Author Interviews, PLoS, Urinary Tract Infections / 18.12.2015
Complex Bacterial Biofilms Can Rapidly Obstruct Catheters
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Dr. Sandra Wilks[/caption]
MedicalResearch.com Interview with:
Dr Sandra A. Wilks PhD
Senior Research Fellow
IfLS Knowledge Mobilisation Fellow in Healthcare Technologies
Faculty of Natural and Environmental Science & Faculty of Health Sciences
Centre for Biological Sciences,
University of Southampton,
Southampton, UK
Medical Research: What is the background for this study? What are the main findings?
Dr. Wilks: The use of indwelling Foley urinary catheters for extended periods of time results in high risks of urinary tract infections (UTI) and catheter blockages. Blockages are often caused by the presence of Proteus mirabilis, a urease-producing bacterium which results in an increase of the urine pH and the development of crystalline biofilms. Biofilms develop when bacteria attach to a surface, forming a community structure, held together by extracellular polymeric substances (EPS). Once in a biofilm, bacteria exhibit high resistance to the action of antibiotics and are protected by other stress factors. The crystalline biofilms resulting from the presence of Proteus are highly complex environments and cause complete blockage of the catheter within days. Such blockages cause pain and trauma for patients, and result in high demands on healthcare resources.
In this study, we have used an advanced microscopy technique (episcopic differential interference contrast, EDIC microscopy developed by Best Scientific) to track the development of these crystalline encrustations on two commonly used catheter materials; silicone and hydrogel latex. We have identified four distinct stages to crystalline biofilm formation;
Dr. Sandra Wilks[/caption]
MedicalResearch.com Interview with:
Dr Sandra A. Wilks PhD
Senior Research Fellow
IfLS Knowledge Mobilisation Fellow in Healthcare Technologies
Faculty of Natural and Environmental Science & Faculty of Health Sciences
Centre for Biological Sciences,
University of Southampton,
Southampton, UK
Medical Research: What is the background for this study? What are the main findings?
Dr. Wilks: The use of indwelling Foley urinary catheters for extended periods of time results in high risks of urinary tract infections (UTI) and catheter blockages. Blockages are often caused by the presence of Proteus mirabilis, a urease-producing bacterium which results in an increase of the urine pH and the development of crystalline biofilms. Biofilms develop when bacteria attach to a surface, forming a community structure, held together by extracellular polymeric substances (EPS). Once in a biofilm, bacteria exhibit high resistance to the action of antibiotics and are protected by other stress factors. The crystalline biofilms resulting from the presence of Proteus are highly complex environments and cause complete blockage of the catheter within days. Such blockages cause pain and trauma for patients, and result in high demands on healthcare resources.
In this study, we have used an advanced microscopy technique (episcopic differential interference contrast, EDIC microscopy developed by Best Scientific) to track the development of these crystalline encrustations on two commonly used catheter materials; silicone and hydrogel latex. We have identified four distinct stages to crystalline biofilm formation;
- (1) an initial foundation layer (conditioning film) formed by individual 'colonising' P. mirabilis cells, which occurred in less than 1 hour;
- (2) this was rapidly followed by a sheet-like microcrystalline material (after 24 hours) that covers this conditioning film;
- (3) after 4 days exposure, large amounts of crystalline material was seen to extend out from the surface with;
- (4) defined struvite crystals embedded within the structure and P. mirabilis visible throughout. This pattern was the same on both materials.
Dr. Carlos del Rio[/caption]
MedicalResearch.com Interview Questions
Carlos del Rio, MD
Chair, HIV Medicine Association
Department of Medicine
Hubert Professor and Chair of the Department of Global Health at the Rollins School of Public Health Professor of Medicine in the Division of Infectious Diseases
Emory University School of Medicine
MedicalResearch.com Editor's note: Dr. Carlos del Rio discusses the statement from the Infectious Diseases Society of America (IDSA), HIV Medicine Association (HIVMA) and the Pediatric Infectious Diseases Society (PIDS) regarding the news that Express Scripts is taking steps to improve access to obtaining pyrimethamine for patients with toxoplasmosis.
Medical Research: What is the background for this Express Scripts announcement?
Dr. del Rio: The HIV Medicine Association (HIVMA) and the Infectious Diseases Society of America initially heard from our members (ID and HIV clinicians) in August about the 5000% price increase in Daraprim® (from $13.50 to $750 per tablet) following Turing Pharmaceuticals’ acquisition of the rights to distribute Daraprim® from Impax Laboratories, Inc.
Dr. McHugh[/caption]
MedicalResearch.com Interview with:
Leo McHugh, Ph.D.
Director, Bioinformatics
Immunexpress
Seattle, Washington
Medical Research: What is the background for this study? What are the main findings?
Dr. McHugh: Sepsis is the leading cause of child mortality in the world, and in developing countries kills more adults than breast cancer, prostate cancer and HIV combined. Approximately 30% of people admitted to ICU have sepsis, and up to 50% of these patients die. It’s a major cost burden also, costing the US health system $17 billion per year. The best way to reduce costs and improve patient outcomes is to detect sepsis early and with confidence, so that appropriate treatments can be applied. Each hour delay in the detection of sepsis has been reported to correspond to an 8% increase in mortality. So the need for a rapid and accurate diagnostic is recognized. Traditional methods rely on detection of the specific pathogen causing the infection, and these methods often take more than 24 hours, and find a pathogen in only 30% of clinically confirmed cases because they’re trying to detect a minuscule amount of pathogen or pathogenic product in the blood. Our approach was to use the host’s own immune system, which is highly tuned to respond to the presence of pathogens. Around 30% of all genes are dysregulated in sepsis, so there is a huge signal base to draw from. The trick with using multi marker host response is to pick out the specific combination of gene expression patterns that cover the broad range of patients that present with sepsis and who may present either early or late in the episode, thus with different gene activation patterns.
This paper describes a simple combination of such genes that can be used to detect sepsis and performs over the full range of patients irrespective of stage of infection or severity of infection. In it’s current format, the test is manual and takes 4-6 hours, and is a great advance on the current tools, however the methods we’ve used are specifically designed to meet requirements to port this assay onto a fully automated Point of Care platform that could deliver a result in under 90 minutes.
Dr. Meyerhans[/caption]
MedicalResearch.com Interview with:
Andreas Meyerhans, PhD
ICREA Research Professor at the University Pompeu Fabra
Infection Biology Group
Department of Experimental and Health Sciences
Universitat Pompeu Fabra
Barcelona Spain
Medical Research: What is the background for this study? What are the main findings?
Dr. Meyerhans: In brief, chronic HIV infections lead to a dampening of HIV-specific killer cells. This phenomenon is named exhaustion and is mediated by inhibitory proteins, such as PD-1, on the cell surface. A consequence of exhaustion is a reduction of the immune control over virus expansion.
We have studied the effect of blocking the negative signaling from the inhibitory proteins by means of PD-1/PD-L1 pathway inhibition on effector and regulatory T cells (Treg). We found that one can augment antiviral immune control only when the virus load was well controlled in the HIV-infected individuals i.e. by antiviral drugs. In that case, PD-1/PD-L1 pathway blockage led to an expansion of anti-HIV killer cells over Treg cells. This latter are suppressive white blood cells also subject to the same inhibitory pathway regulation. In contrast, when blood cells from viremic HIV-infected individuals were analyzed, Treg cells expanded efficiently and thus reduced the effector to regulatory T cell ratio that controls HIV. Taken together, our data point to Treg cells as an important component in the outcome of PD-1/PD-L1 pathway inhibitor therapies and suggest a net gain in anti-HIV immune responses only when the HIV loads are well controlled during the administration of these novel compounds.
Dr. Andrew Auld[/caption]
MedicalResearch.com Interview with:
Dr. Andrew Auld MD, MSc
Prof. Paludan[/caption]
MedicalResearch.com Interview with:
Professor Søren Riis Paludan DMSc, PhD
Department of Biomedicine
Aarhus University
Denmark
Medical Research: What is the background for this study? What are the main findings?
Prof. Paluden: We were interested in understanding the first immune reactions that occur when an organism meets an infectious agent (virus or bacteria).
The main finding is that we have identified an immune reaction that is activated as the microbe disturbed the mucus layer at mucosal surfaces. This is an immune reaction occuring earlier than what has been thought previously, and may represent a mechanism that enables the organism to fight most microbes that we meet without mounting strong immune responses. This is important, since strong immune reactions - in addition to contributing to elimination of microbes - also have negative effects such as fever, etc.
Prof. Molina[/caption]
MedicalResearch.com Interview with:
Dr Jean-Michel Molina
Department of Infectious Diseases
Saint-Louis Hospital and University of Paris Diderot
Paris France
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Molina: Men who have sex with men (MSM) are disproportionately affected by HIV worldwide and represent the today in Europe the largest group in which new HIV infections are diagnosed with no decrease over the last 8 years.
The first study assessing preexposure prophylaxis (PrEP) efficacy among MSM was published in 2010 (the Iprex study) which reported for the first time a 44% reduced incidence of HIV in those randomized to receive daily tenofovir/emtricitabine TDF/FTC (one pill per day) as compared to placebo. Adherence to a daily pill regimen was found to be challenging however since only half of the participants (according to drug detection in blood) were taking their daily regimen. Post-hoc analyses suggested that among those with drugs detectable in plasma, PrEP efficacy could be as high as 92%. However, long term adherence to a daily regimen represents the Achille’s heel of daily PrEP, as shown later in other large PrEP trials among women in Africa (VOICE and Fem-PrEP).
Based on data from animal models we wished to assess whether PrEP with TDF/FTC taken on demand, at the time of sexual activity, could improve adherence, thereby efficacy and also improve safety and cost.
In this randomized double blind placebo controlled trial, on demand PrEP with TDF/FTC reduced the incidence of HIV by 86% in the intent to treat analysis as compared to placebo, and the only 2 participants who became infected in the TDF/FTC arm after more than a year of follow-up, had discontinued the use of PrEP months before infection.
The ANRS Ipergay study reports therefore a very high efficacy of PrEP, similar to that also reported in another PrEP study carried out in the UK among MSM with daily TDF/FTC (PROUD), which results were disclosed at the same time. Both studies have increased awareness about the real potential of PrEP and have had a strong impact on WHO and European guidelines.
Prof. Maillard[/caption]
MedicalResearch.com Interview with:
Prof. Jean-Yves Maillard
Professor of Pharmaceutical Microbiology
College of Biomedical and Life Sciences
Cardiff School of Pharmacy and Pharmaceutical Sciences
Cardiff University
Cardiff United Kingdom
Medical Research: What is the background for this study? What are the main findings?
Prof. Maillard: Environmental surfaces in healthcare and other settings become contaminated with a variety of infectious agents which may survive long enough to infect susceptible hosts, either directly or through secondary vehicles such as hands. Therefore, routine decontamination of environmental surfaces, in particular those that are frequently touched, is crucial to reduce the risk of infections. Such decontamination is often performed by wiping the target surface with disinfectant-soaked or pre-wetted wipes. However, the label claims of wipes marketed for this purpose are often based upon testing that does not reflect their field use, where contact times are frequently no more than a few seconds with wide variations in the pressure applied during wiping. In addition, wipes impregnated with a disinfectant or detergent can potentially transfer microbial contaminants to a wider area, when the same wipe is used on multiple surfaces.
A device called the ‘Wiperator’ was invented to address these issues. It can be used to test wipes with predetermined pressures, wiping times and number of wiping strokes, using a standardized rotary action. It can not only assess the decontaminating efficiency of the test wipe, but also its ability to transfer the acquired contamination to clean surfaces. The test procedure developed using the device is now a standard (E2967) of ASTM International, a highly-respected standards-setting organization.
The Wiperator was used in a multi-laboratory collaborative to test commercially-available wipes for their ability to decontaminate metal disks that had been experimentally-contaminated with vegetative bacteria representing healthcare-associated pathogens. The used wipes were subsequently tested for their potential to transfer viable bacteria to clean surfaces. The contact time for wiping and transfer was 10 seconds. Only one of the wipes tested reduced the contamination to an undetectable level while not transferring any viable bacteria to a clean surface. All others left behind detectable levels of contamination on the wiped disks and transferred the contamination to clean surfaces.
Dr. Jerome Leis[/caption]
MedicalResearch.com Interview with:
Jerome A. Leis, MD MSc FRCPC
Staff physician, General Internal Medicine and Infectious Diseases
Physician Lead, Antimicrobial Stewardship Team
Staff member, Centre for Quality Improvement and Patient Safety
Sunnybrook Health Sciences Centre
Assistant Professor, Department of Medicine, University of Toronto
Medical Research: What is the background for this study? What are the main findings?
Dr. Leis: Overuse of urinary catheters leads to significant morbidity among hospitalized patients. In most hospitals, discontinuation of urinary catheters relies on individual providers remembering to re-assess whether patients have an ongoing reason for a urinary catheter. We engaged all of the attending physicians to agree on the appropriate reasons for leaving a urinary catheter in place and developed a medical directive for nurses to remove all urinary catheters lacking these indications. This nurse-led intervention resulted in a significant reduction in urinary catheter use and catheter-associated urinary tract infections, compared with wards that continued to rely on usual practice.
Dr. Bacharier[/caption]
MedicalResearch.com Interview with:
Leonard B. Bacharier, MD
Professor of pediatrics
Clinical Director, Division of Allergy, Immunology and Pulmonary Medicine
St Louis School of Medicine
Washington University
St Louis, Missouri
Medical Research: What is the background for this study? What are the main findings?
Dr. Bacharier: Oral corticosteroids such as prednisone have become the standard of care for children whose colds tend to progress and lead to severe wheezing and difficulty breathing.
“But there are some studies that suggest these treatments don’t consistently work for young children. That’s why we want to find ways to prevent upper respiratory infections from progressing to lower respiratory tract illnesses. Once the episode gets going, standard interventions are less effective than would be desired”, reported Dr. Bacharier.
