scholarly journals A Modified R-Type Bacteriocin Specifically Targeting Clostridium difficile Prevents Colonization of Mice without Affecting Gut Microbiota Diversity

mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Dana Gebhart ◽  
Stephen Lok ◽  
Simon Clare ◽  
Myreen Tomas ◽  
Mark Stares ◽  
...  
Keyword(s):  
Health Care ◽  
Clostridium Difficile ◽  
Gut Microbiota ◽  
Genome Mining ◽  
Health Care Facilities ◽  
Enteric Infection ◽  
Colonization Resistance ◽  
Content Type ◽  
Strain Type ◽  
Type Strains

ABSTRACT Clostridium difficile is a leading cause of nosocomial infections worldwide and has become an urgent public health threat requiring immediate attention. Epidemic lineages of the BI/NAP1/027 strain type have emerged and spread through health care systems across the globe over the past decade. Limiting person-to-person transmission and eradicating C. difficile, especially the BI/NAP1/027 strain type, from health care facilities are difficult due to the abundant shedding of spores that are impervious to most interventions. Effective prophylaxis for C. difficile infection (CDI) is lacking. We have genetically modified a contractile R-type bacteriocin (“diffocin”) from C. difficile strain CD4 to kill BI/NAP1/027-type strains for this purpose. The natural receptor binding protein (RBP) responsible for diffocin targeting was replaced with a newly discovered RBP identified within a prophage of a BI/NAP1/027-type target strain by genome mining. The resulting modified diffocins (a.k.a. Avidocin-CDs), Av-CD291.1 and Av-CD291.2, were stable and killed all 16 tested BI/NAP1/027-type strains. Av-CD291.2 administered in drinking water survived passage through the mouse gastrointestinal (GI) tract, did not detectably alter the mouse gut microbiota or disrupt natural colonization resistance to C. difficile or the vancomycin-resistant Enterococcus faecium (VREF), and prevented antibiotic-induced colonization of mice inoculated with BI/NAP1/027-type spores. Given the high incidence and virulence of the pathogen, preventing colonization by BI/NAP1/027-type strains and limiting their transmission could significantly reduce the occurrence of the most severe CDIs. This modified diffocin represents a prototype of an Avidocin-CD platform capable of producing targetable, precision anti-C. difficile agents that can prevent and potentially treat CDIs without disrupting protective indigenous microbiota. IMPORTANCE Treatment and prevention strategies for bacterial diseases rely heavily on traditional antibiotics, which impose strong selection for resistance and disrupt protective microbiota. One consequence has been an upsurge of opportunistic pathogens, such as Clostridium difficile, that exploit antibiotic-induced disruptions in gut microbiota to proliferate and cause life-threatening diseases. We have developed alternative agents that utilize contractile bactericidal protein complexes (R-type bacteriocins) to kill specific C. difficile pathogens. Efficacy in a preclinical animal study indicates these molecules warrant further development as potential prophylactic agents to prevent C. difficile infections in humans. Since these agents do not detectably alter the indigenous gut microbiota or colonization resistance in mice, we believe they will be safe to administer as a prophylactic to block transmission in high-risk environments without rendering patients susceptible to enteric infection after cessation of treatment.

scholarly journals Impact of Oral Fidaxomicin Administration on the Intestinal Microbiota and Susceptibility to Clostridium difficile Colonization in Mice

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
N. J. Ajami ◽  
J. L. Cope ◽  
M. C. Wong ◽  
J. F. Petrosino ◽  
L. Chesnel
Keyword(s):  
Clostridium Difficile ◽  
Gut Microbiota ◽  
16S Rrna Gene Sequencing ◽  
Taxonomic Structure ◽  
Rrna Gene ◽  
Colonization Resistance ◽  
Content Type ◽  
Rrna Gene Sequencing ◽  
Hospital Acquired ◽  
Predetermined Time

ABSTRACT Clostridium difficile infection (CDI), a common cause of hospital-acquired infections, typically occurs after disruption of the normal gut microbiome by broad-spectrum antibiotics. Fidaxomicin is a narrow-spectrum antibiotic that demonstrates a reduced impact on the normal gut microbiota and is approved for the treatment of CDI. To further explore the benefits of this property, we used a murine model to examine the effects of fidaxomicin versus vancomycin on gut microbiota and susceptibility to C. difficile colonization while tracking microbiota recovery over time. Mice were exposed to fidaxomicin or vancomycin by oral gavage for 3 days and subsequently challenged with C. difficile spores at predetermined time points up to 21 days postexposure to antibiotics. Fecal samples were subsequently collected for analysis. Twenty-four hours postchallenge, mice were euthanized and the colon contents harvested. The microbiota was characterized using 16S rRNA gene sequencing. All fidaxomicin-exposed mice (except for one at day 8) were resistant to C. difficile colonization. However, 9 of 15 vancomycin-exposed mice were susceptible to C. difficile colonization until day 12. All vancomycin-exposed mice recovered colonization resistance by day 16. Bacterial diversity was similar prior to antibiotic exposure in both arms and decreased substantially after exposure. A shift in taxonomic structure and composition occurred after both exposures; however, the shift was greater in vancomycin-exposed than in fidaxomicin-exposed mice. In summary, compared with vancomycin, fidaxomicin exposure had less impact on microbiota composition, promoted faster microbial recovery, and had less impact on the loss of C. difficile colonization resistance.

scholarly journals Preventable Patient Harm: a Multidisciplinary, Bundled Approach to Reducing Clostridium difficile Infections While Using a Glutamate Dehydrogenase/Toxin Immunochromatographic Assay/Nucleic Acid Amplification Test Diagnostic Algorithm

2018 ◽  
Vol 56 (9) ◽  
Author(s):  
Katherine Schultz ◽  
Emily Sickbert-Bennett ◽  
Ashley Marx ◽  
David J. Weber ◽  
Lauren M. DiBiase ◽  
...  
Keyword(s):  
Health Care ◽  
Nucleic Acid ◽  
Clostridium Difficile ◽  
Glutamate Dehydrogenase ◽  
Care Facility ◽  
Health Care Facilities ◽  
Nucleic Acid Amplification ◽  
Immunochromatographic Assay ◽  
Optimal Method ◽  
Content Type

ABSTRACT Health care facility-onset Clostridium difficile infections (HO-CDI) are an important national problem, causing increased morbidity and mortality. HO-CDI is an important metric for the Center for Medicare and Medicaid Service's (CMS) performance measures. Hospitals that fall into the worst-performing quartile in preventing hospital-acquired infections, including HO-CDI, may lose millions of dollars in reimbursement. Under pressure to reduce CDI and without a clear optimal method for C. difficile detection, health care facilities are questioning how best to use highly sensitive nucleic acid amplification tests (NAATs) to aid in the diagnosis of CDI. Our institution has used a two-step glutamate dehydrogenase (GDH)/toxin immunochromatographic assay/NAAT algorithm since 2009. In 2016, our institution set an organizational goal to reduce our CDI rates by 10% by July 2017. We achieved a statistically significant reduction of 42.7% in our HO-CDI rate by forming a multidisciplinary group to implement and monitor eight key categories of infection prevention interventions over a period of 13 months. Notably, we achieved this reduction without modifying our laboratory algorithm. Significant reductions in CDI rates can be achieved without altering sensitive laboratory testing methods.

scholarly journals Gut Microbiota and Colonization Resistance against Bacterial Enteric Infection

2019 ◽  
Vol 83 (3) ◽  
Author(s):  
Q. R. Ducarmon ◽  
R. D. Zwittink ◽  
B. V. H. Hornung ◽  
W. van Schaik ◽  
V. B. Young ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Current Knowledge ◽  
Shigella Flexneri ◽  
Enteric Infection ◽  
Nutrient Competition ◽  
Colonization Resistance ◽  
Content Type ◽  
Clostridioides Difficile ◽  
Serovar Typhimurium ◽  
Enteric Infections

SUMMARYThe gut microbiome is critical in providing resistance against colonization by exogenous microorganisms. The mechanisms via which the gut microbiota provide colonization resistance (CR) have not been fully elucidated, but they include secretion of antimicrobial products, nutrient competition, support of gut barrier integrity, and bacteriophage deployment. However, bacterial enteric infections are an important cause of disease globally, indicating that microbiota-mediated CR can be disturbed and become ineffective. Changes in microbiota composition, and potential subsequent disruption of CR, can be caused by various drugs, such as antibiotics, proton pump inhibitors, antidiabetics, and antipsychotics, thereby providing opportunities for exogenous pathogens to colonize the gut and ultimately cause infection. In addition, the most prevalent bacterial enteropathogens, includingClostridioides difficile,Salmonella entericaserovar Typhimurium, enterohemorrhagicEscherichia coli,Shigella flexneri,Campylobacter jejuni,Vibrio cholerae,Yersinia enterocolitica, andListeria monocytogenes, can employ a wide array of mechanisms to overcome colonization resistance. This review aims to summarize current knowledge on how the gut microbiota can mediate colonization resistance against bacterial enteric infection and on how bacterial enteropathogens can overcome this resistance.

scholarly journals Antibiotic-Induced Alterations of the Murine Gut Microbiota and Subsequent Effects on Colonization Resistance against Clostridium difficile

mBio ◽  
2015 ◽  
Vol 6 (4) ◽  
Author(s):  
Alyxandria M. Schubert ◽  
Hamide Sinani ◽  
Patrick D. Schloss
Keyword(s):  
Clostridium Difficile ◽  
Gut Microbiota ◽  
Normal Structure ◽  
The United States ◽  
Context Dependency ◽  
Dependent Manner ◽  
Colonization Resistance ◽  
Bacterial Populations ◽  
Content Type ◽  
Antibiotic Perturbations

ABSTRACTPerturbations to the gut microbiota can result in a loss of colonization resistance against gastrointestinal pathogens such asClostridium difficile. AlthoughC. difficileinfection is commonly associated with antibiotic use, the precise alterations to the microbiota associated with this loss in function are unknown. We used a variety of antibiotic perturbations to generate a diverse array of gut microbiota structures, which were then challenged withC. difficilespores. Across these treatments we observed thatC. difficileresistance was never attributable to a single organism, but rather it was the result of multiple microbiota members interacting in a context-dependent manner. Using relative abundance data, we built a machine learning regression model to predict the levels ofC. difficilethat were found 24 h after challenging the perturbed communities. This model was able to explain 77.2% of the variation in the observed number ofC. difficileper gram of feces. This model revealed important bacterial populations within the microbiota, which correlation analysis alone did not detect. Specifically, we observed that populations associated with thePorphyromonadaceae,Lachnospiraceae,Lactobacillus, andAlistipeswere protective and populations associated withEscherichiaandStreptococcuswere associated with high levels of colonization. In addition, a population affiliated with theAkkermansiaindicated a strong context dependency on other members of the microbiota. Together, these results indicate that individual bacterial populations do not drive colonization resistance toC. difficile. Rather, multiple diverse assemblages act in concert to mediate colonization resistance.IMPORTANCEThe gastrointestinal tract harbors a complex community of bacteria, known as the microbiota, which plays an integral role preventing its colonization by gut pathogens. This resistance has been shown to be crucial for protection againstClostridium difficileinfections (CDI), which are the leading source of hospital-acquired infections in the United States. Antibiotics are a major risk factor for acquiring CDI due to their effect on the normal structure of the indigenous gut microbiota. We found that diverse antibiotic perturbations gave rise to altered communities that varied in their susceptibility toC. difficilecolonization. We found that multiple coexisting populations, not one specific population of bacteria, conferred resistance. By understanding the relationships betweenC. difficileand members of the microbiota, it will be possible to better manage this important infection.

Patient satisfaction with the quality of care in Ghana’s health-care institutions

2019 ◽  
Vol 13 (2) ◽  
pp. 160-170 ◽  
Author(s):  
Aaron Asibi Abuosi ◽  
Mahama Braimah
Keyword(s):  
Health Care ◽  
Patient Satisfaction ◽  
Quality Of Care ◽  
Service Delivery ◽  
National Survey ◽  
Health Care Facilities ◽  
Health Facilities ◽  
Content Type ◽  
Care Facilities

Purpose The purpose of this study was to examine patient satisfaction with the quality of care in Ghana’s health-care facilities using a disaggregated approach. Design/methodology/approach The study was a cross-sectional national survey. A sample of 4,079 males and females in the age group of 15-49 years were interviewed. Descriptive statistics, principal component analysis and t-tests were used in statistical analysis. Findings About 70 per cent of patients were satisfied with the quality of care provided in health-care facilities in Ghana, whereas about 30 per cent of patients were fairly satisfied. Females and insured patients were more likely to be satisfied with the quality of care, compared with males and uninsured patients. Research limitations/implications Because data were obtained from a national survey, the questionnaire did not include the type of facility patients attended to find out whether satisfaction with the quality of care varied by the type of health facility. Future studies may, therefore, include this. Practical implications The study contributes to the literature on patient satisfaction with the quality of care. It highlights that long waiting time remains an intractable problem at various service delivery units of health facilities and constitutes a major source of patient dissatisfaction with the quality of care. Innovative measures must, therefore, be adopted to address the problem. Originality/value There is a paucity of research that uses a disaggregated approach to examine patient satisfaction with the quality of care at various service delivery units of health facilities. This study is a modest contribution to this research gap.

Willingness to pay for traditional, complementary and alternative medicine (TCAM) among Malaysian adults

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
M.Z.Y. Koh ◽  
Yen-Nee Goh
Keyword(s):  
Health Care ◽  
Willingness To Pay ◽  
Alternative Medicine ◽  
Complementary And Alternative Medicine ◽  
Health Care Facilities ◽  
Partial Least Square ◽  
Least Square ◽  
Public Health Care ◽  
Content Type ◽  
Complementary And Alternative

Purpose Health plays a crucial role in the daily lives and supporting health is the important role of medicine. With the availability of traditional, complementary and alternative medicine (TCAM), the demands and willingness to pay among users are increasing. Hence, this study aims to determine the psychological factors influencing the willingness to pay for TCAM among Malaysian adults. Design/methodology/approach In total, 300 completed self-administered questionnaires were collected from Malaysian adults using a purposive sampling method through intercepts at public health-care facilities. A structural equation modelling approach using partial least square was used to test the hypotheses. Findings The findings show that attitude, subjective norms, perceived price and knowledge have a significant impact on willingness to pay for TCAM. Surprisingly, there was no relationship found between perceived behavioural control and health consciousness on willingness to pay for TCAM. Originality/value The findings of this study are expected to provide better insights into TCAM use among Malaysian adults. The results are also important to encourage health-care institutions and practitioners to educate the general public on the safety of TCAM to ensure more health benefits to the users.

Nurses' knowledge and attitude towards COVID-19 in the context of the acute health care settings in Jordan

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Sajidah Alhwamdih ◽  
Hamzeh Y. Abunab ◽  
Abdullah Ahmad Algunmeeyn ◽  
Imad Alfayoumi ◽  
Sana Hawamdeh
Keyword(s):  
Health Care ◽  
Acute Care ◽  
Health Care Facilities ◽  
Content Type ◽  
Increased Risk ◽  
Level Of Knowledge ◽  
Acute Care Settings ◽  
Knowledge And Attitude ◽  
High Level ◽  
Nurses Knowledge

Purpose Nurses are at the front line in facing the COVID-19 outbreak and are at increased risk of becoming infected and might be the source of transmission in health-care facilities and the community. The purpose of this study is to assess the knowledge and attitude toward COVID1-19 among nurses in acute care settings in Jordan. This is expected to help with the global initiative to combat the COVID-19 epidemic. Design/methodology/approach A cross-sectional design was used to survey nurses' knowledge and attitude of COVID-19 among Jordanian nurses working in acute care settings. Findings The grand mean of knowledge items response was 8.94, implying that respondents possessed a high level of knowledge. The overall attitude score was positive for the participants, with a mean score of 5.93. Moreover, the results showed a significant relationship between knowledge and attitude scores. Originality/value The findings suggest that nurses in Jordan showed a high level of knowledge and a positive attitude toward COVID-19 during the outbreak's rapid rise period. This study showed specific aspects of knowledge and attitudes that should be focused on in future awareness and educational programs to promote all preventive and safety measures of COVID-19.

Indoor air in healing environments

Facilities ◽  
2019 ◽  
Vol 37 (9/10) ◽  
pp. 600-623 ◽  
Author(s):  
Marco Gola ◽  
Gaetano Settimo ◽  
Stefano Capolongo
Keyword(s):  
Health Care ◽  
Air Quality ◽  
Indoor Air ◽  
Management Strategies ◽  
Health Care Facilities ◽  
Chemical Pollution ◽  
Content Type ◽  
Starting Point ◽  
Care Facilities ◽  
Maintenance Activities

Purpose Several countries have carried out air quality monitoring in professional workplaces where chemicals are used. Health-care spaces have been less investigated. This paper aims to define a protocol, as developed by a research group, for inpatient rooms to understand the state of the art and to suggest design and management strategies for improving process quality. Design/methodology/approach Starting from the ISO-16000 standard and guidelines for monitoring activities, a protocol is defined for a one year investigation, with passive samplers. Through data analysis of the investigations and analysis of the cleaning and finishing products, heating, ventilation and air conditioning and maintenance activities, etc., it is possible to highlight the potential influences of chemical pollution. Findings A methodology is defined for understanding the chemical pollution and the possible factors related to construction materials, cleaning products and maintenance activities. Research limitations/implications The paper analyzes only a limited number of case studies because the monitoring activity is still in progress. Practical implications The investigation offers a starting point for a wide tool for the definition of design, maintenance and management strategies in health-care facilities. Social implications The research project, aimed at improving the knowledge of indoor air quality (IAQ) in inpatient rooms, is a starting point for a supporting tool for future regulations concerning health-care facilities. Originality/value IAQ is an issue on which many governments are focusing. Several health-care researchers have reported studies that aim at improving users’ health. Most investigations are about biological and physical risks, but chemical risks have been less studied. The paper suggests some design and management strategies for inpatient room.

Confidentiality and security of information in the public health-care facilities to curb HIV/AIDS trauma among patients in Africa

2020 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Ngoako Solomon Marutha ◽  
Olefhile Mosweu
Keyword(s):  
Public Health ◽  
Health Care ◽  
Health Care Facilities ◽  
Public Health Care ◽  
Chronic Patients ◽  
Aids Patients ◽  
Content Type ◽  
The Public ◽  
Care Facilities ◽  
Hiv Aids

Purpose This study sought to investigate a framework for ensuring the confidentiality and security of information at the public health-care facilities to curb HIV/AIDS trauma among patients in Africa. In most instances, trauma to HIV/AIDS patients accelerate because of their personal information relating to the state of illness leaks to public people. Design/methodology/approach This qualitative study used literature to study confidentiality and security of information at the public health-care facilities to curb HIV/AIDS trauma among patients in Africa. Findings The study revealed that confidentiality and security of information has been neglected, in most instances, at the health-care facilities, and this has, to some extent, affected HIV/AIDS patients negatively, leading to trauma, stigma and skipping of treatment by patients resulting in accelerated mortality among chronic patients. The study recommends that patients’ information be always strictly controlled and kept confidential and secured at all the times, especially that of HIV/AIDS patients. Practical implications The proposed framework can be used by health-care facilities to guide the management and promotion of the confidentiality and security of information in the public health-care facilities to curb additional trauma to HIV/AIDS patients in the context of Africa, and even beyond. Originality/value The study provides a framework to ensure the confidentiality and security of information at the public health-care facilities to curb additional trauma to HIV/AIDS patients.

scholarly journals Cwp19 Is a Novel Lytic Transglycosylase Involved in Stationary-Phase Autolysis Resulting in Toxin Release inClostridium difficile

mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Sandra Wydau-Dematteis ◽  
Imane El Meouche ◽  
Pascal Courtin ◽  
Audrey Hamiot ◽  
René Lai-Kuen ◽  
...  
Keyword(s):  
Health Care ◽  
Clostridium Difficile ◽  
Stationary Phase ◽  
Catalytic Domain ◽  
Brain Heart Infusion ◽  
Surface Protein ◽  
Wild Type ◽  
Content Type ◽  
Lytic Transglycosylase ◽  
Cell Autolysis

ABSTRACTClostridium difficileis the major etiologic agent of antibiotic-associated intestinal disease. Pathogenesis ofC. difficileis mainly attributed to the production and secretion of toxins A and B. Unlike most clostridial toxins, toxins A and B have no signal peptide, and they are therefore secreted by unusual mechanisms involving the holin-like TcdE protein and/or autolysis. In this study, we characterized the cell surface protein Cwp19, a newly identified peptidoglycan-degrading enzyme containing a novel catalytic domain. We purified a recombinant His6-tagged Cwp19 protein and showed that it has lytic transglycosylase activity. Moreover, we observed that Cwp19 is involved in cell autolysis and that aC. difficilecwp19mutant exhibited delayed autolysis in stationary phase compared to the wild type when bacteria were grown in brain heart infusion (BHI) medium. Wild-type cell autolysis is correlated to strong alterations of cell wall thickness and integrity and to release of cytoplasmic material. Furthermore, we demonstrated that toxins were released into the extracellular medium as a result of Cwp19-induced autolysis when cells were grown in BHI medium. In contrast, Cwp19 did not induce autolysis or toxin release when cells were grown in tryptone-yeast extract (TY) medium. These data provide evidence for the first time that TcdE and bacteriolysis are coexisting mechanisms for toxin release, with their relative contributionsin vitrodepending on growth conditions. Thus, Cwp19 is an important surface protein involved in autolysis of vegetative cells ofC. difficilethat mediates the release of the toxins from the cell cytosol in response to specific environment conditions.IMPORTANCEClostridium difficile-associated disease is mainly known as a health care-associated infection. It represents the most problematic hospital-acquired infection in North America and Europe and exerts significant economic pressure on health care systems. Virulent strains ofC. difficilegenerally produce two toxins that have been identified as the major virulence factors. The mechanism for release of these toxins from bacterial cells is not yet fully understood but is thought to be partly mediated by bacteriolysis. Here we identify a novel peptidoglycan hydrolase inC. difficile, Cwp19, exhibiting lytic transglycosylase activity. We show that Cwp19 contributes toC. difficilecell autolysis in the stationary phase and, consequently, to toxin release, most probably as a response to environmental conditions such as nutritional signals. These data highlight that Cwp19 constitutes a promising target for the development of new preventive and curative strategies.

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