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Background SARS-CoV-2 has been responsible for considerable mortality worldwide, owing in particular to pulmonary failures such as ARDS, but also to other visceral failures and secondary infections. Recent progress in the characterization of the immunological mechanisms that result in severe organ injury led to the emergence of two successive hypotheses simultaneously tested here: hyperinflammation with cytokine storm syndrome or dysregulation of protective immunity resulting in immunosuppression and unrestrained viral dissemination. Methods In a prospective observational monocentric study of 134 patients, we analysed a panel of plasma inflammatory and anti-inflammatory cytokines and measured monocyte dysregulation via their membrane expression of HLA-DR. We first compared the results of patients with moderate forms hospitalized in an infectious disease unit with those of patients with severe forms hospitalized in an intensive care unit. In the latter group of patients, we then analysed the differences between the surviving and non-surviving groups and between the groups with or without secondary infections. Findings Higher blood IL-6 levels, lower quantitative expression of HLA-DR on blood monocytes and higher IL-6/mHLA-DR ratios were statistically associated with the risk of severe forms of the disease and among the latter with death and the early onset of secondary infections. Interpretation The unique immunological profile in patients with severe COVID-19 corresponds to a moderate cytokine inflammation associated with severe monocyte dysregulation. Individuals with major CSS were rare in our cohort of hospitalized patients, especially since the use of corticosteroids, but formed a very severe subgroup of the disease. Funding None.

To investigate the prevalence of neuro-functional disability and its determinants 12 months after community-acquired bacterial meningitis (CABM) in adult patients.In a prospective multicenter cohort study (COMBAT), all consecutive cases of CABM were enrolled and followed up for 12 months. Neuro-functional disability at 12 months was evaluated using a combination of the Glasgow Outcome Scale (functional disability), and the modified Rankin Disability Scale (physical disability). Factors associated with neuro-functional disability were identified by multivariate logistic regression.Among 281 patients, 84 (29.9%) patients exhibited neuro-functional disability at 12 months: 79 (28.1%) with functional disability and 51 (18.1%) with physical disability. Overall, 6 patients (2.1%) died during the follow-up. The most common pathogen identified was Streptococcus pneumoniae (131/272, 48.2%); 77/268 patients (28.7%) had a physical disability at hospital discharge. Factors independently associated with 12-month neuro-functional disability were a pneumococcal meningitis (adjusted OR = 2.8; 95% confidence interval (CI) = [1.3; 6.7]), the presence of a physical disability at hospital discharge (aOR = 2.3; 95%CI = [1.2; 4.4]) and the presence of behavioral disorders at hospital-discharge (aOR = 5.9; 95%CI = [1.6; 28.4]). Dexamethasone use was not significantly associated with neuro-functional disability (OR = 0.2; 95%CI = [ 0.1;1.3]).Neuro-functional disability is frequently reported 12 months after CABM. Detailed neurological examination at discharge is needed to improve the follow-up.NCT01730690.

Pneumocost is a prospective study that aimed at documenting the costs of the management of patients hospitalized with a pneumococcal pneumonia and the post-discharge costs during a 6-month period in the French context. Billing data were used to document hospital costs. Resource use during the follow-up period was collected through phone interviews at month 1, 3 and 6. Descriptive statistics and multivariate analyses were performed. We used generalized linear models with log-link functions to estimate parameters associated with hospital and follow-up costs of patients. Five hundred twenty-four patients were enrolled in 40 public centers from October 2011 to April 2014. Average age was 63 (SD 17); 55.0% of them were male. Average length of stay was 15 days (SD 23). Average cost of stay for the French Sickness Fund was €7293 (SD €7363). Average cost of follow-up was €1242 (SD €3000) and decreased steadily through time. When controlling for patient’s socioeconomic characteristics, severity of disease and hospital stay, results showed a concave relationship between hospital costs and age. Obesity, the severity of the disease and comorbidities were associated with constantly increasing inpatient costs. Concerning follow-up costs, we found the same concave relationship with age, while gender, a history of pneumonia and severity of the disease were the most important predictors of high costs after discharge. Pneumocost is the first French study providing a robust estimation of the cost of managing invasive pneumococcal pneumonia in the French context.

Background Community Acquired Pneumococcal Pneumonia is a lung infection that causes serious health problems and can lead to complications and death. The aim of this study was to observe and analyze health related quality of life after a hospital episode for patients with community acquired pneumococcal pneumonia in France. Methods A total of 524 individuals were enrolled prospectively in the study and were followed for 12 months after hospital discharge. Presence of streptococcus pneumoniae was confirmed by microbiological sampling. Quality of life was reported at four different points of time with the EQ-5D-3 L health states using the French reference tariff. Complete data on all four periods was available for 269 patients. We used descriptive and econometric analysis to assess quality of life over time during follow-up, and to identify factors that impact the utility indexes and their evolution through time. We used Tobit panel data estimators to deal with the bounded nature of utility values. Results Average age of patients was 63 and 55% of patients were men. Negative predictors of quality of life were the severity of the initial event, history of pneumonia, smokers, age and being male. On average, quality of life improved in the first 6 months after discharge and stabilized beyond. At month 1, mean utility index was 0.53 (SD: 0.34) for men and 0.45 (SD: 0.34) for women, versus mean of 0.69 (SD: 0.33) and 0.70 (SD: 0.35) at Month 12. “Usual activities” was the dimension the most impacted by the disease episode. Utilities for men were significantly higher than for women, although male patients were more severe. Individuals over 85 years old did not improve quality of life during follow-up, and quality of life did not improve or deteriorated for 34% of patients. We found that length of hospital stay was negatively correlated with quality of life immediately after discharge. Conclusion This study provides with evidence that quality of life after an episode of community acquired pneumococcal pneumonia improves overall until the sixth month after hospital discharge, but older patients with previous history of pneumonia may not experience health gains after the initial episode.

Recurrent staphylococcal skin and soft tissue infections may recur despite decontamination and multiple courses of antibiotic therapy and may dramatically impair the patient's quality of life. We report successful use of long-term azithromycin prophylaxis in a recurrent laryngitis and a scalp folliculitis due to methicillin-susceptible Staphylococcus aureus.

Resume La France metropolitaine est devenue un pays ou les residents sont a risque de contracter une hepatite A : en 20 ans, la seroprevalence chez les sujets de 20 ans est passee de 50 % a moins de 10 %. Pour cette raison, la prophylaxie autour d’un cas index devient un probleme majeur, car le risque d’hepatite A dans l’entourage proche d’un malade est important. Les immunoglobulines polyvalentes sont recommandees dans plusieurs pays, mais aucune marque d’immunoglobulines n’a cette indication en France. De plus, les immunoglobulines sont cheres et peu efficaces. Le vaccin contre l’hepatite A administre au jeune enfant ou a l’adolescent permet de rompre la chaine epidemique et de proteger tres efficacement l’adulte en limitant la circulation des virus. De nombreux pays proposent une vaccination precoce des sujets a risques autour du cas index, vaccination generalement conseillee dans la semaine qui suit le premier contact avec le contaminateur. Meme si des donnees plus precises et plus nombreuses manquent pour generaliser cette recommandation, elle doit etre prise en compte. Il s’agit donc d’une decision medicale individuelle prise apres discussion du risque entre le medecin et la famille du patient.

Key points France has changed from a country where hepatitis A is endemic to one where residents are at risk of hepatitis A infection: in 20 years, the seroprevalence in 20-year-olds has fallen from 50% to less than 10%. Prophylaxis for close contacts of an index case has therefore become a major problem because their risk of hepatitis A is high. Polyvalent immunoglobulins are recommended in several countries, but no immunoglobulins are approved for this indication in France. Immunoglobulins are also expensive and only slightly efficacious. A vaccine against hepatitis A administered to young children or adolescents can break the epidemic chain and protect adults very effectively by limiting virus circulation. Many countries propose early vaccination to at-risk contacts, with vaccination generally advised within a week of the initial infectious contact. Although more specific and more plentiful data are still necessary before this recommendation can be generalized, it must be taken into account. This medical decision should thus be made on an individualized basis after discussion between the physician and family about the risk.

Summary Objective Describe the clinical appearance, microorganisms involved, and prognosis of diabetic foot osteomyelitis. Method Retrospective study of 48 patients seen in 2004 for presumed osteomyelitis (exposed bone or suggestive radiographic or clinical picture). Specimens for culture came from swabs of wound discharge, needle aspiration and bone biopsy. Results Forty-eight patients with diabetes and contiguous osteomyelitis of the foot were followed for a year. The principal microorganisms isolated were Staphylococcus aureus (58%) and Gram-negative bacilli (29%); 58% of the infections were monomicrobial, 31% of the microorganisms multidrug-resistant, and 85% of the patients were hospitalized, for a median duration of 30 days. Healing occurred in 40 patients, although 15 required amputation first, and 18 had a new infection at a different site (11 involving osteomyelitis) in the year after antibiotic treatment ended. Perspectives Diabetic foot osteomyelitis is a serious disease in view of its site and the microorganisms involved, which are often multidrug-resistant. There is a clear predominance of S. aureus . Medical treatment has an increasingly important role in its management and requires that samples be properly collected for bacteriological testing. The prognosis for these infections, which remains grim in view of the amputation rate and the high risk of new infection, could be improved by reinforcing prevention measures.

The safety and immunogenicity of a monovalent inactivated vaccine against Leptospira interrogans serogroup Icterohaemorrhagiae was evaluated in 84 volunteers according to the route of administration, i.e., subcutaneous (SC) or intramuscular (IM), in a double-blind randomised trial. The volunteers were randomised into four groups: SC vaccine; IM vaccine; SC placebo; and IM placebo. Primary vaccination comprised two injections on day 0 and day 14, with a booster after 6 months. A second booster was given 30 months after primary vaccination. Local reactions within 1 h of injections were rare, with no difference between vaccine groups. Local reactions within 3 h were more frequent after the second, third and fourth SC injections than after IM injections. Systemic reactions never occurred within 1 h of vaccination and were rare within 3 days; the rates were comparable for the different vaccine groups. Evolution of the antibody responses, as assessed by microscopic agglutination tests and specific IgG and IgM ELISAs, were similar for both injection routes. IgG seroconversion rates after the first booster were 97% (95% CI 80–100%) for the SC vaccine group, and 96% (95% CI 80–100%) for the IM vaccine group, and both reached 100% for IgG after the second booster. The safety and immunogenicity of the anti-leptospiral vaccine were both good. Monitoring of antibody levels established that a booster dose triggered a strong antibody response in fully vaccinated subjects at 30 months after primary vaccination.

Resume Objectif Evaluer une strategie d’isolement et de depistage a l’admission dans un service de maladies infectieuses en periode endemo-epidemique pour l’enterocoque resistant aux aux glycopeptides (ERG) au CHU de Clermont-Ferrand. Methodes Depuis le 15/11/2004, des l’admission en maladies infectieuses, un depistage systematique de l’ERG a ete realise par ecouvillonnage rectal avec isolement du patient en cas d’antecedent (a) d’hospitalisation > 24 h dans un service a risque du CHU et/ou (b) d’antibiotherapie a large spectre d’une duree superieure a 48 h Un depistage hebdomadaire a ete pratique pour les patients hospitalises plus d’une semaine avec une antibiotherapie a large spectre ou ayant une sonde urinaire depuis plus d’une semaine ou neutropeniques durant l’hospitalisation. Resultats Jusqu’au 15/5/2005, sur 341 ecouvillonnages rectaux, 12 (3,5%) etaient positifs pour l’ERG: 8 a l’admission et 4 en cours d’hospitalisation. Quatre-vingt-un patients ont ete isoles des l’admission. Une etude cas temoin a confirme la pertinence des criteres d’isolement. Les mesures d’isolement ont ete acceptees par les patients a partir du moment ou elles etaient bien expliquees. Aucun nouveau cas n’a ete observe de mai a juillet 2005. Conclusion Une strategie d’isolement basee sur des facteurs de risque avec un depistage systematique a l’admission parait etre un moyen efficace pour controler une epidemie a ERG, tant parce qu’elle permet d’isoler des patients que parce qu’elle oblige l’equipe medicale et paramedicale a rester mobilisee.

Staphylococcus aureus is the main cause of diabetic foot osteomyelitis (DFO) and can be treated medically or by surgery. We investigated the outcome of consecutive patients with a diagnosis of S aureus DFO retrospectively in 4 hospitals according to the type of management, medical (including debridement at bedside) or surgical. The outcome was classified as either favorable or failure (relapse, impaired wound healing, or amputation). Seventy-four patients with S aureus DFO, including 26 with methicillin-resistant S aureus, were included with a mean duration of follow-up of 21 ± 1 months. As part of the initial treatment, 47% underwent bone surgery followed with a short course of antibiotic. Others were treated with antibiotic therapy alone with bedside debridement. The outcome was favorable for 84% of these patients, with similar rates in the surgical and medical groups (80% vs 87%, P > .05). Patients in the medical group were less frequently hospitalized (49% vs 94%, P < .001) and had a shorter length of hospital stay (17 ± 3 vs 50 ± 12 days, P = .004). Patients in the surgery group received a shorter course of antibiotic therapy (10 ± 2 vs 11 ± 1 weeks, P = .001) with fewer side effects (9% vs 33%, P = .01). The type of management was not associated with subsequent new episode of noncontiguous DFO, which developed in 32% of cases. In conclusion, except significant differences in duration of hospitalization and antibiotic therapy, medical and surgical management of S aureus DFO had similar outcomes with a cure rate >80%.

Objectifs PNEUMOCOST est une etude observationnelle prospective multicentrique incluant des patients hospitalises en France pour une pneumonie communautaire a pneumocoque. L’objectif primaire etait d’estimer le cout du traitement des patients sur une periode de 6 mois apres la sortie de l’hopital. Alors que 550 patients devaient etre inclus les resultats sont presentes pour 455 patients dont les donnees cliniques etaient completes. Methodes Criteres d’inclusion : âge > 18 ans, pneumonie confirmee par radiographie, infection a pneumocoque confirmee microbiologiquement. Criteres d’exclusion : grossesse, patients inclus dans un essai clinique, patients hospitalises depuis plus de 48 h pour un autre motif, patients incapables de repondre a un questionnaire. Resultats Caracteristiques des patients : 54,6 % d’hommes. Âge moyen : 63 ans (min : 19 ; max : 96). 77,3 % des patients avaient ≥ 50 ans. Diagnostic de l’infection a pneumocoque : la detection de l’antigene urinaire a ete effectuee dans 73,4 % des cas ; l’hemoculture dans 37,4 % et 22,6 % ont realise les deux tests. Les resultats des tests de sensibilite aux antibiotiques sont dans le Tableau 1 . Hospitalisation Duree moyenne du sejour : 13,8 jours (E–T 14,8 ; min 1 ; max 221). Au total, 40 % des patients avaient ete en reanimation ou en soins intensifs, pendant une duree moyenne de 3,3 jours (E–T 6,6). La duree du sejour augmentait avec le score de Charlson de 10,5 jour pour un score de 0 a 17,4 jours pour un score ≥ 6. Le risque d’etre admis en reanimation augmentait avec le score de Fine de 14 % pour la classe 1 a 49 % pour la classe 4. La mortalite parmi les patients hospitalises etait faible ( n = 8). Le cout moyen du sejour (point de vue de la Securite Sociale) etait de 6962 € (E–T 6933 €). La distribution des couts etait tres asymetrique : 25 % des sejours representaient 56 % des couts totaux de l’ensemble des sejours de l’echantillon. Conclusion Ces resultats confirment l’impact economique eleve de la maladie. Comme aucune augmentation significative de l’efficacite des antibiotiques n’est attendue, les strategies de prevention comme la vaccination sont essentielles pour diminuer le cout de la maladie.

The aims of this study were to assess the sociodemographic, epidemiological, clinical, and biological characteristics of French patients co-infected with human immunodeficiency virus-hepatitis C virus (HIV-HCV), as well as the management of their HCV infection. Data on 509 HIV-HCV co-infected patients, followed up at six French University Hospitals, were collected using a questionnaire. Student's t-test, Pearson's chi-square, Fisher's exact, and Fisher-Freeman-Halton's exact tests were used. The mean age of the patients was 38.3 years, and the male to female sex ratio 2.08; 88% of patients were born in Metropolitan France, and 20% were dependent on health benefits; 74% were intravenous drug users and 14% blood or blood product recipients. Forty-seven percent were in CDC classification stage A, 18% had a CD4+ count of200, and 79% were undergoing current antiretroviral treatment. HCV RNA was positive in 84% (50% type 1, 13% untypable). Forty-four percent had normal alanine aminotransferase (ALT) levels, 24% alcohol consumption15 g/day, and 51% had undergone liver biopsy (10% of which had cirrhosis). Histological grade was not related to ALT level or CD4+ count. Overall, 40% of patients had been treated for HCV infection. HCV treatment was significantly associated with performance of liver biopsy, histological grade, ALT level, CD4+ count, Centers for Disease Control (CDC) classification, but not with age or alcohol consumption. Rate of early response to treatment was fifty percent among patients treated with bitherapy. Eighty-nine percent of all patients with previous or current anti-HCV treatment had undergone liver biopsy. In conclusion, despite the difficulties in managing hepatitis C in HIV-infected patients, almost one-half of all patients in this study had received anti-HCV treatment.

Background: We designed a prospective study in the Puy-de-Dome region of France to identify factors associated with a hospitalization decision by general practitioners (GPs) for patients with community-acquired pneumonia (CAP). Patients and Methods: 95 voluntary GPs were recruited to report over the period (February 1993 to March 1994) patients diagnosed with CAP defined as acute onset of fever associated with focal pulmonary crackles and/or radiological changes consistent with a pulmonary infection in patients over 3 years of age, living in the community. Results: 37 of the 175 CAP patients (21.4%) were hospitalized. Univariate analysis showed that the hospitalization decision was related to age > 65 years, retirement, history of cardiovascular disease, other extra-pulmonary chronic disease, chest auscultation findings, tachypnea at rest and altered mental status. Multivariate analysis identified four variables associated with hospitalization: living alone at home (OR = 3.75), history of cardiovascular disease (OR = 2.54), other chronic medical medical conditions excluding pulmonary diseases (OR = 4.28) and tachypnea at rest (OR = 3.33). The hospitalization decision by GPs for patients with CAP takes into account social conditions, co-morbid conditions of the patients and the severity of CAP.

Purpose To provide the key role of ophthalmologists in the management of syphilis presenting with ocular involvement, describe the increase of patients diagnosed with syphilis infection presenting ophthalmological involvement and their clinical features. Methods Retrospective, observational case series analysis: patients were selected retrospectively based on serological criteria: VDRL>1 and TPHA>80, with upper cut-off limit TPHA 1280). Among these patients, patients presenting ophthalmological involvement were analyzed further. Results Over the 10-year period, among 126 patients diagnosed with syphilis, 22 patients with various ocular involvements were treated. The resurgence of syphilis has also been registered in ophthalmology. Among the specialized departments, ophthalmology ranks second in number of cases of syphilis infection diagnosed: 77% of patients with ocular involvement are diagnosed in ophthalmology. Conclusion This underlines the central diagnostic role of ophthalmologists, as in cases of eye involvement, if ophthalmologists ignore the infection, diagnosis will rarely be picked up in other care units, especially given that visual symptoms are isolated in 80% of cases.

Hospital laboratory reports of parainfluenza virus (PIV) infections from England and Wales between 1975 and 1997 were analysed with regard to PIV type and seasonality, and in addition, those between 1985–1997 with regard to age, sex and clinical features. Laboratory-based surveillance data highlight striking differences in the seasonality of different PIV types. PIV-3 reports demonstrated a clear annual epidemic cycle, with a peak usually occurring in late spring or summer, whereas peaks of PIV-1 and PIV-2 occurred at one or two year intervals, in the late autumn or early winter. PIV-4 also occurred most frequently in the late autumn or early winter, but a clear epidemic cycle could not be identified. Laboratory surveillance data also provide insight into the age and disease distribution of PIV infection in children and indicate severity of PIV infection in immunosuppressed adults. Of 8221 PIV reports received between 1985–1997, PIV-3 accounted for 70.8, PIV-1 for 17.2, PIV-2 for 7.5, and PIV-4 for 1.1; 64.1 of reports came from infants under one year, 24.4 from children aged 1–4 years and 7.2 from individuals aged 5 years or older, with an excess of males in all age groups. Bronchiolitis, croup and pneumonia occurred in association with all PIV types. In children under 1 year, PIV-2 infections were more likely to be associated with bronchiolitis than infections with other PIV types. In children under 15 years, croup was more frequently associated with PIV-1 and PIV-2 than with PIV-3 or PIV-4. In 392 (7.2) of the reported PIV infections between 1989 and 1997 an underlying condition was implicated, which included immunosuppression or chronic cardiac or pulmonary disease. Considerable morbidity is associated with PIV infections in infants and young children and would make the widescale use of a vaccine a valuable public health intervention. Surveillance information is essential to guide the development and use of preventive measures as well as to monitor their effectiveness.

This virulent clone has already spread to other continents., We report 2 outbreaks of Panton-Valentine leukocidin–positive, doxycycline-resistant, methicillin-susceptible Staphylococcus aureus infections in French soldiers operating in Côte d’Ivoire. In a transssectional survey, nasal carriage of this strain was found in 2.9% of 273 soldiers about to be sent to Côte d’Ivoire and was associated with prior malaria prophylaxis with doxycycline.

Internationally adopted children may suffer from different pathologies, including infectious diseases contracted in the country of origin. We evaluated the frequency of infectious diseases that may disseminate from adoptees to adoptive families on their arrival in France. All children who attended the clinic for international adoption in Clermont-Ferrand from January 2009 through to December 2011 were eligible for inclusion in the study. Standardized medical records dedicated to international adoption were retrospectively reviewed for demographic data, clinical diagnosis, and biological and radiological results. Data were completed by phone interviews with adoptive families after informed consent. One hundred and forty-two medical records were retrospectively reviewed and 86% of families agreed to be interviewed. One hundred and seventy-one potentially transmissible infections were diagnosed in 142 children, 12% (n = 20) of which were transmitted to adoptive families. Most of these infections were benign and transmission was restricted to the close family. Tinea was diagnosed in 44 adoptees and transmitted in 15 cases. Panton Valentine leukocidin producing methicillin-sensitive S. aureus (MSSA) was transmitted to an adoptive father who required hospitalization for bursitis. Transmission also occurred for CMV (n = 1), hepatitis A (n = 1), giardiasis (n = 1), scabies (n = 1), Moluscum (n = 2) and pediculosis (n = 2). Two cases of chronic hepatitis B and latent tuberculosis were diagnosed without subsequent transmission. In conclusion, infectious diseases are common in internationally adopted children and should be detected shortly after arrival to avoid transmission.

Background Flexibility of vaccination schedule and lower antigen content can facilitate pandemic vaccine coverage. We assessed the immune response and safety of AS03-adjuvanted A/California/7/2009 H1N1 pandemic vaccine containing half of the registered adult haemagglutinin (HA) antigen content, administered as a two-dose schedule at intervals of 21 days or 6 months in both young and elderly adults. Methods In this open-label randomized trial, healthy adults aged 18–60 years (N = 163) and >60 years (N = 143) received AS03A-adjuvanted A/California/7/2009 H1N1 vaccine containing 1.9 μg HA on Day 0. A second dose was given on Day 21 (n = 177) or Day 182 (n = 106). Haemagglutination-inhibition (HI) antibody responses were analyzed on Days 0, 21, 42, 182, 364 and additionally on Day 203 for subjects vaccinated on Day 182. Solicited and unsolicited adverse events were recorded. Results The HI antibody response in both age strata 21 days after the first dose met and exceeded all regulatory acceptance criteria although the results suggested a lower response in the older age stratum (geometric mean titres [GMTs] for HI antibodies of 420.5 for subjects aged 18–60 years and 174.4 for those >60 years). A second dose of AS03A adjuvanted A/H1N1/2009 vaccine induced a further increase in antibody titres and the response was similar whether the second dose was administered at 21 days (GMTs of 771.8 for 18–60 years and 400.9 for >60 years) or 6 months (GMTs of 708.3 for 18–60 years and 512.1 for >60 years) following the first dose. Seroprotection rates remained high at 6 months after one dose or two doses while at 12 months rates tended to be higher for the 6 month interval schedule (93.3% for 18–60 years and 80.4% for >60 years) than the 21 day schedule (82.3% for 18–60 years and 50.0% for >60 years). Reactogenicity/safety profiles were similar for both schedules, there was no evidence of an increase in reactogenicity following the second dose. Conclusions The results indicate that flexibility in the dosing interval for AS03A adjuvanted vaccine may be possible. Such flexibility could help to reduce the logistic stress on delivery of pandemic vaccination programmes. Trial registration ClinicalTrials.gov, NCT00975884

International audience; In adults with a tetanus-prone injury, combined vaccines such as Tdap-IPV (REPE VAX (R)) can boost immunity against several diseases simultaneously. This Phase IIIb, parallel-group, open-label trial compared antibody responses to Tdap-IPV and tetanus monovalent vaccine (TMV; Vaccin Tetanique Pasteur (R) or Tetavax (R)) against tetanus toxoid 10 and 28 d post-vaccination. Between July and December 2009, four centers in France and five in Germany recruited healthy adults who had received a tetanus-containing vaccine 5-10 y previously. Participants were randomized 1: 1 to receive at the first visit a single dose (0.5 mL) of Tdap-IPV or TMV, with follow-up visits at Day 10 and Day 28. Outcomes: per protocol (PP) population immunogenicity at Day 10 (primary) and at Day 28 (secondary); safety throughout the study. Of 456 adults randomized, 223 received Tdap-IPV and 233 received TMV (PP population: 183 and 199 participants, respectively). All participants receiving Tdap-IPV and 99.0% receiving TMV had an anti-tetanus antibody concentration >= 0.1 IU/mL, confirming non-inferiority of Tdap-IPV to TMV (95% confidence interval of the difference: -1.2, 3.6). Number of adverse events reported was comparable in each group. Injection-site reactions were reported by 76.6% participants receiving Tdap-IPV and 74.6% receiving TMV. Systemic events (e. g., malaise, myalgia and headache) were reported in 47.7% and 39.7% of the Tdap-IPV and the TMV groups, respectively. Tdap-IPV is effective and well-tolerated for use in the management of tetanusprone injuries in emergency settings in persons for whom a booster against diphtheria, pertussis and poliomyelitis is also needed. ClinicalTrials.govidentifier: NCT00928785. Research sponsored by Sanofi Pasteur MSD.

International audience; OBJECTIVES: The aim of the study was to assess whether an isolated positive catheter culture is predictive of a subsequent bloodstream infection in intensive care unit patients. DESIGN: Retrospective clinical study between 2000 and 2007. SETTING: Intensive care unit of a university hospital. SUBJECTS: All arterial, central venous, and dialysis catheters yielding selected pathogenic microorganisms from isolated positive catheter cultures. Positive catheter culture was defined by a catheter tip culture performed with the Brun-Buisson technique yielding ≥103 colony-forming units/mL; isolated positive catheter culture by a positive catheter culture without concomitant bloodstream infection due to the microorganism of the positive catheter culture evidenced within 48 hrs before or after catheter removal; and subsequent bloodstream infection by a bloodstream infection developing between 48 hrs and 30 days after catheter removal and due to a selected pathogenic microorganism of an isolated positive catheter culture. Active antibiotic therapy was active if at least one of the antibiotics administered was effective against the selected pathogenic microorganism of the positive catheter culture. INTERVENTION: None. MEASUREMENT AND MAIN RESULTS: The end point of the study was the ratio of the number of subsequent bloodstream infections to that of selected pathogenic microorganisms isolated from positive catheter culture 30 days after catheter removal. A total of 138 isolated positive catheter cultures for 149 selected pathogenic micro-organisms was included in the study. Only two cases (1.3%) of subsequent bloodstream infection were evidenced, one resulting from Escherichia coli and the other from Staphylococcus epidermidis. The incidence of subsequent bloodstream infection did not differ with regard to the presence or absence of active antibiotics at catheter removal: zero of 23 vs. two of 121 (p = 1), respectively. CONCLUSIONS: Our results suggest that the risk of subsequent bloodstream infection in intensive care unit patients when the Brun-Buisson technique is used to define isolated positive catheter culture is low.

Surgical percutaneous bone biopsy specimen after a 14-day antibiotic-free period represents the gold standard of care for diabetic foot osteomyelitis but may be difficult to implement in many institutions. We evaluate a simplified strategy based on the results of per-wound bone specimen culture. For that purpose, we retrospectively reviewed the charts of 80 consecutive patients with diabetic osteomyelitis and bone sample obtained via the wound after a careful debridement. The outcome was defined as favourable if there was a complete healing of the wound with no sign of infection and stable or improved bone X-ray 6 months after antibiotic therapy completion. Culture of bone specimens was positive in 96% of patients, although half of the patients did receive a course of antimicrobials within 14 days of the bone specimen being obtained. A total of 129 bacterial isolates were obtained from bone cultures with a mean of 1.6 ± 1 isolates per patient (Staphylococcus aureus: 33%; coagulase-negative staphylococci: 14%; streptococci: 9%; enterococci: 12%; corynebacteria: 4%; Gram-negative bacilli: 20%; anaerobes: 4%). Forty-six percent of cultures were monomicrobial. The mean duration of follow-up from diagnosis was 17 ± 1 months. Six months after discontinuation of antibiotics, six patients (7.5%) had died, nine were considered as therapeutic failures and 65 were considered as cured. Fifty-four of these 65 patients had follow-up data available at 1 year and remained in remission. In conclusion, a simplified procedure based on the culture of bone sample obtained via the ulcer after a careful debridement of the wound is effective in the medical management of diabetic foot osteomyelitis.

France has changed from a country where hepatitis A is endemic to one where residents are at risk of hepatitis A infection: in 20 years, the seroprevalence in 20-year-olds has fallen from 50% to less than 10%. Prophylaxis for close contacts of an index case has therefore become a major problem because their risk of hepatitis A is high. Polyvalent immunoglobulins are recommended in several countries, but no immunoglobulins are approved for this indication in France. Immunoglobulins are also expensive and only slightly efficacious. A vaccine against hepatitis A administered to young children or adolescents can break the epidemic chain and protect adults very effectively by limiting virus circulation. Many countries propose early vaccination to at-risk contacts, with vaccination generally advised within a week of the initial infectious contact. Although more specific and more plentiful data are still necessary before this recommendation can be generalized, it must be taken into account. This medical decision should thus be made on an individualized basis after discussion between the physician and family about the risk.

To evaluate a strategy based on screening and isolation at admission to a department of infectious diseases during an epidemic of vancomycin-resistant Enterococcus (VRE) at the University Hospital of Clermont-Ferrand.Systematic screening for VRE by anal swabs began on November 15, 2004. Patients were isolated on admission if (a) they had been hospitalized more than 24 h in an at-risk department of our hospital or (b) they had received a course of wide-spectrum antimicrobial therapy for longer than 48 h in the three months preceding admission. Patients hospitalized in our department were screened weekly if they were treated with wide-spectrum antibiotics, had a urinary catheter left in place for one week, or were neutropenic.Through May 15, 2005, 12 (3.5%) of 341 swabs were found to be positive for VRE: eight were detected on admission and four during hospitalization. In all, 81 patients were isolated on admission. A case-control study confirmed that the criteria for patient isolation were indeed risk factors for VRE. Isolation was well accepted when it was clearly explained. No new case has been detected since March 2005.An isolation strategy based on known risk factors for VRE with systematic screening on admission appears to be an effective way to control an outbreak of VRE, perhaps in part because it helps to keep the medical staff alert to this problem. Isolation is well tolerated as long as it is explained clearly.

Describe the clinical appearance, microorganisms involved, and prognosis of diabetic foot osteomyelitis.Retrospective study of 48 patients seen in 2004 for presumed osteomyelitis (exposed bone or suggestive radiographic or clinical picture). Specimens for culture came from swabs of wound discharge, needle aspiration and bone biopsy.Forty-eight patients with diabetes and contiguous osteomyelitis of the foot were followed for a year. The principal microorganisms isolated were Staphylococcus aureus (58%) and Gram-negative bacilli (29%); 58% of the infections were monomicrobial, 31% of the microorganisms multidrug-resistant, and 85% of the patients were hospitalized, for a median duration of 30 days. Healing occurred in 40 patients, although 15 required amputation first, and 18 had a new infection at a different site (11 involving osteomyelitis) in the year after antibiotic treatment ended.Diabetic foot osteomyelitis is a serious disease in view of its site and the microorganisms involved, which are often multidrug-resistant. There is a clear predominance of S. aureus. Medical treatment has an increasingly important role in its management and requires that samples be properly collected for bacteriological testing. The prognosis for these infections, which remains grim in view of the amputation rate and the high risk of new infection, could be improved by reinforcing prevention measures.

Background Lemierre's syndrome presents a classic clinical picture, the pathophysiology of which remains obscure. Attempts have been made to trace genetic predispositions that modify the host detection of pathogen or the resultant systemic reaction. Case presentation A 17-year old female, with no previous medical history, was admitted to the intensive care unit for septic shock, acute respiratory distress syndrome and Lemierre's syndrome. Her DNA was assayed for single nucleotide polymorphisms previously incriminated in the detection of the pathogen, the inflammatory response and the coagulation cascade. We observed functional variations in her Toll like 5 receptor (TLR 5) gene and two coagulation variations (Tissue Factor (TF) 603 and Plasminogen-Activator-Inhibitor-1 (PAI-1) 4G-4G homozygosity) associated with thrombotic events. Conclusion The innate immune response and the prothrombogenic mutations could explain, at least in part, the symptoms of Lemierre's syndrome. Genomic study of several patients with Lemierre's syndrome may reveal its pathophysiology.

The present study was carried out to assess the effects of protease inhibitor (PI) therapy on basal whole body protein metabolism and its response to acute amino acid-glucose infusion in 14 human immunodeficiency virus (HIV)-infected patients. Patients treated with PIs (PI+, 7 patients) or without PIs (PI−, 7 patients) were studied after an overnight fast during a 180-min basal period followed by a 140-min period of amino acid-glucose infusion. Protein metabolism was investigated by a primed constant infusion of l-[1-13C]leucine. Dual-energy X-ray absorptiometry for determination of fat-free mass (FFM) and body fat mass measured body composition. In the postabsorptive state, whole body leucine balance was 2.5 times ( P < 0.05) less negative in the PI+ than in the PI− group. In HIV-infected patients treated with PIs, the oxidative leucine disposal during an acute amino acid-glucose infusion was lower (0.58 ± 0.09 vs. 0.81 ± 0.07 μmol·kg FFM−1·min−1 using plasma [13C]leucine enrichment, P = 0.06; or 0.70 ± 0.10 vs. 0.99 ± 0.08 μmol·kg FFM−1·min−1 using plasma [13C]ketoisocaproic acid enrichment, P = 0.04 in PI+ and PI− groups, respectively) than in patients treated without PIs. Consequently, whole body nonoxidative leucine disposal (an index of protein synthesis) and leucine balance (0.50 ± 0.10 vs. 0.18 ± 0.06 μmol·kg FFM·−1·min−1 in PI+ and PI− groups respectively, P < 0.05) were significantly improved during amino acid-glucose infusion in patients treated with PIs. However, whereas the response of whole body protein anabolism to an amino acid-glucose infusion was increased in HIV-infected patients treated with PIs, any improvement in lean body mass was detected.

French immunisation schedule recommends tetanus and poliomyelitis vaccine every 10 years and influenza every year after the age of 65. Several other vaccinations related to occupational health are implemented. Travellers or immunocompromised people who could be exposed to infections need some other vaccinations, too. Pneumoccocal vaccine coverage is insufficient. Reinforcing diphteria immunization is considered, using a recently licensed combined vaccine. Maintenance of immunity against "childhood infectious diseases" preventable with vaccinations is a new challenge; measles, rubella and pertussis occur now quite often in adults: the risk of complications is higher in these ages (measles), or expose to specific risk (rubella in pregnant women); adults may even become the source of the contamination of younger people (many infants affected with whooping cough have contracted the disease from their own parents). The immunisation against these diseases should be prosecuted in adults. Related with the development of more efficacious new vaccines, the indications of pneumococcus, meningococcus or varicella vaccines should be defined in some populations of adults. Immunization policy of adults should be revised in order to continue the vaccination program of childhood. Some infections that may affect adults should be prevented by improving vaccine application. A real adult immunisation schedule and recommendations should be set up towards populations at risk of preventable infections. The implementation of these recommendations should be reinforced.

Background: The nucleoside reverse transcriptase inhibitors used for the treatment of HIV-positive persons are now clearly associated with metabolic disorders. We determined the prevalence of and risk factors for hyperlactatemia in HIV-positive persons to assess the relevance of lactate venous blood concentrations during antiretroviral therapy. Methods: We conducted a prospective cross-sectional study of venous lactate determinations with 282 consecutive HIV-positive persons who, in addition to a physical examination, had blood samples taken every 3–4 months for routine biochemical, immunologic, and viral assessment. The frequencies of hyperlactatemia and lactic acidosis were determined, and the risk factors were analyzed by a multivariate logistic regression model. The effect of modification of antiretroviral therapy in patients with moderate hyperlactatemia was also assessed. Results: From 782 blood lactate determinations, we identified 65 (23%) patients with moderate hyperlactatemia and 5 (1.8%) with lactate concentrations >5 mmol/L (2 with severe lactic acidosis; 0.7%). Older age, drug regimens containing stavudine [adjusted odds ratio (OR) = 2.5] or a combination of stavudine-didanosine (adjusted OR = 3.1), and the use of buprenorphine (adjusted OR = 14.7) were independent predictors of hyperlactatemia. Among 65 patients with moderate hyperlactatemia, 39 did not have their treatments changed, and 26 had a new combination therapy that was associated with a clinical improvement and a more pronounced decrease in lactate (−1.66 vs −0.99 mmol/L; P Conclusions: Chronic compensated and moderate hyperlactatemia was common in our population study. Measurement of lactate, under standardized conditions, may be useful in optimizing management of HIV-positive persons on antiretroviral therapy.

Enterovirus meningitis is well documented in children. However, there is a paucity of reports in adults, despite the availability of genome detection (RT-PCR) in cerebrospinal fluid (CSF), which provides a rapid and reliable diagnosis. The clinical course and management of 30 cases of entero-virus proven meningitis prospectively diagnosed between August 1999 and November 2000 in immunocompetent adults were analysed, and laboratory and clinical strategies evaluated. Patient age ranged between 17 and 43 (median 29). The analysis of clinical, biological, and epidemiological data showed the difficulty of recognising enterovirus meningitis in adults. Characteristic symptoms were either inconstant (the association of fever/headache/stiff neck) or misleading (the presence of vesicular lesions). CSF data showed moderate pleocytosis but a predominance of lymphocytes in only 12/27 (44%) patients. An epidemiological background was present in 10/30 (33%) patients, but 10/30 (33%) patients were admitted during cold months. Consequently, although the detection of enterovirus genome in CSF was positive in all cases, the results were communicated within a median of 6 days [2-9] after admission, mainly because the aetiology was not considered early enough. Management of patients varied between departments and between individual physicians, with measures ranging from computed tomography (33%) to the prescription of aciclovir (20%) or antibiotics (53%). Enterovirus meningitis should not be underestimated in adults. Management could be improved and standardised, and costs reduced by more systematic year-round use of enterovirus RT-PCR in meningitis, provided results are rapid.