Developing a new weapon in the war against superbugs

Australian microbiologists have shown that a newly discovered natural antibiotic, teixobactin, could be effective in treating bacterial lung conditions such as tuberculosis and those commonly associated with COVID-19. 

Teixobactin was discovered in 2015 by a team led by Professor Kim Lewis at Northeastern University in Boston in 2015. His company is now developing it as a human therapeutic.

The new University of Melbourne research is the first to explain how teixobactin works in relation to the superbug Staphylococcus aureus -- also known as MRSA.

MRSA is among bacteria responsible for several difficult-to-treat infections in humans, particularly post-viral secondary bacterial infections such as COVID-19 chest infections and influenza.

See:

Maytham Hussein, John A. Karas, Elena K. Schneider-Futschik, Fan Chen, James Swarbrick, Olivia K. A. Paulin, Daniel Hoyer, Mark Baker, Yan Zhu, Jian Li, Tony Velkov. The Killing Mechanism of Teixobactin against Methicillin-Resistant Staphylococcus aureus: an Untargeted Metabolomics Study. mSystems, 2020; 5 (3) DOI: 10.1128/mSystems.00077-20

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

New tool to distinguish between viral & bacterial infections

Antibiotics are lifesaving drugs, but overuse is leading to antibiotic resistance, one of the world's most pressing health threats. Scientists identified 11 genetic markers in blood that accurately distinguished between viral and bacterial infections 80 to 90 percent of the time. The finding is important because physicians don't have a good way to confirm bacterial infections like pneumonia and more-often-than-not default to an antibiotic.

Scientists from the University's National Institutes of Health-funded Respiratory Pathogens Research Center identified 11 genetic markers in blood that accurately distinguished between viral and bacterial infections (antibiotics help us fight bacterial infections, but aren't effective and shouldn't be used to treat viruses). The finding, published in the journal Scientific Reports, is important because physicians don't have a good way to confirm bacterial infections like pneumonia and more-often-than-not default to an antibiotic.

"It's extremely difficult to interpret what's causing a respiratory tract infection, especially in very ill patients who come to the hospital with a high fever, cough, shortness of breath and other concerning symptoms," said Ann R. Falsey, M.D., lead study author, professor and interim chief of the Infectious Diseases Division at UR Medicine's Strong Memorial Hospital. "My goal is to develop a tool that physicians can use to rule out a bacterial infection with enough certainty that they are comfortable, and their patients are comfortable, foregoing an antibiotic."

Falsey's project caught the attention of the federal government; she's one of 10 semifinalists in the Antimicrobial Resistance Diagnostic Challenge, a competition sponsored by NIH and the Biomedical Advanced Research and Development Authority to help combat the development and spread of drug resistant bacteria. Selected from among 74 submissions, Falsey received $50,000 to continue her research and develop a prototype diagnostic test, such as a blood test, using the genetic markers her team identified.

A group of 94 adults hospitalized with lower respiratory tract infections were recruited to participate in Falsey's study. The team gathered clinical data, took blood from each patient, and conducted a battery of microbiologic tests to determine which individuals had a bacterial infection (41 patients) and which had a non-bacterial or viral infection (53 patients). Thomas J. Mariani, Ph.D., professor of Pediatrics and Biomedical Genetics at URMC, used complex genetic and statistical analysis to pinpoint markers in the blood that correctly classified the patients with bacterial infections 80 to 90 percent of the time.

"Our genes react differently to a virus than they do to bacteria," said Mariani, a member of the Respiratory Pathogens Research Center (RPRC). "Rather than trying to detect the specific organism that's making an individual sick, we're using genetic data to help us determine what's affecting the patient and when an antibiotic is appropriate or not."

Falsey, co-director of the RPRC, and Mariani say that the main limitation of their study is the small sample size and that the genetic classifiers selected from the study population may not prove to be universal to all patients.

A patent application has been filed for their method of diagnosing bacterial infection. Edward Walsh, M.D., professor of Infectious Diseases, and Derick Peterson, Ph.D., professor of Biostatics and Computational Biology at URMC, also contributed to the research.

According to the Centers for Disease Control and Prevention, antibiotic resistant bacteria cause at least 2 million infections and 23,000 deaths each year in the United States. The use of antibiotics is the single most important factor leading to antibiotic resistance around the world.

See:

Soumyaroop Bhattacharya, Alex F. Rosenberg, Derick R. Peterson, Katherine Grzesik, Andrea M. Baran, John M. Ashton, Steven R. Gill, Anthony M. Corbett, Jeanne Holden-Wiltse, David J. Topham, Edward E. Walsh, Thomas J. Mariani, Ann R. Falsey. Transcriptomic Biomarkers to Discriminate Bacterial from Nonbacterial Infection in Adults Hospitalized with Respiratory Illness. Scientific Reports, 2017; 7 (1) DOI: 10.1038/s41598-017-06738-3Posted by Dr. Tim Sandle

Antimicrobial Resistance in the Environment

The class of chemicals characterized as biocides are used in all parts of society from home to hospital, to farms and industry. The presence of biocides selects for genes in microorganisms that can protect against their lethal effects. These biocide resistance genes are often the same genes as antibiotic resistance genes (i.e. cross-resistance), or they can be co-located on plasmids, for example, which means when biocides are present the microorganism will also co-select for antibiotic resistance genes (i.e. co-resistance).

Dr. Andrew C Singer has written an interesting blog post on antimicrobial resistance. Here is an extract:

“The problem with antimicrobial resistance (AMR), globally, is the combination of: 1) increased prevalence of antibiotic resistance; 2) rapid spread of AMR due to global travel; 3) antibiotic misuse; and 4) too few new antimicrobials in development. National, regional and global AMR Action Plans have been drafted to tackle many of these problems. Thorough reviews, such as the O’Neill AMR Reviews, provide a useful overview of these challenges and some mitigation measures. However, symptomatic of the O’Neill Reviews and AMR Action Plans is their under appreciation of the role that the environment plays in the selection, spread and transmission of AMR. Discussions of the environment are typically limited to the pharmaceutical manufacturing plants as a source of antibiotics and the role that sewage and farm run-off can play in dissemination of antibiotics. The discussions on these issues are superficial and narrow in scope.

Current AMR Action Plans and the O’Neill Reviews see antibiotics as the primary driver of AMR; hence, all mitigating measures are focused solely on reducing their use and release into the environment. This vision of the challenge of AMR is not helpful as it omits other AMR drivers that could be, on their own, more important than antibiotics for selecting, maintaining and spreading AMR in the environment, let alone as a collective group of AMR drivers.”

The full post can be accessed here.

Posted by Dr. Tim Sandle

World Antibiotic Awareness Week

World Antibiotic Awareness Week (16-20 November 2015) and the Antibiotic Guardian campaign. This is an annual event marked throughout Europe.

The objective for the 2015 Antibiotic Guardian campaign is for at least 100,000 healthcare professionals and members of the public to have committed to at least one pledge for prudent use of antibiotics on the Antibiotic Guardian website.

Pledge and post the following:

“I have pledged to be an #AntibioticGuardian. You can make a pledge too via http://www.antibioticguardian.com”

Antibiotic Guardian has been developed by Public Health England (PHE) in collaboration with Department of Health’s Expert Advisory Committee on Antimicrobial Resistance and Healthcare Associated Infections (ARHAI); the Department for Environment Food and Rural Affairs (DEFRA), the Devolved Administrations and professional bodies/ organisations towards the ‘One Health’ initiative.

Posted by Tim Sandle

Teixobactin: A New Class of Antibiotic

A new antibiotic has been discovered: Teixobactin. This in itself represents a significant breakthrough since it is the first new type of antibiotic to be discovered since the late 1980s. The discovery carries more significance especially in the era of antibiotic crisis, in which a rising number of microbial strains are evolving resistance to common antibiotic (and in the case of a narrower but more potent range, “multi-drug resistant” which infers resistance to more than one type of antibiotic.) Though we welcome the new antibiotic, their discovery reports are addressed in much of the popular media (and, unfortunately, in some of the scientific press) are always tainted by hyperbole. (And, unfortunately, in some of the scientific press) is tainted with hyperbole. 

This is the opening of a new paper by Tim Sandle, considering the issues around the headline grabbing new antibiotic discovery.

The reference is:

Sandle, T. (2015) Teixobactin: A New Class of Antibiotic, SOJ Microbiology & Infectious Diseases, 3 (1): 1-2

To view a copy, please see: Antibiotic

Posted by Tim Sandle

Emergence of new antibiotics

Resistance also increases the cost of health care with lengthier stays in hospital and more intensive care required. This one aspect has seen a step-forward in relation to the unveiling of two new antibiotics. The first of the new antibiotics is called Dalvance. This is an intravenous drug that can treat skin and soft tissue infections. The second drug is called Oritavancin. Oritavancin is a lipoglycopeptide with bactericidal activity against Gram-positive bacteria. The drug was the subject of a clinical trial study led by G. Ralph Corey of Duke University, and the success was announced in the June 2014 edition of the journal The New England Journal of Medicine.

Although the emergence of two new antibiotics is promising, and will no doubt save many lives, their emergence represents also highlights the lack of progress in relation to other fields of medicine and how far there is still to go in the battle against bacterial ‘superbugs’.

A review of two new classes of antibiotics to treat skin infections forms the basis of a paper by Tim Sandle for the journal Clinical Journal of Microbiology and Pathology.

The reference is:

Sandle, T. (2014) Emergence of New Antibiotics. J Micro Patho Volume 1, Issue 1: 001

The paper can be accessed here.

Posted by Tim Sandle

WHO’s first global report on antibiotic resistance

WHO has released its first global report on antimicrobial resistance. The report indicates “resistance is occurring across many different infectious agents” but the primary focus of the report is on “antibiotic resistance in seven different bacteria responsible for common, serious diseases such as bloodstream infections (sepsis), diarrhoea, pneumonia, urinary tract infections and gonorrhea.” What appears to be of greatest concern is the worldwide presence of bacteria resistant to carbapenems, hard-hitting, “last resort” antibiotics.

The new WHO report provides the most comprehensive picture of antibiotic resistance to date, with data from 114 countries.

A new report by WHO–its first to look at antimicrobial resistance, including antibiotic resistance, globally–reveals that this serious threat is no longer a prediction for the future, it is happening right now in every region of the world and has the potential to affect anyone, of any age, in any country. Antibiotic resistance–when bacteria change so antibiotics no longer work in people who need them to treat infections–is now a major threat to public health.

“Without urgent, coordinated action by many stakeholders, the world is headed for a post-antibiotic era, in which common infections and minor injuries which have been treatable for decades can once again kill,” says Dr Keiji Fukuda, WHO’s Assistant Director-General for Health Security. “Effective antibiotics have been one of the pillars allowing us to live longer, live healthier, and benefit from modern medicine. Unless we take significant actions to improve efforts to prevent infections and also change how we produce, prescribe and use antibiotics, the world will lose more and more of these global public health goods and the implications will be devastating.”

Key findings of the report

The report, "Antimicrobial resistance: global report on surveillance", notes that resistance is occurring across many different infectious agents but the report focuses on antibiotic resistance in seven different bacteria responsible for common, serious diseases such as bloodstream infections (sepsis), diarrhoea, pneumonia, urinary tract infections and gonorrhoea. The results are cause for high concern, documenting resistance to antibiotics, especially “last resort” antibiotics, in all regions of the world.

Key findings from the report include:

• Resistance to the treatment of last resort for life-threatening infections caused by a common intestinal bacteria, Klebsiella pneumoniae–carbapenem antibiotics–has spread to all regions of the world. K. pneumoniae is a major cause of hospital-acquired infections such as pneumonia, bloodstream infections, infections in newborns and intensive-care unit patients. In some countries, because of resistance, carbapenem antibiotics would not work in more than half of people treated for K. pneumoniae infections.
• Resistance to one of the most widely used antibacterial medicines for the treatment of urinary tract infections caused by E. coli–fluoroquinolones–is very widespread. In the 1980s, when these drugs were first introduced, resistance was virtually zero. Today, there are countries in many parts of the world where this treatment is now ineffective in more than half of patients.
• Treatment failure to the last resort of treatment for gonorrhoea–third generation cephalosporins–has been confirmed in Austria, Australia, Canada, France, Japan, Norway, Slovenia, South Africa, Sweden and the United Kingdom. More than 1 million people are infected with gonorrhoea around the world every day.
• Antibiotic resistance causes people to be sick for longer and increases the risk of death. For example, people with MRSA (methicillin-resistant Staphylococcus aureus) are estimated to be 64% more likely to die than people with a non-resistant form of the infection. Resistance also increases the cost of health care with lengthier stays in hospital and more intensive care required.

Ways to fight antibiotic resistance

The report reveals that key tools to tackle antibiotic resistance–such as basic systems to track and monitor the problem–show gaps or do not exist in many countries. While some countries have taken important steps in addressing the problem, every country and individual needs to do more.

Other important actions include preventing infections from happening in the first place–through better hygiene, access to clean water, infection control in health-care facilities, and vaccination–to reduce the need for antibiotics. WHO is also calling attention to the need to develop new diagnostics, antibiotics and other tools to allow healthcare professionals to stay ahead of emerging resistance.

This report is kick-starting a global effort led by WHO to address drug resistance. This will involve the development of tools and standards and improved collaboration around the world to track drug resistance, measure its health and economic impacts, and design targeted solutions.

How to tackle resistance

People can help tackle resistance by:

• using antibiotics only when prescribed by a doctor;
• completing the full prescription, even if they feel better;
• never sharing antibiotics with others or using leftover prescriptions.

Health workers and pharmacists can help tackle resistance by:

• enhancing infection prevention and control;
• only prescribing and dispensing antibiotics when they are truly needed;
• prescribing and dispensing the right antibiotic(s) to treat the illness.

Policymakers can help tackle resistance by:

• strengthening resistance tracking and laboratory capacity;
• regulating and promoting appropriate use of medicines.

Policymakers and industry can help tackle resistance by:

• fostering innovation and research and development of new tools;
• promoting cooperation and information sharing among all stakeholders.

The report–which also includes information on resistance to medicines for treating other infections such as HIV, malaria, tuberculosis and influenza–provides the most comprehensive picture of drug resistance to date, incorporating data from 114 countries.

Highlights of the report by WHO region

WHO African Region

The report reveals major gaps in tracking of antibiotic resistance in the WHO African Region, with data gathered in a limited number of countries. While it is not possible to assess the true extent of the problem with the data available, that which is available is worrying. Significant resistance is reported for several bacteria that are spread in hospitals and communities. This includes significant E. coli resistance to third generation cephalosporins and fluoroquinolones–two important and commonly used types of antibacterial medicine. In some parts of the region, as many as 80% of of Staphylococcus aureus infections are reported to be resistant to methicillin (MRSA), meaning treatment with standard antibiotics does not work.

WHO Region of the Americas

The Pan American Health Organization, WHO’s Regional Office for the Americas, coordinates the collection of data on antibiotic resistance from hospitals and laboratories in 21 countries in the Region. The results show high levels of E. coliresistance to third generation cephalosporins and fluoroquinolones–two important and commonly used types of antibacterial medicine–in the Americas. Resistance to third generation cephalosporins in K. pneumoniae is also high and widespread. In some settings, as many as 90% of Staphylococcus aureus infections are reported to be methicillin-resistant (MRSA), meaning treatment with standard antibiotics does not work.

WHO Eastern Mediterranean Region

Data in the report show extensive antibiotic resistance across the WHO Eastern Mediterranean Region. In particular, there are high levels of E. coli resistance to third generation cephalosporins and fluoroquinolones–two important and commonly used types of antibacterial medicine. Resistance to third generation cephalosporins in K. pneumoniae is also high and widespread. In some parts of the Region, more than half of Staphylococcus aureus infections are reported to be methicillin-resistant (MRSA), meaning that treatment with standard antibiotics does not work. The report reveals major gaps in tracking of antibiotic resistance in the Region. WHO’s Regional Office for the Eastern Mediterranean has identified strategic actions to contain drug resistance and is supporting countries to develop comprehensive national policies, strategies and plans.

WHO European Region

The report reveals high levels of resistance to third generation cephalosporins in K. pneumoniae throughout the WHO European Region. In some settings, as many as 60% of Staphylococcus aureus infections are reported to be methicillin-resistant (MRSA), meaning that treatment with standard antibiotics does not work. The report finds that although most countries in the EU have well-established national and international systems for tracking antibiotic resistance, countries in other parts of the Region urgently need to strengthen or establish such systems. WHO’s Regional Office for Europe and its partners are supporting these countries through the newly-established Central Asian and Eastern European Surveillance of Antimicrobial Resistance network (CAESAR). The aim of CAESAR is to set up a network of national systems to monitor antibiotic resistance in all countries of the WHO European Region for standardized data collection so that information is comparable.

WHO South-East Asia Region

The available data reveal that antibiotic resistance is a burgeoning problem in WHO’s South-East Asia Region, which is home to a quarter of the world’s population. The report’s results show high levels of E. coli resistance to third generation cephalosporins and fluoroquinolones—two important and commonly used types of antibacterial medicine–in the Region. Resistance to third generation cephalosporins in K. pneumoniae is also high and widespread. In some parts of the Region, more than one quarter of Staphylococcus aureus infections are reported to be methicillin-resistant (MRSA), meaning that treatment with standard antibiotics does not work. In 2011, the health ministers of the Region articulated their commitment to combat drug resistance through the Jaipur Declaration. Since then, there has been growing awareness of the need for appropriate tracking of drug resistance, and all countries have agreed to contribute information to a regional database. Dr Poonam Khetrapal Singh, WHO Regional Director for South-East Asia, has identified drug resistance as a priority area of WHO’s work in the Region.

WHO Western Pacific Region

Collaboration on tracking of antibiotic resistance between countries in the WHO Western Pacific Region was established in the 1980s, but suffered setbacks following a series of emergencies in the early 2000s. However, many countries in the region have long-established national systems for tracking resistance. Recently, WHO’s Regional Office for the Western Pacific has taken steps to revive the regional collaboration. The report reveals high levels of E. coli resistance to fluoroquinolones–an important and commonly used type of antibacterial medicine–in the Region. Resistance to third generation cephalosporins in K. pneumoniae is also widespread. In some parts of the Region, as many as 80% of Staphylococcus aureus infections are reported to be methicillin-resistant (MRSA), meaning that treatment with standard antibiotics does not work.

The report can be accessed in full here.



Posted by Tim Sandle

Tackling antimicrobial resistance

The looming disaster of antimicrobial resistance is a well-known one, but what is European strategy for tackling this ‘catastrophic threat’?  In an article for Laboratory News Tim Sandle examines the strategy and discusses the key implications.The link for the article is located below.

Antibiotic resistance more typically occurs when a sub-population of a microorganism survive the treatment of a bacterial population with an antimicrobial. Here as the sub-population regenerates, resistance is transferred to newly formed clones. It is an increasing problem, especially in the hospital setting.

The European Union has drawn up a strategy to slow-down the rate of antibiotic resistance. This strategy is dissected in the article, along with the global implications of the antibiotic resistance threat. The article can be accessed, for free, on-line here: Lab News.

The reference is:

Sandle, T. (2014) Taking on the resistance, Laboratory News, March 2014, pp20-21

Posted by Tim Sandle

Addressing antibiotic resistance

Humans face the very real risk of a future without antibiotics. The implications of this are that life expectancy could fall due to people dying from diseases that are readily treatable today. One concern for the future is the re- emergence of diseases that are ‘officially’ extinct, such as tuberculosis (a disease caused by Mycobacterium tuberculosis). The other concern is that without effective antibiotics, human society will no longer be able to conduct the types of medical procedures that can lead to immunosuppression. Such therapies include those for cancer treatments or to address autoimmune disorders.

With regard to this serious issue, Tim Sandle has written a review article for the journal Microbiology & Infectious Diseases. The article can be accessed on-line here: SOJ Microbiology and Infectious Diseases or, alternatively, contact Tim Sandle.

Sandle, T. (2014) Novel Methods to Address Antimicrobial Resistance, SOJ Microbiology & Infectious Diseases, 2 (1): 2-3

Posted by Tim Sandle

New generation of biocides

A new generation of antibacterial materials have been developed. These are synthetic materials covered in nano-spikes resembling those found on insect wings. The material is an effective killer of microorganisms.

As reported in the Scientist, the material is a type of black silicon. The synthetic material is studded with needle-shaped nanostructures which serve as a potent antibacterial agent. Test have shown that the material can kill some 450,000 cells per minute in just one square centimeter.

Remarkably, what has been shown is that certain nanostructures can kill bacteria based on texture alone. The particles physically distort the microbial cell wall and break open the cell, thereby killing the microorganism.

The idea for the material, Sci News notes, came about after researchers recognized that dragonflies (Diplacodes bipunctata) also have similar nanopillars on their wings, and that black silicon was known for a similar nano-texture. The material is manufactured using bespoke ion-beam technology.

The importance of the new material is that it is potentially transferable to any material or fabric, and thus it has a great potential application in hospitals. A key advantage is that, unlike antibiotics, it would be far more difficult for bacteria to evolve structural resistance to black silicon.

The research was led by Elena Ivanova of Swinburne University of Technology in Australia, and the findings have been published in the journal Nature Communications. The article is titled "Bactericidal activity of black silicon".

Posted by Tim Sandle