Informational resources used by farmers with ruminants and monogastrics for animal health monitoring: importance of sensory indicators.

Managers of health in livestock systems are asked to shift from a curative approach to a more preventive approach. This change requires sociological and technical reconfiguration and raises the issue of how changes are implemented by farmers and their technical support ecosystem (advisors, trainers, veterinarians). Here, we report work conducted in western France by an Agricultural European Innovation Partnership Operational Group bringing together animal scientists and sociologists to advance knowledge on animal health in a range of livestock sectors, i.e. dairy cattle, beef cattle, small ruminants (sheep, goats), poultry and pigs. In this study, our aim was to answer this question: what are the Informational Resources (I.R.) that farmers use to promote animal health of their herds? First, we used a survey to characterize 129 I.R. used by advisors, then, we used statistical analysis to classify these I.R. into six clusters. Second, we organized eight focus-group sessions that involved a total of 50 farmers from across all livestock sectors to find out how they mobilize the I.R. and what they see as important for animal health monitoring practice. Finally, we performed individual interviews with 42 farmers to expand the data captured in the collective focus groups. Results showed that farmers and advisors have a broad and diverse range of I.R. to help monitor animal health. We identified six clusters of I.R.: regulatory tools, periodic reports, tools for farmer-led monitoring, tools and indicators for national reference datasets, slaughterhouse and laboratory indicators, and training delivered to farmers. During focus group, livestock farmers identified some of their I.R. within these clusters but they also cited other daily routines that help them monitor animal health that were not cited by advisors. We found that farmers mainly use sensory indicators (typically smell, sight, touch) in their daily practice whereas advisors mainly use relatively sophisticated retrospective monitoring tools. Farmers also cited the importance of indicators that can rapidly objectify any change in animal condition, behavior, or health. This work finds a split in the distribution of animal health management roles, with farmers implementing daily checks whereas advisors run periodic health surveillance, thus revealing differentiated roles and needs between farmers and their advisors.

Pharmacokinetic interaction between rifampicin and clindamycin in staphylococcal osteoarticular infections.

OBJECTIVES: Oral combination of clindamycin and rifampicin is relevant for the treatment of staphylococcal osteoarticular infection (SOAIs). However, rifampicin induces CYP3A4, suggesting a pharmacokinetic interaction with clindamycin with unknown pharmacokinetic/pharmacodynamic (PK/PD) consequences. This study aimed to quantify clindamycin PK/PD markers before and during rifampicin co-administration in SOAI. METHODS: Patients with SOAI were included. After initial intravenous antistaphylococcal treatment, oral therapy was started with clindamycin (600 or 750 mg t.i.d.), followed by addition of rifampicin 36 h later. Population PK analysis was performed using the SAEM algorithm. PK/PD markers were compared with and without rifampicin co-administration, each patient being his own control. RESULTS: In 19 patients, clindamycin median (range) trough concentrations were 2.7 (0.3-8.9) mg/L and <0.05 (<0.05-0.3) mg/L before and during rifampicin administration, respectively. Rifampicin co-administration increased clindamycin clearance by a factor 16 and reduced the AUC0-8h/MIC by a factor 15 (P < 0.005). Clindamycin plasma concentrations were simulated for 1000 individuals, without and with rifampicin. Against a susceptible Staphylococcus aureus strain (clindamycin MIC 0.0625 mg/L), >80% of individuals would reach all proposed PK/PD targets without co-administration of rifampicin, even with low clindamycin dose. For the same strain, when rifampicin was co-administered, the probability to reach clindamycin PK/PD targets dropped to 1% for %fT>MIC = 100% and to 6% for AUC0-24h/MIC > 60, even with high clindamycin dose. CONCLUSION: Rifampicin co-administration with clindamycin has a high impact on clindamycin exposure and PK/PD targets in SOAI, which could result in clinical failure even for fully susceptible strains.

The intravenous vancomycin prescription practices of French infectious disease specialists: A cross-sectional observational study.

INTRODUCTION: Vancomycin prescription modalities remain non-consensual. We examined and evaluated the vancomycin prescription habits of infectious disease specialists in France. METHODS: Through an anonymized online questionnaire sent to members of the French Infectious Diseases Society, detailed information on vancomycin prescription modalities was collected. RESULTS: Out of the 712 physicians contacted, 179 (25%) completed the questionnaire; 174 (97%) of them routinely prescribed intravenous vancomycin: 95 (55%) by continuous infusion only, 12 (7%) by intermittent infusion, while 67 (38%) used the two modalities. Among continuous administration users, 157 (97%) applied a loading dose of 15 mg/kg or less (n = 80, 49%), 20-25 mg/kg (n = 33, 20%), or 30 mg/kg or more (n = 45, 28%); 143 (88%) used a maintenance dosage of 30 mg/kg/day and 157 (97%) carried out drug monitoring. CONCLUSION: In France, infectious disease specialists favor continuous administration of vancomycin using a loading dose, with systematic monitoring of vancomycin serum concentrations.

Expression of CTX-M-15 limits the efficacy of ceftolozane/tazobactam against Escherichia coli in a high-inoculum murine peritonitis model.

OBJECTIVES: Among carbapenem-sparing therapies, ceftolozane/tazobactam has been proposed for the treatment of infections due to CTX-M-15-producing Escherichia coli. However, few data exist on its in vivo activity in infections associated with a high bacterial inoculum. METHODS: We analysed ceftolozane/tazobactam activity against susceptible E. coli CFT073-RR and its CTX-M-15-producing transconjugant E. coli CFT073-RR Tc blaCTX-M-15, in vitro at low and high inocula, and in a high-inoculum murine model of peritonitis. RESULTS: Against E. coli CFT073-RR Tc blaCTX-M-15, ceftolozane/tazobactam bactericidal effect was impaired in vitro with only a minor inoculum effect; this translated into reduced activity compared with imipenem in the mouse peritonitis model. CONCLUSIONS: Combination of extended spectrum ß-lactamase expression and high inoculum size may be a clinical situation at risk of reduced bactericidal activity of ceftolozane/tazobactam.

Mortality in Escherichia coli bloodstream infections: antibiotic resistance still does not make it.

BACKGROUND: Escherichia coli bloodstream infections (BSIs) account for high mortality rates (5%-30%). Determinants of death are unclear, especially since the emergence of ESBL producers. OBJECTIVES: To determine the relative weight of host characteristics, bacterial virulence and antibiotic resistance in the outcome of patients suffering from E. coli BSI. METHODS: All consecutive patients suffering from E. coli BSI in seven teaching hospitals around Paris were prospectively included for 10 months. E. coli isolates were sequenced using Illumina NextSeq technology to determine the phylogroup, ST/ST complex (STc), virulence and antimicrobial resistance gene content. Risk factors associated with death at discharge or Day 28 were determined. RESULTS: Overall, 545 patients (mean ± SD age 68.5 ±âŸ16.5 years; 52.5% male) were included. Mean Charlson comorbidity index (CCI) was 5.6 (± 3.1); 19.6% and 12.8% presented with sepsis and septic shock, respectively. Portals of entry were mainly urinary (51.9%), digestive (41.9%) and pulmonary (3.5%); 98/545 isolates (18%) were third-generation cephalosporin resistant (3GC-R), including 86 ESBL producers. In-hospital death (or at Day 28) was 52/545 (9.5%). Factors independently associated with death were a pulmonary portal of entry [adjusted OR (aOR) 6.54, 95% CI 2.23-19.2, P = 0.0006], the iha_17 virulence gene (aOR 4.41, 95% CI 1.23-15.74, P = 0.022), the STc88 (aOR 3.62, 95% CI 1.30-10.09, P = 0.014), healthcare-associated infections (aOR 1.98, 95% CI 1.04-3.76, P = 0.036) and high CCI (aOR 1.14, 95% CI 1.04-1.26, P = 0.006), but not ESBL/3GC-R. CONCLUSIONS: Host factors, portal of entry and bacterial characteristics remain major determinants associated with mortality in E. coli BSIs. Despite a high prevalence of ESBL producers, antibiotic resistance did not impact mortality. (ClinicalTrials.gov identifier: NCT02890901.).

A Rapid CRISPR/Cas-based Mutagenesis Assay in Zebrafish for Identification of Genes Involved in Thyroid Morphogenesis and Function.

The foregut endoderm gives rise to several organs including liver, pancreas, lung and thyroid with important roles in human physiology. Understanding which genes and signalling pathways regulate their development is crucial for understanding developmental disorders as well as diseases in adulthood. We exploited unique advantages of the zebrafish model to develop a rapid and scalable CRISPR/Cas-based mutagenesis strategy aiming at the identification of genes involved in morphogenesis and function of the thyroid. Core elements of the mutagenesis assay comprise bi-allelic gene invalidation in somatic mutants, a non-invasive monitoring of thyroid development in live transgenic fish, complementary analyses of thyroid function in fixed specimens and quantitative analyses of mutagenesis efficiency by Illumina sequencing of individual fish. We successfully validated our mutagenesis-phenotyping strategy in experiments targeting genes with known functions in early thyroid morphogenesis (pax2a, nkx2.4b) and thyroid functional differentiation (duox, duoxa, tshr). We also demonstrate that duox and duoxa crispants phenocopy thyroid phenotypes previously observed in human patients with bi-allelic DUOX2 and DUOXA2 mutations. The proposed combination of efficient mutagenesis protocols, rapid non-invasive phenotyping and sensitive genotyping holds great potential to systematically characterize the function of larger candidate gene panels during thyroid development and is applicable to other organs and tissues.

[Influenzae and pneumococcal vaccination rate in an internal medicine ward]. / Couverture vaccinale antigrippale et antipneumococcique dans un service de médecine interne.

INTRODUCTION: Vaccination against influenza virus and Streptococcus pneumoniae is a global health priority and authorities, on the basis of recent publications, have recently updated French recommendations. The aim of this study was to describe the influenzae and pneumococcal vaccination's rate in an internal medicine ward. MATERIAL AND METHODS: All patients consecutively hospitalized during a 10 week-period in an internal medicine ward were included. The reasons for non-vaccination and the impact of an educational program for corrective measures were reported. RESULTS: Overall, 198 consecutive patients were included; 93 (47%) were immunocompromised; 142 (71.2%) had an indication for pneumococcal vaccination and 171 (86.4%) for influenza vaccination but only 16.2% and 55% of them were vaccinated against these microorganisms, respectively. Prior pneumococcal vaccination was more frequently observed in immunocompromised patients than in non-immunocompromised patients (21.1 versus 6.4%; P=0.029), but no significant difference was observed for influenza vaccine. Corrective measures were initiated in 46 patients (39%), non-immunized against S. pneumoniae. CONCLUSION: These results underline the very low prevalence of pneumococcal vaccination rate in at-risk hospitalized patients, as compared with influenza, despite recent recommendations.

Untargeted next-generation sequencing-based first-line diagnosis of infection in immunocompromised adults: a multicentre, blinded, prospective study.

OBJECTIVE: Infections are the major cause of morbidity and mortality in immunocompromised patients. Improving microbiological diagnosis in these patients is of paramount clinical importance. METHODS: We performed this multicentre, blinded, prospective, proof-of-concept study, to compare untargeted next-generation sequencing with conventional microbiological methods for first-line diagnosis of infection in 101 immunocompromised adults. Patients were followed for 30 days and their blood samples, and in some cases nasopharyngeal swabs and/or biological fluids, were analysed. At the end of the study, expert clinicians evaluated the results of both methods. The primary outcome measure was the detection rate of clinically relevant viruses and bacteria at inclusion. RESULTS: Clinically relevant viruses and bacteria identified by untargeted next-generation sequencing and conventional methods were concordant for 72 of 101 patients in samples taken at inclusion (κ test=0.2, 95% CI 0.03-0.48). However, clinically relevant viruses and bacteria were detected in a significantly higher proportion of patients with untargeted next-generation sequencing than conventional methods at inclusion (36/101 (36%) vs. 11/101 (11%), respectively, p <0.001), and even when the latter were continued over 30 days (19/101 (19%), p 0.003). Untargeted next-generation sequencing had a high negative predictive value compared with conventional methods (64/65, 95% CI 0.95-1). CONCLUSIONS: Untargeted next-generation sequencing has a high negative predictive value and detects more clinically relevant viruses and bacteria than conventional microbiological methods. Untargeted next-generation sequencing is therefore a promising method for microbiological diagnosis in immunocompromised adults.

Body Composition and Anti-Neoplastic Treatment in Adult and Older Subjects - A Systematic Review.

BACKGROUND: The estimation of the risk of poor tolerance and overdose of antineoplastic agents protocols represents a major challenge in oncology, particularly in older patients. We hypothesize that age-related modifications of body composition (i.e. increased fat mass and decreased lean mass) may significantly affect tolerance to chemotherapy. METHOD: We conducted a systematic review for the last 25 years (between 1990 and 2015), using US National library of Medicine Medline electronic bibliographic database and Embase database of cohorts or clinical trials exploring (i) the interactions of body composition (assessed by Dual X-ray Absorptiometry, Bioelectrical Impedance Analyses, or Computerized Tomography) with pharmacokinetics parameters, (ii) the tolerance to chemotherapy, and (iii) the consequences of chemotherapies or targeted therapies on body composition. RESULTS: Our search identified 1504 articles. After a selection (using pre-established criteria) on titles and abstract, 24 original articles were selected with 3 domains of interest: impact of body composition on pharmacokinetics (7 articles), relationship between body composition and chemotoxicity (14 articles), and effect of anti-cancer chemotherapy on body composition (11 articles). The selected studies suggested that pharmacokinetic was influenced by lean mass, that lower lean mass could be correlated with toxicity, and that sarcopenic patients experienced more toxicities that non-sarcopenic patients. Regarding fat mass, results were less conclusive. No studies specifically explored the topic of body composition in older cancer patients. CONCLUSIONS: Plausible pathophysiological pathways linking body composition, toxicity, and pharmacokinetics are sustained by the actual review. However, despite the growing number of older cancer patients, our review highlighted the lack of specific studies in the field of anti-neoplastic agents toxicity regarding body composition conducted in elderly.

[Liver abscess]. / Abcès hépatiques.

Liver abscess is a rare and severe infection. Incidence increases because of aging of population, advances in liver and biliary surgery including liver transplantation, and immunodeficiency factors. Diagnosis depends mainly on imaging and needle aspiration for microbiological identification. Treatment is based on antibiotics, percutaneous or surgical drainage, and control of the primary source.

Activity of temocillin in a lethal murine model of infection of intra-abdominal origin due to KPC-producing Escherichia coli.

OBJECTIVES: Temocillin is a 6-α-methoxy derivative of ticarcillin that shows in vitro activity against Enterobacteriaceae producing Klebsiella pneumoniae carbapenemase (KPC). Our objective was to assess in vivo temocillin activity against KPC-producing Escherichia coli. METHODS: Isogenic derivatives of the WT E. coli CFT073 producing KPC-2, KPC-3 or OXA-48 were constructed. An experimental murine model of intra-abdominal infection with sepsis was used. Mice were treated subcutaneously with temocillin 200 mg/kg every 2 h for 24 h, reproducing the duration of time that the free serum concentration of temocillin exceeded the MIC in humans with a regimen of 2 g every 12 h or 2 g every 8 h. Blood, peritoneal fluid (PF) and spleen were collected; 24 h survival and sterility rates were assessed. RESULTS: Temocillin MICs were 8, 16, 32, and 256 mg/L for the susceptible strain and KPC-2-, KPC-3-, and OXA-48-producing strains, respectively. In mice treated with temocillin, significant bacterial reduction was obtained in PF, blood, and spleen for the susceptible strain and KPC-2- and KPC-3-producing strains (P < 0.001) but not for the OXA-48-producing strain. Sterility rates in PF were 53%, 10%, 0% and 0% (P < 0.001) and sterility rates in blood were 77%, 40%, 3% and 0% (P < 0.001), while survival rates were 97%, 97%, 57%, 0% (P < 0.001) for mice infected with the susceptible strain and KPC-2-, KPC-3- and OXA-48-producing strains, respectively. CONCLUSIONS: In a lethal-infection model with bacteraemia from intra-abdominal origin, temocillin retained significant activity in PF, blood and spleen and prevented death in mice by effectively working against KPC-producing E. coli with temocillin MICs ≤16 mg/L.

[Computerized ranking test in three French universities: Staff experience and students' feedback]. / Épreuves informatisées de type ECNi: retour d'expérience sur un test multiuniversité.

BACKGROUND: The year 2016 will be pivotal for the evaluation of French medical students with the introduction of the first computerized National Ranking Test (ECNi). The SIDES, online electronic system for medical student evaluation, was created for this purpose. All the universities have already organized faculty exams but few a joint computerized ranking test at several universities simultaneously. We report our experience on the organization of a mock ECNi by universities Paris Descartes, Paris Diderot and Paris 13. METHODS: Docimological, administrative and technical working groups were created to organize this ECNi. Students in their fifth year of medical studies, who will be the first students to sit for the official ECNi in 2016, were invited to attend this mock exam that represented more than 50% of what will be proposed in 2016. A final electronic questionnaire allowed a docimological and organizational evaluation by students. An analysis of ratings and rankings and their distribution on a 1000-point scale were performed. RESULTS: Sixty-four percent of enrolled students (i.e., 654) attended the three half-day exams. No difference in total score and ranking between the three universities was observed. Students' feedback was extremely positive. Normalized over 1000 points, 99% of students were scored on 300 points only. Progressive clinical cases were the most discriminating test. CONCLUSION: The organization of a mock ECNi involving multiple universities was a docimological and technical success but required an important administrative, technical and teaching investment.

Cefotaxime and Amoxicillin-Clavulanate Synergism against Extended-Spectrum-ß-Lactamase-Producing Escherichia coli in a Murine Model of Urinary Tract Infection.

We investigated the efficacies of cefotaxime (CTX) and amoxicillin (AMX)-clavulanate (CLA) (AMC) against extended-spectrum-ß-lactamase (ESBL)-producing Escherichia coli in vitro and in a murine model of urinary tract infection (UTI). MICs, the checkerboard dilution method, and time-kill curves were used to explore the in vitro synergism between cefotaxime and amoxicillin-clavulanate against two isogenic E. coli strains-CFT073-RR and its transconjugant, CFT073-RR Tc bla(CTX-M-15)-harboring a bla(CTX-M-15) plasmid and a bla(OXA-1) plasmid. For in vivo experiments, mice were separately infected with each strain and treated with cefotaxime, amoxicillin, and clavulanate, alone or in combination, or imipenem, using therapeutic regimens reproducing time of free-drug concentrations above the MIC (fT≥MIC) values close to that obtained in humans. MICs of amoxicillin, cefotaxime, and imipenem were 4/>1,024, 0.125/1,024, and 0.5/0.5 mg/liter, for CFT073-RR and CFT073-RR Tc bla(CTX-M-15), respectively. The addition of 2 mg/liter of clavulanate (CLA) restored the susceptibility of CFT073-RR Tc bla(CTX-M-15) to CTX (MICs of the CTX-CLA combination, 0.125 mg/liter). The checkerboard dilution method and time-kill curves confirmed an in vitro synergy between amoxicillin-clavulanate and cefotaxime against CFT073-RR Tc bla(CTX-M-15). In vivo, this antibiotic combination was similarly active against both strains and as effective as imipenem. In conclusion, the cefotaxime and amoxicillin-clavulanate combination appear to be an effective, easy, and already available alternative to carbapenems for the treatment of UTI due to CTX-M-producing E. coli strains.

Empirical therapies among adults hospitalized for community-acquired upper urinary tract infections: A decision-tree analysis of mortality, costs, and resistance.

BACKGROUND: Poor outcomes occur when patients with serious infections receive antibiotics to which the organisms are resistant. METHODS: Decision trees simulated in-hospital mortality, costs, incremental cost-effectiveness ratio per life year saved, and carbapenem resistance according to 3 empirical antibiotic strategies among adults hospitalized for community-acquired (CA) upper urinary tract infections (UTIs): ceftriaxone (CRO) plus gentamicin (GM) in the intensive care unit (ICU), imipenem (IMP), and individualized choice (IMP or CRO) based on clinical risk factors for CA- extended-spectrum ß-lactamase (ESBL). RESULTS: The estimated prevalence of CA-ESBL on admission was 5% (range, 1.3%-17.6%); 3% and 97% were admitted to the ICU and medical ward (MW), respectively. In the ICU, CRO plus GM was dominated; IMP was cost-effective (incremental cost-effectiveness ratio: €4,400 per life year saved compared with individualized choice). In the MW, IMP had no impact on mortality and was less costly (-€142 per patient vs CRO, -€38 vs individualized choice). The dominance of IMP was consistent in sensitivity analyses. Compared with CRO, colonization by carbapenem-resistant pathogens increased by an odds ratio of 4.5 in the IMP strategy. CONCLUSION: Among the ICU patients, empirical IMP therapy reduces mortality at an acceptable cost. Among MW patients, individualized choice or CRO is preferred to limit carbapenem resistance at a reasonable cost.

Clinical spectrum of urine cultures positive for ESBL-producing Escherichia coli in hospitalized patients and impact on antibiotic use.

OBJECTIVE: We wanted to describe the clinical features associated with urinalysis positive for ESBL-producing Escherichia coli and their impact on antibiotic use. METHODS: We performed a prospective observational study in 13 French hospitals of the Paris area for 3 consecutive months. We included all patients with urine cultures positive for ESBL-producing E. coli. RESULTS: One hundred and seventeen of the 218 patients (54%) presented with asymptomatic bacteriuria, 31 (14%) with cystitis, and 70 (32%) with a parenchymal infection. Nineteen patients with asymptomatic bacteriuria (16%) received antibiotics. Forty-one with parenchymal infections (59%) received a carbapenem. A carbapenem alternative could have been used in every patient treated with a carbapenem, according to antibiotic susceptibility testing results. CONCLUSIONS: Urinary tract infections accounted for 46% of E. coli ESBL positive urinalysis. Fifty percent of parenchymal infections were treated with a carbapenem.

Escherichia coli bacteraemia in pregnant women is life-threatening for foetuses.

In order to improve knowledge on Escherichia coli bacteraemia during pregnancy, we studied clinical data and performed molecular characterization of strains for 29 E. coli bacteraemia occurring in pregnant women. Bacteraemia mostly occurred in the third trimester of pregnancy (45%) and was community-acquired (79%). Portals of entry were urinary (55%) and genital (45%). E. coli strains belonged mainly to phylogroups B2 (72%) and D (17%). Four clonal lineages (i.e. sequence type complex (STc) 73, STc95, STc12 and STc69) represented 65% of the strains. The strains exhibited a high number of virulence factor coding genes (10 (3-16)). Six foetuses died (27%), five of them due to bacteraemia of genital origin (83%). Foetal deaths occurred despite adequate antibiotic regimens. Strains associated with foetal mortality had fewer virulence factors (8 (6-10)) than strains involved in no foetal mortality (11 (4-12)) (p 0.02). When comparing E. coli strains involved in bacteraemia with a urinary portal of entry in non-immunocompromised pregnant vs. non-immunocompromised non-pregnant women from the COLIBAFI study, there was no significant difference of phylogroups and virulence factor coding genes. These results show that E. coli bacteraemia in pregnant women involve few highly virulent clones but that severity, represented by foetal death, is mainly related to bacteraemia of genital origin.

Escherichia coli bacteraemia in adults: age-related differences in clinical and bacteriological characteristics, and outcome.

To explore the specificities of Escherichia coli bacteraemia in the elderly, the demographic, clinical and bacteriological characteristics and in-hospital mortality rate of 'young' (18-64 years, n = 395), 'old' (65-79 years, n = 372) and 'very old' (⩾80 years, n = 284) adult patients of the multicentre COLIBAFI cohort study were compared. Clinical and bacteriological risk factors for death were jointly identified by logistic regression and multivariate analysis within each group. 'Young' and 'old' patients had more comorbidities than 'very old' patients (comorbidity score: 1·5 ± 1·3 and 1·6 ± 1·2 vs. 1·2 ± 1·2, respectively; P < 0·001), and were more frequently nosocomially infected (22·3% and 23·8% vs. 8·8%, respectively; P < 0·001). 'Old' patients had the poorest prognosis (death rate: 16·4% vs.10·4% for 'young' and 12·0% for 'very old' patients, respectively; P = 0·039). Risk factors for death were age group-specific, suggesting a host-pathogen relationship evolving with age.

The emergence of linezolid resistance among Enterococci in intestinal microbiota of treated patients is unrelated to individual pharmacokinetic characteristics.

Linezolid is an antimicrobial agent for the treatment of multiresistant Gram-positive infections. We assessed the impact of linezolid on the microbiota and the emergence of resistance and investigated its relationship with plasma pharmacokinetics of the antibiotic. Twenty-eight patients were treated for the first time with linezolid administered orally (n = 17) or parenterally (n = 11) at 600 mg twice a day. Linezolid plasma pharmacokinetic analysis was performed on day 7. Colonization by fecal enterococci, pharyngeal streptococci, and nasal staphylococci were assessed using selective media with or without supplemental linezolid. The resistance to linezolid was characterized. The treatment led to a decrease of enterococci, staphylococci, and streptococci in the fecal (P = 0.03), nasal, and pharyngeal (P < 0.01) microbiotas. The appearance of resistant strains was observed only in enterococci from the fecal microbiota between the 7th and 21st days of treatment in four patients (14.3%). The resistance was mainly due for the first time to the mutation G2447T in the 23S rRNA gene. No pharmacokinetic parameters were significantly different between the patients, regardless of the appearance of resistance. The emergence of linezolid resistance during treatment was observed only in the intestinal microbiota and unrelated to pharmacokinetic parameters. However, colonization by Gram-positive bacteria was reduced as a result of treatment in all microbiotas.

Hyperosmotic stress induces cell cycle arrest in retinal pigmented epithelial cells.

Osmotic changes occur in many tissues and profoundly influence cell function. Herein, we investigated the effect of hyperosmotic stress on retinal pigmented epithelial (RPE) cells using a microarray approach. Upon 4-h exposure to 100 mM NaCl or 200 mM sucrose, 79 genes were downregulated and 72 upregulated. Three gene ontology categories were significantly modulated: cell proliferation, transcription from RNA polymerase II promoter and response to abiotic stimulus. Fluorescent-activated cell sorting analysis further demonstrated that owing to hyperosmotic stimulation for 24 h, cell count and cell proliferation, as well as the percentage of cells in G0/G1 and S phases were significantly decreased, whereas the percentage of cells in G2/M phases increased, and apoptosis and necrosis remained unaffected. Accordingly, hyperosmotic conditions induced a decrease of cyclin B1 and D1 expression, and an activation of the p38 mitogen-activated protein kinase. In conclusion, our results demonstrate that hypertonic conditions profoundly affect RPE cell gene transcription regulating cell proliferation by downregulation cyclin D1 and cyclin B1 protein expression.

[Intermittent prolonged fever triggered by efforts]. / Fièvre prolongée intermittente survenant à l'effort.

INTRODUCTION: Fever of unknown origin is a common reason for care in internal medicine. The wide variety of possible etiologies makes it difficult to standardize the diagnostic work-up that has to be primarily guided by the interview and physical examination. CASE REPORT: We report a case of prolonged fever having as main characteristics to be intermittent and triggered by efforts. The diagnosis of cerebrospinal fluid shunt infection with Propionibacterium acnes was finally made. In reaching this conclusion, many tests were needed, including renal explorations with biopsy showing an aspect of shunt nephritis. CONCLUSION: Prolonged fever of unknown origin in a patient having prosthetic material should raise the suspicion of prosthesis infection (especially if the fever is associated with efforts).