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

Evolution of Total and Integrated HIV-1 DNA and Change in DNA Sequences in Patients with Sustained Plasma Virus Suppression

AbstractBlood samples from patients with plasma HIV-1 RNA <20 copies/ml for more than 2 years were studied. Significant decreases in total and integrated HIV-1 DNA were observed during the first 15 months of suppressive therapy before the concentrations became stable. Clonal analysis of HIV-1 pol demonstrated that the proportions of resistance mutations in DNA sequences after 2 years were lower than those in baseline DNA and RNA sequences. The changes in the clonal composition of HIV-1 env populations in three patients with evidence of changes in HIV-1 pol populations indicated a shift from predominantly R5-like viruses to predominantly X4-like viruses in two patients and the persistence of predominantly X4-like viruses in the third. Our analyses indicate the reemergence of ancestral sequences from long-lived cells or the residual production of wild-type virus from anatomic sites with limited access to antiretroviral drugs and the preferential infection of cells expressing CXCR4

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

Outbreak of Leishmania braziliensis cutaneous leishmaniasis, Saül, French Guiana [letter]

New World cutaneous leishmaniasis (CL), a zoonotic disease, is increasingly seen among travelers returning from Latin American countries, particularly from Bolivia, Belize, and French Guiana (1). The epidemiology of CL in the Americas is heterogeneous and has complex variations in transmission cycles, reservoir hosts, and sandfly vectors. Changing human activities that affect these factors may have resulted in the emergence of species with distinct pathogenic potentials and responses to therapy. In the Guianan ecoregion complex, leishmaniasis is endemic, and 5 coexisting Leishmania parasite species are known to infect humans: L. guyanensis, L. braziliensis, L. amazonensis, L. naiffi, and L. lainsoni. Among these species, L. guyanensis accounts for ≈85% of CL cases (2). We report an outbreak of 7 cases of L. braziliensis CL that occurred among 24 scientists who participated in a field mission at Limonade Creek in Saül, French Guiana, during October 10–25, 2013. Saül is an isolated village in the Amazonian rainforest (3°55′18′′N, 53°18′02′′W)

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

HIV-1 Residual Viremia Correlates with Persistent T-Cell Activation in Poor Immunological Responders to Combination Antiretroviral Therapy

BACKGROUND:The clinical significance and cellular sources of residual human immunodeficiency virus type 1 (HIV-1) production despite suppressive combination antiretroviral therapy (cART) remain unclear and the effect of low-level viremia on T-cell homeostasis is still debated. METHODOLOGY/PRINCIPAL FINDINGS:We characterized the recently produced residual viruses in the plasma and short-lived blood monocytes of 23 patients with various immunological responses to sustained suppressive cART. We quantified the residual HIV-1 in the plasma below 50 copies/ml, and in the CD14(high) CD16(-) and CD16+ monocyte subsets sorted by flow cytometry, and predicted coreceptor usage by genotyping V3 env sequences. We detected residual viremia in the plasma of 8 of 10 patients with poor CD4+ T-cell reconstitution in response to cART and in only 5 of 13 patients with good CD4+ T-cell reconstitution. CXCR4-using viruses were frequent among the recently produced viruses in the plasma and in the main CD14(high) CD16(-) monocyte subset. Finally, the residual viremia was correlated with persistent CD4+ and CD8+ T-cell activation in patients with poor immune reconstitution. CONCLUSIONS:Low-level viremia could result from the release of archived viruses from cellular reservoirs and/or from ongoing virus replication in some patients. The compartmentalization of the viruses between the plasma and the blood monocytes suggests at least two origins of residual virus production during effective cART. CXCR4-using viruses might be produced preferentially in patients on cART. Our results also suggest that low-level HIV-1 production in some patients may contribute to persistent immune dysfunction despite cART

Les méningites aiguës à liquide non purulent, d'allure virale (étude rétrospective de 342 cas (01/01/200-31/12/2000))

TOULOUSE3-BU Santé-Centrale (315552105) / SudocTOULOUSE3-BU Santé-Allées (315552109) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Antibiothérapie en médecine de ville (enquête de pratique à propos de 633 prescriptions)

TOULOUSE3-BU Santé-Centrale (315552105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Prévention des maladies du voyageur (place des vaccins actuels et à venir)

Le voyageur non immun doit faire face à bon nombre d'infections potentielles qui peuvent être prévenues pour certaines par une chimioprophylaxie adaptée, des mesures hygiéno-diététiques ou par la vaccination. Les hépatites A et B, la typhoïde, l'encéphalite japonaise ou à tiques d'Europe, les méningites à méningocoques A, C, Y et W135, la fièvre jaune et la rage sont les exemples qui ont été ici développés. Les critères de vaccination dépendent du risque infectieux propre au pays visité, du mode de vie du voyageur et de son état. La vaccination tient une place essentielle dans la médecine des voyages et a un intérêt majeur dans la santé publique pour de nombreux pays. Ceci montre l'importance toujours plus grande du développement de nouveaux vaccins à l'instar de ceux contre la dengue ou contre le paludisme.TOULOUSE3-BU Santé-Centrale (315552105) / SudocTOULOUSE3-BU Santé-Allées (315552109) / SudocSudocFranceF