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Most people living with HIV need antiretroviral therapy to control their infection and experience viral relapse in case of treatment interruption, because of viral reservoir (proviruses) persistence. Knowing that proviruses are very diverse and most of them are defective in treated individuals, we aimed to characterize the HIV blood reservoirs of posttreatment controllers (PTCs), rare models of drug-free remission, in comparison with spontaneous controllers and treated individuals.

It is not known whether the adverse events (AEs) associated with the administration of lopinavir and ritonavir (LPV/r) in the treatment of COVID-19 are concentration-dependent. In a retrospective study of 65 patients treated with LPV/r and therapeutic drug monitoring (TDM) for severe forms of COVID-19 (median age: 67; males: 41 [63.1%]), 33 (50.8%) displayed a grade ≥2 increase in plasma levels of hepatobiliary markers, lipase and/or triglycerides. A causal relationship between LPV/r and the AE was suspected in 9 of the 65 patients (13.8%). At 400 mg b.i.d., the plasma trough concentrations of LPV/r were high and showed marked interindividual variability (median [interquartile range]: 16,600 [11,430-20,842] ng/ml for lopinavir and 501 [247-891] ng/ml for ritonavir). The trough lopinavir concentration was negatively correlated with body mass index, while the trough ritonavir concentration was positively correlated with age and negatively correlated with prothrombin activity. However, the occurrence of abnormal laboratory values was not associated with higher trough plasma concentrations of LPV/r. Further studies will be needed to determine the value of TDM in LPV/r-treated patients with COVID-19.

In order to assess the measures involved in the control of tuberculosis in the Somme Department, France, five years after the implementation of the French National Tuberculosis Program, we found it essential to describe the precise epidemiology on this disease. All reported cases of tuberculosis between 2007 and 2011 were retrospectively included and a descriptive analysis of the incidence of the disease and patients’ characteristics was conducted. 175 cases were reported. After an increase in the incidence of TB (x105) between 2007 and 2008 from 5.8 to 6.8, it has steadily declined for 2 years (4.9 in 2010) before rising in 2011 with a record of 7.6. In 2010 and 2011, the incidence in children aged less than five years old, respectively 5.7 and 8.5 was greater than the incidence of the department (p=0.8). Approximately 7% of cases were diagnosed during an investigation around a case of tuberculosis and 6.3% in targeted screening. Among tuberculosis cases with pulmonary localization (145 cases), 57.7% patients had positive sputum smear. After the suspension of the compulsory BCG vaccination, particular attention must be paid in children during a screening procedure around a case of tuberculosis. Key words: Tuberculosis, epidemiology, Somme, France.

In France, the number of hospitals involved in clinical research and committed to a quality approach is increasing. The objective of such approaches is to ensure the safety of patients involved in research projects by improving quality.The University Hospital of Amiens has chosen to certify all its clinical research activities in the same scope according to the ISO 9001: 2015 standard.Action planning has been established and a head of quality management has been appointed to oversee this process.The activities in the five departments of our university hospital jointly certified in December 2019, are: activities related to internal and external sponsors, as well as methodology and monitoring of clinical research projects conducted in the Clinical Research and Innovation Department (CRID); help with clinical research investigations in the Clinical Research Center (CRC); management of the pathway of therapeutic units used in clinical research (excluding the manufacture of drugs) in the Clinical Trials Unit (CTU) of the Hospital Pharmacy; the conservation and provision of biological resources (tissues and fluids) for cancer research in the Tumor bank of Picardy; the collection, reception, preparation, quality control, conservation and provision of biological resources for research purposes. These activities fall within the framework of legal and regulatory activities and the provision of secure storage in the Biological Resources Center already ISO 9001 certified since 2004 and NF S96-900: 2011 certified since 2009.The choice of a common quality approach has brought together more than 70 persons from 5 departments involved in clinical research projects within a single certificate with the aim of continuous improvement.

Adrien Chan Sui Ko,1,* Alexandre Candellier,2,* Marie Mercier,3 Cedric Joseph,1 Hortense Carette,3 Damien Basille,3 Sylvie Lion-Daolio,4 Stephanie Devaux,3 Jean-Luc Schmit,1 Jean-Philippe Lanoix,1 Claire Andrejak3 1Department of Infectious Diseases, Centre Hospitalier Universitaire Amiens-Picardie, Amiens, 80054, France; 2Department of Nephrology, Centre Hospitalier Universitaire Amiens-Picardie, Amiens, 80054, France; 3Department of Pneumology, Centre Hospitalier Universitaire Amiens-Picardie, Amiens, 80054, France; 4Department of Orthopedy, Centre Hospitalier Universitaire Amiens-Picardie, Amiens, 80054, France*These authors contributed equally to this workCorrespondence: Adrien Chan Sui Ko, Department of Infectious Diseases, Centre Hospitalier Universitaire Amiens-Picardie, Amiens, 80054, France, Email chansuiko.adrien@chu-amiens.frAbstract: Persistent COVID-19 symptoms may be related to residual inflammation, but no preventive treatment has been evaluated. This study aimed to analyze, in a prospective cohort, whether corticosteroid use in the acute phase of COVID-19 in hospitalized patients may reduce the risk of persistent COVID-19 symptoms. A total of 306 discharged patients, including 112 (36.6%) from the ICU, completed a structured face-to-face assessment 4 months after admission. Of these, 193 patients (63.1%) had at least one persistent symptom, mostly dyspnea (38.9%) and asthenia (37.6%). One-hundred and four patients have received corticosteroids. In multivariable adjusted regression analysis, corticosteroid use was not associated with the presence of at least one symptom (OR=1.00, 95% CI: 0.58– 1.71, p=0.99) or with the number of persistent symptoms (p=0.74). Corticosteroid use remained ineffective when analyzing the ICU subpopulation separately. Our study suggests that corticosteroid use had no impact on persistent symptoms after COVID-19 in discharged patients.Keywords: COVID-19, persistent symptoms, corticosteroid use, long COVID-19, asthenia

Since December 2019, an emerging infectious viral disease implicating a coronavirus SARS-CoV-2 has caused a global pandemic. Elderly people, being more fragile, are the most affected by the severity and lethality of this disease. The NH and LTCU of the Amiens University Hospital registered their first Covid-19 cases in February 2020, which lead to the opening of a Covid-19 dedicated unit and of specific protocol for confinement. This descriptive study was analyzing the prevalence of Covid-19 seroconversion within the NH and the LTCU of the Amiens University Hospital. Both this screening test and the nasopharyngeal swab PCRs were in order to assess the impact of the Covid-19 epidemic in NH and LTCU. On June 15th and 16th, the serological tests for Covid-19 were positive for 146 (66.1%) of the residents tested. The seroconversion rate was significantly different (p 0.001) between the NH (88.7%) and the LTCU (45.6%). During the epidemic, there was no excess mortality index within the NH and LTCU services of the Amiens University Hospital. Among frail patients, the role of immunosenescence can be discussed to account for the absence of this inflammatory reaction. This study showed that isolating the infected patient in a dedicated unit significantly reduces the risk of seroconversion and contamination compared to isolating them within their own unit.

In the context of a second wave of SARS-CoV-2 transmission, the use of saliva sampling has become an issue of real importance. SARS-CoV-2 RNA screening was performed on nasopharyngeal and saliva swabs collected from 501 individuals from residential homes for the elderly. The saliva samples were collected at the same time as the nasopharyngeal samples. Nasopharyngeal samples yielded positive results for 26 individuals, only two of whom also tested positive with saliva swabs. In this context, saliva collected by swabbing the fluid is not an ideal sample.

International audience; The global pandemic of coronavirus disease 2019 (COVID-19) has challenged healthcare systems worldwide. Lockdown, social distancing, and screening are thought to be the best means of stopping the virus from spreading and thus of preventing hospital capacity from being overloaded. However, it has also been suggested that effective outpatient treatment can control pandemics. We adapted a mathematical model of the beneficial effect of lockdown on viral transmission and used it to determine which characteristics of outpatient treatment would stop an epidemic. The data on confirmed cases, recovered cases, and deaths were collected from Sante Publique France. After defining components of the epidemic flow, we used a Morris global sensitivity analysis with a 10-level grid and 1000 trajectories to determine which of the treatment parameters had the largest effect. Treatment effectiveness was defined as a reduction in the patients' contagiousness. Early treatment initiation was associated with better disease control-as long as the treatment was highly effective. However, initiation of a treatment with a moderate effectiveness rate (5%) after the peak of the epidemic was still better than poor distancing (i.e. when compliance with social distancing rules was below 60%). Even though most of today's COVID-19 research is focused on inpatient treatment and vaccines, our results emphasize the potentially beneficial impact of even a moderately effective outpatient treatment on the current pandemic.

International audience; No abstract available

ObjectivesHealthcare workers are more likely to be infected by SARS-CoV-2. In order to assess the infectious risk associated with working in a hospital, we sought to estimate the proportion of healthcare professionals infected with SARS-CoV-2 by screening staff in a University Medical Center in France.SettingA hospital-wide screening campaign (comprising a serological test and a questionnaire) ran from 18 May to 26 July 2020.Primary and secondary outcome measuresThe seroprevalence rate was analysed in a multivariate analysis according to sociodemographic variables (age, sex and profession), exposure to SARS-CoV-2 and symptoms.ResultsA total of 4840 professionals were included, corresponding to 74.5% of the centre’s staff. The seroprevalence rate (95% CI) was 9.7% (7.0% to 12.4%). Contact with a confirmed case of COVID-19 was significantly associated with seropositivity (OR (95% CI: 1.43, (1.15 to 1.78)). The seroprevalence rate was significantly higher among nursing assistants (17.6%) than among other healthcare professionals. The following symptoms were predictive of COVID-19: anosmia (OR (95% CI): 1.55, (1.49 to 1.62)), ageusia (1.21, (1.16 to 1.27)), fever (1.15, (1.12 to 1.18)), myalgia (1.03, (1.01 to 1.06)) and headache (1.03, (1.01 to 1.04)).

Aims Coronavirus disease 2019 (COVID‐19) is a rapidly progressing pandemic, with four million confirmed cases and 280,000 deaths at the time of writing. Some studies have suggested that diabetes is associated with a greater risk of developing severe forms of COVID‐19. The primary objective of the present study was to compare the clinical features and outcomes in hospitalized COVID‐19 patients with vs. without diabetes. Methods All consecutive adult patients admitted to Amiens University Hospital (Amiens, France) with confirmed COVID‐19 up until April 21st, 2020, were included. The composite primary endpoint comprised admission to the intensive care unit (ICU) and death. Both components were also analyzed separately in a logistic regression analysis and a Cox proportional hazards model. Results A total of 433 patients (median age: 72; 238 (55%) men; diabetes: 115 (26.6%)) were included. Most of the deaths occurred in non‐ICU units and among older adults. Multivariate analyses showed that diabetes was associated neither with the primary endpoint (odds ratio (OR): 1.12; 95% confidence interval (CI): 0.66‐1.90) nor with mortality (hazard ratio: 0.73; 95%CI: 0.40‐1.34) but was associated with ICU admission (OR: 2.06; 95%CI 1.09‐3.92, p=0.027) and a longer length of hospital stay. Age was negatively associated with ICU admission and positively associated with death. Discussion Diabetes was prevalent in a quarter of the patients hospitalized with COVID‐19; it was associated with a greater risk of ICU admission but not with a significant elevation in mortality. Further investigation of the relationship between COVID‐19 severity and diabetes is warranted. This article is protected by copyright. All rights reserved.

Aims To describe the characteristics of patients hospitalized with COVID-19 (including their long-term at-home medication use), and compare them with regard to the course of the disease. To assess the association between renin–angiotensin system inhibitors (RASIs) and disease progression and critical outcomes. Methods and results All consecutive hospitalized patients with laboratory-confirmed COVID-19 in a university hospital in Amiens (France) were included in this study. The primary composite endpoint was admission to an intensive care unit (ICU) or death before ICU admission. Univariable and multivariable logistic regression models were used to identify factors associated with the composite endpoint. Between 28 February 2020 and 30 March 2020, a total of 499 local patients tested positive for SARS-CoV-2. Of these, 231 were not hospitalized {males 33%; median [interquartile range (IQR)] age: 44 (32–54)}, and 268 were hospitalized [males 58%; median (IQR) age: 73 (61–84)]. A total of 116 patients met the primary endpoint: 47 died before ICU admission, and 69 were admitted to the ICU. Patients meeting the primary endpoint were more likely than patients not meeting the primary endpoint to have coronary heart disease and to have been taking RASIs; however, the two subsets of patients did not differ with regard to median age. After adjustment for other associated variables, the risk of meeting the composite endpoint was 1.73 times higher (odds ratio 1.73, 95% confidence interval 1.02–2.93) in patients treated at baseline with a RASI than in patients not treated with this drug class. This association was confirmed when the analysis was restricted to patients treated with antihypertensive agents. Conclusions We highlighted a potential safety signal for RASIs, the long-term use of which was independently associated with a higher risk of severe COVID-19 and a poor outcome. Due to the widespread use of this important drug class, formal proof based on clinical trials is needed to better understand the association between RASIs and complications of COVID-19.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), causing the COVID-19, has been declared as pandemic by the World Health Organization. Epidemiological and clinical characteristics of patients with COVID-19 have been largely reported but biological risk factors have not yet been well described. In this retrospective and monocentric study, we explored 35 hematological and biochemical parameters, routinely measured at the Amiens University Hospital laboratory, between February 21, 2020 and March 30, 2020 for patients diagnosed with COVID-19. 154 patients were included in this study. We compared biological parameters collected at hospital admission between patients who survived or not after hospitalization. Non survivor patients displayed lower hemoglobin (p=0.02) and bicarbonate concentrations (p=0.03) and higher potassium concentration (p=0.03) compared to the survivors. We then compared these biological parameters between patients hospitalized in conventional care units and patients hospitalized in intensive care units (ICU). Numerous biological examinations had significant variations, including lymphocyte and neutrophil counts, bicarbonate, calcium and C Reactive Protein concentrations. In multivariate Cox analysis, risk factors for aggravation (defined as ICU admission or death) included low bicarbonate levels and hyponatremia. A significant worse overall survival was associated with hyponatremia, hyperkaliemia and prothrombin time > 16.8 seconds. We then proposed a prognostic score, to be validated in a future prospective study. Thus, these biological parameters, easily available, could help clinicians to identify high risk patients at an early stage of infection.

In the present journal, recommendations for management of community-acquired pneumonia were recently published [1]. Within preventive measures, the importance of vaccination of health-care personal...

Objective: The aim of this study was to evaluate tropism prediction performances of three algorithms [geno2pheno false-positive rate 10% (G2P10), position-specific scoring matrix (PSSM) and a combination of the 11/25 and net charge rules] and to investigate the viral and host factors potentially involved in the X4 or R5 prediction in human immunodeficiency virus-1 (HIV-1) patients. Methods: Viral tropism was determined in 179 HIV-1-infected patients eligible for CCR5 antagonist therapy. HIV-1 RNA or DNA was extracted and amplified for env gp120 sequencing. In parallel, demographic, viral, immunological and clinical determinants were analyzed. Results: According to the G2P10 algorithm, 48 patients harbored X4 or X4R5 virus. The tropism prediction was concordant for 87.7 and 88.2% of samples when comparing G2P10 with PSSM or with a combination of the 11/25 and net charge rules, respectively. X4 prediction was significantly associated with more than 35 amino acids in the V3 domain (p < 0.0001) and loss of an N-linked glycosylation site (p < 0.0001). Of the factors studied, only the nadir CD4 T-cell count was significantly associated with X4 tropism (p = 0.01). Conclusion: We determined that the X4 virus detection is closely linked to the nadir CD4 T-cell count below 100 cells/mm3 that must be taken into account when considering a CCR5 antagonist therapy switch.

BACKGROUND: Intrapartum intravenous zidovudine (ZDV) prophylaxis is a long-standing component of prevention of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) in high-resource countries. In some recent guidelines, intravenous ZDV is no longer systematically recommended for mothers receiving combination antiretroviral therapy (cART) with low viral load. We evaluated the impact of intravenous ZDV according to viral load and obstetrical conditions. METHODS: All HIV-1-infected women delivering between 1 January 1997 and 31 December 2010 in the French Perinatal Cohort (ANRS-EPF) were analyzed if they received ART during pregnancy and did not breastfeed. We identified maternal and obstetrical characteristics related to lack of intravenous ZDV and compared its association with MTCT rate and other infant parameters, according to various risk factors. RESULTS: Intravenous ZDV was used in 95.2% of the 11 538 deliveries. Older age, multiparity, and preterm and vaginal delivery were associated with lack of intravenous ZDV (n = 554). In women who delivered with viral load ≥1000 copies/mL, the overall MTCT rate was higher without than with intravenous ZDV (7.5% vs 2.9%; P = .01); however, there was no such difference when the neonate received postnatal intensification therapy. Among them, 77% of women who had viral load

International audience; Physicians play a primary role in vaccination of the population. Strong initial training of medical students is therefore essential to enable them to fulfill this role. This cross-sectional nationwide online survey conducted between September 2015 and January 2016 obtained 2,118 completed surveys from 6,690 eligible respondents (response rate, 32%) at 27 of 32 medical schools in France regarding their education about vaccination. The data were analyzed in April-June 2016. The survey covered their knowledge, attitudes, practices, and perceptions, and assessed their level of perceived preparedness for their future practice as interns. Around a third of the students (n=708, 34%) felt insufficiently prepared for questions about vaccination, especially for communicating with patients on side effects (n=1,381, 66%) and strategies to respond to vaccine hesitancy (n=1,217, 58%). The mean knowledge score was 26/45 (SD=7.9). Lecture courses, which are the main education method used in French medical schools (1,891/5,660 responses, 33%), were considered effective by only 11% of students (693/6,155 responses), whereas practical training was significantly associated with better perceived preparedness (p

Multiple types of human papillomavirus (HPV) are responsible for most cervical cancers but also cause anal cancers-especially in HIV-positive patients. Furthermore, men who have sex with men (MSM) are twice as likely to develop anal cancers as non-MSM. A simple screening test for HPV infection would be useful in these patients. The aim of our study was to evaluate the detection of HPV by real-time polymerase chain reaction (PCR) in urine as a marker of anal infection in MSM. The study included 52 HIV-positive MSM treated at Amiens University Hospital (Amiens, France). After obtaining informed consent, we performed an anal swab and gathered 10 mL of first-void urine. Samples were extracted and amplified in a real-time PCR. Genotypes were determined with a PapilloCheck(®) system (Greiner Bio-One, Frickenhausen, Germany). The anal test was the gold standard for calculating the characteristics of the urine test. The sensitivity of the urine test for diagnosing anal HPV infection was 15%, the specificity was 66%, the positive predictive value was 87.5%, and negative predictive value was 4.5%. The prevalence of anal HPV infection in the study population was 94%. Genotype 42 was the most common. The anal HPV viral load was significantly lower in men in a stable relationship than in single men. However, there was no statistically significant relationship between anal viral load and anal intraepithelial lesions. We conclude that urine-based HPV is a poor predictor of anal HPV infection in HIV-positive MSM.

Resume Objectifs Definir la meilleure strategie d'identification de la bacterie responsable et de demande d'examens d'imagerie ; rediger des conseils utilisables en pratique quotidienne sur le traitement medicamenteux et non medicamenteux des spondylodiscites bacteriennes non tuberculeuses de l'adulte. Methodes Ces propositions ont ete redigees par un rhumatologue et un infectiologue a partir de leur experience et de l'analyse de la litterature, puis confrontees a l'avis de quatre experts. La recherche d'articles publies en anglais ou en francais s'est faite sur medline de 1975 a mai 2006 en utilisant les mots cles : infectious spondylodiscitis, infectious spondylitis, spondylodiscitis, discitis, vertebral osteomyelitis, spine infection, bone and joint infections. Resultats Quatre-vingt-cinq articles ont ete selectionnes pour etre lus dans leur integralite. Il n'y a aucune etude prospective randomisee controlee publiee a ce jour sur ce sujet. Sauf situation exceptionnelle (neutropenie ou sepsis mal tolere), le traitement antibiotique n'est debute que lorsque l'on a la certitude d'avoir isole la bacterie responsable par des hemocultures ou une ponction biopsie discale. Le traitement d'attaque necessite une association bactericide de deux antibiotiques synergiques a posologie elevee. La duree totale du traitement antibiotique doit etre au moins de 12 semaines. Le bilan initial comprend systematiquement des radiographies du rachis et du thorax, une IRM du rachis. Dans les spondylodiscites par voie hematogene a streptocoque et a staphylocoque, l'echographie cardiaque peut etre demandee systematiquement. Des radiographies centrees sur le disque infecte sont systematiquement demandees a un et trois mois apres le debut des antibiotiques et a trois mois apres la fin des antibiotiques. Une IRM de controle est le plus souvent inutile si l'evolution clinique et biologique est favorable. S'il y avait initialement un abces collecte, ou si l'evolution est defavorable, une IRM de controle peut etre demandee apres un mois de traitement. Une surveillance clinique et biologique pendant la totalite du traitement antibiotique et dans les six mois qui suivent son arret est indispensable. Conclusions Des propositions a partir d'etudes descriptives et d'avis d'experts ont pu etre redigees. Elles devraient permettre d'optimiser et d'uniformiser le traitement des spondylodiscites. Des etudes complementaires avec notamment des etudes prospectives randomisees multicentriques comparant un traitement intraveineux a un traitement per os d'emblee ou des durees de traitement differentes sont necessaires pour ameliorer la valeur scientifique de ces propositions.

Pneumocystis jirovecii ITS and DHPS genotypes were identified in 3 patient groups developing diverse forms of P. jirovecii infections: 13 patients with Pneumocystis pneumonia, 8 patients merely colonized by the fungus, and 19 immunocompetent infants with bronchiolitis developing mild P. jirovecii infection. Common P. jirovecii genotypes were found in the 3 patient groups, suggesting that common sources of P. jirovecii were involved in the fungus acquisition, and that transmission cycles of P. jirovecii infections in these patient groups are not independent. Parasitized patients, whatever the form of parasitism they present, may be part of a common reservoir for P. jirovecii.

Introduction Depuis quelques annees, la quantification de Pneumocystis jirovecii ( P. jirovecii ) par PCR quantitative (qPCR) dans des echantillons de lavage broncho-alveolaire (LBA) et l’application de valeurs seuils d’interpretation a cette quantification ont aide a differencier les diagnostics de pneumonie a Pneumocystis (PPC) et de colonisation pulmonaire. Ainsi, un nombre de copies d’ADN de P. jirovecii situe au-dessous de la valeur seuil inferieure permettrait d’exclure le diagnostic de PPC avec une sensibilite de 100 % tandis qu’un nombre de copies situe au-dessus de la valeur seuil superieure permettrait de retenir ce diagnostic avec une specificite de 100 %. Le LBA, considere comme prelevement de reference pour detecter P. jirovecii , presente pourtant des contre-indications a sa realisation. Notre objectif a ete de definir et d’evaluer des seuils d’interpretation pour des echantillons recueillis de maniere moins invasive. Materiels et methodes Les patients inclus retrospectivement ont ete classes en trois groupes : le groupe « PPC prouvee » incluait les patients chez lesquels l’examen direct du LBA etait positif ; le groupe « colonisation » incluait les patients chez lesquels l’examen direct du LBA etait negatif et qui avaient presente une evolution clinique favorable en l’absence de traitement anti- Pneumocystis ; le groupe « diagnostic indetermine » incluait les patients chez lesquels l’examen direct du LBA etait negatif mais qui presentaient des symptomes compatibles avec une PPC ayant motive l’instauration d’un traitement anti- Pneumocystis . La charge fongique a ete determinee par qPCR dans les couples d’echantillons LBA/non-LBA recueillis chez ces patients. Une correlation entre la charge fongique des LBA et celle des non-LBA a ete recherchee a l’aide du test de Spearman. Resultats Vingt-sept couples d’echantillons ont ete analyses. Ils avaient ete preleves chez 23 patients dont huit presentaient une PPC (huit LBA et neuf non-LBA), sept n’avaient pas de diagnostic determine (sept LBA et 10 non-LBA) et huit etaient colonises (huit LBA et huit non-LBA). Une correlation entre la charge fongique des LBA et celle des non-LBA a ete mise en evidence (R2 = 0,6 ; p = 2,4 × 10 −5 , test de Spearman). Cette correlation a permis de calculer les seuils pour les non-LBA a partir de ceux prealablement definis par le laboratoire pour les LBA (seuils inferieur et superieur de 1,6 × 103 et 2 × 104 copies/μL). En appliquant les valeurs ainsi obtenues (4,4 × 102 et 3,5 × 103 copies/μL), nous obtenons une sensibilite de 100 % au seuil inferieur et une specificite de 100 % au seuil superieur pour le diagnostic de PPC dans les echantillons non-LBA. Conclusion Ces donnees permettent d’envisager la possibilite de poser le diagnostic de PPC pour un patient chez qui la realisation d’un LBA serait contre-indiquee. Ces seuils d’interpretation ne sont toutefois qu’une aide pour le biologiste et le dialogue clinico-biologique reste indispensable.

The aim of this study was to evaluate tropism prediction performances of three algorithms [geno2pheno false-positive rate 10% (G2P10), position-specific scoring matrix (PSSM) and a combination of the 11/25 and net charge rules] and to investigate the viral and host factors potentially involved in the X4 or R5 prediction in human immunodeficiency virus-1 (HIV-1) patients.Viral tropism was determined in 179 HIV-1-infected patients eligible for CCR5 antagonist therapy. HIV-1 RNA or DNA was extracted and amplified for env gp120 sequencing. In parallel, demographic, viral, immunological and clinical determinants were analyzed.According to the G2P10 algorithm, 48 patients harbored X4 or X4R5 virus. The tropism prediction was concordant for 87.7 and 88.2% of samples when comparing G2P10 with PSSM or with a combination of the 11/25 and net charge rules, respectively. X4 prediction was significantly associated with more than 35 amino acids in the V3 domain (p0.0001) and loss of an N-linked glycosylation site (p0.0001). Of the factors studied, only the nadir CD4 T-cell count was significantly associated with X4 tropism (p = 0.01).We determined that the X4 virus detection is closely linked to the nadir CD4 T-cell count below 100 cells/mm(3) that must be taken into account when considering a CCR5 antagonist therapy switch.

In countries where highly active antiretroviral therapy (HAART) is available, cardiovascular disease is a major cause of morbidity and mortality in patients infected by the human immunodeficiency virus (HIV). Vascular calcification is used as subclinical marker of atherosclerosis. As vascular calcification is now considered to be an active, inflammatory process, its evaluation in HIV-infected patients may thus be clinically relevant. The primary objective of the present study was to determine and compare the prevalence of abdominal aortic calcification (using the multislice spiral computed tomography) in HIV-positive patients receiving HAART and in HIV-negative control subjects. The secondary objective was to determine the risk factors associated with the presence of abdominal aortic calcification in HIV-positive patients. Seventy-seven HIV-positive patients and 77 HIV-negative controls were included in the study. We found that the prevalence of abdominal aortic calcification was similar in the two groups. Furthermore, the mean abdominal aortic calcification score was not significantly higher in HIV-positive patients than in controls. The following parameters were correlated with the aortic calcification score: age (p

Late diagnosis of HIV infection is associated with a lower survival rate. Because of several consecutive cases of late diagnosis of AIDS occurring in truck drivers, a retrospective study was carried out in the northwest of France. Truck drivers were significantly associated with a late diagnosis of HIV infection (P = 0.009) and an increased risk of death (P = 0.03). Consequently, prevention and HIV-testing campaigns targeting this profession appear necessary.

Infectious complications are common in patient with multiple myeloma. However, Paecilomyces variotii, a common saprophytic fungus, rarely causes human infection. We report the first case of P. variotii fungemia in this illness with good response with adapted anti-mycotic treatment.

A 39-year-old citizen from Martinique of African descent (overseas French territory, West French Indies), having lived in metropolitan France since July 2002, was admitted to Amiens University Hospital Center, Amiens, France, on 11 November 2003. The patient presented with fever, dyspnea, asthenia

PURPOSE OF REVIEW This review provides an update on microbiological and therapeutic data in febrile neutropenic patients in general and those with bacterial lung sepsis in particular. Although the Infectious Diseases Society of America updated its guidelines on febrile neutropenia in 2010, changing epidemiological factors and the spread of new drug resistance constitutes challenges for initial treatment of this condition. RECENT FINDINGS Lung sepsis stands out because of the frequent absence of microbiological identification. We review the use of newly available, novel, broad-spectrum antibiotics (linezolid, tigecycline, daptomycin, etc.) in this indication. SUMMARY Although the incidence of Gram-negative infections in neutropenic fever is leveling off, there is a worrying increase in resistance. New drugs are available but not well studied in febrile neutropenia; daptomycin and tigecycline should not be used in suspected lung sepsis in these patients. New diagnostic tools (such as the procalcitonin assay and the LightCycler SeptiFast assay, Roche Molecular Systems) appear to be unhelpful in febrile neutropenia, although more data on fungal sepsis are required. There are no specific features of the treatment of pneumonia or septic shock in neutropenic fever, but both conditions increase the mortality rate.

Background The chemotherapy used to treat lung cancer causes febrile neutropenia in 10 to 40% of patients. Although most episodes are of undetermined origin, an infectious etiology can be suspected in 30% of cases. In view of the scarcity of data on lung cancer patients with febrile neutropenia, we performed a retrospective study of the microbiological characteristics of cases recorded in three medical centers in the Picardy region of northern France. Methods We analyzed the medical records of lung cancer patients with neutropenia (neutrophil count < 500/mm3) and fever (temperature > 38.3°C). Results The study included 87 lung cancer patients with febrile neutropenia (mean age: 64.2). Two thirds of the patients had metastases and half had poor performance status. Thirty-three of the 87 cases were microbiologically documented. Gram-negative bacteria (mainly enterobacteriaceae from the urinary and digestive tracts) were identified in 59% of these cases. Staphylococcus species (mainly S. aureus) accounted for a high proportion of the identified Gram-positive bacteria. Bacteremia accounted for 60% of the microbiologically documented cases of fever. 23% of the blood cultures were positive. 14% of the infections were probably hospital-acquired and 14% were caused by multidrug-resistant strains. The overall mortality rate at day 30 was 33% and the infection-related mortality rate was 16.1%. Treatment with antibiotics was successful in 82.8% of cases. In a multivariate analysis, predictive factors for treatment failure were age >60 and thrombocytopenia < 20000/mm3. Conclusion Gram-negative species were the most frequently identified bacteria in lung cancer patients with febrile neutropenia. Despite the success of antibiotic treatment and a low-risk neutropenic patient group, mortality is high in this particular population.

Summary Background The global number of non-tuberculous mycobacteria (NTM) pulmonary infections is increasing. Treatment decisions and management are difficult and the prognosis of these infections has been rarely evaluated. Methods The aim of this study was to evaluate management and prognosis of patients with NTM pulmonary infection in a French teaching hospital. In this study, we evaluated management of patients satisfying the ATS (American Thoracic Society) criteria for NTM pulmonary infection in Amiens hospital from 1992 to 2002 and retrospectively compared this management to ATS guidelines. Short-term and long-term survival was also described. Results Thirty-one patients satisfying the ATS criteria for NTM pulmonary infection were included: 15 patients were infected with Mycobacterium xenopi , nine with Mycobacterium avium intracellulare , four with Mycobacterium kansasii and three patients were infected with rapidly growing mycobacteria. Twenty-seven patients had past or concomitant diseases responsible for local or systemic immunosuppression. Eleven patients were not treated. In the 20 treated patients, 13 different antibiotic combinations were used, often comprising three or more drugs. The median survival was 15 months. Twenty-one patients (67%) died before 5 years of follow-up. Thirty per cent of deaths were attributed to NTM pulmonary infection. Adjusting treatment to the results of susceptibility tests or ATS guidelines was not associated with any significant difference in survival. Conclusion As the high mortality rate may be related to concomitant diseases, management of NTM pulmonary infection also depends on comorbidities, and should be defined according to the severity of underlying diseases.

Objectives To develop recommendations about identifying the causative organism, obtaining imaging studies, and selecting pharmacological and non-pharmacological treatments in adults with pyogenic discitis and vertebral osteomyelitis (PDVO). Methods A rheumatologist and an infectiologist drafted recommendations based on their personal experience and a review of studies in English or French retrieved on Medline using the following search terms: “infectious spondylodiscitis”, “infectious spondylitis”, “spondylodiscitis”, “discitis”, “vertebral osteomyelitis”, “spine infection”, and “bone and joint infections”. The recommendations were submitted to four experts for validation. Results 85 articles were selected for detailed review. No prospective randomized controlled trials were identified. Antimicrobial therapy should be initiated only after recovery of the causative organism in blood cultures or percutaneous disk biopsy specimens, except in patients with neutropenia or severe sepsis. The initial treatment rests on a combination of two bactericidal and synergistic antimicrobials in high dosages. The total duration of antimicrobial therapy should be 12 weeks at least. Radiographs of the spine and chest and magnetic resonance imaging (MRI) of the spine should be performed routinely during the initial evaluation. In PDVO due to hematogenous dissemination of a streptococcus or staphylococcus, routine echocardiography may be in order. Radiographs centered on the affected disk should be obtained 1 and 3 months into antimicrobial therapy and 3 months after treatment discontinuation. Follow-up MRI is usually unnecessary when the clinical and laboratory abnormalities respond to treatment. If not, or if the initial investigations show a collected abscess, a repeat MRI after 1 month of antimicrobial treatment may be useful. Clinical and laboratory follow-up is mandatory throughout antimicrobial therapy and during the first 6 months after treatment discontinuation. Conclusions Recommendations based on descriptive studies and expert opinion were developed. They can be expected to improve the quality and uniformity of PDVO management. Further studies are needed to improve the level of evidence that is available for developing recommendations. In particular, prospective randomized multicenter studies should be performed to compare the intravenous to the oral route for initial antimicrobials administration and to compare different treatment durations.

Pneumococcal pneumonia remains a common disease with a high mortality rate. Between 1995 and 2000, we prospectively analyzed 95 consecutive adult cases of community-acquired bacteraemic pneumococcal pneumonia treated in a single centre. The incidence of pneumococcal resistance to penicillin increased from 19 to 50% during the study period. Multivariate analysis showed that only age and recent hospitalization were independently associated with fatal outcome. The proportion of penicillin-resistant strains was slightly but not significantly higher among patients who died before the fourth hospital day than among those who died later. Patients who died before D4 were more likely to have a recent history of hospitalization, cancer and/or chemotherapy. It thus appears that infection by a resistant pneumococcal strain is not in itself a gravity factor in this setting, but that their acquisition is associated with pejorative clinical features.

Pneumocystis jiroveci (human-derived Pneumocystis ) infections can display a broad spectrum of clinical presentations, of which pulmonary colonization with the fungus may represent an important part, occurring frequently in patients with various underlying diseases and presenting alternative diagnoses of acute pneumocystosis ( Pneumocystis carinii pneumonia [PCP]). There are few data concerning the P. jiroveci genotypes involved in pulmonary colonization, whereas several genotypes responsible for PCP in immunocompromised patients have been described. In this study, P. jiroveci genotypes have retrospectively been investigated and compared in 6 colonized patients and in 11 patients with PCP who were in the same hospital. Seventeen archival bronchoalveolar lavage samples were genotyped at internal-transcribed spacer 1 (ITS1) and ITS2 of the nuclear rRNA operon. Fourteen different genotypes were identified, of which 1 was found only in colonized patients, 10 were found only in patients with PCP, and 3 were found in both patient populations. Mixed infections were diagnosed in 2 of the 6 colonized patients and in 6 of the 11 patients with PCP. The results show that similar genotypes can be responsible for PCP as well as pulmonary colonization. There is a high diversity of genotypes in colonized patients and in patients with PCP. Mixed infections may occur in these two patient populations. These shared features of P. jiroveci ITS genotypes in colonized patients and patients with PCP suggest that human populations infected by P. jiroveci , whatever the clinical manifestation, may play a role as a common reservoir for the fungus.

BACKGROUND : Transfusion-associated bacterial contamination (TABC), probably the most frequent transfusion-transmitted infection, may induce serious adverse events. Systematic information and documentation on determinants are lacking. STUDY DESIGN AND METHODS : The Bacthem Study is a French matched case-control study assessing TABC determinants. Included were cases of TABC reported in France in a 2-year period, as determined from uniform definitions. Information on recipient-, blood component-, and donor-related potential determinants was collected on site. ORs were estimated by conditional logistic regression. RESULTS : Of the 158 cases of suspected TABC reported, 41 that involved transfusion with 25 RBCs and 16 platelet concentrates were included. Gram-negative rods accounted for nearly half of the bacteria species involved and for all six deaths. In comparison with the risk of TABC for patients receiving RBCs for anemia, the risk was higher for patients receiving RBCs for pancytopenia (OR, 7.3; 95% CI, 1.3-41.0) and for those receiving platelets for thrombocytopenia (OR, 5.3; 95% CI, 1.2-24.1). Other potential determinants were platelet transfusion for pancytopenia (OR, 4.5; 95% CI, 0.5-40.0), immunosuppressive treatment (OR, 2.8; 95% CI, 0.7-10.6), shelf-life of more than 1 day for platelets or 8 days for RBCs (OR, 2.6; 95% CI, 0.7-9.6), and more than 20 previous donations by donors (OR, 1.9; 95% CI, 0.7-5.3). CONCLUSION : This first comparative study revealed TABC determinants that suggest approaches for prevention.

Answer: Concurrent pulmonary infection with both Pneumocystis jirovecii and Histoplasma capsulatum var. capsulatum. The figure in the photo quiz shows a macrophage containing a cluster of Pneumocystis jirovecii trophic forms and one spore of Histoplasma capsulatum. Small trophic forms are about 1.5 to 2 μm in size, with acidophilic nuclei that are clearly identified on the figure, contrary to cytoplasmic shapes that are irregular. The distinctive oval spore, about 2 to 3 μm in size, containing an uncolored vacuole which reduces fungal cytoplasm to a tiny arc, makes it possible to diagnose putative histoplasmosis. This macrophage was the only one that contained both a spore of H. capsulatum and P. jirovecii trophic forms. Two other macrophages containing one spore of H. capsulatum in the absence of P. jirovecii were detected on one slide, indicating the presence of a low fungal burden in the lungs. Cultures of skin biopsy specimens were positive after only 10 days, revealing H. capsulatum, whereas bronchoalveolar lavage (BAL) specimen culture, stored at room temperature, was positive 8 weeks after BAL retrieval, consistent with disseminated histoplasmosis of pulmonary origin. Treatment with liposomal amphotericin B (3 mg/kg/day) followed by itraconazole (200 mg/day) as a secondary prophylaxis provided clinical improvement and absence of relapse until at least January 2005, the month of the patient's departure to another French city. This observation emphasizes the risk of overlooking histoplasmosis in cases of low fungal burden. This low burden, combined with slow fungal growth and the absence of a trained microscopist in an area where histoplasmosis is not endemic, was the cause of a delayed diagnosis. The absence of specific treatment led to dissemination from the lungs. There is evidence that the infection was due to reactivation of latent spores acquired at least 16 months earlier in Martinique. This overseas French territory is an area where histoplasmosis is endemic, in which (i) the incidences of AIDS and histoplasmosis in human immunodeficiency virus (HIV)-infected patients are 0.4/100,000 patients and 1.7% of patients, respectively (1), and (ii) Pneumocystis pneumonia (PCP) and disseminated histoplasmosis represent AIDS-defining illnesses (1, 2). Nonetheless, in Martinique and other areas of endemicity, occurrence of concurrent histoplasmosis and pneumocystosis in AIDS patients has been cited in about 15 instances (3–6) and has not been histologically described until now. (See page 2809 in this issue [doi:10.1128/JCM.01466-12] for photo quiz case presentation.)

Sixty-three cases of monomicrobial enterococcal infections treated with teicoplanin in two open clinical studies in Europe from 1982 to 1989 are presented. Infections were documented as endocarditis (n = 18); septicemia (n = 8); and urinary tract (n = 29), skin/soft-tissue (n = 6), or bone/joint (n = 2) infections. A total of 63 enterococcal strains were isolated; all of 29 strains tested were susceptible to teicoplanin (geometric mean MIC, 0.16 micrograms/mL; range, 0.06-0.5 micrograms/mL). Forty-eight patients were treated with teicoplanin alone and 15 were treated with teicoplanin in combination with an aminoglycoside. The rate of clinical cure was 84.1%; 4.8% of patients clinically improved, 7.9% had clinical recurrence, and 3.2% did not respond to therapy. Bacteriologic eradication was observed in 87.2% of patients; persistence, in 3.2%; recurrence, in 3.2%; and reinfection, in 4.8%. One case was not evaluable bacteriologically. Of 18 patients with endocarditis, 15 were cured with a mean daily dose of 5.4 mg/kg--six with monotherapy and nine with combination therapy. All patients with urinary tract infections were treated with monotherapy, and 89.7% were cured (mean daily dose, 4.6 mg/kg). Lower rates of clinical cure and bacteriologic eradication were observed in septicemic patients without endocarditis (62.5%). This study demonstrated a good efficacy of teicoplanin for the treatment of enterococcal infections due to susceptible strains, but further clinical studies would be useful for establishing optimal dosage and the indications for combination therapy, especially for severe infections.

Antibiotic-associated pseudomembranous colitis is an uncommon but potentially serious adverse reaction, resulting in acute diarrhoea and characterised by colonic pseudomembranes. A direct relationship between the disease, recent antibiotic therapy and proliferation of Clostridium difficile in the colonic lumen was established in the late 1970s. It is thought that antibiotic therapy may alter the enteric flora, enabling C. difficile to proliferate and produce toxins with cytopathic (toxin B or cytotoxin) and hypersecretory (toxin A or enterotoxin) effects on the mucosa. Apart from clindamycin, the first antibiotic recognised to be clearly associated with pseudomembranous colitis, the antimicrobial agents most commonly responsible are cephalosporins and ampicillin (or amoxicillin). However, virtually all antibiotics except parenterally administered aminoglycosides can cause the disease. Vancomycin and metronidazole, 2 drugs used to treat antibiotic-associated pseudomembranous colitis, have also been reported to be responsible for the complication when used parenterally. Pseudomembranous colitis may develop after perioperative prophylactic antibiotic therapy with cephalosporins. Antibiotic-associated pseudomembranous colitis is most frequent in elderly and debilitated patients and in intensive care units. Nosocomial acquisition of C. difficile has been documented. Therefore it has been recommended that enteric isolation precautions should be taken with patients with this disease. The clinical symptoms include watery diarrhoea, abdominal cramping, and frequently fever, leucocytosis and hypoalbuminaemia. Toxic megacolon and acute peritonitis secondary to perforation of the colon are the most serious complications. The pseudomembranes are usually seen during endoscopic procedures, sigmoidoscopy or, if possible, colonoscopy; the most useful microbiological tests for confirmation of the diagnosis include cycloserine cefoxitin fructose agar (CCFA) stool cultures and stool toxin assays on tissues or by immunological techniques. However, cultures and toxin tests may be positive in patients without pseudomembranous colitis or C. difficile-associated diarrhoea. Mild cases may respond to discontinuation of the drug responsible, but therapy with an anticlostridial antibiotic is often necessary: a 10-day course of oral vancomycin, metronidazole or bacitracin should be given. Relapses are seen in 5 to 50% of patients treated. Antibiotic treatment should avoid sporulation leading to other relapses. 'Biotherapy' (lactobacilli, Saccharomyces) has also been proposed.

Introduction : l’infection VIH est une infection virale chronique évoluant sur plusieurs années. Il a été constaté que le diabète de type 2 était plus souvent présent chez les patients infectés du VIH. Les mécanismes sont multiples : une action directe des antirétroviraux et l’infection du VIH en elle-même de par l’inflammation chronique qu’elle induit. L’objectif de notre étude est de déterminer, chez les patients atteints de VIH et ayant développé un diabète de type 2 dans la file active NADIS de la Somme et de l’Oise, le délai de prise en charge du diabète afin d’améliorer les pratiques quotidiennes. Nous avons ensuite regardé la stratégie de prise en charge initiale de ce diabète, et nous avons analysé les facteurs qui pouvaient prédisposer à la survenue plus rapide de diabète. Patients et méthodes : il s’agit d’une étude multicentrique observationnelle et rétrospective. Les données ont été recueillies à partir de la base de données NADIS via les dossiers informatisés. Résultats : le délai moyen de prise en charge du diabète est de 34,35±51 mois. 68,75% des patients diabétiques étaient traités par biguanides et dans la moitié des cas les IP étaient arrêtés. Le délai de survenue du diabète était significativement plus long sous IP cependant ces patients avaient un nadir de CD4 significativement plus bas. Ainsi les IP ne sont pas les seuls traitements pourvoyeurs de diabète. Au plus l’infection du VIH était ancienne, au plus le délai de survenue du diabète était long et ce de manière significative. Cependant il faut tenir compte du fait que la stratégie thérapeutique des antirétroviraux a évolué. Les patients qui, au cours de leur suivi, ont développé un syndrome métabolique avaient un nadir de CD4 plus élevé que ceux qui n’en ont pas développé. Ainsi, il semble que la restauration immune, si celle-ci était nécessaire ou le fait d’empêcher le déficit immunitaire grâce aux antirétroviraux pourrait favoriser le développement d’un syndrome métabolique et d’un diabète. Conclusion : le diabète de type 2 est une comorbidité fréquemment associée à l’infection du VIH. La prise en charge de celle-ci parait essentielle au vu des complications qu’elle pourrait induire. Il faut donc une sensibilisation plus forte des infectiologues dans son dépistage. S’il faut se méfier des antirétroviraux pourvoyeurs de diabète, il faut aussi rester vigilant quant à la restauration immune qu’elle induit et qui peut aussi favoriser l’apparition du diabète.