Research

>Gene-editing tool now being used to develop better antibiotics

January 11, 2019.  https://www.nature.com/articles/s41564-018-0327-z 
More brilliant innovative thinking from University of Wisconsin–Madison! Jason Peters, a UW–Madison professor of pharmaceutical sciences, and his collaborators at the University of California, San Francisco  developed the new system to figure out new weaknesses in the disease-causing pathogens.

The gene-editing tool CRISPR has been repurposed to study which genes are targeted by particular antibiotics. The technique, Mobile-CRISPRi, allows scientists to screen for antibiotic function in a wide range of pathogenic bacteria. Using a form of bacterial sex, known as conjugation, the researchers transferred Mobile-CRISPRi from common laboratory strains into diverse bacteria - allowing researchers to identify how antibiotics inhibit the growth of pathogens. 


Salmonella Bacteria

>Bacteria resistant to antibiotics found in breast milk but Scientists at Helsinki University thinks breast milk can may still help protect babies from dangerous bugs.

The paper, published in the journal Nature Communications, is titled: “Maternal gut and breast milk microbiota affect infant gut antibiotic resistome and mobile genetic elements.”  Download .pdf

Katariina Parnanen    PhD student, University of Helsinki    Sep 24, 2018
“We discovered that despite the fact that breast milk has relatively high concentrations of resistance genes, it turns out that babies who have been breastfed for at least six months, have lower abundances of resistance genes compared to babies who aren’t breastfed.”

Antibiotic resistance has been extensively discussed in the media in recent years, and for a good reason, since antibiotic resistant bacteria pathogens have become increasingly common. Babies don’t have fully developed immune systems and antibodies to protect against infections the same way as adults do, so infections caused by resistant bacteria can have serious health effects in infants if treatment fails. Sadly, it has been estimated that more than 200 000 infants die annually due to resistant septic infections. I hope that our paper can give insight into the development of the infant resistome and that we as a scientific community will find possible solutions to the resistance crisis at hand.

Antibiotic resistance has been the focus of our research group for a long time. One day, my colleagues and I started talking about breast milk during a break. I had thought that breast milk was sterile but I found out, to my big surprise, that I was wrong - one drop of breast milk has dozens of bacteria and other microbes. I thought it was fascinating and I began to wonder if there were also antibiotic resistance genes in breast milk.

A few years passed and many new publications about the infant gut resistome came out. All of them told the same story, small babies, even the ones who have never had antibiotics, have even more resistant bacteria than adults, who on average have had several courses of antibiotics during their life. Still, nobody seemed to know where these resistance genes came from. We decided to dig deeper into this problem.

Read more at:  https://naturemicrobiologycommunity.nature.com/users/170942-katariina-pa...

>Significant breakthrough by scientists at Manchester University developing the first non-antibiotic drug to successfully treat tuberculosis in animals.

https://www.manchester.ac.uk/discover/news/scientists-develop-new-drug-t...
11.09.2018.  One in three people across the world are thought to be infected with the TB, an infectious disease. It is most common in Africa, India and China, but on the rise in the UK with London often described as the TB capital of Europe.  About 1.7 million worldwide die from the TB each year and 7.3 million people were diagnosed and treated in 2018, up from the 6.3 million in 2016.  A TB vaccine was developed over 100 years ago but for the past six decades doctors have been able to use antibiotics against this killer disease. Now the TB bacteria are increasingly developing drug-resistance. 
 
The breakthrough: Mycobacterium Tuberculosis secretes molecules called Virulence Factors -- the cell's secret weapon -which block out the immune response to the infection, making it difficult to treat. The Manchester team identified one Virulence Factor called MptpB as a suitable target, which when blocked allows white blood cells to kill Mycobacterium Tuberculosis in a more efficient way. The drug works by targeting Mycobacterium tuberculosis' defences rather than the bacteria itself and, importantly, it can also take out its increasingly commonly antibiotic resistant strains. As there is nothing similar in humans the MptpB compound which blocks it is not toxic to the human cells. "Because the bacteria hasn't been threatened directly, it is less likely to develop resistance against this new agent, and this will be a major advantage over current antibiotics, for which bacteria had already become resistant.
 
The team hope the compound, developed after 10 years of painstaking research, will be trialled on humans within three to four years. The programme is funded by the Medical Research Council (MRC). 
Source: Materials provided by University of Manchester

>Review of Evidence on Antimicrobial Resistance and Animal Agriculture in Developing Countries

http://a4nh.cgiar.org/files/2015/06/EoD_Consultancy_June15_Ag_Related_AM...

This report has been produced by the International Livestock Research Institute (ILRI) for Evidence on Demand with the assistance of the UK Department for International Development (DFID) contracted through the Climate, Environment, Infrastructure and Livelihoods Professional Evidence and Applied Knowledge Services (CEIL PEAKS) programme, jointly managed by DAI (which incorporates HTSPE Limited) and IMC Worldwide Limited.

>Inappropriate Antibiotic Prescriptions Highest Among Urgent Care Facilities

-According to a study recently published in JAMA Internal Medicine.
https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2...
July 27, 2018. Citation: Palms DL, Hicks LA, Bartoces M, et al. Comparison of antibiotic prescribing in retail clinics, urgent care centers, emergency departments, and traditional ambulatory care settings in the United States [published online July 16, 2018]. JAMA Intern Med.doi:10.1001/jamainternmed.2018.1632

The inappropriate prescribing of antibiotics varies among retail clinics, urgent care centers, medical offices, and emergency departments, according to a study recently published in JAMA Internal Medicine. 

Antibiotic overprescription was highest among urgent care centers.  Of 2.7 million visits to urgent care centers, 1,062,477 (39.0%) visits resulted in the prescription of antibiotics (95% CI, 39.0%-39.1%). Additionally, antibiotics were prescribed in 21,177 (36.4%) of 58,206 visits to retail clinics (95% CI 36.0%-36.8%), 660,450 (13.8%) of 4.8 million visits to emergency departments (95% CI 13.8%-13.8%), and 10,580,312 (7.1%) of 148.5 million visits to medical offices (95% CI 7.1%-7.1%).

Respiratory diagnoses related to inappropriate antibiotic prescription resulted in 441,605 (16%) visits to urgent care facilities, 10,009 (17%) visits to retail clinics, 257,010 (5%) of visits to emergency departments, and 9,203,276 (6%) visits to medical offices. Inappropriate antibiotic prescriptions were highest among urgent care facilities (45.7%), with emergency departments (24.6%), medical offices (17.0%), and retail clinics (14.4%).

The researchers concluded, “There was substantial variability between settings in the percentage of visits at which antibiotics were prescribed among all visits and among visits for antibiotic-inappropriate respiratory diagnoses. These patterns suggest differences in case mix and evidence of antibiotic overuse, especially in urgent care centers …. The finding of the present study that antibiotic prescribing for antibiotic-inappropriate respiratory diagnoses was highest in urgent care centers suggests that unnecessary antibiotic prescribing nationally in all outpatient settings may be higher than the estimated 30%.”

>Researchers transform old drug into new fighter against antibiotic resistance.  

https://www.cbc.ca/news/canada/hamilton/antibiotic-drug-resistance-solut...
6 March 2017. Pentamidine makes antibiotics effective when combined, McMaster University researcher says…

>Natural actives for wound healing: A review.

https://www.ncbi.nlm.nih.gov/pubmed/29722075
2 May 2018: Format: Abstract. Phytother Res.  doi: 10.1002/ptr.6102. [Epub ahead of print] Artem Ataide J1, Caramori Cefali L2, Machado Croisfelt F2, Arruda Martins Shimojo A3, Oliveira-Nascimento L4, Gava Mazzola P4.
Nature has been a source of medicinal treatments for thousands of years, with the use of plants as prototypes for drug development and for the extraction of active compounds. Skin injuries occur regularly in everyday life, and the human skin has the ability to promote repair spontaneously under healthy conditions. However, some intrinsic and external factors may interfere with skin’s natural ability, leading to non-healing lesions and chronic wounds, which directly affect health and quality of life. Thus, attention should be given to this health problem, using an appropriated management when necessary. In this scenario, phytotherapy may be an option for cutaneous wound treatment, although further high-quality studies are needed to firmly establish the clinical efficacy of plants. This article reviews traditionally used natural actives for wound healing, highlighting their characteristics and mode of action
PMID:   29722075

>High levels of antibiotic resistance found worldwide, new surveillance data shows

https://www.who.int/mediacentre/news/releases/2018/antibiotic-resistance...
WHO News release 29 .01.2018
First Release of Surveillance Data on antibiotic resistance reveals high levels of resistance to a number of serious bacterial infections in both high- and low-income countries.  WHO’s new Global Antimicrobial Surveillance System (GLASS), launched in October 2015,  reveals widespread occurrence of antibiotic resistance among 500 000 people with suspected bacterial infections across 22 countries.

The most commonly reported resistant bacteria were Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Streptococcus pneumoniae, followed by Salmonella spp. The system does not include data on resistance of Mycobacterium tuberculosis, which causes tuberculosis (TB), as WHO has been tracking it since 1994 and providing annual updates in the Global tuberculosis report.

 Among patients with suspected bloodstream infection, the proportion that had bacteria resistant to at least one of the most commonly used antibiotics ranged tremendously between different countries – from zero to 82%. Resistance to penicillin – the medicine used for decades worldwide to treat pneumonia – ranged from zero to 51% among reporting countries. And between 8% to 65% of E. coli associated with urinary tract infections presented resistance to ciprofloxacin, an antibiotic commonly used to treat this condition.

 “The report confirms the serious situation of antibiotic resistance worldwide  Some of the world’s most common – and potentially most dangerous – infections are proving drug-resistant” ,says Dr Marc Sprenger, director of WHO’s Antimicrobial Resistance Secretariat. “And most worrying of all, pathogens don’t respect national borders. That’s why WHO is encouraging all countries to set up good surveillance systems for detecting drug resistance that can provide data to this global system.”

 To date, 52 countries (25 high-income, 20 middle-income and 7 low-income countries) are enrolled in WHO’s Global Antimicrobial Surveillance System. For the first report, 40 countries provided information about their national surveillance systems and 22 countries also provided data on levels of antibiotic resistance.

 “The report is a vital first step towards improving our understanding of the extent of antimicrobial resistance. Surveillance is in its infancy, but it is vital to develop it if we are to anticipate and tackle one of the biggest threats to global public health,” says Dr Carmem Pessoa-Silva, who coordinates the new surveillance system at WHO. GLASS will help estimate disease burden, plan diagnostic and treatment services, monitor the effectiveness of control interventions, and design effective treatment regimens to address and prevent future resistance.

 Data presented in this first GLASS report vary widely in quality and completeness. Some countries face major challenges in building their national surveillance systems, including a lack of personnel, funds and infrastructure. GLASS is helping to standardize the way that countries collect data and enable a more complete picture about antimicrobial resistance patterns and trends. 
NB: All data produced by GLASS is available free online and will be updated regularly.

>Resistance Fighter.

https://www.the-scientist.com/profile/resistance-fighter-35388
Stuart Levy has spent a lifetime studying mechanisms of antibiotic resistance and crusading to abolish the use of antibiotics in animal feed.

>High or Low Doses - which is better?

http://science.sciencemag.org/content/352/6287/758.full
Evolutionary biologists are challenging old dogmas about the way antibiotics should be used. Combined with the resistant microbes that have emerged more recently in hospitals and the wider community, this means that in many infections, a few resistant bacteria may be present from the start, Read says. The key issue is not keeping resistance from developing—it's stopping its spread. This is why high doses of antibiotics may backfire: Resistance usually comes with a “fitness cost” that limits growth. A bacterium may have to expend extra energy to pump out an antibiotic, for instance. High doses of antibiotics will kill susceptible bacteria rapidly, leaving resistant ones without any competition—a phenomenon known as competitive release - and giving them the upper hand.  With lower doses, in contrast, resistant bacteria would have to compete with susceptible bacteria, and would remain a minority. An antibiotic given this way simply holds the bacteria in check: The immune system—which seems able to kill resistant and susceptible bacteria equally well—then mops up the infection.

A One Health approach is needed to fight antibiotic resistance – everyone has a role to play to improve antibiotic prescribing and use. Join the global fightback against AMR