Tuesday 29 August 2017

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.


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 IllnessScientific Reports, 2017; 7 (1) DOI: 10.1038/s41598-017-06738-3Posted by Dr. Tim Sandle

Wednesday 23 August 2017

Aging pharmaceutical facilities

The aging facility presents various microbiological contamination risks (and some more recent pharmaceutical product recalls associated with microbial contamination have related to older facilities). These risks include:

Poor facility management

General poor upkeep, leading to peeling paint or torn lagging, presents opportunities for microbial contamination to occur. Risks are more acute for spore forming organisms, such as Bacillus and related genera and with fungal spores.

Changes to facility use

Changes to facility use, in terms of people and equipment, present potential risks. For example, if a facility was designed for a specific number of personnel and the operational level increases, this could present new challenges for contamination control, especially where cleanroom occupancy rates increase (given that people are the primary contamination source within cleanroom environments).

Furthermore, changes to production equipment and layouts can affect airflow directions, especially in relation to aseptic processing. The addition of more equipment to a working space can cause greater heat generation, placing a greater heat load upon air conditioning. If environments are not suitably controlled, this can cause personnel to shed higher levels of skin and thus increase the microbial load into the cleanroom. Additionally, as amounts of equipment increase this can make areas more difficult to clean and disinfect simply because operators cannot maneuver around the equipment footprint. Poor air circulation also brings with it other risks, such as undetected fungal growth A related area is with the air supply system from variable air volume boxes. Here the air volumes supplied into cleanrooms may not be as originally designed. This not only affects air supply volumes but also air exchange rates and clean-up times. These physical parameters are essential for keeping particles (viable and inert) in suspension and for removing them from cleanrooms. This factor can be overlooked because most cleanroom monitoring systems assess pressure differentials rather than air supply volumes.

Degradation to fabric

Cracks in walls, tears to vinyl, and the degradation of construction joints can lead to microbial contamination events. Here unclean areas can become exposed to cleanrooms and microorganisms can reside in cracks. Where cracks occur, cleaning solutions will often not be able to penetrate.

A further risk with weakened or broken joints is that high airflow velocities can drag unsuitable air into cleanrooms from plant areas. This can lead to turbulent mixing and the potential entailment of contamination. This can be assessed through airflow visualization.

Regular inspection and a sound repair program can overcome these problems, together with the fitting of high quality seals such as compressed rubber gaskets.

Building void spaces

The voids between adjacent cleanrooms or between cleanrooms and the outside environment will accumulate dust, and within the dust there will be spore-forming microorganisms. Such environments will not have any impact unless they are disturbed. Here contamination will arise when facilities are modified, such as knocking through a wall in order to expand a cleanroom. Good control measures should be in place when modifications take place including partitioning off areas, vacuuming dust and regular cleaning followed by sporicidal disinfection.

Excerpted from the chapter: Risk Considerations for Aging Pharmaceutical Facilities:

Sandle, T. (2017) Risk and Microbiological Contamination, PDA Letter, Volime LIII (7),  (July 2017, pp8 at: https://www.pda.org/pda-letter-portal/archives/full-article/pda-summer-reading-for-2017

Posted by Dr. Tim Sandle

Sunday 20 August 2017

Key Challenges of Packaging and Labeling in Pharma Products

The Dire Issues of Barcodes and labeling

Barcodes are very standard tools that have been around for decades. Barcodes were first introduced and used in the Pharmaceutical Industry in the 1970’s. Many people do not truly know the critical role that barcodes must perform throughout society. When it comes to the pharmaceutical business, however; barcodes must be assigned to EACH and EVERY individual product before distribution.

Guest post by Marvin Magusara

According to HDMA Guidelines for Bar Coding in the Pharmaceutical Supply Chain, distributed by Cardinal Health, Inc. with permission from HDMA; The FDA (Food and Drugs Administration), culminated a two-year review process back in February 2004. This two-year review process enforced a rule that required barcoding of the NDC (National Drug Code) on the majority of pharmaceutical and biological packages.

What is this Nation Drug Code? What role does it play and why is it imperative

The National Drug Code, or NDC for short, is a 10-digit code assigned to all pharmaceutical products to help identify each individual item. A serious problem may arise when this code is incorrect or not applied as should be. The risk of counterfeiting becomes higher without the use of this coding. Pharmaceutical distribution becomes a lot easier with the NDC. The efficient computer systems can now systematically track and trace the outgoing, incoming, and even lost products worldwide.

The NDC is also necessary for labeling. If the label on a package is incorrect, laborers will unknowingly handle the wrong product. Laborers must be able to readily identify cases before processing them. The labels on the cases play an important role because it helps pharmaceuticals companies determine what kind of healthcare product is stored within the case. Homogeneous cases, or cases that harbor only one single product from the same lot, have to be labeled appropriately to identify the kind of product in the case, and how many are stored inside of the case.

It is no question as to whether this method implemented by the FDA is imperative or not. Of course, this conjures up another issue.

How must the National Drug Code be printed?

This question may seem simple. However, the answer is a complicated and complex one. NDC’s must be published in a DISTINCT and methodological order. If the barcode label is written incorrectly without quality assurance; the barcode will also be printed incorrectly and less likely to be looked over again.

The NDC is formulated by a series of numbers within three different formats. Within those formats, the numbers are separated by hyphens (Ex. 0001-4756-23). Each NDC, regardless of the number order, has to always equal up to 10 digits. It’s important to know that even one missing number could be detrimental to the packaging process.

Braille regulations and what they represent

Braille, as you may know, is a particular kind of language to help guide blind people through their daily lives. As sight seeing civilians, we may not show much concern for braille and the importance it has. However, pharmaceutical companies have to consider the idea of making sure all of their patients are satisfied with their product. The society of the blind is still prone to becoming sick due to weakened immune systems.

According to the European Directive 2004/27/EC – Article 56(a), all medicine that is being sold in the European Union must have the product name in Braille on the packaging.

Making sure Braille is printed correctly

The majority of the human population may not know how to read braille, however; the needs of the blind must be met appropriately when deciphering this particular language. A set of principles has been drawn between the EBU (European Blind Union) and the RNIB (Royal National Institute of Blind People) to make sure a provided braille code can be used in multiple European countries. This provided braille code will help many blind patients confirm that they have received the right package. A Braille inspection is a top priority.

Let’s take the time to speculate. Say, for instance, the braille code happened to be printed incorrectly. Not only would this depreciate the value of the pharmaceutical product, but it may also prove to be insufficient for the consumer or patient. A small, or rather, a huge mistake like misprinting could cause a well-known pharmaceutical company to lose out on millions or even billions of dollars. This speculation may sound farfetched, but unless the healthcare company itself thinks about the potential losses, mistakes will be made without a double-check.

Two specific types of pharmaceutical packaging

The way healthcare products are packaged can determine the general outcome of the effectiveness of the pharmaceutical medicine. According to Pharmaceutical Blister Packaging, Part 1, by Ron Pilchik; Packaging by itself has grown to become a $280 billion dollar industry. It has also become one of the largest industry sectors in the world.

There are people of different sizes, ages, abilities, and disabilities that can be affected by the way their medicine is packaged. The negligence of pharmaceutical laborers can cause the seal of a container to be broken or loosely sealed. Blister packaging has proven to be one of the most efficient ways of making sure medicine is free of contamination. It is also proven to keep medication fresh for a longer period of time, increasing the shelf life of the product. Blister packagings have become a universal kind of method to prolong the general effectiveness of healthcare products. This serves a great purpose in allowing consumers to feel confident about their medication. Another type of packaging is a bottle-shaped container.

The good and bad of blister and bottle packaging

As mentioned in the above paragraph, blister packaging helps conserve healthcare medicine for longer and better use. It also protects medication from becoming soiled by the water or by the air. Blister packaging makes it easier for the usually forgetful person to monitor when they have taken their medication. It may seem difficult to point out a negative aspect of blister packaging, however; this method of packaging actually proves to be an issue for the elder community. According to an internal source in the pharmaceutical business, pharmacists are often requested to extract the medication from the blister packages, and then slipping them into bottles. It must be understood that this is a timely process.

Bottle packaging makes it easier for consumers and patients to pour out the desired amount directly into a tool in their hands. Easy access is an important concept, however; this also means easy access for undesired elements. A bottle could very well chip or crack. This error in the package could go unseen. Some bottles containers have loose caps that are not correctly screwed on. With these issues in mind, it becomes easy to notice the big difference in between blister packaging and bottle packing.


Barcodes, labeling, printing, and packaging play important roles in the Pharmaceutical Industry while presenting their own challenges. The labels on case packages or mixed packages should represent what is contained on the inside. Braille should be formatted and printed efficiently to ensure the health and wellbeing of their blind patients are met. When health products are being packaged, the type of package should be considered for effectiveness and safety.

FDA cGMP for Medical Gases

New draft FDA guidance of interest "Current Good Manufacturing Practice for Medical Gases Guidance for Industry."

The introduction to the document reads: "This guidance is intended to assist manufacturers of medical gases in complying with applicable current good manufacturing practice (CGMP) regulations (21 CFR parts 210 and 211).  Medical gases are generally regulated as finished pharmaceuticals and are subject to CGMP requirements regardless of the processing stage. Compliance with applicable CGMP requirements helps to ensure the safety, identity, strength, quality, and purity of medical gases. Medical gases that are not manufactured, processed, packed, or held according to applicable CGMP requirements can cause serious injury or death."

To access the document, go to FDA compressed gas

Posted by Dr. Tim Sandle

Friday 18 August 2017

Cranberries may aid the gut microbiome

Using the model beneficial bacterium bifidobacteria, researchers tested the hypothesis that cranberries might be a candidate for a new supplement to boost gut health. Bifidobacteria are found in adults to some degree but the highest concentrations are found in the gut microbiome of newborn, breast-fed babies.

This study provides the first evidence that certain bifidobacteria do consume xyloglucans, and the ones that do exhibit a special metabolism that is not typical. Specifically, these bifidobacteria produce formic acid while consuming xyloglucans and less lactic acid than is typically secreted.


Ezgi Özcan, Jiadong Sun, David C. Rowley, David A. Sela. A human gut commensal ferments cranberry carbohydrates to produce formateApplied and Environmental Microbiology, 2017; AEM.01097-17 DOI: 10.1128/AEM.01097-17

Posted by Dr. Tim Sandle

Wednesday 16 August 2017

Helium ions reveal how viruses attack bacteria

Bacteria and viruses can be imaged with helium ions in contrast to electrons which are the standard workhorse in nanoscale microscopy, report scientists. Helium ions, being more massive than electrons, can be focused to a much tighter spot down to the atomic length scales. By measuring the electrons generated by the ion bombardment, an image can be formed from the sample with biological features visible below the nanometer (one billionth of a meter) length.

The novel technique, called helium ion microscopy (HIM), was used to image hard-to-see interaction between bacteria and viruses infecting bacteria, or so called bacteriophages. These phages are currently actively considered as a novel "smart weapon" against bacterial infections, which are becoming more and more difficult to treat with traditional antibiotics. The images demonstrated in clear images the different stages of how the phages in question attacked the bacteria (E. coli), for example showing the process where the virus has latched onto the bacterial surface, grabbing it with a tentacle like structure, and being in the process of injecting its genome into the bacterial cell.

In addition to imaging, the researchers also demonstrated that the ions can be used as a nanoscale scalpel, to cut portions off individual bacterial cells, or to reveal bacterial colonies under the surfaces of samples. They feel confident that HIM offers many more possibilities in the future to help to study microbes and viruses in their natural state, interacting with each other and other cells.


Miika Leppänen, Lotta-Riina Sundberg, Elina Laanto, Gabriel Magno de Freitas Almeida, Petri Papponen, Ilari J. Maasilta. Imaging Bacterial Colonies and Phage-Bacterium Interaction at Sub-Nanometer Resolution Using Helium-Ion MicroscopyAdvanced Biosystems, 2017; 1700070 DOI: 10.1002/adbi.201700070

Posted by Dr. Tim Sandle

Sunday 13 August 2017

Pharmig News

The latest edition of Pharmig News has been published. This is edition #68.

Inside the issue is part 1 of Pharmig’s survey of best practices for culture media, a regulatory news round-up, the chairman’s perspective, review of ‘Making Pharmaceuticals’, and news on training courses…and more!

Copies have been sent to member organizations. For details on how to get hold of a copy, please email: info@pharmig.org.uk

Sandle, T. (2017) Industry practices relating to culture media use: The Pharmig survey (Part 1), Pharmig News, No. 68, pp2-7

Posted by Dr. Tim Sandle

FDA unveils plan to eliminate orphan designation backlog

U.S. Food and Drug Administration unveiled a strategic plan to eliminate the agency’s existing orphan designation request backlog and ensure continued timely response to all new requests for designation with firm deadlines. The agency’s Orphan Drug Modernization Plan comes a week after FDA Commissioner Scott Gottlieb committed to eliminating the backlog within 90 days and responding to all new requests for designation within 90 days of receipt during his testimony before a Senate subcommittee.

As authorized under the Orphan Drug Act, the Orphan Drug Designation Programprovides orphan status to drugs and biologics that are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases, which are generally defined as diseases that affect fewer than 200,000 people in the United States. Orphan designation qualifies the sponsor of the drug for various development incentives, including tax credits for clinical trial costs, relief from prescription drug user fee if the indication is for a rare disease or condition, and eligibility for seven years of marketing exclusivity upon approval. A request for orphan designation is one step that can be taken in the drug development process and is different than the filing of a marketing application with the FDA.

Currently, the FDA has about 200 orphan drug designation requests that are pending review. The number of orphan drug designation requests has steadily increased over the past five years. In 2016, the FDA’s Office of Orphan Products Development received 568 new requests for designation – more than double the number of requests received in 2012. The increased interest in the program is a positive development for those with rare diseases and under this new plan, the agency remains committed to advancing the program to ensure it can efficiently and adequately review these requests.

This is the first element of several efforts the FDA will undertake under its new “Medical Innovation Development Plan,” which is aimed at ensuring that the FDA’s regulatory tools and policies are modern, risk based, and efficient. The goal of the plan is to seek ways the FDA can help facilitate the development of safe, effective and transformative medical innovations that have the potential to significantly impact disease and reduce overall health care costs.

This is an edited version of the FDA press release, full details can be found here.

Posted by Dr. Tim Sandle

Pharmig News #67

Posted by Dr. Tim Sandle

Saturday 12 August 2017

Single Entity Injectable Drug Products

The FDA is requiring the removal of ratio expressions of strength from the labeling of single-entity injectable drug products (i.e., drug products that contain only one active ingredient) and replacement with the amount per unit of volume (e.g., mg/mL).

For example, Epinephrine Injection 1:1,000 will now be labeled as Epinephrine Injection 1 mg/mL. The FDA is requiring the changes to help prevent medication errors related to strength being expressed as a ratio on labeling. There have been several reports of medication errors indicating that ratio expressions are confusing to health care providers and contributed to the errors. Some of the medication errors resulted in serious adverse outcomes, including death. The United States Pharmacopeia (USP) instituted a new labeling standard in an effort to reduce medication errors related to confusion with ratio expressions.

This revision affects Epinephrine Injection, Isoproterenol Hydrochloride Injection, and Neostigmine Methylsulfate Injection.

For further details see: FDA

Posted by Dr. Tim Sandle

Wednesday 9 August 2017

GMP Short Notice and Unannounced Inspections

An interesting blog post from the UK MHRA:

The Human Medicines Regulations 2012 as amended; regulation 325 ‘Rights of Entry’ states that an inspector may at any reasonable time enter premises. This allows for the MHRA to perform inspections both at short notice (may be a few days) or unannounced (no notice given). The use of these inspection types allows us to investigate issues that pose a significant risk to public health without obstruction and to work efficiently. We spend a lot of time planning and scheduling inspections but unfortunately there are times when things don’t go to plan and we can find ourselves with the following scenarios:
  1. There are times when we have no choice for logistical or health & safety reasons but to cancel or postpone a planned inspection at very short notice (for example because an inspector can no longer travel and there is no other available staff to back fill).
  2. A planned inspection finishes early or is postponed at the last minute (for example if a site is found not to ready to be inspected or an incident at the site means we can no longer inspect).
  3. Risk information dictates a change to the prioritisation of an inspection.
  4. A last-minute change to meeting requirements means some inspectors are then free to inspect.
See more at: MHRA

Posted by Dr. Tim Sandle

Monday 7 August 2017

New book: Aseptic and Sterile Processing: Control, Compliance and Future Trends

New book: Aseptic and Sterile Processing: Control, Compliance and Future Trends. Edited by Tim Sandle and Edward C. Tidswell.

Sterile medical products comprise of medical devices, drugs, and biologics. Some are completed  by a terminal sterilization step, thousands of the sterile products found in hospitals, clinics and pharmacies are manufactured by aseptic processing.  These are products intended for patients who have weak or compromised immune systems. This means a contaminated product will the patient’s condition worse or result in death. This places a considerable emphasis upon environmental control and sterility assurance. Despite this concerns of regulatory agencies suggest weaknesses in adequately determining the risk factors that are presented to aseptic and sterile products processing.

To help to check against this rise in regulator concerns, DHI and PDA have published the most important text discussing aseptic and sterile manufacturing to be published in the last decade. The book considers the state of sterile products manufacturing both today and tomorrow. The book is edited by two leading experts in aseptic and sterile products manufacture: Dr. Tim Sandle and Dr. Edward Tidswell.

To produce this comprehensive text the editors sought out leading industry and academic figures to help reassess current risks and technologies, and to represent new developments in the field. The aim was to produce a book that was foremost practical, but also grounded in sound science. Among the subjects covered are contamination risks, regulations, bioburden control, endotoxin control, water systems, depyrogenation, filtration, microbial contamination risks to cleanrooms, environmental monitoring, aseptic process simulations, single-use disposable technology, disinfection, sterility testing, cleanroom operator controls, risk assessment, human error and rapid methods.

Among the subject matter experts enlisted are: David Hussong, James Agalloco, James Akers, Maik W. Jornitz, Teri C. Soli, James Vesper, Hal Baseman, Anne Marie Dixon-Heathman, Michael Miller, Mark Trotter, Karen Zink McCullough, Matts Ramstorp, Crystal Booth, Mark Hunter and others highly experienced in their specialist subjects.

The lessons from the leading practitioners are aimed squarely at those involved with aseptic and sterile processing. Such readers will be able take away many learning points and apply these principles to aseptic and sterile processing within the pharmaceutical and healthcare sectors. The book will also appeal to students of pharmaceutical sciences.

A central theme with the new book is that it is time for a new paradigm in relation to our understanding sterility, given that many microorganisms cannot be cultured. This places a renewed emphasis upon assurance and controls; a thorough science-based risk assessment of processes; and by taking advantage of the best available technologies.

Aseptic and Sterile Processing: Control, Compliance and Future Trends is available from the PDA Bookstore, at: https://store.pda.org/ProductCatalog/Product.aspx?ID=3850 

Santitization of Pharmaceutical Facilities

A new paper on cleaning and disinfecting pharmaceutical and healthcare facilities has been published. Here is the abstract:

Maintaining environmental control including microbiological contamination in a pharmaceutical manufacturing environment is primarily dependent on the facility sanitization program. Sanitization considerations are specific for facility rooms, equipment, and personnel. Sanitization comprises cleaning and disinfection. Cleaning is necessary prior to the application of disinfectant to enable sufficient contact time of the disinfecting agent with the surface. Disinfectants vary in their spectrum of activity, modes of action, sites of action in microorganisms, and efficacy. Disinfectants kill vegetative micro-organisms but do not necessarily kill bacterial spores. There are many different types and categorizations of disinfectants such as non-oxidizing disinfectants and oxydizing agents. Many pharmaceutical manufacturers will have two “in-use” disinfectants and a third disinfectant for major contamination incidents. Rotation of disinfectants is often implemented to satisfy the requirements of regulators. Cleaning and disinfection must be detailed in a Standard Operating Procedure (SOP) to ensure consistency of practice. The effectiveness of cleanroom sanitization is assessed through the site environmental monitoring program. Viable monitoring is undertaken using microbiological growth medium. Regulatory agencies expect the pharmaceutical manufacturer to have evaluated the efficacy of disinfectants. While suspension testing is useful for initial screening, comparative surface (or carrier) testing is more relevant. USP <1072> lists common materials used in clean rooms that should be considered when developing disinfectant surface testing. To demonstrate the effectiveness of a disinfectant, it must be challenged using a panel of organisms that is reflective of the natural microflora of the facility. The biocidal activity of the disinfectant should be taken into account when selecting the panel of organisms. The use of microbial isolates from the manufacturing facility is increasingly becoming a regulatory expectation. Surface tests cannot demonstrate the effect of a range of environmental factors in actual environmental conditions. Field trials are an important part of the qualification of a sanitizer to determine if cleaning techniques are suitable and if the cleaning frequencies of cleanrooms require modification.

The reference is:

Sandle, T. (2017) Santitization of Pharmaceutical Facilities, IVT Special Edition Utility Qualification Volume II, pp56-62

For further details, please contact Tim Sandle

Special cleaning and disinfection book offer for readers:


 Posted by Dr. Tim Sandle

Sunday 6 August 2017

Teixobactin - new antibiotic update

Scientists have produced new, effective and simplified forms of teixobactin - a new generation antibiotic which defeats multi-drug resistant infections such as MRSA - as part of a pioneering research effort to tackle antimicrobial resistance.
The team, led by Dr. Ishwar Singh at the University of Lincoln, UK, has pinpointed exactly which amino acid in the newly discovered teixobactin antibiotic makes it so successful at killing off harmful MRSA bacteria, which are resistant to many other antibiotics. The research team has adapted this rare molecule so that it can be easily used in the production of new drugs.
The breakthrough comes after the team successfully produced a number of synthetic derivatives of the highly potent teixobactin - hailed as a 'game-changer' in the fight against antimicrobial resistance - and became the first in the world to document its three-dimensional molecular make-up. These developments represent important steps to understanding how the powerful antibiotic functions and which building blocks are needed for it to work effectively.
Their newest study, which directly targets MRSA bacteria, overcomes a further barrier in the race to combat drug resistant bacteria.

Singh, a specialist in novel drug design and development from the University of Lincoln's School of Pharmacy, explained, "The scientific community has found it extremely difficult, time-consuming and expensive to synthetically produce the amino acid, enduracididine, which makes teixobactin so effective at killing a range of pathogens without detectable resistance.
"Teixobactin was first isolated from soil microorganisms (which do not grow under laboratory conditions) - the natural source of nearly all antibiotics developed since the 1940s - but in order for it to be developed as a potential treatment, several versions must be produced via chemical synthesis to overcome the hurdles of drug development. Last year we were successful in producing man-made forms of the antibiotic, but now we have increased its potency against MRSA. The key amino acid, enduracididine, is important for high potency but it has also been a bottleneck in the wider production of powerful teixobactin derivatives and their advancement as new drugs. We have now developed several potent molecules with very similar effects to natural teixobactin, and we believe this takes us a step closer towards the clinic."

MRSA is a type of bacteria that is resistant to many widely-used antibiotics, which means it is harder to treat than other infections. This 'superbug' mainly affects people who are staying in hospital and while they can usually be treated with certain antibiotics, concerns are growing around the world about the rate at which bacteria are developing resistance to existing drugs.
It has been predicted that by 2050 an additional 10 million people will succumb to drug resistant infections each year. The development of new antibiotics which can be used as a last resort when other drugs are ineffective is therefore a crucial area of study for healthcare researchers around the world.
The bacteria against which teixobactin is effective have, thus far, not shown any detectable resistance and given its mechanisms, scientists are also confident that resistance is unlikely to evolve in the future.
Singh is working with colleagues from the School of Life Sciences and the School of Chemistry at the University of Lincoln to develop teixobactin into a viable drug.
Dr. Edward Taylor, a lecturer in Life Sciences at Lincoln, said, "Antimicrobial resistance is spreading faster than the introduction of new antibiotics, which means there are major concerns about a possible health crisis. The recently discovered teixobactin has shown tremendous promise due to its potent activity, particularly against resistant pathogens such as MRSA, which is why it is the focus of important research here at Lincoln and around the world. Several other research groups substituted the rare enduracididine amino acid in teixobactin with commercially available building blocks, but the resulting products were much less active than the natural product. Our study aimed to find the most suitable replacement for this rare molecule, and we found that amino acids which have a similar structure and functional group were most effective."
The group found that three of the molecules they tested showed very promising activity against MRSA bacteria, and their research will now continue as they aim to produce several versions of teixobactin which could eventually become commercially available drugs.
The study is published in the Royal Society of Chemistry journal, Chemical Communications.

Special offers