allowed to predict correctly a complete response to treatment in 14/18 cases.

Conclusion: FDG PET/CT allows an accurate pre-therapeutic mapping of LNTB and helps for early TB confirmation. The SUVmax follow up is a potential tool for monitoring the treatment response.
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http://dx.doi.org/10.1016/j.nucmedbio.2017.04.003DOI Listing
July 2017

Cayor worm removal... made simple!

J Travel Med 2016 Apr 4;23(4). Epub 2016 May 4.

Tropical and Infectious Diseases Department, University Hospital of Strasbourg, 1, place de l'hôpital, Nouvel Hôpital Civil, Strasbourg, France.

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http://dx.doi.org/10.1093/jtm/taw025DOI Listing
April 2016

First Case of Human Cerebral Taenia martis Cysticercosis.

J Clin Microbiol 2015 Aug 27;53(8):2756-9. Epub 2015 May 27.

Laboratoire de Parasitologie et de Mycologie Médicale, Plateau Technique de Microbiologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France Institut de Parasitologie et Pathologie Tropicale, Fédération de Médecine Translationelle, Université de Strasbourg, Strasbourg, France.

Taenia martis is a tapeworm affecting mustelids, with rodents serving as intermediate hosts. The larval stage (cysticercus) has been found before only rarely in humans or primates. We hereby describe a case of cerebral T. martis cysticercosis in a French immunocompetent patient, confirmed by DNA analyses of biopsy material.
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http://dx.doi.org/10.1128/JCM.01033-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508436PMC
August 2015

Implementation of Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry in Routine Clinical Laboratories Improves Identification of Coagulase-Negative Staphylococci and Reveals the Pathogenic Role of Staphylococcus lugdunensis.

J Clin Microbiol 2015 Jul 15;53(7):2030-6. Epub 2015 Apr 15.

Laboratoire de Microbiologie, Hôpitaux Universitaires, Strasbourg, France.

The use of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for staphylococcal identification is now considered routine in laboratories compared with the conventional phenotypical methods previously used. We verified its microbiological relevance for identifying the main species of coagulase-negative staphylococci (CoNS) by randomly selecting 50 isolates. From 1 January 2007 to 31 August 2008, 12,479 staphylococci were isolated with phenotypic methods, of which 4,594 were identified as Staphylococcus aureus and 7,885 were coagulase negative staphylococci. Using MALDI-TOF MS from 1 January 2011 to 31 August 2012, 14,913 staphylococci were identified, with 5,066 as S. aureus and 9,847 as CoNS. MALDI-TOF MS allowed the identification of approximately 85% of the CoNS strains, whereas only 14% of the CoNS strains were identified to the species level with phenotypic methods because they were often considered contaminants. Furthermore, the use of MALDI-TOF MS revealed the occurrence of recently characterized Staphylococcus species, such as S. pettenkoferi, S. condimenti, and S. piscifermentans. Microbiological relevance analysis further revealed that some species displayed a high rate of microbiological significance, i.e., 40% of the S. lugdunensis strains included in the analysis were associated with infection risk. This retrospective microbiological study confirms the role of MALDI-TOF MS in clinical settings for the identification of staphylococci with clinical consequences. The species distribution reveals the occurrence of the recently identified species S. pettenkoferi and putative virulent species, including S. lugdunensis.
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http://dx.doi.org/10.1128/JCM.00177-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4473201PMC
July 2015

Primary musculoskeletal hydatid cyst of the thigh: Diagnostic and curative challenge for an unusual localization.

Can J Infect Dis Med Microbiol 2013 ;24(3):e99-e101

Service des maladies infectieuses, centre hospitalo-universitaire de Strasbourg, Strasbourg, France.

Primary muscular echinococcosis is an uncommon localization of hydatid cysts. The nonspecific clinical presentation and possible post-therapeutic complications lead to problems for the diagnosis of this infection and the support of the patient. The authors describe an unusual case of double hydatid cyst of the vastus intermedius muscle. After a precise preoperative evaluation based on clinical, radiological and biological examinations, a surgical excision by pericystectomy combined with perioperative chemotherapy enabled the authors to treat the patient and to prevent postoperative complications. The diagnostic tools and the treatment of this particular type of echinococcosis are discussed.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3852467PMC
http://dx.doi.org/10.1155/2013/829471DOI Listing
January 2014

Cerebral vasculitis associated with Schistosoma mansoni infection.

BMC Infect Dis 2012 Sep 14;12:220. Epub 2012 Sep 14.

Unité des Maladies Infectieuses, Centre Hospitalier Universitaire La Réunion, Site Sud, BP 350, 97448, Saint-Pierre, Ile de la Réunion, France.

Background: Cerebral involvement in schistosomiasis is not rare, but it is underdiagnosed because of the lack of clinical suspicion and the frequency of asymptomatic forms. Neurologic complications are generally supported by granuloma formation around ectopic eggs which have migrated to the brain. Moreover, vascular lesions and cerebral arteritis have been well documented in histopathological studies. Nevertheless, cerebral vasculitis in later stages of the Schistosoma mansoni infection have not yet been described in living subjects.

Case Presentation: A 28-year-old french woman had a stroke linked with cerebral vasculitis, 6 monthes after returning from Burkina-Faso. At the same time, a S. mansoni disseminated infection was diagnosed. She suffered from a new stroke after undertaking praziquantel therapy, which lead us to associate the S. mansoni infection and cerebral vasculitis.

Conclusion: This is the first report of such association, since cerebral vasculitis has never been described in later stages of the S. mansoni infection. Although the causal link between the two pathologies could not be proved, we suggest that S. mansoni is able to cause severe vascular damage in cerebral vessels. Schistosomiasis must be investigated in the event of a brain infarct in young people, particularly in patients originating or returning from an endemic area.
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http://dx.doi.org/10.1186/1471-2334-12-220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3482565PMC
September 2012

Impact of malnutrition and social determinants on survival of HIV-infected adults starting antiretroviral therapy in resource-limited settings.

AIDS 2012 Jun;26(9):1161-6

Department of Infectious Diseases, Nouvel Hopital Civil, Strasbourg, France.

Objectives: Determining the impact of malnutrition, anaemia and social determinants on survival once starting antiretroviral therapy (ART) in a cohort of HIV-infected adults in a rural HIV care centre in Sihanoukville, Cambodia.

Methods: Retrospective and descriptive cohort study of adults starting ART between December 2004 and July 2009. We used the Kaplan-Meier and Cox regression survival analyses to identify predictors of death.

Results: Out of 1002 patients, 49.7% were men; median age was 40; median time of follow-up was 2.4 years and 10.4% died during the follow-up. At baseline, median CD4 cell count was 83 cells/μl, 79.9% were at WHO stage III or IV. In multivariate analysis, malnutrition appeared to be a strong and independent risk factor of death; 11.2% had a BMI less than 16 kg/m and hazard ratio was 6.97 [95% confidence interval (CI), 3.51-13.89], 21.5% had a BMI between 16 and 18 kg/m and hazard ratio was 2.88 (95% CI, 1.42-5.82), 30.8% had a BMI between 18 and 20 kg/m and hazard ratio was 2.18 (95% CI, 1.09-4.36). Severe anaemia (haemoglobin≤8.4 g/dl) and CD4 cell count below 100 cells/μl also predicted mortality, hazard ratio were 2.25 (95% CI, 1.02-4.34) and 2.29 (95% CI, 1.01-2.97), respectively. Social determinants were not significantly associated with death in univariate analysis.

Conclusion: Malnutrition and anaemia are strong and independent prognostic factors at the time of starting ART. Nutritional cares are essential for the clinical success of HIV programs started in developing countries.
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http://dx.doi.org/10.1097/QAD.0b013e328353f363DOI Listing
June 2012