Intestinal Domination and the Risk of Bacteremia in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Infectious Disease Service, Department of Medicine.
Clinical Infectious Diseases (Impact Factor: 8.89). 06/2012; 55(7):905-14. DOI: 10.1093/cid/cis580
Source: PubMed


Bacteremia is a frequent complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). It is unclear whether changes in the intestinal microbiota during allo-HSCT contribute to the development of bacteremia. We examined the microbiota of patients undergoing allo-HSCT, and correlated microbial shifts with the risk of bacteremia.

Fecal specimens were collected longitudinally from 94 patients undergoing allo-HSCT, from before transplant until 35 days after transplant. The intestinal microbiota was characterized by 454 pyrosequencing of the V1-V3 region of bacterial 16S ribosomal RNA genes. Microbial diversity was estimated by grouping sequences into operational taxonomic units and calculating the Shannon diversity index. Phylogenetic classification was obtained using the Ribosomal Database Project classifier. Associations of the microbiota with clinical predictors and outcomes were evaluated.

During allo-HSCT, patients developed reduced diversity, with marked shifts in bacterial populations inhabiting the gut. Intestinal domination, defined as occupation of at least 30% of the microbiota by a single predominating bacterial taxon, occurred frequently. Commonly encountered dominating organisms included Enterococcus, Streptococcus, and various Proteobacteria. Enterococcal domination was increased 3-fold by metronidazole administration, whereas domination by Proteobacteria was reduced 10-fold by fluoroquinolone administration. As a predictor of outcomes, enterococcal domination increased the risk of Vancomycin-resistant Enterococcus bacteremia 9-fold, and proteobacterial domination increased the risk of gram-negative rod bacteremia 5-fold.

During allo-HSCT, the diversity and stability of the intestinal flora are disrupted, resulting in domination by bacteria associated with subsequent bacteremia. Assessment of fecal microbiota identifies patients at highest risk for bloodstream infection during allo-HCST.

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Available from: Lauren Lipuma, Sep 30, 2015
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    • "La perte de l'effet barrière conduit à l'augmentation des densités intestinales en bactéries normalement maintenues à basses concentrations, comme les entérocoques résistants à la vancomycine ou les entérobactéries, notamment suite à la prise d'antibiotiques actifs contre les bactéries anaérobies comme la clindamycine [20] [21]. Cette augmentation de la concentration des bactéries résistantes aux antibiotiques conduit à un risque plus élevé de diffusion dans l'environnement [21], de translocation digestive [22] ou d'infections urinaires [23] à ces bactéries. "
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    ABSTRACT: Background Previous studies of infant fecal samples have failed to clarify the role of gut bacteria in the pathogenesis of NEC. We sought to characterize bacterial communities within intestinal tissue resected from infants with and without NEC. Methods 26 intestinal samples were resected from 19 infants, including 16 NEC samples and 10 non-NEC samples. Bacterial 16S rRNA gene sequences were amplified and sequenced. Analysis allowed for taxonomic identification, and quantitative PCR was used to quantify the bacterial load within samples. Results NEC samples generally contained an increased total burden of bacteria. NEC and non-NEC sample sets were both marked by high inter-individual variability and an abundance of opportunistic pathogens. There was no statistically significant distinction between the composition of NEC and non-NEC microbial communities. K-means clustering enabled us to identify several stable clusters, including clusters of NEC and midgut volvulus samples enriched with Clostridium and Bacteroides. Another cluster containing both NEC and non-NEC samples was marked by an abundance of Enterobacteriaceae and decreased diversity among NEC samples. Conclusions The results indicate that NEC is a disease without a uniform pattern of microbial colonization, but that NEC is associated with an abundance of strict anaerobes and a decrease in community diversity.
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    • "In the present study, duration of therapy with specific antibiotics was considered, unlike many earlier studies [12,13,16,17,19-22,24,27,28,30]. Exposure to anti-anaerobic antibiotics has been linked to VRE gastrointestinal tract colonisation [45] and bacteraemia [10,46]; however, the VRE genotype was either vanA VRE [10,46] or not determined [45]. In our study, an increase in duration of therapy with metronidazole (an anti-anaerobic antibiotic) was linked to VRE bacteraemia. "
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