Emergence of resistance after therapy with antibiotics used alone or combined in a marine model

A murine model of peritonitis allowing detection and quantification of in-vivo acquired resistance during short term therapy has been used in order to evaluate the capacity of antimicrobial combinations to limit emergence of resistance, as compared to individual components of the regimens. Mice were challenged intraperitoneally with 108 cfu of bacteria. Two hours later, a single antibiotic dose was injected subcutaneously: amikacin (15 mg/kg), ceftriaxone (50 mg/kg), pefloxacin (25 mg/kg), amikacin + ceftriaxone, amikacin + pefloxacin or ceftriaxone + pefloxacin. Escherichia coli and Staphylococcus aureus never became resistant. Single drug therapy yielded resistant mutants in Enterobacter cloacae, Serratia marcescens, Klebsiella pneumoniae and Pseudomonas aeruginosa as follows: 74% of ceftriaxone-treated animals, 57% of pefloxacin treated animals and 27% of amikacin treated animals. All the tested combinations reduced the frequency of in-vivo acquired resistance produced by single drugs, and no combination selected resistance when the separate agents of the combination did not. Combining antimicrobial agents limits the risk of emergence of resistance during antibiotic therap

Development of β-Lactam-Resistant Enterobacter cloacae in Mice

We compared the ability of four newer β-lactam compounds to produce resistance in an experimental model of Enterobacter cloacae infection. Mice infected intraperitoneally developed resistance depending on antibiotic treatment and the dose given. Percentages of mice in which resistance was observedwere as follows: 100% after ceftriaxone (50 mg/kg, two doses); 87% after ceftriaxone (50 mg/kg, one dose); 35% after ceftriaxone (500 mg/kg, one dose); and 21% after carumonam (25 mg/kg, two doses). No resistance occurred after therapy with either BMY 28142(25 mg/kg, two doses) or Sch 34343 (50 mg/kg, two doses). Heterogeneous resistance to 13-lactams among the cells within a given Enterobacter population accounted for these differences. The minimal concentration inhibiting the growth of the preexisting resistant variants, together with the antibiotic concentrations obtained in the peritoneal fluid, were associated with further emergence of resistance in the mouse treated with this antibioti

T regulatory cells disrupt the CCL20-CCR6 axis driving Th17 homing to the gut

Background: During HIV-1 infection, the integrity of the intestinal immune barrier is disrupted due to a deep depletion of CD4 + T cells in the gut. The translocation of microbial products from the gut lumen into the bloodstream has been linked with systemic inflammation. Despite long-term effective cART, CD4 + T cells in the lamina propria are incompletely restored in most individuals. Aims: Among the chemotactic axes involved in CD4 + T cell homing to the gut, we focused on the CCR6-CCL20 axis as it governs Th17 cells homing, a T cell subset exerting a major role in antimicrobial immunity. We aimed to assess the factors regulating the expression of CCL20 by the enterocytes, and notably the role of the cytokines produced by Treg and Th17 cells. Methods: Small bowel biopsies were obtained by endoscopy in 20 HIV-1 + and 10 HIV-1-individuals. Intestinal lymphocytes phenotype was analyzed by flow cytometry. CCL20 mRNA was quantified by qRT-PCR. The effect of PRR ligands and cytokines on CCL20 expression was explored using an ex-vivosystem of human primary enterocytes. A coculture was done between the enterocytes and Th17/Treg cells. The expression of CCL20 by the enterocytes was evaluated by qRT-PCR and ELISA

e-Pilly TROP Maladies infectieuses tropicales

L’e-Pilly TROP est un ouvrage d’infectiologie tropicale destiné aux médecins et aux étudiants en médecine des pays francophones du Sud. La prise en compte des différents niveaux de la pyramide sanitaire dans ces pays le rend aussi accessible aux infirmiers des centres de santé communautaires urbains et des structures de santé intermédiaires des zones rurales. Par définition, les Pays En Développement accroissant progressivement leurs capacités de diagnostic biologique et de traitement, les outils de prise en charge correspondent aux moyens des niveaux périphériques comme à ceux des niveaux hospitaliers de référence

Antiretroviral-naive and -treated HIV-1 patients can harbour more resistant viruses in CSF than in plasma

Objectives The neurological disorders in HIV-1-infected patients remain prevalent. The HIV-1 resistance in plasma and CSF was compared in patients with neurological disorders in a multicentre study. Methods Blood and CSF samples were collected at time of neurological disorders for 244 patients. The viral loads were >50 copies/mL in both compartments and bulk genotypic tests were realized. Results On 244 patients, 89 and 155 were antiretroviral (ARV) naive and ARV treated, respectively. In ARV-naive patients, detection of mutations in CSF and not in plasma were reported for the reverse transcriptase (RT) gene in 2/89 patients (2.2%) and for the protease gene in 1/89 patients (1.1%). In ARV-treated patients, 19/152 (12.5%) patients had HIV-1 mutations only in the CSF for the RT gene and 30/151 (19.8%) for the protease gene. Two mutations appeared statistically more prevalent in the CSF than in plasma: M41L (P = 0.0455) and T215Y (P = 0.0455). Conclusions In most cases, resistance mutations were present and similar in both studied compartments. However, in 3.4% of ARV-naive and 8.8% of ARV-treated patients, the virus was more resistant in CSF than in plasma. These results support the need for genotypic resistance testing when lumbar puncture is performe

Salmonella enterica Serotype Typhi with Nonclassical Quinolone Resistance Phenotype

We report Salmonella enterica serotype Typhi strains with a nonclassical quinolone resistance phenotype (i.e., decreased susceptibility to ciprofloxacin but with susceptibility to nalidixic acid) associated with a nonsynonymous mutation at codon 464 of the gyrB gene. These strains, not detected by the nalidixic acid disk screening test, can result in fluoroquinolone treatment failure

Une approche quantitative de la loi de Beer- Lambert avec un smartphone. Seconde partie.

International audienceDans la première partie de cet article nous avons étudié expérimentalement l'absorption de la lumière dans un milieu matériel et confronté les résultats obtenus à la loi de Beer-Lambert. Dans cette seconde partie, support théorique de la première, nous présentons un modèle physique qui décrit quantitativement les observations de la partie 1 et établit la loi de Beer-Lambert. Pour terminer nous nous intéressons à l'absorbance en lumière polychromatique après avoir rappelé à l'aide du modèle de Drude que l'interaction matière-rayonnement dépend de la fréquence de l'onde incidente. I. Quelques éléments théoriques Le but ici n'est pas de développer systématiquement la théorie de la diffusion de la lumière que l'on trouve facilement dans de nombreux ouvrages [1] mais d'introduire les concepts pertinents et les lois associées de la façon la plus parlante possible. Nous présentons un modèle corpusculaire, dans lequel la lumière est conçue comme un flot de photons impactant des obstacles dilués dans un solvant. Cette approche, à caractère mécanique, nous semble plus intuitive que les démonstrations usuelles basées sur la conservation de l'énergie

Awareness of vaccination status and its predictors among working people in Switzerland

BACKGROUND: Adult vaccination status may be difficult to obtain, often requiring providers to rely on individual patient recall. To determine vaccination status awareness and the sociodemographic predictors of awareness for tetanus, hepatitis A and B, tick born encephalitis (TBE) and influenza vaccination. METHODS: Multivariate analyses were used to evaluate a questionnaire survey of 10 321 employees (4070 women and 6251 men aged 15–72 years) of two companies in Switzerland. RESULTS: Among 10 321 respondents, 75.5% reported knowing their tetanus vaccination status, 64.1% hepatitis A, 61.1% hepatitis B, 64.3% TBE and 71.9% influenza. Between 1 in 4 and 1 in 3 employees were not aware of their vaccination status. Differences in awareness for the five vaccinations considered correlated with gender and language. These differences persisted in multivariate analyses. CONCLUSION: Women employees, German-speaking employees and employees who paid more attention to their diet were more often aware of their vaccination status. A more reliable and readily accessible data source for vaccination status is needed in order to capitalize on opportunities to update vaccinations among Swiss employees

Foamy Macrophages from Tuberculous Patients' Granulomas Constitute a Nutrient-Rich Reservoir for M. tuberculosis Persistence

Tuberculosis (TB) is characterized by a tight interplay between Mycobacterium tuberculosis and host cells within granulomas. These cellular aggregates restrict bacterial spreading, but do not kill all the bacilli, which can persist for years. In-depth investigation of M. tuberculosis interactions with granuloma-specific cell populations are needed to gain insight into mycobacterial persistence, and to better understand the physiopathology of the disease. We have analyzed the formation of foamy macrophages (FMs), a granuloma-specific cell population characterized by its high lipid content, and studied their interaction with the tubercle bacillus. Within our in vitro human granuloma model, M. tuberculosis long chain fatty acids, namely oxygenated mycolic acids (MA), triggered the differentiation of human monocyte-derived macrophages into FMs. In these cells, mycobacteria no longer replicated and switched to a dormant non-replicative state. Electron microscopy observation of M. tuberculosis–infected FMs showed that the mycobacteria-containing phagosomes migrate towards host cell lipid bodies (LB), a process which culminates with the engulfment of the bacillus into the lipid droplets and with the accumulation of lipids within the microbe. Altogether, our results suggest that oxygenated mycolic acids from M. tuberculosis play a crucial role in the differentiation of macrophages into FMs. These cells might constitute a reservoir used by the tubercle bacillus for long-term persistence within its human host, and could provide a relevant model for the screening of new antimicrobials against non-replicating persistent mycobacteria