Thursday, 30 April 2020

Changes to medical devices in the European Union


The European Union Medical Device Directives (MDD) 93/42/EEC will transition to the Medical Device Regulation (MDR) 2017/745 on 26 May 2020.  New changes stemming from the transition establishes “economic operator” (e.g. distributor, importer) and states that each economic operator and previous operators in the distribution chain must adhere to regulations. 

Medical Devices Regulation (EU) 2017/745 will replace the current Medical Device Directive (MDD) and the Active Implantable Medical Device Directive (AIMD), whereas the IVDR will replace the In vitro Diagnostic Directive (IVDD). Both regulations bring a series of important improvements to conformity assessment for medical devices with the intention to:


Improve the quality, safety and reliability of medical devices placed on the European market.
Strengthen transparency of information related to medical devices for consumers and practitioners.
Enhance vigilance and market surveillance of devices in use.



Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Wednesday, 29 April 2020

FDA Biosimilars and Interchangeable Biosimilars


New FDA guidance provides recommendations to applicants seeking licensure under section 351(k) of the Public Health Service (PHS) Act of a proposed biosimilar or proposed interchangeable biosimilar for fewer than all of the reference product’s licensed conditions of use.


This guidance also provides recommendations on the submission of a supplement to a licensed 351(k) biologics license application (BLA) seeking to add a condition of use that previously has been licensed for the reference product to the labeling of a licensed biosimilar or interchangeable product, including considerations related to the timing of such submissions.

For further details see: https://www.fda.gov/media/134932/download

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Tuesday, 28 April 2020

Bacteria on the International Space Station no more dangerous than earthbound strains


Shortly after the National Aeronautics and Space Administration (NASA) installed the water dispenser aboard the ISS in 2009, periodic sampling showed that two bacteria, Burkholderia cepacia and later on, Burkholderia contaminans were contaminating the drinking water. These microbes belong to a group of related Burkholderia species that cause opportunistic lung infections in people with underlying health conditions and are very difficult to kill using common sterilization techniques. The bacteria have persisted in the water dispenser despite periodic flushing with an extra-strength iodine cleaning solution.

To learn more about these bacteria, researchers sequenced the genomes of 24 strains collected from 2010 to 2014. All of the B. cepacia and B. contaminans strains were highly similar, and likely descended from original populations of these two bacteria that were present in the water dispenser when it left Earth.

The researchers conclude that the two bacterial species living within the dispenser are no more dangerous than similar strains that might be encountered on Earth. In the event of an infection, the bacteria can still be treated with common antibiotics.


The authors add: "Within each species, the 19 B. cepacia and 5 B. contaminans recovered from the ISS were highly similar on a whole genome scale, suggesting each population may have stemmed from two distinct founding strains. The differences that can be observed among the isolates of the same species are primarily located within putative plasmids. We find that the populations of Burkholderia present in the ISS PWS are likely are not more virulent than those that might be encountered on planet, as they maintain a baseline ability to lyse macrophage, but remain susceptible to clinically used antibiotics."

See:

Aubrie O’Rourke, Michael D. Lee, William C. Nierman, R. Craig Everroad, Chris L. Dupont. Genomic and phenotypic characterization of Burkholderia isolates from the potable water system of the International Space Station. PLOS ONE, 2020; 15 (2): e0227152 DOI: 10.1371/journal.pone.0227152

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Monday, 27 April 2020

The advantages of enzymatic detergents


Contaminated flexible endoscopes are the medical devices occasionally associated with outbreaks of health care-associated infection. To minimise the risk, effective cleaning and disinfection of flexible endoscopes must be undertaken. For this process to be effective, several steps need to be followed in a controlled manner. The first step, where a detergent is used at the pre-washer / disinfectant stage, is critical for the removal of soil and in preventing a biofilm community from developing. This step requires the use of a suitable detergent by following a detailed protocol.

In relation to this subject, Tim Sandle has written an article.

Here is the abstract:

Enzymatic detergents are considered to be more effective due to their ability to digest different types of soils and hence facilitate the cleaning process. However, there are additional factors that need to be controlled when using these types of detergent, not least healthcare worker safety. This article examines the differences between these detergents, specifically for the manual cleaning of flexible endoscopes, and considers the factors that need to be practiced for the safe and effective application of enzymatic detergents.

The reference is:

Sandle, T. (2020) The advantages of enzymatic detergents, The Clinical Services Journal, 19 (1): 47-49

For details, contact Tim Sandle.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Sunday, 26 April 2020

Mirrored chip could enable handheld dark-field microscopes


Scientists generate dark-field images by fitting standard microscopes with often costly components to illumine the sample stage with a hollow, highly angled cone of light. When a translucent sample is placed under a dark-field microscope, the cone of light scatters off the sample's features to create an image of the sample on the microscope's camera, in bright contrast to the dark background.

Now, engineers at MIT have developed a small, mirrored chip that helps to produce dark-field images, without dedicated expensive components. The chip is slightly larger than a postage stamp and as thin as a credit card. When placed on a microscope's stage, the chip emits a hollow cone of light that can be used to generate detailed dark-field images of algae, bacteria, and similarly translucent tiny objects.


The new optical chip can be added to standard microscopes as an affordable, downsized alternative to conventional dark-field components. The chip may also be fitted into hand-held microscopes to produce images of microorganisms in the field.

See:

Cécile A. C. Chazot, Sara Nagelberg, Christopher J. Rowlands, Maik R. J. Scherer, Igor Coropceanu, Kurt Broderick, Yunjo Kim, Moungi G. Bawendi, Peter T. C. So, Mathias Kolle. Luminescent surfaces with tailored angular emission for compact dark-field imaging devices. Nature Photonics, 2020; DOI: 10.1038/s41566-020-0593-1

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Saturday, 25 April 2020

Mediterranean diet promotes gut bacteria linked to 'healthy aging'


Eating a Mediterranean diet for a year boosts the types of gut bacteria linked to 'healthy' ageing, while reducing those associated with harmful inflammation in older people, indicates a five-country study.

As ageing is associated with deteriorating bodily functions and increasing inflammation, both of which herald the onset of frailty, this diet might act on gut bacteria in such a way as to help curb the advance of physical frailty and cognitive decline in older age, suggest the researchers.

Previous research suggests that a poor/restrictive diet, which is common among older people, particularly those in long term residential care, reduces the range and types of bacteria (microbiome) found in the gut and helps to speed up the onset of frailty.

The researchers therefore wanted to see if a Mediterranean diet might maintain the microbiome in older people's guts, and promote the retention or even proliferation of bacteria associated with 'healthy' ageing.

They analysed the gut microbiome of 612 people aged 65 to 79, before and after 12 months of either eating their usual diet (n = 289) or a Mediterranean diet (n = 323), rich in fruits, vegetables, nuts, legumes, olive oil and fish and low in red meat and saturated fats, and specially tailored to older people (NU-AGE diet).

The participants, who were either frail (n=28), on the verge of frailty (n=151), or not frail (n=433) at the beginning of the study, lived in five different countries: France, Italy, Netherlands, Poland, and the UK.

Sticking to the Mediterranean diet for 12 months was associated with beneficial changes to the gut microbiome. It was associated with stemming the loss of bacterial diversity; an increase in the types of bacteria previously associated with several indicators of reduced frailty, such as walking speed and hand grip strength, and improved brain function, such as memory; and with reduced production of potentially harmful inflammatory chemicals.
More detailed analysis revealed that the microbiome changes were associated with an increase in bacteria known to produce beneficial short chain fatty acids and a decrease in bacteria involved in producing particular bile acids, overproduction of which are linked to a heightened risk of bowel cancer, insulin resistance, fatty liver and cell damage.


The changes were largely driven by an increase in dietary fibre and associated vitamins and minerals -- specifically, C, B6, B9, copper, potassium, iron, manganese, and magnesium.
The findings were independent of the person's age or weight (body mass index), both of which influence the make-up of the microbiome.



See:

Tarini Shankar Ghosh, Simone Rampelli, Ian B Jeffery, et al. Mediterranean diet intervention alters the gut microbiome in older people reducing frailty and improving health status: the NU-AGE 1-year dietary intervention across five European countries. Gut, 2020; gutjnl-2019-319654 DOI: 10.1136/gutjnl-2019-319654
Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Friday, 24 April 2020

Random gene pulsing generates patterns of life


A team of Cambridge scientists working on the intersection between biology and computation has found that random gene activity helps patterns form during development of a model multicellular system.

We all start life as a single cell, which multiplies and develops into specialised cells that carry out different functions. This complex process relies on precise controls along the way, but these new findings suggest random processes also contribute to patterning.

In research, the scientists from James Locke's team at the Sainsbury Laboratory Cambridge University and collaborators at Microsoft Research describe their discovery of surprising order in randomness while studying bacterial biofilms.


A biofilm develops when free-living single-celled bacteria attach to a surface and aggregate together to start multiplying and spreading across the surface. These multiplying individual cells mature to form a three-dimensional structure that acts like a multicellular organism.
And while individual cells can survive on their own, these bacteria prefer to work together with biofilms being the dominant form found in nature.

The biofilm consortium provides bacteria with various survival advantages like increased resistance to environmental stresses.

The researchers developed a new time-lapse microscopy technique to track how genetically identical single cells behave as the living biofilm developed.

See:

Eugene Nadezhdin, Niall Murphy, Neil Dalchau, Andrew Phillips, James C. W. Locke. Stochastic pulsing of gene expression enables the generation of spatial patterns in Bacillus subtilis biofilms. Nature Communications, 2020; 11 (1) DOI: 10.1038/s41467-020-14431-9

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Thursday, 23 April 2020

ICH Guideline on reproductive toxicology (pharma)



ICH has published a new document: “Guideline on reproductive toxicology: Detection of Toxicity to Reproduction for Human Pharmaceuticals” [ICH S5 (R3)]

The purpose of this document is to recommend international standards for, and promote harmonization of, the assessment of nonclinical developmental and reproductive toxicity (DART) testing required to support human clinical trials and marketing authorization for pharmaceuticals. The guideline describes potential strategies and study designs to supplement available data to identify, assess, and convey risk.

General concepts and recommendations are also provided that should be considered when interpreting study data. This is a revision of the ICH guideline “S5 Detection of Toxicity to Reproduction for Medicinal Products” that was originally published in 1993. This revision brings the guideline into alignment with other ICH guidelines, elaborates on the use of exposure margins in dose level selection, incorporates a section on risk assessment, and expands the scope to include vaccines and biopharmaceuticals. It also describes qualification of alternative assays, potential scenarios of use, and provides options for deferral of developmental toxicity studies. To assess a human pharmaceutical’s effect on reproduction and development, there should generally be information available that addresses the potential impact of exposure to a pharmaceutical and, when appropriate, its metabolites (ICH M3, ICH S6) on all stages of reproduction and development.


This document comes into effect in the EU on 30 July 2020

For details see: https://www.ema.europa.eu/en/documents/scientific-guideline/ich-s5-r3-guideline-reproductive-toxicology-detection-toxicity-reproduction-human-pharmaceuticals_en.pdf

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Wednesday, 22 April 2020

International collaboration on GMP inspections



The section on International collaboration on GMP inspections has been updated in regard to manufacturers of sterile medicines. EMA and its European and international partners have launched a pilot programme to share information on GMP inspections of manufacturers of sterile medicines located outside the participating countries and to organise joint inspections of manufacturing sites of common interest.

The prerequisites for sterile products are:
  • They are sterile (in all probability, based on the control of sterility
  • assurance).
  • Pyrogen free (apyrogenic).
  • Free of visible particles

Other key quality attributes for sterile products are:
  • Chemical/biological purity.
  • Correct dose/strength – correctly labelled .
  • Correct physical form e.g. colour, particle size, viscosity.
  • No physical contaminants.


Batch release is the process of reviewing and approving all pharmaceutical product manufacturing and control records and it performed by the Quality Unit to determine compliance with all established approved written procedures before a batch is released. The process of batch release, and the authority and training of the persons eligible to do so, varies according to different GMP systems.


The products in scope include sterile medicines for human use of chemical origin and certain therapeutic biotechnology - derived products, such as monoclonal antibodies and recombinant proteins. Vaccines, cell and gene therapies and plasma derived pharmaceuticals are currently out of the scope of this pilot.

For further details, see: https://www.ema.europa.eu/en/human-regulatory/research-development/compliance/good-manufacturing-practice/international-collaboration-gmp-inspections

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Tuesday, 21 April 2020

Qualification of Atomic Absorption / Atomic Emission Spectrometers


EDQM has published a guidance for the qualification of Atomic Absorption / Atomic Emission Spectrometers.

The document is the tenth Annex of the core document “Qualification of Equipment”, and it should be used in combination with it when planning, performing and documenting the Atomic absorption (AA) spectrometer/ Atomic emission (AE) spectrometer qualification process. For AE spectrometer only atomization in flame is considered (Inductively coupled plasma-atomic emission spectrometry is not covered by this guideline).

The core document contains the Introduction and general forms for Level I and II of qualification, which are common to all type of instruments and the present annex contains instrument-related recommendations on parameters to be checked at Level III and IV of qualification and the corresponding typical acceptance limits, as well as practical examples on the methodology that can be used to carry out these checks.

The frequency of performing the checks should be defined by each OMCL. Level III (Periodic and motivated instrument calibration/checks) and IV (In-use instrument checks) qualifications must be carried out as an ISO 17025 requirement. Requirements and (if applicable) corresponding typical acceptance limits (given in bold) should be applied; however other appropriately justified approaches are acceptable. Exemplary procedures provided in this document have non-binding character. They can be helpful when carrying out the required qualification.

Nevertheless, it is left to the professional judgement and background experience of each OMCL to decide on the most relevant procedures to be undertaken in order to provide evidence that their AA/ AE spectrometers are working properly and are suitable for their intended use. If the qualification of equipment is done by the manufacturer or an external service provider, it is the responsibility of the OMCL to make sure that this is in line with the requirements set out in this guideline.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Monday, 20 April 2020

Fungi: A Handbook for Life Science Manufacturers and Researchers


A new text has been issued, designed to help identify and ameliorate fungal and mold problems and contains a wealth of information as a guide and reference. Many topics are discussed relevant to the food and agriculture industries, including the biology of fungi, outbreaks associated with pharmaceutical drug products and medical devices, mycotoxins, fungal biodegradation and remediation, and strategies for a rapid and accurate fungal identification. The text also contains a lengthy fungal glossary.

The book is Fungi: A Handbook for Life Science Manufacturers and Researchers, edited by Jeanne Moldenhauer.

I'm pleased to have contributed two chapters:

Sandle, T. (2020) An anatomy of fungal spores: Formation, dispersal and transfer risk. In Moldenhauer, J. (Ed.) Fungi: A handbook for Life Science Manufacturers and Researchers, DHI Publishing, River Grove, IL, USA, pp101-148

Sandle, T. (2020) Investigating sources of fungi in pharmaceutical and healthcare facilities and taking appropriate action. In Moldenhauer, J. (Ed.) Fungi: A handbook for Life Science Manufacturers and Researchers, DHI Publishing, River Grove, IL, USA, pp247-286

The book is available via the PDA Bookstore.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Sunday, 19 April 2020

EU GMP Annex 21


Annex 21 to the EU-GMP Guidelines has been published as a draft (on 20th March 2020), titled "Importation of medicinal Products".

The Annex is aimed at Manufacturing and Importation Authorisation holders (MIA holders) who import human or veterinary medicinal products from third countries.
The Annex does not cover products that do not have a marketing authorisation in the EU/EEA and are directly re-exported.

The Annex includes:

·         Physical transfer from the third country to the EU/EEA
·         Certification by the Qualified Person (QP) (link with the requirements of Annex 16)
·         Requirements for equipment and facilities
·         Required documentation

·         GMP requirements for manufacturers and exporters in third countries
·         Qualification and audits under the responsibility of the importing company and the Qualified Person (QP)
·         Import testing
·         Contractual regulations between all companies or persons involved in the import

For details, see: https://ec.europa.eu/health/sites/health/files/files/gmp/importation_medicinalproducts_draftannex21_en.pdf

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Saturday, 18 April 2020

New, shorter treatment to prevent TB to be rolled out


The Aurum Institute and its partners, as part of the IMPAACT4TB project, have announced that five high-burden TB countries will roll out a new, shorter drug regimen (known as 3HP) to prevent TB.

Countries that will initially provide the new regimen with funding from Unitaid, U.S. PEPFAR and the Global Fund include Cambodia, Ethiopia, Kenya, Malawi, South Africa and Zimbabwe. More than 120,000 patient courses of 3HP will be delivered by the project to 12 countries in 2020. An additional 1 million patient courses are expected to reach low- and middle-income countries by the end of the year, through the combined support of Unitaid, Global Fund, the Stop TB Partnership’s Global Drug Facility (GDF) and PEPFAR.

The new regimen consists of three months of rifapentine and isoniazid treatment. The previous standard of care—isoniazid preventive therapy (IPT)—was long and complex, with people required to take a pill daily for six to 36 months. The 3HP regimen, taken only once a week for 12 weeks, offers numerous benefits for infected individuals, clinicians and programs. Evidence shows that it’s as effective as IPT in preventing progression to active TB disease, has fewer side effects, more patients complete the regimen and is easier for patients to take.

“Effective TB prevention will be a game-changer in the global fight to eliminate tuberculosis,” said Robert Matiru, director of programmes at Unitaid. “This new, shorter regimen, which has until now been unaffordable, offers a great opportunity to turn the tide against TB and protect those who are at highest risk. Preventing this deadly, airborne disease is even more important at a time when the entire world fights to control the threat of COVID-19 and where health systems are being stretched beyond their limits.”

TB remains the world’s deadliest infectious disease. In 2018 alone, 10 million people fell ill from the disease which killed around 1.5 million people, over 95% of whom were living in low- and middle-income countries. TB can lie dormant for decades before it strikes; this is called “latent TB.” People with latent infection—almost a quarter of the globe—have no symptoms, are not contagious and most of them don’t know they are infected. If left untreated, latent infection can develop into active TB, the form of TB that makes people sick and is capable of being transmitted from one person to another.

“This is an exciting new step in the fight to end TB, as it is safer, shortens the duration of preventive therapy and provides more options for those at highest risk of developing active TB,” said Dr Tereza Kasaeva, Director of the Global TB programme at WHO. “WHO, through its regional and country offices, is committed to support scale-up of TB preventive treatment in countries to achieve the UN HLM targets. These countries will pave the way for 3HP rollout in other TB high burden countries.”

During this first phase, 3HP will first be given to those at highest risk of progressing from TB infection to TB disease, notably people living with HIV (PLHIV) and children under the age of five. People living with HIV are 20 to 37 times more likely to move from latent to active TB than those without HIV infection. Often, their infection goes unnoticed until it’s too late, and as a result people being successfully treated for HIV are now dying from TB.

At the UN High-Level Meeting on TB in 2018, world leaders committed to providing TB preventive therapy to at least 30 million people, including 6 million people living with HIV, by 2022, 4 million children under 5 years and 20 million household contacts.

“Children up to five years of age are at highest risk of progressing from TB infection to disease, yet only about 25% of those who are eligible for it start TB preventive therapy,” said Dr Matteo Zignol, Unit Head a.i., TB prevention, diagnosis, treatment, care and innovation, WHO Global TB Programme. “The scale-up of 3HP among these vulnerable populations will go a long way towards not only saving lives, but also reducing the overall burden of TB disease.”

In October 2019, Unitaid, the Global Fund and Sanofi announced a new price agreement for rifapentine (Priftin®), which drastically discounted the price of 3HP. The agreement with Sanofi lowered a patient treatment course of Priftin® from $45 to $15 (a 66% discount). The discounted price was made available to the public sectors of low-income countries, lower-middle income countries and upper-middle income countries with a high burden of TB and TB/HIV.

“As of 2018, only 65 countries reported initiating 1.8 million people living with HIV and around 350,000 children under the age on TB preventive therapy—well below the targets set at the UN High-Level Meeting on TB which took place in September 2018,” said Gavin Churchyard, founder and CEO of the Aurum Institute. “Until recently, price remained a key barrier to scale-up of short course regimens such as 3HP. Now that this barrier has been removed, it’s time to get serious about preventing TB, particularly during the SARS-CoV2 pandemic, as there is some evidence to suggest that active TB may worsen the clinical outcome of Covid19 disease.”


“Unitaid is committed to establishing a healthy market for TB preventive therapy, in line with the political commitments made at the UN high-level meeting on TB,” said Philippe Duneton, Unitaid Executive Director a.i. “Moving forward, we intend to support the entry of at least one more generic supplier of the FDC, as well as other rifapentine-based formulations, including for children.”

“This is only the first step, and in the coming months the Aurum Institute and its IMPAACT4TB partners will be working to roll out 3HP to all 12 of its project countries, which represent almost 50% of the global TB burden,” said Karin Kanewske Turner, Director of the IMPAACT4TB Project, from the Aurum Institute.  

 Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Friday, 17 April 2020

Graphite nanoplatelets on medical devices kill bacteria and prevent infections


Graphite nanoplatelets integrated into plastic medical surfaces can prevent infections, killing 99.99 per cent of bacteria which try to attach – a cheap and viable potential solution to a problem which affects millions, costs huge amounts of time and money, and accelerates antibiotic resistance. This is according to research from Chalmers University of Technology, Sweden, in the journal Small.

Every year, over four million people in Europe are affected by infections contracted during health-care procedures, according to the European Centre for Disease Prevention and Control (ECDC). Many of these are bacterial infections which develop around medical devices and implants within the body, such as catheters, hip and knee prostheses or dental implants. In worst cases implants need to be removed.

Bacterial infections like this can cause great suffering for patients, and cost healthcare services huge amounts of time and money. Additionally, large amounts of antibiotics are currently used to treat and prevent such infections, costing more money, and accelerating the development of antibiotic resistance.

“The purpose of our research is to develop antibacterial surfaces which can reduce the number of infections and subsequent need for antibiotics, and to which bacteria cannot develop resistance. We have now shown that tailored surfaces formed of a mixture of polyethylene and graphite nanoplatelets can kill 99.99 per cent of bacteria which try to attach to the surface,” says Santosh Pandit, postdoctoral researcher in the research group of Professor Ivan Mijakovic at the Division of Systems Biology, Department of Biology and Biotechnology, Chalmers University of Technology.

Infections on implants are caused by bacteria that travel around in the body in fluids such as blood, in search of a surface to attach to. When they land on a suitable surface, they start to multiply and form a biofilm – a bacterial coating.

Previous studies from the Chalmers researchers showed how vertical flakes of graphene, placed on the surface of an implant, could form a protective coating, making it impossible for bacteria to attach – like spikes on buildings designed to prevent birds from nesting. The graphene flakes damage the cell membrane, killing the bacteria. But producing these graphene flakes is expensive, and currently not feasible for large-scale production.

“But now, we have achieved the same outstanding antibacterial effects, but using relatively inexpensive graphite nanoplatelets, mixed with a very versatile polymer. The polymer, or plastic, is not inherently compatible with the graphite nanoplatelets, but with standard plastic manufacturing techniques, we succeeded in tailoring the microstructure of the material, with rather high filler loadings, to achieve the desired effect. And now it has great potential for a number of biomedical applications,” says Roland Kádár, Associate Professor at the Department of Industrial and Materials Science at Chalmers.

The nanoplatelets on the surface of the implants prevent bacterial infection but, crucially, without damaging healthy human cells. Human cells are around 25 times larger than bacteria, so while the graphite nanoplatelets slice apart and kill bacteria, they barely scratch a human cell.

“In addition to reducing patients’ suffering and the need for antibiotics, implants like these could lead to less requirement for subsequent work, since they could remain in the body for much longer than those used today,” says Santosh Pandit. “Our research could also contribute to reducing the enormous costs that such infections cause health care services worldwide.”

In the study, the researchers experimented with different concentrations of graphite nanoplatelets and the plastic material. A composition of around 15-20 per cent graphite nanoplatelets had the greatest antibacterial effect – providing that the morphology is highly structured.

“As in the previous study, the decisive factor is orienting and distributing the graphite nanoplatelets correctly. They have to be very precisely ordered to achieve maximum effect,” says Roland Kádár.

The study was a collaboration between the Division of Systems and Synthetic Biology at the Department of Biology and Biological Engineering, and the Division of Engineering Materials at the Department of Industrial and Materials Science at Chalmers, and the medical company Wellspect Healthcare, who manufacture catheters, among other things. The antibacterial surfaces were developed by Karolina Gaska when she was a postdoctoral researcher in the group of Associate Professor Roland Kádár.

The researchers’ future efforts will now be focused on unleashing the full potential of the antibacterial surfaces for specific biomedical applications.

Read the scientific article, ‘Pre-controlled Alignment of Graphite Nanoplatelets in Polymeric Composites Prevents Bacterial Attachment’ in the journal Small.
Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Thursday, 16 April 2020

New approach to unraveling Clostridium difficile


Biologists at the University of California San Diego are drawing parallels from newly developed models of the common fruit fly to help lay the foundation for novel therapies to fight the pathogen's spread.

As with most bacterial pathogens, C. difficile secretes toxins that enter host cells, disrupt key signaling pathways and weaken the host's normal defense mechanisms. The most potent strains of C. difficile unleash a two-component toxin that triggers a string of complex cellular responses, culminating in the formation of long membrane protrusions that allow the bacteria to attach more effectively to host cells.

UC San Diego scientists created strains of fruit flies that are capable of expressing the active component of this toxin, known as "CDTa." The strains allowed them to study the elaborate mechanisms underlying CDTa toxicity in a live model system focused on the gut, which is key since the digestive system of these small flies is surprisingly similar to that of humans.


The fruit fly model gave the researchers a clear path to examine genetic interactions disrupted at the hands of CDTa. They ultimately found that the toxin induces a collapse of networks that are essential for nutrient absorption. As a result, the model flies' body weight, fecal output and overall lifespan were severely reduced, mimicking symptoms in human C. difficile-infected patients.

See:

Ruth Schwartz, Annabel Guichard, Nathalie C. Franc, Sitara Roy, Ethan Bier. A Drosophila Model for Clostridium difficile Toxin CDT Reveals Interactions with Multiple Effector Pathways. iScience, 2020; 100865 DOI: 10.1016/j.isci.2020.100865

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Wednesday, 15 April 2020

Potential role of inanimate surfaces for the spread of coronaviruses


The novel human coronavirus SARS-CoV-2 has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described, probably via droplets but possibly also via contaminated hands or surfaces. In a recent review on the persistence of human and veterinary coronaviruses on inanimate surfaces it was shown that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days. Some disinfectant agents effectively reduce coronavirus infectivity within 1 minute such 62%–71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite. Other compounds such as 0.05%–0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. An effective surface disinfection may help to ensure an early containment and prevention of further viral spread.
For details on this new research see: Kampf

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Tuesday, 14 April 2020

Bacteria killed by light-activated coating


To stop the spread of disease, it could be used to coat phone screens and keyboards, as well as the inside of catheters and breathing tubes, which are a major source of healthcare-associated infections (HCAIs).

The most well-known HCAIs are caused by Clostridioides difficile (C. difficile), methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli). They commonly occur during in-patient medical or surgical treatment, or from visiting a healthcare setting and pose a serious health threat.

The research is the first to show a light activated antimicrobial coating successfully killing bacteria in low intensity, ambient light (300 Lux), such as that found in wards and waiting rooms. Previously, similar coatings needed intense light (3,000 Lux), like that found in operating theatres, to activate their killing properties.

The new bactericidal coating is made of tiny clusters of chemically modified gold embedded in a polymer with crystal violet -- a dye with antibacterial and antifungal properties.

First author, Dr Gi Byoung Hwang (UCL Chemistry), said: "Dyes such as crystal violet are promising candidates for killing bacteria and keeping surfaces sterile as they are widely used to disinfect wounds. When exposed to bright light, they create reactive oxygen species, which in turn kill bacteria by damaging their protective membranes and DNA. This is amplified when they are paired with metals such as silver, gold and zinc oxide."

The team of chemists, chemical engineers and microbiologists created the bactericidal coating using a scalable method and tested how well it killed S. aureus and E. coli against control coatings and under different lighting conditions.

Sample surfaces were treated with either the bactericidal coating or a control coating before being inoculated with 100,000 colony forming units (CFU) per ml of either S. aureus and E. coli. The growth of the bacteria was investigated under dark and white light conditions between 200 -- 429 Lux.


They found that in ambient light, a control coating of crystal violet in a polymer alone did not kill either bacteria. However, in the same lighting conditions, the bactericidal coating led to a 3.3 log reduction in the growth of S. aureus after six hours and a 2.8 log reduction in the growth of E. coli after 24 hours.

See:

Gi Byoung Hwang, He Huang, Gaowei Wu, Juhun Shin, Andreas Kafizas, Kersti Karu, Hendrik Du Toit, Abdullah M. Alotaibi, Layla Mohammad-Hadi, Elaine Allan, Alexander J. MacRobert, Asterios Gavriilidis, Ivan P. Parkin. Photobactericidal activity activated by thiolated gold nanoclusters at low flux levels of white light. Nature Communications, 2020; 11 (1) DOI: 10.1038/s41467-020-15004-6

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

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