Development of the preterm infant gut microbiota is emerging as a critical research priority1. Since preterm infants almost universally receive early and often extended antibiotic therapy2, it is important to understand how these interventions alter gut microbiota development3-6. Analysis of 401 stools from 84 longitudinally sampled preterm infants demonstrates that meropenem, cefotaxime and ticarcillin–clavulanate are associated with significantly reduced species richness. In contrast, vancomycin and gentamicin, the antibiotics most commonly administered to preterm infants, have non-uniform effects on species richness, but these can be predicted with 85% accuracy based on the relative abundance of only two bacterial species and two antibiotic resistance (AR) genes at treatment initiation. To investigate resistome development, we functionally selected resistance to 16 antibiotics from 21 faecal metagenomic expression libraries. Of the 794 AR genes identified, 79% had not previously been classified as AR genes. Combined with deep shotgun sequencing of all stools, we find that multidrug-resistant members of the genera Escherichia, Klebsiella and Enterobacter, genera commonly associated with nosocomial infections, dominate the preterm infant gut microbiota. AR genes that are enriched following specific antibiotic treatments are generally unique to the specific treatment and are highly correlated with the abundance of a single species. The most notable exceptions include ticarcillin–clavulanate and ampicillin, both of which enrich for a large number of overlapping AR genes, and are correlated with Klebsiella pneumoniae. We find that all antibiotic treatments are associated with widespread collateral microbiome impact by enrichment of AR genes that have no known activity against the specific antibiotic driver.
SummaryThe proliferation of genetically modified mouse models has exposed phenotypic variation between investigators and institutions that has been challenging to control1-5. In many cases, the microbiota is the presumed culprit of the variation. Current solutions to account for phenotypic variability include littermate and maternal controls or defined microbial consortia in gnotobiotic mice6,7. In conventionally raised mice, the microbiome is transmitted from the dam2,8,9. Here we show that microbially–driven dichotomous fecal IgA levels in WT mice within the same facility mimic the effects of chromosomal mutations. We observed in multiple facilities that vertically-transmissible bacteria in IgA-Low mice dominantly lowered fecal IgA levels in IgA-High mice after cohousing or fecal transplantation. In response to injury, IgA-Low mice showed increased damage that was transferable by fecal transplantation and driven by fecal IgA differences. We found that bacteria from IgA-Low mice degraded the secretory component (SC) of SIgA as well as IgA itself. These data indicate that phenotypic comparisons between mice must take into account the non-chromosomal hereditary variation between different breeders. We propose fecal IgA as one marker of microbial variability and conclude that cohousing and/or fecal transplantation enables analysis of progeny from different dams.
There was a high prevalence of TCD colonization on admission. In contrast to past studies, TCD colonization was not associated with recent antimicrobial or healthcare exposures. Additional investigation is needed to determine the role of asymptomatic TCD carriers on hospital-onset CDI incidence.
In this study, significant aerosol generation was only observed during NMA, both alone and during bronchoscopy. Minimal viable bacteria were recovered, mostly common environmental organisms. Although more research is needed, these data suggest that some of the procedures considered to be aerosol-generating may pose little infection risk to HCP.
BackgroundDespite appropriate therapy, Candida bloodstream infections are associated with a mortality rate of approximately 40 %. In animal models, impaired immunity due to T cell exhaustion has been implicated in fungal sepsis mortality. The purpose of this study was to determine potential mechanisms of fungal-induced immunosuppression via immunophenotyping of circulating T lymphocytes from patients with microbiologically documented Candida bloodstream infections.MethodsPatients with blood cultures positive for any Candida species were studied. Non-septic critically ill patients with no evidence of bacterial or fungal infection were controls. T cells were analyzed via flow cytometry for cellular activation and for expression of positive and negative co-stimulatory molecules. Both the percentages of cells expressing particular immunophenotypic markers as well as the geometric mean fluorescence intensity (GMFI), a measure of expression of the number of receptors or ligands per cell, were quantitated.ResultsTwenty-seven patients with Candida bloodstream infections and 16 control patients were studied. Compared to control patients, CD8 T cells from patients with Candidemia had evidence of cellular activation as indicated by increased CD69 expression while CD4 T cells had decreased expression of the major positive co-stimulatory molecule CD28. CD4 and CD8 T cells from patients with Candidemia expressed markers typical of T cell exhaustion as indicated by either increased percentages of or increased MFI for programmed cell death 1 (PD-1) or its ligand (PD-L1).ConclusionsCirculating immune effector cells from patients with Candidemia display an immunophenotype consistent with immunosuppression as evidenced by T cell exhaustion and concomitant downregulation of positive co-stimulatory molecules. These findings may help explain why patients with fungal sepsis have a high mortality despite appropriate antifungal therapy. Development of immunoadjuvants that reverse T cell exhaustion and boost host immunity may offer one way to improve outcome in this highly lethal disorder.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1182-z) contains supplementary material, which is available to authorized users.
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