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1.
Trans Am Clin Climatol Assoc ; 131: 178-197, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32675857

RESUMO

The Human Microbiome Initiative of NIH, begun in 2007, has opened the door to the power of the intestinal microbiome in health and disease. The 100 trillion gut microbes influence body function through three pathways: (1) via the neural route where 500 million neurons of the enteric nervous system (the body's second brain) connect to the brain and spinal cord, (2) via the immune route where the gut-immune capacity prevents infection and elicits immune response to vaccines, and (3) by the hormonal route wherein biologically active chemicals are released from enteroendocrine cells to control mood and body functions. Through research, the identification of diseases and disorders associated with abnormal microbiome ("dysbiosis") has increased in number with potential for reversibility. Our team has developed an orally administered fecal microbiota transplantation product that is effective in reversing dysbiosis in recurrent Clostridioides difficile (C. difficile) and is being used to reverse abnormal microbiomes in chronic dysbiotic disorders.

2.
Dig Dis Sci ; 65(3): 741-756, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32008133

RESUMO

Reduction in diversity of the intestinal microbiome (dysbiosis) is being identified in many disease states, and studies are showing important biologic contributions of microbiome to health and disease. Fecal microbiota transplantation (FMT) is being evaluated as a way to reverse dysbiosis in diseases and disorders in an attempt to improve health. The published literature was reviewed to determine the value of FMT in the treatment of medical disorders for which clinical trials have recently been conducted. FMT is effective in treating recurrent C. difficile infection in one or two doses, with many healthy donors providing efficacious fecal-derived products. In inflammatory bowel disease (IBD), FMT may lead to remission in approximately one-third of moderate-to-severe illnesses with one study suggesting that more durable FMT responses may be seen when used once medical remissions have been achieved. Donor products differ in their efficacy in treatment of IBD. Combining donor products has been one way to increase the potential value of FMT in treating chronic disorders. FMT is being explored in a variety of clinical settings affecting different organ systems outside CDI, with positive preliminary signals, in treatment of functional constipation, immunotherapy-induced colitis, neurodegenerative disease, as well as prevention of cancer-related disorders like graft versus host disease and decolonization of patients with recurrent urinary tract infection due to antibiotic-resistant bacteria. Currently, intense research is underway to see how the microbiome products like FMT can be harnessed for health benefits.


Assuntos
Transplante de Microbiota Fecal/métodos , Gastroenteropatias/microbiologia , Gastroenteropatias/terapia , Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/fisiologia , Transplante de Microbiota Fecal/tendências , Humanos , Doadores Vivos
3.
Chem Commun (Camb) ; 55(27): 3971-3974, 2019 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-30874700

RESUMO

We described an effective way to generate a Co3O4 mesocrystal array with well-developed porosity, simply by uniting a coupled interface with hydrazine treatment. Due to the fast electron transfer and sufficient active sites, the Ti mesh-supported Co3O4 nanoneedles electrode could provide a current density of 49.9 mA cm-2 at 570 mV OER overpotential and has exceptionally high stability.

4.
Microb Pathog ; 128: 97-99, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30579944

RESUMO

Enteroaggregative E. coli strains are important causes of diarrhea worldwide and are the second most important bacterial cause of travelers' diarrhea (TD). Pathogenicity of EAEC is not completely understood. We investigated the occurrence of putative virulence related genes (VRG), aatA, aggR and aaiC, in a nested case-control study of a cohort of US travelers >18 years of age, visited either Guatemala or Mexico. Fecal samples were collected between 2008 and 2012 from patients with TD from whom a HEp-2 cell adherent EAEC strain was identified (Cases) and from healthy subjects in the same locale without diarrhea from whom enteric pathogens were not isolated (Controls). Thirty-one subjects with acquired TD at destination was compared with 32 healthy controls. aaiC was the most expressed virulence related gene in 21 (67.7%) cases vs. 2 (6.3%) controls, (P < 0.000). aggR was found in 18 (58.1%) cases vs. 1 (3.1%) control, (P < 0.000). aatA in 9 (29.0%) cases vs. 1 (3.1%) control (P < 0.006). With genes combined, aaiC+aggR were seen together in 18 (58.1%) cases vs. 1 (3.1%) control (P < 0.000); aaiC+aatA were identified in 9 (29.0%) cases vs. 1 (3.1%) control (P < 0.006); aggR+aatA were present in 9 (29.0%) cases vs. 1 (3.1%) control, (P < 0.006). All three putative genes, aaiC+aggR+aatA were found in 9 (29.0%) cases vs. 1 (3.1%) control, (P < 0.006). The PCR products showed that aaiC, aggR, and aatA occurred in higher frequency and were more commonly associated with EAEC in cases of TD acquired in the two countries of study, as compared to controls. aaiC was found in all cases from Guatemala. Further research is needed to study geographic and host factors in EAEC-causing travelers' diarrhea.


Assuntos
Proteínas da Membrana Bacteriana Externa/genética , Diarreia/microbiologia , Proteínas de Escherichia coli/genética , Escherichia coli/genética , Genes Bacterianos/genética , Transativadores/genética , Viagem , Fatores de Virulência/genética , Adulto , Estudos de Casos e Controles , Diarreia/epidemiologia , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Fezes/microbiologia , Guatemala/epidemiologia , Humanos , México/epidemiologia , Prevalência , Virulência/genética
5.
Nat Med ; 25(1): 188, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30479380

RESUMO

In the version of this article originally published, an author was missing from the author list. Alexander J. Lazar should have been included between Jorge M. Blando and James P. Allison. The author has been added to the list, and the author contributions section has been updated to include Alexander J. Lazar's contribution to the study. The error has been corrected in the print, PDF and HTML versions of the manuscript.

6.
PLoS One ; 13(11): e0205064, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30388112

RESUMO

BACKGROUND: Fecal microbiota transplantation (FMT) via colonoscopy or enema has become a commonly used treatment of recurrent C. difficile infection (CDI). AIMS: To compare the safety and preliminary efficacy of orally administered lyophilized microbiota product compared with frozen product by enema. METHODS: In a single center, adults with ≥ 3 episodes of recurrent CDI were randomized to receive encapsulated lyophilized fecal microbiota from 100-200 g of donor feces (n = 31) or frozen FMT from 100 g of donor feces (n = 34) by enema. Safety during the three months post FMT was the primary study objective. Prevention of CDI recurrence during the 60 days after FMT was a secondary objective. Fecal microbiome changes were examined in first 39 subjects studied. RESULTS: Adverse experiences were commonly seen in equal frequency in both groups and did not appear to relate to the route of delivery of FMT. CDI recurrence was prevented in 26 of 31 (84%) subjects randomized to capsules and in 30 of 34 (88%) receiving FMT by enema (p = 0.76). Both products normalized fecal microbiota diversity while the lyophilized orally administered product was less effective in repleting Bacteroidia and Verrucomicrobia classes compared to frozen product via enema. CONCLUSIONS: The route of delivery, oral or rectal, did not influence adverse experiences in FMT. In preliminary evaluation, both routes appeared to show equivalent efficacy, although the dose may need to be higher for lyophilized product. Spore-forming bacteria appear to be the most important engrafting organisms in FMT by the oral route using lyophilized product. TRIAL REGISTRATION: ClinicalTrials.gov NCT02449174.


Assuntos
Infecções por Clostridium/terapia , Clostridium difficile/isolamento & purificação , Enema/métodos , Transplante de Microbiota Fecal/métodos , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Cápsulas , Criopreservação , Enema/efeitos adversos , Transplante de Microbiota Fecal/efeitos adversos , Feminino , Liofilização , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
7.
Microbiome ; 6(1): 201, 2018 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-30409177

RESUMO

BACKGROUND: Travelers' diarrhea (TD) is often caused by enterotoxigenic Escherichia coli, enteroaggregative E. coli, other bacterial pathogens, Norovirus, and occasionally parasites. Nevertheless, standard diagnostic methods fail to identify pathogens in more than 40% of TD patients. It is predicted that new pathogens may be causative agents of the disease. RESULTS: We performed a comprehensive amplicon and whole genome shotgun (WGS) metagenomic study of the fecal microbiomes from 23 TD patients and seven healthy travelers, all of which were negative for the known etiologic agents of TD based on standard microbiological and immunological assays. Abnormal and diverse taxonomic profiles in TD samples were revealed. WGS reads were assembled and the resulting contigs were visualized using multiple query types. A semi-manual workflow was applied to isolate independent genomes from metagenomic pools. A total of 565 genome bins were extracted, 320 of which were complete enough to be characterized as cellular genomes; 160 were viral genomes. We made predictions of the etiology of disease for many of the individual subjects based on the properties and features of the recovered genomes. Multiple patients with low-diversity metagenomes were predominated by one to several E. coli strains. Functional annotation allowed prediction of pathogenic type in many cases. Five patients were co-infected with E. coli and other members of Enterobacteriaceae, including Enterobacter, Klebsiella, and Citrobacter; these may represent blooms of organisms that appear following secretory diarrhea. New "dark matter" microbes were observed in multiple samples. In one, we identified a novel TM7 genome that phylogenetically clustered with a sludge isolate; it carries genes encoding potential virulence factors. In multiple samples, we observed high proportions of putative novel viral genomes, some of which form clusters with the ubiquitous gut virus, crAssphage. The total relative abundance of viruses was significantly higher in healthy travelers versus TD patients. CONCLUSION: Our study highlights the strength of assembly-based metagenomics, especially the manually curated, visualization-assisted binning of contigs, in resolving unusual and under-characterized pathogenic profiles of human-associated microbiomes. Results show that TD may be polymicrobial, with multiple novel cellular and viral strains as potential players in the diarrheal disease.


Assuntos
Diarreia/microbiologia , Escherichia coli Enterotoxigênica/genética , Escherichia coli Enterotoxigênica/isolamento & purificação , Genoma Bacteriano/genética , Genoma Viral/genética , Doença Relacionada a Viagens , Citrobacter/classificação , Citrobacter/genética , Citrobacter/isolamento & purificação , Diarreia/diagnóstico , Enterobacter/classificação , Enterobacter/genética , Enterobacter/isolamento & purificação , Escherichia coli Enterotoxigênica/classificação , Humanos , Klebsiella/classificação , Klebsiella/genética , Klebsiella/isolamento & purificação , Metagenoma , Metagenômica/métodos , Anotação de Sequência Molecular , Norovirus/genética , Norovirus/isolamento & purificação , Análise de Sequência de DNA
8.
Nat Med ; 24(12): 1804-1808, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30420754
9.
J Travel Med ; 25(1)2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30462260

RESUMO

Background: The novel oral antibiotic formulation Rifamycin SV-MMX®, with a targeted delivery to the distal small bowel and colon, was superior to placebo in treating travellers' diarrhea (TD) in a previous study. Thus, a study was designed to compare this poorly absorbed antibiotic with the systemic agent ciprofloxacin. Methods: In a randomized double-blind phase 3 study (ERASE), the efficacy and safety of Rifamycin SV-MMX® 400 mg twice daily (RIF-MMX) was compared with ciprofloxacin 500 mg twice daily in the oral treatment of TD. Overall, 835 international visitors to India, Guatemala or Ecuador with acute TD were randomized to receive a 3-day treatment with RIF-MMX (n = 420) or ciprofloxacin (n = 415). Primary endpoint was time to last unformed stool (TLUS), after which clinical cure was declared. Stools samples for microbiological evaluation were collected at the baseline visit and the end of treatment visit. Results: Median TLUS in the RIF-MMX group was 42.8 h versus 36.8 h in the ciprofloxacin group indicating non-inferiority of RIF-MMX to ciprofloxacin (P = 0.0035). Secondary efficacy endpoint results including clinical cure rate, treatment failure rate, requirement of rescue therapy as well as microbiological eradication rate confirmed those of the primary analysis indicating equal efficacy for both compounds. While patients receiving ciprofloxacin showed a significant increase of Extended Spectrum Beta Lactamase Producing-Escherichia coli (ESBL-E. Coli) colonization rates after 3-days treatment (6.9%), rates did not increase in patients receiving RIF-MMX (-0.3%). Both drugs were well-tolerated and safe. Conclusion: The novel multi-matrix formulation of the broad-spectrum, poorly absorbed antibiotic Rifamycin SV was found non-inferior to the systemic antibiotic ciprofloxacin in the oral treatment of non-dysenteric TD with the advantage of a lower risk of ESBL-E. Coli acquisition.


Assuntos
Antibacterianos/administração & dosagem , Ciprofloxacino/administração & dosagem , Diarreia/tratamento farmacológico , Farmacorresistência Bacteriana Múltipla , Infecções por Escherichia coli/tratamento farmacológico , Rifamicinas/administração & dosagem , Administração Oral , Adulto , Diarreia/microbiologia , Diarreia/prevenção & controle , Equador , Escherichia coli Enterotoxigênica/efeitos dos fármacos , Infecções por Escherichia coli/prevenção & controle , Feminino , Guatemala , Humanos , Índia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Viagem , Resultado do Tratamento
10.
FEMS Microbiol Lett ; 365(22)2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30299475

RESUMO

Irritable bowel syndrome (IBS) affects 10%-20% of people. Increased numbers of Escherichia coli (E. coli) correlate with symptoms, and patients respond to antimicrobials targeting E. coli. We examined whether specific E. coli strains, phylogroups and pathotypes are associated with IBS. We evaluated 218 E. coli isolates from 33 IBS patients and 23 healthy controls. RAPD analysis revealed 89 E. coli strains (29 controls, 60 IBS), spanning the A, B1, B2 and D phylogroups. Strains were similarly enriched in virulence genes associated with extraintestinal pathogenic E. coli (ExPEC) and/or adherent-invasive E. coli (AIEC). Three strains harbored a diarrheagenic virulence gene (2 IBS, 1 control). Escherichia coli capable of invading epithelial cells or replicating in macrophages were detected in 53% of IBS and 50% controls, and 67% IBS and 45% controls respectively (P > 0.05). AIEC were identified in 33% of IBS patients vs 20% of controls (P = 0.35). Virulence genes ibeA, ColV and pduC were associated with intramacrophage persistence; ibeA and ColV were associated with epithelial invasion and AIEC pathotype (P < 0.05). IBS patients and controls are commonly colonized by E. coli that resemble ExPEC and display pathogen-like behavior in vitro, similar to CD-associated AIEC. The relationship of these resident pathosymbiont E. coli to IBS warrants further investigation.


Assuntos
Infecções por Escherichia coli/microbiologia , Escherichia coli/patogenicidade , Síndrome do Intestino Irritável/microbiologia , Adulto , Idoso , Escherichia coli/genética , Feminino , Humanos , Macrófagos/microbiologia , Masculino , Pessoa de Meia-Idade , Virulência/genética
11.
Anaerobe ; 48: 110-114, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28801119

RESUMO

Freezing donor fecal microbiota has simplified fecal microbiota transplantation (FMT) in the treatment of recurrent C. difficile infection (CDI). However, the optimal storage time for the frozen FMT products remains unknown. Using an established murine model of CDI, stability and efficacy of frozen and lyophilized FMT product was studied at time points from 2 months to 15 months. DNA was extracted from fecal samples from the mice with identification of specific bacterial species by real-time quantitative PCR (qPCR). FMT product stability and efficacy were measured by occurrence of diarrhea in the challenged mice together with stability of the microbiota composition. The results were analyzed and compared by SAS statistical software. All mice treated with only C. difficile developed diarrhea within 72 h. Mice treated with frozen (n = 5/group), lyophilized (n = 5/group) products stored for ≤ 7-month or fresh FMT product (n = 22) were protected from post C. difficile challenge diarrhea. There was no difference between frozen and lyophilized products (n = 5/group) stored for ≤ 7 months 95% CI 1.00 (0.38-2.64) and 1.00 (0.38-2.64), respectively. Prevention if CDI by frozen and lyophilized product was not different for storage of 9-, 11- and 15-months. qPCR results demonstrated there were no significant quantitative change in Bacteroides and Clostridium species during any of the storage times (P > 0.05). In the present study, frozen and lyophilized FMT products were stored up to 7 months without losing microbiota composition and therapeutic efficacy. The animal model described may be useful to study stability of human microbiota designed for FMT.


Assuntos
Infecções por Clostridium/terapia , Criopreservação/métodos , Transplante de Microbiota Fecal/métodos , Animais , Infecções por Clostridium/microbiologia , Clostridium difficile/crescimento & desenvolvimento , Clostridium difficile/patogenicidade , Modelos Animais de Doenças , Congelamento , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Resultado do Tratamento
12.
ChemSusChem ; 10(14): 2875-2879, 2017 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-28612461

RESUMO

Oxygen vacancies can help to capture oxygen-containing species and act as active centers for oxygen evolution reaction (OER). Unfortunately, effective methods for generating a high amount of oxygen vacancies on the surface of various nanocatalysts are rather limited. Here, we described an effective way to generate oxygen-vacancy-rich surface of transition metal oxides, exemplified with Co3 O4 , simply by constructing highly coupled interface of ultrafine Co3 O4 nanocrystals and metallic Ti. Impressively, the amounts of oxygen vacancy on the surface of Co3 O4 /Ti surpassed the reported values of the Co3 O4 modified even under highly critical conditions. The Co3 O4 /Ti electrode could provide a current density of 23 mA cm-2 at an OER overpotential of 570 mV, low Tafel slope, and excellent durability in neutral medium. Because of the formation of a large amount of oxygen vacancies as the active centers for OER on the surface, the TOF value of the Co3 O4 @Ti electrode was optimized to be 3238 h-1 at an OER overpotential of 570 mV, which is 380 times that of the state-of-the-art non-noble nanocatalysts in the literature.


Assuntos
Cobalto/química , Nanopartículas/química , Nanotecnologia , Óxidos/química , Oxigênio/química , Titânio/química , Água/química , Animais , Eletroquímica , Eletrodos , Engenharia , Oxirredução
13.
Am J Trop Med Hyg ; 96(1): 83-87, 2017 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-28077742

RESUMO

Enterotoxigenic Escherichia coli (ETEC) can be attributed to around 200 million diarrheal episodes and 380,000 deaths in the developing regions. Travelers' diarrhea occurs in 15-40% of travelers to developing regions with ETEC being the most important etiologic agent. This study aims to describe the distribution of enterotoxins and colonization factor (CF) profiles of ETEC isolates from stool samples of adult travelers acquiring diarrhea in Mexico, Guatemala, and India and a group of children with acute diarrhea in Houston, TX, between 2007 and 2012. The heat-labile/heat-stable (LT/ST) enterotoxins and CFs from 252 patients were determined using polymerase chain reaction assay. Among the 252 ETEC isolates, 15% were LT-only, 58% were ST-only, and 28% produced both LT and ST. The distribution of LT-only (12-15%) and ST-only (55-56%) isolates was similar between Latin American and Indian sites. The most prevalent CF was CS21, expressed in 65% of the isolates followed by CS6 (25%) and CS3 (17%). Among the international travelers, 64% of the ETEC isolates expressed CS21. CS21 was expressed in 46% of isolates from Latin America compared with 96% of isolates from India (P < 0.0001). CS21 was expressed in 85% isolates from Houston children. CS21 was increasingly found in ST-only (P = 0.003) and ST/LT (P = 0.026) ETEC compared with LT-only ETEC. High frequency of finding CS21 among recent isolates of ETEC over a wide geographic distribution warrants additional studies on this CF. Highly conserved CS21 is an important target for potential multivalent ETEC vaccines.


Assuntos
Escherichia coli Enterotoxigênica/isolamento & purificação , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Portador Sadio , Guatemala/epidemiologia , Humanos , Índia/epidemiologia , México/epidemiologia , Texas/epidemiologia , Viagem
14.
Pediatr Infect Dis J ; 36(4): 379-383, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27977555

RESUMO

BACKGROUND: The management of Clostridium difficile infection (CDI) in children is complicated by recurrence rates of 20%-30%. The identification of risk factors associated with recurrent disease might allow early recognition of those children at highest risk. METHODS: Pediatric patients with CDI were identified through clinical laboratory records at 2 tertiary-care children's hospitals from March 2013 through May 2014. Subjects were enrolled and followed for 60 days to assess for recurrent CDI (rCDI). Blood samples were obtained at enrollment to evaluate host interleukin (IL)-8 polymorphisms and anti-toxin A antibody levels; stool samples were obtained for inflammatory markers (lactoferrin, calprotectin, IL-8) and C. difficile ribotype 027 strain status. Thirty days post enrollment, another serum sample was obtained to compare antibody responses. RESULTS: Of the 28 pediatric patients enrolled, 27 completed follow-up and 8 (30%) experienced rCDI. At enrollment, children with malignancy had significantly lower stool calprotectin, lactoferrin and IL-8 than those without malignancy. There was a trend toward increased stool inflammatory markers in those who later developed rCDI. The IL-8 A/A genotype was not associated with recurrent disease. No patients were found to have ribotype 027 or an antibody increase to toxin A. CONCLUSIONS: The rate of rCDI in our pediatric cohort was 30%. Children with rCDI had a trend toward higher fecal inflammatory markers with the initial infection, and these values were lower in children with malignancy. Fecal lactoferrin, calprotectin and IL-8 should be further studied to determine their value in predicting the risk of rCDI in children.


Assuntos
Biomarcadores/análise , Infecções por Clostridium/epidemiologia , Clostridium difficile , Citocinas/análise , Inflamação/metabolismo , Adolescente , Criança , Pré-Escolar , Fezes/química , Feminino , Humanos , Lactente , Intestinos/fisiopatologia , Masculino , Estudos Prospectivos , Recidiva , Fatores de Risco
15.
Langmuir ; 32(50): 13358-13366, 2016 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-27993022

RESUMO

Oil/water separation has inspired much research interest because of the damages caused to our natural environment due to oily wastewater. As a leader of advanced separation materials, electrospun polymeric fibrous mats having the properties of special surface wettability, high specific surface area, and high porosity will be a good membrane material for the separation of oily wastewater. Herein, we first prepared pH-responsive polymer poly(dimethylsiloxane)-block-poly(4-vinylpyridine) (PDMS-b-P4VP) mat using electrospinning technology. The PDMS-b-P4VP fibrous mat with a thickness of around 250 µm exhibits good pH-switchable oil/water wettability and is able to effectively separate oil or water from layered oil/water mixtures by gravity driven through adjusting the pH value. Stemming from its porous structure and pH-switchable superwettability, the electrospun PDMS-b-P4VP fibrous mat achieved controllable separations with high fluxes of approximately 9000 L h-1 m-2 for oil (hexane) and 27 000 L h-1 m-2 for water. In addition, extended studies on the polymer/silica nanoparticulate (silica NP) composite fibrous mats show that the addition of an inorganic component improves the thermal stability, pH-switchable wettability, and separation performance of the fibrous mats (approximately 9000 L h-1 m-2 for hexane and 32 000 L h-1 m-2 for water). It can be concluded from the results that both polymer fibrous mats and silica-filled composite fibrous mats are good candidates for on-demand layered oil/water mixture separation.

16.
Gut Microbes ; 6(2): 110-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25695334

RESUMO

Alterations in the gut microbiota are correlated with ailments such as obesity, inflammatory bowel disease, and diarrhea. Up to 60% of individuals traveling from industrialized to developing countries acquire a form of secretory diarrhea known as travelers' diarrhea (TD), and enterotoxigenic Escherichia coli (ETEC) and norovirus (NoV) are the leading causative pathogens. Presumably, TD alters the gut microbiome, however the effect of TD on gut communities has not been studied. We report the first analysis of bacterial gut populations associated with TD. We examined and compared the gut microbiomes of individuals who developed TD associated with ETEC, NoV, or mixed pathogens, and TD with no pathogen identified, to healthy travelers. We observed a signature dysbiotic gut microbiome profile of high Firmicutes:Bacteroidetes ratios in the travelers who developed diarrhea, regardless of etiologic agent or presence of a pathogen. There was no significant difference in α-diversity among travelers. The bacterial composition of the microbiota of the healthy travelers was similar to the diarrheal groups, however the ß-diversity of the healthy travelers was significantly different than any pathogen-associated TD group. Further comparison of the healthy traveler microbiota to those from healthy subjects who were part of the Human Microbiome Project also revealed a significantly higher Firmicutes:Bacteriodetes ratio in the healthy travelers and significantly different ß-diversity. Thus, the composition of the gut microbiome in healthy, diarrhea-free travelers has characteristics of a dysbiotic gut, suggesting that these alterations could be associated with factors such as travel.


Assuntos
Bactérias/classificação , Infecções por Caliciviridae/microbiologia , Diarreia/microbiologia , Disbiose , Infecções por Escherichia coli/microbiologia , Microbioma Gastrointestinal , Viagem , Bactérias/genética , Humanos
17.
Pediatr Infect Dis J ; 33(9): 924-8, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25361022

RESUMO

BACKGROUND: Clostridium difficile infection (CDI) is an increasingly important cause of morbidity in hospitalized children. We describe the recent epidemiology of pediatric CDI at a children's hospital, compare community-associated (CA) and hospital-associated (HA) infections and identify risk factors for severe disease. METHODS: Children with CDI at Texas Children's Hospital were identified from February 1, 2011, to October 31, 2011. Severe CDI was defined as the presence of a CDI-related complication or ≥2 clinical features: fever, bloody stools, leukocytosis, hypoalbuminemia or elevated creatinine. Standard epidemiologic definitions were used. RESULTS: One-hundred and nine unique patients 1-21 years of age with CDI were identified throughout the study period. The proportions of CA-CDI (41%) and HA-CDI (46%) were similar, whereas community-onset indeterminate CDI (13%) was less common. Children with malignancy or solid organ transplantation were more likely to have HA-CDI. Conversely, all children with inflammatory bowel disease had CA-CDI. Twenty-three patients (21%) met criteria for severe disease and 8 experienced a CDI-related complication, including 1 death attributable to CDI. On multivariate analysis, the presence of a gastrostomy tube (adjusted odds ratio: 3.09; 95% confidence interval: 1.07-8.94) and having community-onset indeterminate disease (adjusted odds ratio: 4.62; 95% confidence interval: 1.28-16.67) were found to be associated with severe CDI. CONCLUSIONS: A substantial proportion of pediatric CDI is CA and there are clinical differences between children with CA-CDI and HA-CDI. Children with CDI frequently experience severe disease, whereas complications are uncommon. Early identification and treatment of CDI should be pursued in children with gastrostomy tube and recent hospitalization.


Assuntos
Clostridium difficile , Enterocolite Pseudomembranosa/epidemiologia , Neoplasias/epidemiologia , Índice de Gravidade de Doença , Adolescente , Adulto , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/epidemiologia , Infecção Hospitalar/epidemiologia , Enterocolite Pseudomembranosa/complicações , Feminino , Gastrostomia , Hospitais Pediátricos , Humanos , Lactente , Doenças Inflamatórias Intestinais/epidemiologia , Intubação Gastrointestinal , Masculino , Transplante de Órgãos , Fatores de Risco , Texas , Adulto Jovem
18.
J Travel Med ; 21(6): 369-76, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25345982

RESUMO

BACKGROUND: Rifamycin SV is under development for treatment of travelers' diarrhea (TD) in a new oral formulation, Rifamycin SV MMX (RIF-MMX; Santarus Inc., San Diego, CA, USA), which targets its delivery to the colon, making it a unique rifamycin drug. METHODS: This was a randomized, double-blind, phase 3 study of adult travelers to Mexico or Guatemala experiencing acute diarrhea. A total of 264 patients received RIF-MMX (2 × 200 mg twice daily for 3 days, n = 199) or placebo (n = 65) in a 3 : 1 ratio. The primary endpoint was the length of time between the administration of first dose of study drug and passage of the last unformed stool (TLUS; after which clinical cure was declared). Other endpoints included eradication of pathogens from the stools, pathogen minimum inhibitory concentration (MIC), and adverse events (AEs). RESULTS: TLUS was significantly shorter in the RIF-MMX group (median: 46.0 hours) compared with placebo (median: 68.0 hours; p = 0.0008) and a larger percentage of RIF-MMX treated patients (81.4%) achieved clinical cure compared with placebo patients (56.9%). TLUS was significantly shorter in the subgroups of patients with enteroaggregative, enterotoxigenic, or diffusely adherent Escherichia coli infections (p = 0.0035) with nonsignificant activity against invasive bacteria (p = 0.3804). Overall pathogen eradication rates were numerically higher in the RIF-MMX group (67.0%) compared with placebo (54.8%) but the difference did not reach significance (p = 0.0836). In vitro resistance to rifamycin SV was observed in some bacteria remaining after treatment of patients with RIF-MMX but was not associated with lower efficacy in them. AEs appeared to be more frequent with placebo (38.5%) than with RIF-MMX (29.6%). CONCLUSIONS: RIF-MMX shortened the duration of TD in patients with a broad range of pathogens and was well tolerated. The unique pharmacokinetic properties of the drug offer evidence that TD pathogens work at the level of the colon.


Assuntos
Diarreia/tratamento farmacológico , Infecções por Escherichia coli/tratamento farmacológico , Fármacos Gastrointestinais/administração & dosagem , Rifamicinas/administração & dosagem , Viagem , Administração Oral , Adulto , Diarreia/microbiologia , Diarreia/prevenção & controle , Método Duplo-Cego , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/prevenção & controle , Feminino , Guatemala , Humanos , Masculino , México , Rifaximina , Resultado do Tratamento , Adulto Jovem
19.
Diabetes Res Clin Pract ; 105(3): 285-94, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25015315

RESUMO

Diabetes-related hospitalization and hospital utilization is a serious challenge to the health care system, a situation which may be further aggravated by nosocomial Clostridium difficile (C. difficile) infection (CDI). Studies have demonstrated that diabetes increases the risk of recurrent CDI with OR (95% CI) 2.99 (1.88, 4.76). C. difficile is a gram-positive, spore-forming anaerobic bacterium which is widely distributed in the environment. Up to 7% of healthy adults and up to 45% of infants may have asymptomatic intestinal carriage of C. difficile. A large number of strains of C. difficile have been identified. A number of PCR or sequence-based molecular typing methods are available for typing C. difficile isolates. C. difficile virulence evolved independently in the highly epidemic lineages, associated with the expression of toxin genes and other virulence factors. This article briefly reviews recent progresses in the bateriology of C. difficile and highlights the limited knowledge of potential mechanisms for the increased risk of CDI in diabetes which warrants further research.


Assuntos
Clostridium difficile , Complicações do Diabetes/microbiologia , Enterocolite Pseudomembranosa/microbiologia , Fatores de Virulência , Adulto , Clostridium difficile/classificação , Clostridium difficile/patogenicidade , Fezes/microbiologia , Humanos , Lactente , Reação em Cadeia da Polimerase/métodos , Fatores de Virulência/classificação
20.
Infect Control Hosp Epidemiol ; 35(6): 667-73, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24799643

RESUMO

OBJECTIVE: To evaluate the accuracy of real-time polymerase chain reaction (PCR) for Clostridium difficile-associated disease (CDAD) detection, after hospital CDAD rates significantly increased following real-time PCR initiation for CDAD diagnosis. DESIGN: Hospital-wide surveillance study following examination of CDAD incidence density rates by interrupted time series design. SETTING: Large university-based hospital. PARTICIPANTS: Hospitalized adult patients. METHODS: CDAD rates were compared before and after real-time PCR implementation in a university hospital and in the absence of physician and infection control practice changes. After real-time PCR introduction, all hospitalized adult patients were screened for C. difficile by testing a fecal specimen by real-time PCR, toxin enzyme-linked immunosorbent assay, and toxigenic culture. RESULTS: CDAD hospital rates significantly increased after changing from cell culture cytotoxicity assay to a real-time PCR assay. One hundred ninety-nine hospitalized subjects were enrolled, and 101 fecal specimens were collected. C. difficile was detected in 18 subjects (18%), including 5 subjects (28%) with either definite or probable CDAD and 13 patients (72%) with asymptomatic C. difficile colonization. CONCLUSIONS: The majority of healthcare-associated diarrhea is not attributable to CDAD, and the prevalence of asymptomatic C. difficile colonization exceeds CDAD rates in healthcare facilities. PCR detection of asymptomatic C. difficile colonization among patients with non-CDAD diarrhea may be contributing to rising CDAD rates and a significant number of CDAD false positives. PCR may be useful for CDAD screening, but further study is needed to guide interpretation of PCR detection of C. difficile and the value of confirmatory tests. A gold standard CDAD diagnostic assay is needed.


Assuntos
Clostridium difficile/isolamento & purificação , Infecção Hospitalar/diagnóstico , Enterocolite Pseudomembranosa/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real/normas , Adulto , Idoso , Clostridium difficile/genética , Infecção Hospitalar/epidemiologia , Enterocolite Pseudomembranosa/epidemiologia , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População , Reprodutibilidade dos Testes
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