Tag: antibiotic resistance

Categories : Diseases, Syndromes and ConditionsTags :

International Travellers at Risk of MDR Bacteria

On By ModernMedia

International travellers are at risk of picking up a number of drug-resistant pathogens, according to a new European study.

In the COVID pandemic, international travel has become a distant memory for most of those used to it. As restrictions are lifted and international travel resumes, travellers are still at risk from other dangerous pathogens. In recent years, the rise of intestinal multidrug resistant gram-negative (MDR-GN) bacteria around the world poses a serious health threat, with MDR clones of E.coli and Klebsiella pneumoniae threatening more antibiotic resistant infections around the world. The spread of MDR-GN is a known threat in long-term care facilities, with residents forming a reservoir for the microbes but is also common in international travel as well. It is well documented that international travel results in the spread of multidrug-resistant E. coli, with up to 80% of travellers returning from high-risk regions being colonised by MDR-GN bacteria for up to a year. However, the existing research only compared participants before and after travel. A group of researchers from Universities of Basel, Birmingham, Helsinki and Oslo, and the Wellcome Sanger Institute set out to investigate the spread of such bacteria on a day by day basis.

Over a period of three weeks, the researchers monitored the health of a group of European travellers in the Lao People’s Democratic Republic by analysing daily information returns and stool samples. They found that by the end of the study period, 70% of the travellers had been colonised. The bacterial strains colonised travellers staying at the same hotel and spending time in one another’s company. In one case, a participant was colonised by taking a shower in another’s bathroom.

“International travel is strongly linked to the spread of MDR-GN bacteria, with transmission highest in India and Southeast Asia, Africa and South America,” said senior study author Professor Alan McNally, University of Birmingham. “Travellers visiting these high-risk regions are at substantial risk of acquiring the bacteria. Colonisation by MDR-GN bacteria is a highly dynamic process. We found constant ‘competition’ between circulating strains acquired by individual hosts and the travelers’ ‘native’ bacteria. Travellers can pick up the bacteria even during short visits and further spread the strains after returning home.”

All of the participants had acquired extended-spectrum beta-lactamases (ESBL) during their stay in Laos. ESBL enzymes create resistance within the body to most beta-lactam antibiotics, including penicillins, cephalosporins, and aztreonam. Infections with ESBL-producing organisms have proved difficult to treat. Also, all but one participant acquired multiple strains of bacteria with 83 unique strains identified (53 E. coli, 10 Klebsiella, 20 other ESBL-GN species), with up to four other participants sharing strains.

Study co-senior author, Professor Jukka Corander, at the University of Oslo and the Wellcome Sanger Institute, commented: “Our study reveals the true scale and complexity at which drug-resistant bacteria colonise the intestinal tract during travel, demonstrating that it has been seriously underestimated previously.

“In addition, several of our participants lost some of their travel-acquired ESBL-GN strains while still abroad – indicating that previous studies solely employing pre- and post-travel sampling have under-reported the extent to which travellers are colonised by ESBL-GN.”

Source: News-Medical.Net

Journal information: Kantele, A., et al. (2021) Dynamics of intestinal multidrug-resistant bacteria colonisation contracted by visitors to a high-endemic setting: a prospective, daily, real-time sampling study. The Lancet Microbe. doi.org/10.1016/S2666-5247(20)30224-X.

Categories : AntibioticsTags :

Prevalence of Antibiotic Resistance is Underestimated

On By ModernMedia

Antibiotic resistance to pathogenic bacteria in humans has spread farther than expected, as it has been discovered that bacteria can swap DNA far more readily than thought possible.

A growing threat, antibiotic resistance has emerged faster than thought possible. Some 33 000 deaths have occurred to antibiotic resistant infections in Europe alone, and finding new antibiotics or even alternatives are a top research priority. Totally different strains of bacteria can swap genetic information through the use of containers called plasmids. Plasmids are small containers of DNA which are kept outside of their chromosomes. When two bacteria come into contact, they can copy plasmids to one another in a process called conjugation (also known as “bacterial sex“). This is the most important means by which bacteria spread antibiotic resistance.

“In recent years, we’ve seen that resistance genes spread to human pathogens to a much greater degree than anyone expected,” said Jan Zrimec, a researcher in systems and synthetic biology at the Chalmers University of Technology. “Many of the genes appear to have originated in a wide array of bacterial species and environments, such as soil, water, and plant bacteria.

“This has been difficult to explain because although conjugation is very common, we’ve thought that there was a distinct limitation for which bacterial species can transfer plasmids to each other. Plasmids belong to different mobility groups or MOB groups, so they can’t transfer between just any bacterial species.”

Among his developments, he has written an algorithm that can sift through substantial amounts of plasmid DNA to pick out sections of DNA which are necessary for conjugation (known as oriT regions, where the enzyme relaxase can bind to and snip out DNA). This algorithm can then sort the plasmids into groups based on their oriT regions. His new method differs from the standard one because it analyses oriT regions by their physiochemical properties instead of searching DNA for the enzyme sequence for relaxase, or the point where it can bind to. This method is less time-consuming and resource intensive than the standard one.

Previously, it was thought that a plasmid had to have both the relaxase enzyme and the oriT sequence to bind to, but a bacterial cell can have an oriT region for conjugation to occur. With his new algorithm, he has been able to explore the DNA of 4600 plasmids from different bacteria found in nature.
– There may be eight times as many oriT regions than those discovered with standard methods.
– There may be twice as many mobile plasmids as previously known.
– There also may be twice as many bacterial species with mobile plasmids as previously known.
– More than half the plasmids have an oriT group matching to an enzyme for conjugation from a plasmid that already been classified in a different MOB group. This means that they could be transferred from a different plasmid in the same cell.

The last finding suggests that there may be far greater interchange between bacteria than had been previously been believed.

“This has been a major limitation of the research field up to now,” Zrimec said. “I hope that the methods will be able to benefit large parts of the research into antibiotic resistance, which is an extremely interdisciplinary and fragmented area. The methods can be used for studies aiming to develop more effective limitations to antibiotic use, instructions for how antibiotics are to be used, and new types of substances that can prevent the spread of resistance genes at the molecular level.”

Source: News-Medical.Net

Journal information: Zrimec, J. (2021) Multiple plasmid origin‐of‐transfer regions might aid the spread of antimicrobial resistance to human pathogens. MicrobiologyOpen.doi.org/10.1002/mbo3.1129.

Categories : AntibioticsTags :

Single Water Molecule Is the Key to Macrolide Resistance

On By ModernMedia

High resolution molecular structures produced by researchers at the University of Illinois Chicago show that the effectiveness of the macrolides class of antibiotics – and bacterial resistance to it – depends on interaction with a single water molecule. 

Macrolides have a broad spectrum of use against most gram-positive bacteria and are a widely used treatment  for a variety of infections. Clarithromycin, for example, is used as a mainstay treatment for respiratory infections. Due to antibiotic overuse, antibiotic resistance has emerged Macrolides interrupt protein biosynthesis in the ribosomes of pathogenic bacteria, and are one of the most successful classes of antibiotics to use this mechanism of action. The macrolides accomplish this by entering the cell and binding to the bacteria’s ribosomes, preventing them from manufacturing and releasing new proteins. As a result of the halt in protein synthesis, the bacteria can no longer grow or replicate. However, mutations came about that rendered the bacteria resistant.

Seeking to understand how the bacteria came about their resistance, the researchers learned how to capture images of the ribosome and the macrolide invading it. The researchers discovered that precisely one water molecule was required for the antibiotic to bind to the ribosome.

Corresponding author Yury Polikanov, associate professor of biological sciences at UIC, said: “We compared the hi-res structures of the ribosomes from sensitive and resistant bacteria and noticed that a water molecule that is needed for the tight antibiotic binding was not present in the ribosomes from the drug-resistant bugs. In the ribosomes from the drug-resistant bacteria, there was simply no room for this water molecule.”

The mutation that conferred macrolide resistance adds a pair of methyl groups to where the macrolide molecule normally binds to the ribosome, and the water molecule instead disrupts the binding.  

“We are very much excited by this discovery,” Polikanov said. “Because we now know how exactly macrolide antibiotics interact with their target, the ribosome. This discovery is important because it will inform and facilitate the development of new antibiotics that do not need this water molecule for binding. There is a huge demand for such drugs that are able to kill even those bacteria that became resistant to the currently used drugs.”

Source: News-Medical.Net

Journal information: Svetlov, M.S., Syroegin, E.A., Aleksandrova, E.V. et al. Structure of Erm-modified 70S ribosome reveals the mechanism of macrolide resistance. Nat Chem Biol (2021). https://doi.org/10.1038/s41589-020-00715-0

Categories : UncategorizedTags :

Antibiotic Overuse by Children’s Hospitals Contributing to Antibiotic Resistance

On By ModernMedia

Children’s hospitals may be contributing to antibiotic resistance by overprescription of antibiotics, according to a recent study.

The study, conducted by the University of Alabama at Birmingham (UAB),   found that in 51 children’s hospitals across the United States, rates of antibiotic administration ranged from 22% to 52%. Approximately a quarter of children receiving antibiotics were receiving them incorrectly. This adds to a growing body of evidence that points to antibiotics overuse and misuse by children’s hospitals – which ought to know better.Study co-author, Dr Jason Newland said, “There’s no doubt: We’ve seen some extra use of antibiotics, The impact of the pandemic on antibiotic use will be significant.

“The study’s numbers are likely an underestimate since the research involved 32 children’s hospitals already working together on proper antibiotic use. Newland said the US’ more than 250 children’s hospitals need to improve. Even though COVID fears have reduced the numbers of children’s hospital visits, antibiotics are still being prescribed via telemedicine.

“I hear a lot about antibiotic use for the ‘just in case’ scenarios,” said Dr Joshua Watson, at Nationwide Children’s Hospital in Ohio. “We underestimate the downsides.”

Dr Shannon Ross, an associate professor of paediatrics and microbiology at UAB, said that not all doctors have been taught the correct use of antibiotics. Regarding this overuse, she said, “Many of us don’t realize we’re doing it. It’s sort of not knowing what you’re doing until someone tells you.”
Unnecessary antibiotic use is a problem, and the pandemic “has thrown a little bit of gas on the fire,” said Dr Mark Schleiss, a paediatrics professor at the University of Minnesota Medical School.

“It’s irresponsible,” said Christina Fuhrman, who almost lost her infant daughter to a Clostridium difficile infection, and who now advocates for correct antibiotic use. Along with parents begging for antibiotics in paediatricians’ offices, the situation is “creating a monster.”
Many studies have attested to the rise of C. diff in children, which causes gastrointestinal problems. A 2017 study found that cases of a certain multidrug-resistant Enterobacteriaceae type rose 700% in American children in just eight years. And a steady stream of research points to the stubborn prevalence in kids of the better-known MRSA, or methicillin-resistant Staphylococcus aureus.

“It’s getting more and more worrisome,” said Ross. “We have had patients we have not been able to treat because we’ve had no antibiotics available.”

Source: News-Medical.Net

Journal information: Tribble A, Lee B, Flett K et al. Appropriateness of Antibiotic Prescribing in United States Children’s Hospitals: A National Point Prevalence Survey. Clinical Infectious Diseases. 2020;71(8):e226-e234. doi:10.1093/cid/ciaa036