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2.
BMC Infect Dis ; 18(1): 605, 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30509202

RESUMO

BACKGROUND: Acute gastroenteritis (AGE) is the leading cause of illness among returning travelers seeking medical care. Multiple types of enteric pathogens can cause travel-acquired AGE and, while bacterial pathogens have a predominant role, the importance of viruses, such as norovirus, is increasingly recognized. There is a lack of information on travel-acquired norovirus incidence among symptomatic and asymptomatic individuals irrespective of healthcare-seeking behavior. Our aim is to estimate the incidence of travel-acquired AGE due to norovirus and to characterize the burden of disease among international travelers from the United States and Europe. METHODS: We describe a prospective cohort study implemented in five US and European sites to estimate the role of AGE due to norovirus among adult international travelers. We enrolled individuals aged 18 years and older who are traveling to regions of moderate-high risk of AGE, or via cruise ship with an international port stop, with a trip duration of 3-15 days. The study will generate a wide range of health and travel-related data for pre-, during, and up to 6-months post-travel. We will identify laboratory-confirmed travel-acquired norovirus infections among both symptomatic and asymptomatic individuals from self-collected whole stool samples tested via quantitative RT-PCR. Coinfections will be identified in a subset of travelers with AGE using a multiplex molecular-based assay. DISCUSSION: This study is unique in design and breadth of data collected. The prospective collection of health and behavioral data, as well as biologic samples from travelers irrespective of symptoms, will provide useful data to better understand the importance of norovirus AGE among international travelers. This study will provide data to estimate the incidence of norovirus infections and AGE and the risk of post-infectious sequelae in the 6-month post-travel period serving as a baseline for future norovirus AGE vaccination studies. This study will contribute valuable information to better understand the role of norovirus in travel-acquired AGE risk and the impact of these infections on a broad set of outcomes.

3.
J Travel Med ; 2018 Nov 20.
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 travelers' diarrhea (TD) in previous study. Thus, a study was designed to compare this poorly absorbed antibiotic to 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 to 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 vs. 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 three 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.

4.
Microbiome ; 6(1): 201, 2018 Nov 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.

5.
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.

6.
FEMS Microbiol Lett ; 365(22)2018 Nov 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.

7.
Int J Infect Dis ; 76: 82-87, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30223088

RESUMO

Non-O157 strains of Shiga toxin-producing Escherichia coli (STEC) are more common causes of acute diarrhea than the better-known O157 strains and have the potential for large outbreaks. This systematic review of the literature identified 129 serogroups as well as 262 different O and H antigen combinations of STEC in cases of epidemic and sporadic disease worldwide. Excluding the results from a single large outbreak of STEC O104:H4 in Germany and France in 2011, the reported frequency of dysenteric illness in patients was 26% (119 of 464) for epidemic disease and 25% (646 of 2588) for sporadic cases. Hemolytic uremic syndrome was identified in 14% of epidemic disease cases and 9% of sporadic illness cases. With the increasing use of PCR-based diagnostics, STEC strain identification may not be possible. Rapid diagnostics are needed for STEC infections to aid the clinician while allowing epidemiologists the opportunity to identify outbreaks and to trace the source of infection.

8.
9.
Int J Infect Dis ; 74: 24-28, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29960098

RESUMO

BACKGROUND: Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea worldwide. As a result, the US Centers for Disease Control and Prevention have designated C. difficile as an urgent threat. Despite the global public health risk posed by CDI, little is known about its epidemiology on the African continent. This article describes the common occurrence of CDI from a cross-section of consecutively seen, randomly enrolled patients presenting with diarrhea at two major hospitals in Kenya. METHODS: Patients presenting with diarrhea at two major hospitals in Kenya from May to July 2017 were enrolled. After signing the informed consent, stool samples, demographic data, medical history, prior antibiotic use, and HIV status were obtained from the patients. C. difficile was detected and validated by toxigenic culture and PCR. RESULTS: The average age of the patients was 35.5 years (range 3-86 years); 59% were male and 41% were female. Out of 105 patient stools tested, 98 (93.3%) were positive for C. difficile by culture. PCR analysis confirmed C. difficile-specific genes, tcdA, tcdB, and tcdC, in the strains isolated from the stools. Further, 82.5% of the stools had C. difficile isolates bearing the frame-shift deletion associated with hypervirulent strains. Remarkably, 91.9% of the stools that tested positive for C. difficile came from patients under 60 years old, with 64.3% being less than 40 years of age. The majority of the patients (85%) reported over-the-counter antibiotic use in the last 30days before the hospital visit. CONCLUSIONS: Together, the results revealed an unusually high incidence of C. difficile in the stools analyzed, especially among young adults who are thought to be less vulnerable. Comprehensive research is urgently needed to examine the epidemiology, risk factors, pathogenesis, comorbidities, clinical outcomes, antibiotic susceptibility, and genetic makeup of C. difficile strains circulating on the African continent.

10.
Dig Liver Dis ; 50(8): 741-749, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29807873

RESUMO

Digestive diseases are a broad range of chronic disorders that substantially and negatively impact the patients' quality of life. Here, we review our current understanding on the pathophysiology of hepatic encephalopathy, irritable bowel syndrome, and diverticular disease, with a special focus on the gut microbiota composition associated with these disorders. Furthermore, we review the current clinical practice for their therapeutic treatments, including probiotics, diet change, non-adsorbable disaccharides, and antibiotics. We highlight that broad-spectrum non-adsorbable antibiotics, such as rifaximin, are quite effective and safe for the treatment of all essayed digestive diseases.


Assuntos
Doenças Diverticulares/microbiologia , Microbioma Gastrointestinal , Encefalopatia Hepática/microbiologia , Síndrome do Intestino Irritável/microbiologia , Antibacterianos/uso terapêutico , Doenças Diverticulares/tratamento farmacológico , Doenças Diverticulares/fisiopatologia , Encefalopatia Hepática/tratamento farmacológico , Encefalopatia Hepática/fisiopatologia , Humanos , Síndrome do Intestino Irritável/tratamento farmacológico , Síndrome do Intestino Irritável/fisiopatologia , Probióticos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Rifamicinas/uso terapêutico , Rifaximina
14.
J Travel Med ; 24(suppl_1): S57-S62, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28881862

RESUMO

Background: The recommendation that antibiotics should be used for routine therapy of travellers' diarrhoea is being reconsidered in view of growing evidence that the therapy may lead to intestinal carriage of multi-drug resistant (MDR) colonic microbiota. This review attempts to put the issues of therapy and MDR acquisition in perspective to help in the establishment of therapeutic recommendations for travellers' diarrhoea. Methods: The existing literature showing the risk and consequences of acquisition of MDR microbiota in antibiotic-treated travellers was reviewed. Issues important to the development of firm evidence-based recommendations for antibiotics use for treatment and prevention of travellers' diarrhoea were researched. Results: Six areas of research needed to allow the development of evidence-based recommendations for antibiotic-treatment and -prevention of travellers' diarrhoea were identified. Conclusions: Increasing worldwide occurrence of antibiotic resistance should alert public health officials of the importance of encouraging local antibiotic stewardship guidelines. Six areas to research are identified in this review to allow the development of evidence-based recommendations for use of antibiotics for treatment and selective prevention of travellers' diarrhoea. An interdisciplinary ISTM Consensus group will consider the data available and develop current recommendations for therapy and chemoprevention of travellers' diarrhoea considering groups who would benefit the most from antimicrobials while recognizing the hazards associated with broad use of these drugs. With interim recommendations and ultimately evidence-based recommendations, guidelines can be developed for management of travellers' diarrhoea considering populations and destinations.


Assuntos
Anti-Infecciosos/uso terapêutico , Diarreia/prevenção & controle , Resistência a Múltiplos Medicamentos , Enterobacteriaceae , Fezes/microbiologia , Viagem , Diarreia/tratamento farmacológico , Enterobacteriaceae/efeitos dos fármacos , Medicina Baseada em Evidências , Humanos
15.
Diagn Microbiol Infect Dis ; 89(3): 235-240, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28931467

RESUMO

Diarrheagenic Escherichia coli (DEC) pathotypes with differing epidemiology and clinical features, are known causes of disease with worldwide occurrence. At a major cancer center in the U.S., we studied patients with cancer and diarrhea for whom a GI Biofire FilmArray multiplex GI panel (BFM) was performed. An enteropathogen was identified in 382 of 2017 (19%) samples distributed across 311 patients. Of these, 60/311(19%) were positive for DEC. Patients receiving hematopoietic stem cell transplants (HSCT) 29/60 (48%) or with a hematologic malignancy 17/60 (28%) accounted for the majority of DEC cases. Enteropathogenic E. coli (EPEC, n=35 [58%]), enteroaggregative E. coli (EAEC, n=10 [17%]) and Shiga toxin producing E. coli (STEC, n=3 [5%]) were the most common DEC identified and peaked in the summer months. Stool cultures confirmed infections in 6/10 (60%) EAEC (five typical AggR+), and EPEC was recovered in 8/35 (22%) samples (all atypical eaeA+, bfp-). DEC was identified in 22 cases (37%) that developed diarrhea >48hours after admission suggesting health care acquisition. Chronic infections were found in 2 EPEC and 1 EAEC cases that were tested at 1month or beyond with shedding that ranged from 58 to >125days. Two patients that underwent hematopoietic stem cell transplantation carried EAEC strains resistant to multiple antibiotics including fluoroquinolones and expressed extended spectrum beta lactamases. While in some instances BFM results were not verified in culture and could represent false positives, DEC pathotypes, especially EPEC and EAEC, caused chronic infections with antimicrobial-resistant strains in a subset of immunosuppressed cancer patients.


Assuntos
Diarreia/microbiologia , Infecções por Escherichia coli/microbiologia , Escherichia coli/genética , Fezes/microbiologia , Epidemiologia Molecular , Neoplasias/complicações , Adolescente , Adulto , Idoso , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Amplificação de Ácido Nucleico , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
16.
Future Microbiol ; 12: 975-985, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28759258

RESUMO

Clostridium difficile infection (CDI) is a major public health problem worldwide. Treatment has become complicated due to the emergence of strains with increased toxigenicity and sporulation rate, together with rampant antibiotics use that disrupts colonization resistance of the colonic microbiota. As a result, there is a critical need for nonantibiotic treatments. Therapies based on inhibiting the toxins, bacterial structures responsible for colonization, virulence and restoration of the gut microbiota are the most important nonantibiotic targets to combat CDI. This report outlines these targets and how they could become the focus of future therapeutic agents. Inhibiting colonization and virulence factors during CDI will disrupt pathogen persistence and decrease exposure to the inflammatory toxins, allowing the immune system to clear the infection.


Assuntos
Antibacterianos/uso terapêutico , Proteínas de Bactérias/efeitos dos fármacos , Toxinas Bacterianas/metabolismo , Infecções por Clostridium/tratamento farmacológico , Clostridium difficile/efeitos dos fármacos , Animais , Anticorpos Monoclonais/uso terapêutico , Proteínas de Bactérias/metabolismo , Infecções por Clostridium/imunologia , Infecções por Clostridium/microbiologia , Clostridium difficile/patogenicidade , Clostridium difficile/fisiologia , Microbioma Gastrointestinal , Humanos , Imunoterapia , Percepção de Quorum/efeitos dos fármacos , Percepção de Quorum/fisiologia , Virulência , Fatores de Virulência
17.
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
18.
J Travel Med ; 24(suppl_1): S57-S74, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-28521004

RESUMO

Background: : Travelers' diarrhea causes significant morbidity including some sequelae, lost travel time and opportunity cost to both travelers and countries receiving travelers. Effective prevention and treatment are needed to reduce these negative impacts. Methods: : This critical appraisal of the literature and expert consensus guideline development effort asked several key questions related to antibiotic and non-antibiotic prophylaxis and treatment, utility of available diagnostics, impact of multi-drug resistant (MDR) colonization associated with travel and travelers' diarrhea, and how our understanding of the gastrointestinal microbiome should influence current practice and future research. Studies related to these key clinical areas were assessed for relevance and quality. Based on this critical appraisal, guidelines were developed and voted on using current standards for clinical guideline development methodology. Results: : New definitions for severity of travelers' diarrhea were developed. A total of 20 graded recommendations on the topics of prophylaxis, diagnosis, therapy and follow-up were developed. In addition, three non-graded consensus-based statements were adopted. Conclusions: : Prevention and treatment of travelers' diarrhea requires action at the provider, traveler and research community levels. Strong evidence supports the effectiveness of antimicrobial therapy in most cases of moderate to severe travelers' diarrhea, while either increasing intake of fluids only or loperamide or bismuth subsalicylate may suffice for most cases of mild diarrhea. Further studies are needed to address knowledge gaps regarding optimal therapies, the individual, community and global health risks of MDR acquisition, manipulation of the microbiome in prevention and treatment and the utility of laboratory testing in returning travelers with persistent diarrhea.


Assuntos
Antibacterianos/uso terapêutico , Diarreia/tratamento farmacológico , Padrões de Prática Médica , Viagem , Humanos , Guias de Prática Clínica como Assunto
20.
Tex Med ; 113(2): 31-36, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-28207078

RESUMO

Emerging and reemerging infections have become prevalent in the United States since the 1970s, causing illness, death, and fear among the public. The published literature was reviewed to offer a perspective on risk factors for disease acquisition and to allow a prediction of the next microbial assault after Ebola and Zika. Four well-integrated factors likely will contribute simultaneously: animals colonized or infected by pathogens capable of human transmission, microbes recurrently changing their virulence, a growing number of susceptible people, and climatic and environmental factors encouraging disease transmission. The next pathogen likely to emerge in an important way in the United States is a new mutant virus arising from a well-established RNA virus family. Standard public health principles, including monitoring general populations for disease, developing new reagents as pathogens arise, implementing control efforts such as effective antibiotic stewardship programs, and vaccine development and administration will minimize damage from the emerging organisms.


Assuntos
Doenças Transmissíveis Emergentes/epidemiologia , Doença pelo Vírus Ebola/epidemiologia , Saúde Pública/tendências , Infecção por Zika virus/epidemiologia , Zoonoses/epidemiologia , Animais , Previsões , Humanos , Estados Unidos
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