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1.
Nat Commun ; 10(1): 2641, 2019 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-31201325

RESUMO

Epsilon toxin (Etx), a potent pore forming toxin (PFT) produced by Clostridium perfringens, is responsible for the pathogenesis of enterotoxaemia of ruminants and has been suggested to play a role in multiple sclerosis in humans. Etx is a member of the aerolysin family of ß-PFTs (aß-PFTs). While the Etx soluble monomer structure was solved in 2004, Etx pore structure has remained elusive due to the difficulty of isolating the pore complex. Here we show the cryo-electron microscopy structure of Etx pore assembled on the membrane of susceptible cells. The pore structure explains important mutant phenotypes and suggests that the double ß-barrel, a common feature of the aß-PFTs, may be an important structural element in driving efficient pore formation. These insights provide the framework for the development of novel therapeutics to prevent human and animal infections, and are relevant for nano-biotechnology applications.


Assuntos
Toxinas Bacterianas/química , Clostridium perfringens/ultraestrutura , Animais , Toxinas Bacterianas/genética , Toxinas Bacterianas/isolamento & purificação , Toxinas Bacterianas/metabolismo , Biotecnologia/métodos , Linhagem Celular , Infecções por Clostridium/microbiologia , Infecções por Clostridium/prevenção & controle , Clostridium perfringens/genética , Clostridium perfringens/metabolismo , Clostridium perfringens/patogenicidade , Microscopia Crioeletrônica , Cães , Enterotoxemia/microbiologia , Enterotoxemia/prevenção & controle , Modelos Moleculares , Mutagênese Sítio-Dirigida , Nanotecnologia/métodos , Conformação Proteica em Folha beta/genética , Multimerização Proteica/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo
2.
Hosp Pract (1995) ; 47(3): 123-129, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31177865

RESUMO

Clostridium difficile (CD) is the most common cause of nosocomial diarrhea. We aim to highlight practice measures for controlling and preventing Clostridium difficile infections (CDI) in the hospital setting. Electronic databases including PubMed, MEDLINE, Google Scholar, ClinicalTrials.gov, and Cochrane Databases were searched for human studies that assessed strategic measures for the prevention of CDI. Bundled interventions can effectively reduce the rates of CDI. Current evidence support the implementation antibiotic stewardship programs, hygiene enhancement, dietary management with probiotics, use of copper surfaces, and the cautious use of PPIs. However, current guidelines do not advocate the use of copper, probiotics, or the discontinuation of PPIs as a means for reducing CDI. We review these practical and evidence-based approaches.


Assuntos
Gestão de Antimicrobianos , Infecções por Clostridium/prevenção & controle , Clostridium difficile , Infecção Hospitalar/prevenção & controle , Hospitais , Humanos , Higiene
3.
Vet Microbiol ; 231: 1-6, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30955794

RESUMO

Neonatal porcine diarrhea (NPD) is a current problem on pig farms and is caused by several enteropathogens. Among them, Clostridioides difficile stands out due to its importance in piglets and zoonotic potential. A non-toxigenic strain of C. difficile (NTCD), named Z31, was previously tested in hamster and piglet experimental models as a strategy to prevent C. difficile infection (CDI). To evaluate the capacity of the strain Z31 to prevent CDI and NPD in one-day-old piglets on a commercial farm, 90 piglets from 16 litters received 1 × 106 spores of Z31 while 84 animals from the same litters served as controls. Animals were clinically evaluated, and fecal samples were collected 24 h after administration and submitted to A/B toxin detection and isolation of C. difficile. Stool samples were also submitted to rotavirus, Escherichia coli, and Clostridium perfringens detection. Administration of Z31 reduced the incidence of CDI in treated animals (7.8%) when compared to the control group (25.0%; P = 0.003). In animals that developed CDI, the intensity of diarrhea was lower in those that received Z31 than in the control group. Neonatal porcine diarrhea was reduced in treated animals when compared to untreated animals (P < 0.001). The present study suggests that Z31 can potentially be used to prevent CDI in piglets on commercial farms.


Assuntos
Infecções por Clostridium/prevenção & controle , Clostridium difficile/fisiologia , Clostridium difficile/patogenicidade , Diarreia/veterinária , Doenças dos Suínos/microbiologia , Animais , Animais Recém-Nascidos , Derrame de Bactérias , Infecções por Clostridium/microbiologia , Clostridium perfringens/isolamento & purificação , Diarreia/microbiologia , Diarreia/prevenção & controle , Escherichia coli Enterotoxigênica/isolamento & purificação , Fazendas , Fezes/microbiologia , Suínos , Doenças dos Suínos/prevenção & controle
4.
J Hosp Infect ; 102(2): 157-164, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30880267

RESUMO

BACKGROUND: Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhoea with peak incidence in late winter or early autumn. Although CDI is commonly associated with hospitals, community transmission is important. AIM: To explore potential drivers of CDI seasonality and the effect of community-based interventions to reduce transmission. METHODS: A mechanistic compartmental model of C. difficile transmission in a hospital and surrounding community was used to determine the effect of reducing transmission or antibiotic prescriptions in these settings. The model was extended to allow for seasonal antibiotic prescriptions and seasonal transmission. FINDINGS: Modelling antibiotic seasonality reproduced the seasonality of CDI, including approximate magnitude (13.9-15.1% above annual mean) and timing of peaks (0.7-1.0 months after peak antibiotics). Halving seasonal excess prescriptions reduced the incidence of CDI by 6-18%. Seasonal transmission produced larger seasonal peaks in the prevalence of community colonization (14.8-22.1% above mean) than seasonal antibiotic prescriptions (0.2-1.7% above mean). Reducing transmission from symptomatic or hospitalized patients had little effect on community-acquired CDI, but reducing transmission in the community by ≥7% or transmission from infants by ≥30% eliminated the pathogen. Reducing antibiotic prescription rates led to approximately proportional reductions in infections, but limited reductions in the prevalence of colonization. CONCLUSION: Seasonal variation in antibiotic prescription rates can account for the observed magnitude and timing of C. difficile seasonality. Even complete prevention of transmission from hospitalized patients or symptomatic patients cannot eliminate the pathogen, but interventions to reduce transmission from community residents or infants could have a large impact on both hospital- and community-acquired infections.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Clostridium/prevenção & controle , Infecções por Clostridium/transmissão , Transmissão de Doença Infecciosa/prevenção & controle , Uso de Medicamentos , Controle de Infecções/métodos , Modelos Teóricos , Adulto , Idoso , Humanos , Lactente , Prescrições/estatística & dados numéricos , Prevalência , Estações do Ano
5.
Poult Sci ; 98(7): 2800-2812, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30877749

RESUMO

The objective of this study was to evaluate performance, diversity, composition, and predicted function of the intestinal microbiota of broilers raised under 3 different methods to induce necrotic enteritis (NE). The chicks in Experiments 1 and 2 were vaccinated against coccidiosis on day 1. Experiment 1: non-challenged and challenged birds were raised in floor pens with new litter and 58 birds/pen. The challenge consisted of Eimeria maxima inoculation on day 14 and Clostridium perfringens via water on days 18 to 19. Cecal microbiota was evaluated on days 18, 21, and 28. Experiment 2: non-challenged and challenged birds were raised in floor pens with recycled litter and 50 birds/pen. The challenge consisted of C. perfringens via feed from days 18 to 20. Ileal and cecal microbiota were evaluated on day 21. In Experiment 3, non-challenged and challenged birds were raised in battery cages with 8 birds/cage. Challenged birds were inoculated with E. maxima on day 14 and with C. perfringens on days 19 to 21. In the 3 experiments, ileal or cecal microbiota or both were analyzed through 16S rRNA sequencing. The performance of the birds was impaired in the 3 studies, regardless of the method used to induce NE. In Experiment 1, the microbiota did not significantly change across ages. In Experiment 2, α-diversity indices were lower in challenged vs. non-challenged birds in both ileal and cecal microbiota. The cecal microbiota composition and function was more affected than the ileal microbiota. In Experiment 3, Chao index (α-diversity) increased in challenged vs. non-challenged birds, and the composition of the ileal and cecal microbiota was not significantly affected. In conclusion, the overall feed conversion ratio was more affected in Experiment 3 (5.2, 11.1, and 30% for Experiments 1, 2, and 3, respectively), which also showed the highest degree of NE lesions. However, the largest variations of diversity and composition of the microbiota were observed in Experiment 2, when birds were raised in floor pens with reused litter, vaccinated against coccidiosis, and challenged with C. perfringens on days 19 to 21.


Assuntos
Enterite/veterinária , Microbioma Gastrointestinal , Necrose/veterinária , Doenças das Aves Domésticas/microbiologia , Criação de Animais Domésticos , Fenômenos Fisiológicos da Nutrição Animal , Animais , Galinhas , Infecções por Clostridium/imunologia , Infecções por Clostridium/prevenção & controle , Infecções por Clostridium/veterinária , Clostridium perfringens/fisiologia , Coccidiose/imunologia , Coccidiose/prevenção & controle , Coccidiose/veterinária , Eimeria/fisiologia , Enterite/microbiologia , Necrose/microbiologia , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/parasitologia , Doenças das Aves Domésticas/prevenção & controle , RNA Ribossômico 16S , Vacinação/veterinária
6.
Vet Microbiol ; 230: 7-13, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30827407

RESUMO

Necrotic enteritis (NE) is an economically important disease of broiler chickens that is caused primarily by Clostridium perfringens strains that produce the NetB toxin. It is controlled in North America principally through the application of in-feed antimicrobials, but alternative control methods, such as vaccination, are urgently needed. We previously identified a cluster of C. perfringens genes prevalent in disease-causing strains, denominated VR-10B, that is predicted to encode a pilus. The current study evaluated the ability of three predicted pilin structural subunits (CnaA, FimA, FimB) to protect against NE in two immunization studies. In the first study, young broiler chickens were immunized twice intramuscularly (i.m.) with CnaA or FimA, which resulted in only a weak serum antibody response, and no reduction in the severity of intestinal lesions following experimental challenge with C. perfringens strain CP1. In the second study, chickens were injected subcutaneously (s.c.) with CnaA, FimB, or a combination of all three proteins, on days 7, 14 and 19, which resulted in a marked antibody response specific to each antigen. Chickens immunized with either CnaA or FimB had significantly reduced NE lesion severity, whereas immunization with all three proteins in combination did not provide protection. Western blot experiments using serum from immunized birds were also performed, providing the first experimental evidence to suggest that this locus may in fact encode a functional pilus structure.


Assuntos
Vacinas Bacterianas/imunologia , Infecções por Clostridium/veterinária , Clostridium perfringens/imunologia , Enterite/veterinária , Proteínas de Fímbrias/imunologia , Doenças das Aves Domésticas/prevenção & controle , Animais , Anticorpos Antibacterianos/sangue , Vacinas Bacterianas/administração & dosagem , Galinhas/imunologia , Infecções por Clostridium/prevenção & controle , Enterite/microbiologia , Enterite/prevenção & controle , Proteínas de Fímbrias/administração & dosagem , Fímbrias Bacterianas/genética , Fímbrias Bacterianas/imunologia , Injeções Intramusculares , Intestinos/patologia , Doenças das Aves Domésticas/microbiologia , Vacinas de Subunidades/administração & dosagem , Vacinas de Subunidades/imunologia
7.
Poult Sci ; 98(8): 3240-3245, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30789214

RESUMO

This study was conducted to evaluate the effect of an encapsulated sodium butyrate (Na-B) with targeted releasing times on growth performance and mitigating the impact of necrotic enteritis in broilers. Two Na-B (30% of Na-B content) products, CMA (2 h releasing time) and CMP (3 to 4 h releasing time), were evaluated in a necrotic enteritis challenge model. The experiment consisted of 4 Na-B treatments (500 and 1,000 ppm of each product) plus 2 control (non-challenged and challenged). A total of 336 Cobb-Cobb male broilers were placed 8 birds per pen into 7 replicate battery cages. On day 14, birds from challenged treatments were orally gavaged with ∼5,000 oocysts of Eimeria maxima. On day 19, 20, and 21, the challenged birds received 1 mL of 108 cfu/mL Clostridium perfringens. Total pen body weight (BW) and feed weight were assessed on day 14, 21, and 28 for BW gain and mortality-adjusted feed conversion ratio (FCR). On day 21, 3 birds were randomly selected per pen and scored for intestinal lesions. The duodenum and jejunum tissue were collected on day 21 and 28 for quantifying intestinal histology. Results revealed that adding CMA at 500 ppm showed significantly higher cumulative BW gain (P < 0.05) compared to the challenged control from day 1 to 21. Adding CMA at 500 ppm also showed the equivalent cumulative FCR that was comparable to the non-challenged control on day 21. The CMA treatments and CMP at 1,000 ppm treatment showed equivalent BW gain compared to the non-challenge control after an additional 7 d post-challenge on day 28. Both products at 500 or 1,000 ppm had the significantly (P < 0.05) lower intestinal lesion scores compared to the challenged control. However, there was no difference in lesion scores among the Na-B treatments. The Na-B product targeted to release in the anterior intestinal tract shows the beneficial effects on BW gain and feed utilization efficiency in current challenge model. Adding encapsulated Na-B product has the potential to mitigate the impact of necrotic enteritis in broilers.


Assuntos
Ácido Butírico/farmacologia , Enterite/prevenção & controle , Necrose/prevenção & controle , Doenças das Aves Domésticas/prevenção & controle , Animais , Peso Corporal/efeitos dos fármacos , Ácido Butírico/administração & dosagem , Galinhas , Infecções por Clostridium/prevenção & controle , Infecções por Clostridium/veterinária , Clostridium perfringens/fisiologia , Coccidiose/prevenção & controle , Coccidiose/veterinária , Preparações de Ação Retardada , Eimeria/fisiologia , Enterite/veterinária , Intestinos/patologia , Masculino , Necrose/veterinária , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/parasitologia
8.
Virulence ; 10(1): 166-179, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30806148

RESUMO

Clostridium perfringens α-toxin is one of the major virulence factors during C. perfringens infection, causing hemolysis of erythrocytes in various species. Here, genetically engineered Lactobacillus casei (pPG-α/L. casei 393) constitutively expressing the toxoid of C. perfringens α-toxin was generated and its immunogenicity in mice for induction of protective immunity against the α-toxin was evaluated via oral immunization. The α-toxoid was constitutively expressed by pPG-α/L. casei 393 without a specific inducer, as confirmed by western blotting, laser confocal microscopy, and flow cytometry. In an experiment on BALB/c mice to evaluate the oral immunogenicity of pPG-α/L. casei 393, significant levels of a specific secretory IgA (sIgA) antibody in the intestinal mucus and feces and an IgG antibody in the serum of the probiotic vaccine group were detected after booster immunization (p < 0.05) as compared with the pPG/L. casei 393 and PBS control groups. These antibodies effectively neutralized C. perfringens natural α-toxin. Moreover, significantly higher levels of cytokines IL-2, IL-4, IL-10, IL-12, IL-17, and interferon (IFN) γ in the serum and increased proliferation of spleen lymphocytes obtained from mice orally immunized with pPG-α/L. casei 393 were detected. With a commercial C. perfringens type A inactivated vaccine as a control, immune protection provided by the probiotic vaccine against C. perfringens α-toxin was evaluated, and 90% and 80% protection rates were observed, respectively. Therefore, strain pPG-α/L. casei 393 effectively elicited mucosal, humoral, and cellular immunity, suggesting that pPG-α/L. casei 393 is a promising candidate for development of a vaccine against C. perfringens α-toxin.


Assuntos
Toxinas Bacterianas/imunologia , Vacinas Bacterianas/imunologia , Proteínas de Ligação ao Cálcio/imunologia , Infecções por Clostridium/prevenção & controle , Lactobacillus casei/genética , Fosfolipases Tipo C/imunologia , Administração Oral , Animais , Anticorpos Antibacterianos/sangue , Toxinas Bacterianas/genética , Proteínas de Ligação ao Cálcio/genética , Infecções por Clostridium/imunologia , Clostridium perfringens , Citocinas/sangue , Feminino , Imunidade Celular , Imunogenicidade da Vacina , Camundongos , Camundongos Endogâmicos BALB C , Organismos Geneticamente Modificados/imunologia , Probióticos , Fosfolipases Tipo C/genética
9.
Clin Nurse Spec ; 33(2): 75-81, 2019 Mar/Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30730451

RESUMO

PURPOSE/OBJECTIVES: The purpose of this project was to design and implement a sustainable program to reduce hospital-acquired cases of Clostridioides difficile. DESCRIPTION OF THE PROJECT: Experiencing higher rates in a large, academic medical center, hospital leaders were assembled. The overall facility rate was 6.9% in 2014 with a first quarter rate of 8.4% in 2015. Individual unit rates were as high as 19.8%. A team of key stakeholders was assembled to plan, execute, and reevaluate targeted solutions. Strategies implemented were an innovative, automated screening tool, an evidence-based prevention bundle; and staff education. OUTCOMES: A facility-wide C difficile prevention program was implemented with a sustained decrease in rates observed from 8.4% in the first quarter of 2015 to 6.0% in the fourth quarter of 2017. The standardized infection ratio ranged from 0.541 to 0.889, consistently below the national mean. CONCLUSION: Clostridioides difficile is a leading cause of hospital-associated diarrhea and a tremendous burden on healthcare systems increasing morbidity, mortality, and financial strain. A multidisciplinary, multifaceted approach was critical to ensure early detection, reduce risk of transmission, and decrease overall rates.


Assuntos
Infecções por Clostridium/prevenção & controle , Clostridium difficile/isolamento & purificação , Infecção Hospitalar/prevenção & controle , Controle de Infecções/organização & administração , Centros Médicos Acadêmicos , Infecções por Clostridium/epidemiologia , Infecção Hospitalar/epidemiologia , Humanos , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Estados Unidos/epidemiologia
10.
Anaerobe ; 56: 78-87, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30771460

RESUMO

Clostridium chauvoei is the etiologic agent of blackleg in cattle, inducing fever, severe myonecrosis, oedemic lesions and ultimately death of infected animals. The pathogen often results in such rapid death that antibiotic therapy is futile and thus vaccination is the only efficient strategy in order to control the disease. The ß-barrel pore forming leucocidin Clostridium chauvoei toxin A (CctA) is one of the best characterised toxins of C. chauvoei and has been shown to be an important virulence factor. It has been reported to induce protective immunity and is conserved across C. chauvoei strains collected from diverse geographical locations for more than 50 years. The aim of this study was to identify the location of the CctA toxin during liquid culture fermentation and to use CctA to develop an in vitro assay to replace the current guinea pig challenge assay for vaccine potency in standard batch release procedures. We report that CctA is fully secreted in C. chauvoei culture and show that it is found abundantly in the supernatant of liquid cultures. Sera from cattle vaccinated with a commercial blackleg vaccine revealed strong haemolysin-neutralizing activity against recombinant CctA which reached titres of 1000 times 28 days post-vaccination. Similarly, guinea pig sera from an official potency control test reached titres of 600 times 14 days post-vaccination. In contrast, ELISA was not able to specifically measure anti-CctA antibodies in cattle serum due to strong cross-reactions with antibodies against other proteins present pre-vaccination. We conclude that haemolysin-neutralizing antibodies are a valuable measurement for protective immunity against blackleg and have the potential to be a suitable replacement of the guinea pig challenge potency test, which would forego the unnecessary challenge of laboratory animals.


Assuntos
Anticorpos Antibacterianos/sangue , Anticorpos Neutralizantes/sangue , Toxinas Bacterianas/imunologia , Vacinas Bacterianas/imunologia , Doenças dos Bovinos/prevenção & controle , Infecções por Clostridium/veterinária , Clostridium chauvoei/imunologia , Animais , Toxinas Bacterianas/metabolismo , Vacinas Bacterianas/administração & dosagem , Bovinos , Infecções por Clostridium/prevenção & controle , Clostridium chauvoei/metabolismo , Meios de Cultura/química , Ensaio de Imunoadsorção Enzimática , Cobaias , Leucocidinas/imunologia , Leucocidinas/metabolismo , Testes de Neutralização , Fatores de Virulência/imunologia
11.
Int J Infect Dis ; 80: 105-110, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30682499

RESUMO

BACKGROUND: Clostridium Difficile Infections (CDIs) have been increasing both in incidence and in severity, representing a big public health concern. AIM: The aim of this study was to evaluate the impact of a recently implemented Critical Pathway (CP) focused on patients with CDI in an Italian Teaching Hospital. METHODS: The CP implementation consisted of intervention aimed to faster diagnosis and appropriateness in admission and discharge point of care; activation of a multidisciplinary team; staff training; information to patients and caregivers. In a pre-post retrospective observational study, volume, process and outcome indicators were analyzed. FINDINGS: A total of 228 patients (128 in 2013 and 100 in 2016) were included. A decrease in the absolute number of access to the Emergency Department (p=0.02) and an increase in hospitalization in more appropriate ward (ie gastroenterology ward, p<0.001) were found. The median hospital length of stay decreased from 20.5 (12.5-31) days in 2013 to 16.5 (7-31) days in 2016 (p=0.05). With regards to outcome indicators, an increase of discharge to home and a decrease of discharge to long term facilities were showed (p=0.01 both). Despite a reduction, no statically significant differences in mortality between 2013 and 2016 were revealed by the analysis. CONCLUSION: In conclusion, we found quality improvement in patient hospital management. Our experience confirms that the implementation of the CP increases the appropriateness in hospital quality of care.


Assuntos
Infecções por Clostridium/epidemiologia , Clostridium difficile/isolamento & purificação , Procedimentos Clínicos , Infecção Hospitalar/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Infecções por Clostridium/prevenção & controle , Infecção Hospitalar/prevenção & controle , Estudos Transversais , Serviço Hospitalar de Emergência , Feminino , Hospitalização , Hospitais de Ensino , Humanos , Incidência , Itália , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Melhoria de Qualidade , Estudos Retrospectivos
12.
Adv Exp Med Biol ; 1125: 139-146, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30689174

RESUMO

Clostridium difficile (C. diff) is the most common causative agent of antibiotic-associated diarrhea and colitis. This spore-forming, obligate anaerobic, gram-positive bacillus is becoming responsible for an increasing number of infections worldwide, both in community and in hospital settings, whose severity can vary widely from an asymptomatic infection to a lethal disease. While discontinuation of antimicrobial agents and antibiotic treatment of the infection remain the cornerstone of therapy, the use of probiotics, especially Saccharomyces boulardii, and more recently of fecal microbiota transplantation have become valid forms of prevention and/or therapy and are here critically examined.


Assuntos
Infecções por Clostridium/prevenção & controle , Infecções por Clostridium/terapia , Enterocolite Pseudomembranosa/prevenção & controle , Enterocolite Pseudomembranosa/terapia , Transplante de Microbiota Fecal , Probióticos/uso terapêutico , Antibacterianos/uso terapêutico , Clostridium difficile , Diarreia/prevenção & controle , Diarreia/terapia , Humanos
13.
Infect Dis Health ; 24(1): 32-43, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30691583

RESUMO

BACKGROUND: In 2011, the Australasian Society for Infectious Diseases (ASID) and the Australian Infection Control Association (AICA), now known as the Australasian College of Infection Prevention and Control (ACIPC), produced a position statement on infection control requirements for preventing and controlling Clostridium difficile infection (CDI) in healthcare settings. METHODS: The statement updated in 2017 to reflect new literature available .The authors reviewed the 2011 position statement and critically appraised new literature published between 2011 and 2017 and relevant current infection control guidelines to identify where new evidence had become available or best practice had changed. RESULTS: The position statement was updated incorporating the new findings. A draft version of the updated position statement was circulated for consultation to members of ASID and ACIPC. The authors responded to all comments received and updated the position statement. CONCLUSIONS: This updated position statement emphasizes the importance of health service organizations having evidence-based infection prevention and control programs and comprehensive antimicrobial stewardship programs, to ensure the risk of C. difficile acquisition, transmission and infection is minimised.


Assuntos
Infecções por Clostridium/prevenção & controle , Clostridium difficile , Infecção Hospitalar/prevenção & controle , Gestão de Antimicrobianos , Infecções por Clostridium/transmissão , Desinfecção , Humanos , Higiene , Controle de Infecções/métodos
14.
Poult Sci ; 98(5): 2211-2219, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30668786

RESUMO

Two dietary sources of zinc (ZnSO4 or organic Zn) were tested in chickens challenged with coccidiosis (Co) or coccidiosis plus Clostridium perfringens (CoCPF). On day 14, the chickens were orally gavaged with ∼5,000 Eimeria maxima sporulated oocysts. On day 19, 20, and 21 chickens challenged with C. perfringens were given a broth culture containing 108 cfu of this bacterium. Productive performance parameters were determined at d 14, 21, and 28. On day 21, necrotic enteritis (NE) lesions were scored, and intestinal permeability was evaluated. Jejunum and cecal tonsils were collected for morphology and gene expression analysis. On day 21, organic Zn improved BW gain by 18.6% (P = 0.07), and FCR by 12% (P = 0.09) in CoCPF challenged chickens vs. birds fed ZnSO4. From 1 to 28, organic Zn increased BW gain (P = 0.02), and improved FCR (P = 0.03) vs. birds fed ZnSO4. At 21 d, NE lesions were only observed in CoCPF birds (P < 0.001), and mortality due to NE was only observed when CoCPF birds were fed ZnSO4 (P = 0.001). Organic Zn fed birds had increased villus height in the jejunum (P = 0.005) and decreased intestinal permeability (P = 0.01) vs. ZnSO4. In the jejunum, organic Zn fed birds showed a downregulation of expression of IL-8 (P = 0.02), and upregulation of IL-10 (P = 0.05) in CoCPF birds vs. ZnSO4- CoCPF birds. As main effect, birds supplemented with organic Zn had higher mRNA expression of TLR-2 (P = 0.02) and IgA (P = 0.01). In the cecal tonsils, organic Zn fed birds showed upregulation of iNOS (P = 0.008) in CoCPF birds vs. ZnSO4-CoCPF birds. Organic Zn supplementation reduced intestinal permeability and attenuated intestinal inflammation of broilers co-challenged with coccidia and C. perfringens.


Assuntos
Ração Animal/análise , Galinhas , Infecções por Clostridium/veterinária , Coccidiose/veterinária , Doenças das Aves Domésticas/imunologia , Zinco/metabolismo , Animais , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismo , Infecções por Clostridium/imunologia , Infecções por Clostridium/prevenção & controle , Clostridium perfringens/fisiologia , Coccidiose/imunologia , Coccidiose/prevenção & controle , Dieta/veterinária , Suplementos Nutricionais/análise , Eimeria/fisiologia , Expressão Gênica/efeitos dos fármacos , Inflamação/imunologia , Inflamação/prevenção & controle , Inflamação/veterinária , Intestinos/efeitos dos fármacos , Intestinos/fisiologia , Jejuno/anatomia & histologia , Jejuno/efeitos dos fármacos , Masculino , Doenças das Aves Domésticas/prevenção & controle , Distribuição Aleatória , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismo
15.
BMC Infect Dis ; 19(1): 51, 2019 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-30642269

RESUMO

BACKGROUND: Clostridium difficile infection (CDI) is an important cause of diarrhea and continues to be a major burden within healthcare institutions and in the community. For a small subset of patients with frequently relapsing CDI who do not have access to fecal microbiota transplantation (FMT), or fail FMT, there are no clear treatment recommendations. We review our experience with prolonged oral vancomycin for secondary prophylaxis of relapsing CDI. METHODS: We performed a retrospective chart review of cases from the C. difficile consultation service at our institution since 2013. The service had three primary physicians providing consultations and performing over 1000 FMTs over the five-year period. Patients with relapsing CDI who were not candidates for FMT, refused, or relapsed after FMT were treated with vancomycin, followed by long-term oral vancomycin at a dose of 125 mg once daily. RESULTS: Twenty patients received at least 8 weeks of once-daily oral vancomycin for prophylaxis of relapsing CDI. Patients had a median age of 80 years, and experienced a median of four episodes of CDI prior to long-term vancomycin. Most were female and 75% had received FMT. Only a single case of C. difficile relapse occurred while on long-term vancomycin during 200 patient-months of follow-up. Amongst those who stopped long-term vancomycin, 31% relapsed within 6 weeks. No adverse events were observed. CONCLUSIONS: For elderly patients with frequently relapsing C. difficile, prolonged vancomycin once daily at a dose of 125 mg orally was effective in preventing further relapse. Vancomycin secondary prophylaxis may be considered in patients who have failed FMT, or in cases where FMT is not available.


Assuntos
Antibioticoprofilaxia/métodos , Infecções por Clostridium/prevenção & controle , Clostridium difficile/patogenicidade , Vancomicina/administração & dosagem , Vancomicina/uso terapêutico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Transplante de Microbiota Fecal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
16.
Anaerobe ; 55: 142-151, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30576791

RESUMO

Clostridium difficile infection is a range of toxin - mediated intestinal diseases that is often acquired in hospitals and small communities in developed countries. The main virulence factors of C. difficile are two exotoxins, toxin A and toxin B, which damage epithelial cells and manifest as colonic inflammation and mild to severe diarrhea. Inhibiting C. difficile adherence, colonization, and reducing its toxin production could substantially minimize its pathogenicity and lead to faster recovery from the disease. This study investigated the efficacy of probiotic secreted bioactive molecules from Lactobacillus acidophilus La-5, in decreasing C. difficile attachment and cytotoxicity in human epithelial cells in vitro. L. acidophilus La-5 cell-free supernatant (La-5 CFS) was used to treat the hypervirulent C. difficile ribotype 027 culture with subsequent monitoring of cytotoxicity and adhesion. In addition, the effect of pretreating cell lines with La-5 CFS in protecting cells from the cytotoxicity of C. difficile culture filtrate or bacterial cell attachment was examined. La-5 CFS substantially reduced the cytotoxicity and cytopathic effect of C. difficile culture filtrate on HT-29 and Caco-2 cells. Furthermore, La-5 CFS significantly reduced attachment of the C. difficile bacterial cells on both cell lines. It was also found that pretreatment of cell lines with La-5 CFS effectively protected cell lines from cytotoxicity and adherence of C. difficile. Our study suggests that La-5 CFS could potentially be used to prevent and cure C. difficile infection and relapses.


Assuntos
Antibacterianos/metabolismo , Antibiose , Toxinas Bacterianas/metabolismo , Infecções por Clostridium/prevenção & controle , Clostridium difficile/crescimento & desenvolvimento , Células Epiteliais/microbiologia , Lactobacillus acidophilus/crescimento & desenvolvimento , Toxinas Bacterianas/toxicidade , Células CACO-2 , Sobrevivência Celular , Clostridium difficile/metabolismo , Meios de Cultura/química , Células Epiteliais/fisiologia , Células HT29 , Humanos , Lactobacillus acidophilus/metabolismo , Modelos Biológicos
17.
Nat Commun ; 9(1): 5233, 2018 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-30531960

RESUMO

Clostridium difficile is the leading cause of nosocomial diarrhea and colitis in the industrialized world. Disruption of the protective gut microbiota by antibiotics enables colonization by multidrug-resistant C. difficile, which secrete up to three different protein toxins that are responsible for the gastrointestinal sequelae. Oral agents that inhibit the damage induced by toxins, without altering the gut microbiota, are urgently needed to prevent primary disease and break the cycle of antibiotic-induced disease recurrence. Here, we show that the anthelmintic drug, niclosamide, inhibits the pathogenesis of all three toxins by targeting a host process required for entry into colonocytes by each toxin. In mice infected with an epidemic strain of C. difficile, expressing all three toxins, niclosamide reduced both primary disease and recurrence, without disrupting the diversity or composition of the gut microbiota. Given its excellent safety profile, niclosamide may address an important unmet need in preventing C. difficile primary and recurrent diseases.


Assuntos
Infecções por Clostridium/prevenção & controle , Clostridium difficile/efeitos dos fármacos , Microbioma Gastrointestinal , Niclosamida/farmacologia , Animais , Anticestoides/farmacologia , Toxinas Bacterianas/antagonistas & inibidores , Toxinas Bacterianas/metabolismo , Células CHO , Células CACO-2 , Linhagem Celular , Infecções por Clostridium/microbiologia , Clostridium difficile/metabolismo , Clostridium difficile/patogenicidade , Cricetulus , Células HCT116 , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Virulência/efeitos dos fármacos
18.
JAMA ; 320(5): 499-500, 2018 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-30027207

RESUMO

Clinical Question: In adults and children prescribed antibiotics, is co-administration of a probiotic associated with a lower risk of symptomatic Clostridium difficile infection without an increase in adverse events? Bottom Line: Moderate-quality evidence suggests that probiotics are associated with a lower risk of C difficile infection and very low-quality evidence suggests that probiotics are associated with fewer adverse events vs placebo or no treatment.


Assuntos
Antibacterianos/efeitos adversos , Infecções por Clostridium/prevenção & controle , Clostridium difficile , Probióticos/uso terapêutico , Adulto , Antibacterianos/uso terapêutico , Criança , Humanos , Hospedeiro Imunocomprometido , Guias de Prática Clínica como Assunto , Literatura de Revisão como Assunto
19.
Acta Gastroenterol Belg ; 81(2): 269-276, 2018 Apr-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30024698

RESUMO

Interest in administration of probiotics to prevent antibiotic-associated diarrhoea (AAD) in hospitalized patients is increasing. We determined the cost of antibiotic-associated diarrhoea in hospital settings for non-complicated and Clostridium difficile (C.diff) complicated AAD, and performed a health-economic analysis of AAD prevention with S. boulardii CNCM I-745 (S. boulardii) from data collected in 1 university and 3 regional hospitals in Flanders. Using a decision tree analytic model, costs and effects of S. boulardii for AAD prevention are calculated. Incremental costs due to AAD, including increased length of hospitalization, were calculated using bottom-up and top-down costing approaches from a hospital, healthcare payer (HCP) and societal perspective. Model robustness was tested using sensitivity analyses. Additional costs per hospitalized patient range from € 277.4 (hospital) to € 2,150.3 (societal) for non-complicated and from € 588.8 (hospital) to € 2,239.1 (societal) for C. diff. complicated AAD. Using S. boulardii as AAD prevention results in cost savings between € 50.3 (bottom-up) and € 28.1 (topdown) per patient treated with antibiotics from the HCP perspective; and € 95.2 and € 14.7 per patient from the societal and hospital perspectives. Our analysis shows the potential for using S. boulardii as AAD prophylactic treatment in hospitalized patients. Based on 831,655 hospitalizations with antibiotic administration in 2014 and € 50.3 cost saving per patient on antibiotics, generalized use of S. boulardii could result in total annual savings up to € 41.8 million for the Belgian HCP.


Assuntos
Antibacterianos/efeitos adversos , Infecções por Clostridium/induzido quimicamente , Infecções por Clostridium/prevenção & controle , Diarreia/induzido quimicamente , Diarreia/prevenção & controle , Hospitalização/economia , Probióticos/economia , Saccharomyces boulardii , Bélgica/epidemiologia , Infecções por Clostridium/epidemiologia , Análise Custo-Benefício , Diarreia/epidemiologia , Feminino , Humanos , Masculino , Prevalência
20.
Med Glas (Zenica) ; 15(2): 122-131, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30047540

RESUMO

Aim To synthesize evidence about the influence of individual antimicrobial stewardship programs (ASP) related to the prevention of Clostridium difficile (C. difficile) infection on primary and secondary outcomes. Methods Relevant databases such as Medline, PUBMED, COCHRANE library and EBSCO were searched from 1 April to 27 April 2017. Additional studies were reached by the manual search for original articles in relevant journals. We included all randomized controlled, quasi-experimental and observational studies, published in the English language from 2007 onward, that evaluated effectiveness of ASP in preventing and controlling C. difficile associated disease (CDAD) among adult inpatients. Results Implementation of ASP interventions was associated with CDAD incidence reduction in 62.5% studies, but no significant differences were reported for the duration of hospitalization, readmission and mortality rate. Improvements in prescribing patterns (decreased antimicrobial use or increased rational use) and microbial outcomes (decreased rates of selected antimicrobial-resistant bacteria) were reported. Evidence on the effects of ASP is mainly limited to the results of studies low in methodological quality with great heterogeneity of outcomes, interventions, and units in which CDAD incidence data were reported. Conclusion Despite the low strength of evidence of reviewed studies, consistency of findings suggest the positive impact of antimicrobial stewardship programs on the prevention and control of nosocomial CDAD. The significance of this problem imposes randomized control trial use as the best instrument to provide highquality evidence. Further studies need to systematically analyse changes in all antibiotic use and its outcomes.


Assuntos
Anti-Infecciosos/uso terapêutico , Gestão de Antimicrobianos , Infecções por Clostridium/prevenção & controle , Clostridium difficile/crescimento & desenvolvimento , Infecção Hospitalar/prevenção & controle , Hospitais , Padrões de Prática Médica , Infecções por Clostridium/microbiologia , Infecção Hospitalar/microbiologia , Surtos de Doenças , Resistência Microbiana a Medicamentos , Hospitalização , Humanos , Avaliação de Programas e Projetos de Saúde
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