Sunday, 12 July 2020

Interview with a microbiologist


Tim Sandle has been interviewed by the Institute of Validation Technology as part of the ‘Meet the Board’ series (Dr Sandle is a regular contributor to the IVT Network).

Here is an extract:

What is your advice to people who want to begin publishing their work but are maybe a little too hesitant to start?

The trick is to start off with something small. The best approach depends on the field and subject matter. With pharmaceuticals and healthcare, writing on a new standard that has been published or describing a new method are good places to start, trying to sum up what the change is about. Much of it is similar to writing an essay at school: introduction, main section, and conclusion. In the introduction say what the article is about; the middle section discuss the subject (for a newish writer limiting this to three main points is a good way of structuring the body of the article); and then summarize at the end. And then proof read.

The subject needs to be something you’re interested in and you need to enjoy writing. Every style is different (varying from the formal to the informal) and there’s no right or wrong way: if you’ve communicated what you want, then it’s worked. The first article I wrote was about 20 years ago and it was about microbiology on the Internet (which, believe it or not, wasn’t in widespread use at the time!) surveying websites.


The full interview can be read here: IVT


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

Saturday, 11 July 2020

New insights into antibiotic mechanisms


Researchers have uncovered new insights into how bacteria respond to stress. When deprived of nutrients, strains of the bacterium Streptococcus pneumoniae mount a coordinated defense. When exposed to antibiotics, the bacterial response is highly disorganized, revealing the bacteria are far less familiar with antibiotics and do not recognize how to respond.

When facing a common -- or historic -- threat such as deprivation of nutrients, the deadly bacterium Streptococcus pneumoniae exerts a highly organized response -- one influenced by the bacteria's genetic evolution and powered by genes that respond cooperatively to stress, the researchers found. But when confronted with antibiotics -- a relatively new form of stress -- the bacterium mounts a confused defense, according to the study "Antibiotics Disrupt Coordination Between Transcriptional and Phenotypic Stress Responses in Pathogenic Bacteria," published today in the journal Cell Reports.

Scienitsts used a process known as RNA sequencing, or RNA-Seq, to assess bacterial genes that are provoked to change, a process known as transcription. This activity has long been viewed as central to understanding how bacteria combat antibiotics and other stressors.

The team paired that analysis with its own technique: transposon insertion sequencing, or Tn-Seq. Developed by van Opijnen, Tn-Seq combs through millions of genetic sequences and singles-out gene functions in bacteria. The advantage of Tn-Seq is that it is able to begin to pinpoint which genes play the most important defensive roles.

During the course of more than two years, the team's RNA-Seq experiments analyzed 800 million genetic sequences and produced 150,000 data points. Tn-Seq analyzed 1.2 billion sequences and produced 300 million data points. The researchers constructed a metabolic model of the coordinated response to deprivation, which placed the responding genes in close proximity to each other. When challenged with antibiotics, the model shows that the response of the physical network breaks down in disorganization and those genes are no longer in close proximity.

See:

Paul A. Jensen, Zeyu Zhu, Tim van Opijnen. Antibiotics Disrupt Coordination between Transcriptional and Phenotypic Stress Responses in Pathogenic BacteriaCell Reports, 2017; 20 (7): 1705 DOI: 10.1016/j.celrep.2017.07.062

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

Thursday, 9 July 2020

Best practices in environmental monitoring


This video provides an overview of the best practices in relation to environmental monitoring, providing microbiologists with a benchmark for their practices, as well as providing advice for those wishing to set up a programme or to take a programme to scale.



The webinar emphasises risk assessment and the importance of corrective and preventative actions. Topics discussed include: -

What environmental is and what it is not -
The objectives of environmental monitoring -
Contamination sources and risks -
Aspects to consider with EM methods -Rapid microbiological methods -Core elements of the EM programme – what, when and how often? -
Data and CAPA -
Profiling microbial contamination


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

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

Wednesday, 8 July 2020

Antimicrobial properties of copper


Copper – for many centuries known for its antimicrobial properties – is increasingly being used in hospitals and other healthcare facilities worldwide as an aid to infection control and reducing healthcare associated infections. This article discusses how antimicrobial surfaces incorporating copper can assist with hospital infection control programmes and the fight against nosocomial infection.
Tim Sandle has written a new article on the antimicrobial properties of copper:

Sandle., T. (2017) Combining copper with effective hygiene, Health Estate Journal, October 2017, pp43-46

For a copy, please contact Tim Sandle

 Posted by Dr. Tim Sandle

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

ASM Releases 2019-2020 Global Report


The American Society of Microbiology's Global Report highlighting international accomplishments in microbiology is now available. ASM's Global Public Health Programs unite scientists around the world as they face public health threats like COVID-19 exacerbated by a rapidly growing human population and increased global mobility. Since the inception of its Global Public Health Programs, ASM has provided training, mentorship and cost-effective solutions in 26 countries around the world.

To access see: https://asm.org/Articles/Global-Public-Health/2019-2020-ASM-Global-Impact-Report?utm_source=RealMagnet&utm_medium=email&utm_content=ASM%5FNews%5F20200706&utm_campaign=Other%20Topics%20ASM%20News%20General

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

Best Practices in Environmental Monitoring - Reviewing your Process for Compliance


This video provides an overview of the best practices in relation to environmental monitoring, providing microbiologists with a benchmark for their practices, as well as providing advice for those wishing to set up a programme or to take a programme to scale.

The webinar emphasises risk assessment and the importance of corrective and preventative actions. Topics discussed include: -

What environmental is and what it is not -
The objectives of environmental monitoring -
Contamination sources and risks -
Aspects to consider with EM methods -Rapid microbiological methods -Core elements of the EM programme – what, when and how often? -
Data and CAPA -
Profiling microbial contamination


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

Tuesday, 7 July 2020

Pathogen biogeography: using a new model to predict disease outbreaks


Data-driven approaches to disease tracking and assessment are often used in predicting and preventing the spread of pathogens, as well as assessing whether a disease outbreak will occur and what the probable impact will be on a given population. Such approaches have been made easier through the digital capture of data and facilitated through forms of artificial intelligence such as machine learning. However, while the quality of data remains a key factor, any attempt of infectious disease prediction rests with the robustness of the model. An emerging area that appears to offer strong predictive power is pathogen biogeography.

Tim Sandle has written a new article for Infectious Disease Hub. The article can be found here.

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

Monday, 6 July 2020

Rogue Biological Indicators: Are They A Real Phenomenon?


Sometimes, unexplained results occur when using biological indicators with sterilization or decontamination processes. This could be attributable to a failure of the sterilization process or, perhaps, due to a mishandling of the biological indicator. Other reasons can be traced to issues of resistance and variations with the biological indicator itself (the effect of ‘creeping resistance’ has been described by some microbiologists to indicate a steady rising of D-values). Atypical results are seemingly more common with hydrogen peroxide vapor cycles (commonly used for isolator bio-decontamination) compared with sterilization cycles based on moist heat. In relation to hydrogen peroxide, another reason for atypical results is due to the occurrence of a rogue biological indicator, and it with this that this paper focuses on.

Tim Sandle has written a new article.

Here is an extract:

A rogue biological indicator is a term applied to a biological indicator which survives a hydrogen peroxide vapor cycle when perhaps it should not, based on the cycle parameters meeting previously established satisfactory profiles and in relation the known characteristics of the organism (that is, all cells should theoretically have been killed). When a positive biological indicator occurs (as evidenced by turbidity in culture media) it is impossible to determine whether the biological indicator met the definition of a ‘rogue’ (where a rogue can occur due to the overlaying of bacterial endospores on the carrier, as well as other reasons, as discussed in the main body of this paper).

As a note of caution, there are various reasons for isolator cycle failures outside of the rogue biological indicator situation and the automatic assumption should be that the reason for a cycle failure is due to a rogue event. As the rogue event assumes a ‘false positive’, the logical steps is to attempt to disprove the ‘false positive’ and to identify an alternative reason for the failure (that is the assumption that the failure is genuine). If no other reason can be attributed then, and only then, should the possibility of the rogue biological indicator be assumed. These issues are explored below.


The reference is:

Sandle, T. (2020) Rogue Biological Indicators: Are They A Real Phenomenon?, Journal of Validation Technology, 26 (1):

For details, please contact Tim Sandle

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

Sunday, 5 July 2020

EU GMP Annex 1: What The ‘Final’ Draft Reveals


This paper reviews the new of EU GMP Annex 1 draft. In doing so the focus is on those aspects that are different to the 2017 draft, rather than spending much time comparing the 2020 draft with the current Annex 1 (which is dated 2009). 

Readers wishing to do this can refer to the 2018 Journal of GxP Compliance review. The reader should note that this paper contains some personal commentary at different points, either in praise of some of the updates or raising concerns about things that have not been changed which should have or with reference to some of the new things that have been added. 

Of course, the reader may not agree but the change is highlighted some that due consideration can be given.

The core focus with the revision is:


  • The global acceptance and implementation of ICH Q9 (Quality Risk Management) (8) and Q10 (Pharmaceutical Quality System), is not reflected in the current Annex. The new draft contains many references to Quality Risk Management (QRM) in particular, emphasizing that QRM should be used as a proactive tool. There are now 92 instances of the word “risk” in the new draft, an increase from 20 in the previous version.
  • There have been advances in sterile manufacturing technology, especially with RABS and isolators. There have also been advances with rapid microbiological methods, which the draft Annex acknowledges.
  • There was some ambiguity with the current version and these needed correction or clarification
  • Annex 1 is often beyond sterile manufacturing, including aspects of non-sterile manufacturing. The scope of the new draft has been modified to reflect this.
  • There is the requirement for a formal, holistic contamination control strategy (which is now abbreviated to ‘CCS’ in the new draft). The expectation now appears to be for a formal document which reflects the site-wide strategy for minimizing contamination control with respect to sterile manufacturing. The requirements of the contamination control strategy have been widened (43 mentions, up from 19 in the 2017 draft), however, with the new draft, extending to the need to fully-understand and review design, procedural, technical and organizational controls. With the term ‘contamination’ it remains that contamination is used too broadly, and it would be useful if, for example, there was a specific microbiological concern that the nature of the contamination is referred to directly. 


The reference is:

Sandle, T. (2020) EU GMP Annex 1: What The ‘Final’ Draft Reveals, Journal of GxP Compliance, 24 92), at: https://www.ivtnetwork.com/article/eu-gmp-annex-1-what-%E2%80%98final%E2%80%99-draft-reveals

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

Saturday, 4 July 2020

Imbalance of gut bacteria linked to bowel cancer


New research suggests that a bacterium commonly found in the gut may, under particular conditions, release a toxin that triggers mutations in the cells found in the lining of the gut and this can lead to bowel cancer.
A bacterium commonly found human intentions could contribute to bowel cancer, under specific conditions, according to new research. The data reveals that a toxin called colibactin, released by a strain of Escherichia coli, triggers unique patterns, or 'fingerprints', of DNA that can cause damage to the cells lining the gut through a process called tumorigenesis.
The reason why there appears to be a connection is because the molecular fingerprints have also been detected in bowel cancer tumours. This evidence indicates a connection between a specific bacterial toxin and the types of genetic changes that are associated with cancer development. A further indication of the connection is with colibactin being frequently isolated from the faeces of cancer patients.
The research team ran experiments using human cells in the laboratory, showing what the effects of the colibactin are. The experimental results confirmed the hypothesis.
The implications of the research suggest that medics should focus on reducing the presence of high-risk bacteria in the gut. However, for the current time those concerned should continue to focus on exercise and with consuming a healthy diet. For those of a certain age (over 55 years is considered to be a higher risk group), it is recommended that they take part in bowel cancer screening
The research study has been published in the science journal Nature. The research paper is titled "Mutational signature in colorectal cancer caused by genotoxic pks E. coli."
Parallel work conducted by the Hubrecht Institute has shown that cancer mutations of the colon can also be triggered by genotoxic E. coli, through the organisms inducing a unique mutational pattern in human DNA. As with the bowel cancer study, colibactin was the attributable cause.

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

Friday, 3 July 2020

The Survival of Coronavirus Sars-Cov-2 On Surfaces and Designing Disinfection Strategies to Eliminate the Virus


Coronaviridae specificities such as pathogenicity and potential environmental resistance, make them a challenging model for the development of efficient means of prevention. The virus is relatively infectious; current data suggests that each infection results in 1.4 to 3.9 new ones (based on the basic reproduction  number or R0 value) when no members of the community are immune and no preventive measures taken.

While most people are practicing ‘social distancing’ (or, more accurately, ‘physical distancing’) and carry out other measures to reduce the spread of SARS-CoV-2, like regular handwashing or hand sanitization, it is also important to ensure that surfaces are regularly cleaned and disinfected. This paper focuses on viral survival on surfaces and appropriate forms of disinfection for those working in the pharmaceutical and healthcare sectors, drawing on the literature published to date.


Sandle, T. (2019) The Survival of Coronavirus Sars-Cov-2 On Surfaces and Designing Disinfection Strategies to Eliminate the Virus, Journal of Validation Technology, 26 (2).

See: https://www.ivtnetwork.com/article/survival-coronavirus-sars-cov-2-surfaces-and-designing-disinfection-strategies-eliminate-vir

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

Thursday, 2 July 2020

Consideration of Covid-19 Prevention Measures For Those Working In GMP Pharmaceuticals And Healthcare Facilities


Aside from expelled droplets through coughing and sneezing, it is not yet established if the virus survives long-term in the air and hence whether it can be classified as ‘airborne.’   This article then considers the measures that employers within the pharmaceutical and healthcare need to have in place in order to maintain staff safety and welfare. Whilst continuing to ensure that Good Manufacturing (GMP) standards are met.


The article also considers the measures that employers within the pharmaceutical and healthcare need to have in place in order to maintain staff safety and welfare. Whilst continuing to ensure that Good Manufacturing (GMP) standards are met. While the focus is on the causative agent of COVID-19, the information presented will help for assessing future pathogen outbreaks where additional public health measures are required.

Sandle, T. (2019) Consideration of Covid-19 Prevention Measures For Those Working In GMP Pharmaceuticals And Healthcare Facilities, Journal of Validation Technology, 26 (2).

See: https://www.ivtnetwork.com/article/consideration-covid-19-prevention-measures-those-working-gmp-pharmaceuticals-and-healthcare-

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

Wednesday, 1 July 2020

COVID-19: Optimal disinfection choices at this challenging time


The respiratory disease, COVID-19, is having a significant global impact, with infection numbers and mortality rates increasing by the day. Investigations are ongoing to try to learn more about this new coronavirus, and clinical trials have commenced in relation to both improved detection tests and with developing vaccines. News reports across multiple platforms, particularly social media, often appear to give conflicting opinions.


Looking at the importance of cleaning and disinfection to address the virus, Tim Sandle has written an article:

Sandle, T. (2020) Optimal disinfection choices at this challenging time, Health Estate Journal, May 2020, pp50-52: https://www.healthestatejournal.com/story/32648/optimal-disinfection-choices-at-this-challenging-time

What is unquestionable is the vital role played by taking robust infection prevention and control measures in healthcare facilities. However, with so many cleaning and disinfection products to choose from, and with limited time for research, this article aims to give an overview for anyone involved in health estates and facilities management of the key considerations when selecting the optimum cleaning products.

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

Tuesday, 30 June 2020

Holistic contamination control is central to revised EU GMP Annex 1


The main focal points from the 2020 draft of EU GMP Annex 1 (titled “Manufacture of Sterile Products”) signal to sterile products manufacturers a shift in regulatory thinking towards environmental controls rather than an over-reliance upon monitoring; with risk-based scientific thinking; and looking at contamination control holistically. The main themes are:

  • The expectation for each facility to have in place a formal, holistic contamination control strategy, focused on minimizing contamination control with respect to sterile manufacturing.
  • Additional requirements for cleanroom classification (beyond ISO 14644 requirements).
  • A major focus on risk-based approaches.
  • Recommendations for the wider use of barrier technology.
  • A strong focus on personnel controls, such as gowning, and training.

In relation to this, Tim Sandle has written an article. The reference is:

Sandle, T. (2020) 2020 Annex 1 Draft: Holistic Changes, Cleanroom Technology, 28 (5): 25-27

This article looks into some of the likely changes that will impact sterile products manufacturers, which can help organisations to stay ahead of the regulatory curve.

For details, please contact Tim Sandle

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

Monday, 29 June 2020

COVID-19 and dental practice


Nobody could fail to miss the media coverage about novel coronavirus COVID-19, with daily and sometimes hourly updates about the ‘killer virus’. What exactly does it mean for dental practices in the UK?


In relation to this, Tim Sandle has written an article. Here is an extract:

"As coronaviruses have a lipid envelope, a wide range of disinfectants are effective. Human coronaviruses can be efficiently inactivated by surface disinfection procedures with 62-71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Other biocidal agents such as 0.05-0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. A virucidal, ethanol-based disinfector/cleaner such as mikrozid liquid could play a useful role in the cleaning and disinfection of hard surfaces, particularly as it is effective against enveloped viruses within one minute."

The reference is:

Sandle, T. (2020) COVID-19 and dental practice, Dental Nursing, April 2020, pp2-3: https://www.magonlinelibrary.com/doi/full/10.12968/denn.2020.16.4.194

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

Sunday, 28 June 2020

Presence of microbial DNA in blood may indicate signs of cancer

A new study indicates that looking for signs of certain microbial DNA in a patient's blood may be tell-tale sign of cancer. The discovery could help to advance cancer detection.

The new technique, which comes from the University of California - San Diego, works on the basis of a straightforward blood draw. When the blood is analyzed, the presence of microbial DNA could reveal whether the patient has cancer and then which type of cancer. The technique has produced accurate results, even for detecting signs of cancer at the early stages.
The basis of the technique came from an earlier study where it was shown that microorganisms invaded a majority of pancreatic cancers. In addition, certain types of microbes were found to be able to break down chemotherapy drugs. This led to the idea that examining a patient's microbiome could play a role in cancer detection.
This represented a shift in thinking, according to one of the scientists involved, Professor Rob Knight, who says: "Almost all previous cancer research efforts have assumed tumors are sterile environments, and ignored the complex interplay human cancer cells may have with the bacteria, viruses and other microbes that live in and on our bodies."
To develop the technique, the researchers examined 18,116 tumor samples, drawn from 10,481 patients. The patients had 33 different cancer types. By using a computer model, the analysis of the data revealed a series of distinct microbial signatures associated with specific cancer types.
For example, there was a connection between the bacterium Fusobacterium species and gastrointestinal cancers. The anaerobic Gram-negative organism has previously been linked with skin ulcers. As a second example, the researchers found an association between Faecalibacterium species and colon cancer. This Gram-positive anaerobe has previously been linked with Crohn's disease.
Such data is now being used to develop machine learning algorithms and with this the potential for a new, rapid cancer detection technology based on liquid biopsies.
The research has been published in the science journal Nature. The peer-reviewed study is titled: "Microbiome analyses of blood and tissues suggest cancer diagnostic approach."

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

Saturday, 27 June 2020

Artificial intelligence finds new antibiotic


Technologists, working with microbiologists, have made a significant breakthrough in the hunt for new antimicrobials. By using artificial intelligence, a new candidate antibiotic has been identified.

The discovery was made using a machine-learning algorithm. This technology enabled scientists to discover a powerful new antibiotic compound.

The importance of the antibiotic has been shown through various tests, where the chemical was challenged against several disease-causing bacteria. Among the microbial cohort were some organisms previously identified to be resistant to mot antibiotics. Further studies were undertaken using mice, yielding similarly successful results.

READ MORE: Genetic testing can identify antibiotic resistance

The reason why there is strong scientific interest in finding new antibiotics is due to the phenomenon of antimicrobial resistance. This is a significant global health issue since the pace at which bacteria are becoming resistant to common antibiotic treatments is increasing. This means that infections that were once easy to treat are no longer certain of being tackled through existing medications. The consequence is that routine operations or transplants now present additional risks.

With the new discovery from MIT, the algorithm processed millions of chemical compounds, processing this vast data set in just a few days. This approach also avoided the necessity of running thousands of experiments; only those compounds selected by the machine learning program as having strong potential need be tested.

The use of computer models for drug screening and other applications is captured by the term “in silico.”

According to lead researcher Professor James Collins: “Our approach revealed this amazing molecule which is arguably one of the more powerful antibiotics that has been discovered.”

He molecule selected has been named halicin (with a reference to the computer in 2001: A Space Odyssey). The drug was shown to be effective against Escherichia coli, as part of the tests. Further bacterial killing effects were demonstrated using other organisms of concern, such as Clostridium difficile, Acinetobacter baumannii, and Mycobacterium tuberculosis.

The bacterial killing properties of halicin arise from the compound’s ability to disrupt the electrochemical gradient across bacterial cell membranes, which triggers cell death.

ALSO READ: Antibiotic use may lead to heart problems

The research has been published in the journal Cell. The research paper is titled “A Deep Learning Approach to Antibiotic Discovery.”

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

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