New class of antibiotic could fight resistance for 30 years

A new class of antibiotic has been discovered thanks to a new technique that could yield more of the same – an incredible boon in our fight against antimicrobial resistance.

Scientists in the US have discovered a new class of antibiotic that has been shown to kill Staph and Strep throat infections in mice. They say the way it kills bacteria will make it very difficult for them to evolve resistance in response to the attacks.

Last month, a report chaired by US economist Jim O’Neill predicted that 300 million people will die prematurely by the year 2050 thanks to antimicrobial resistance, if nothing is done to solve the problem. The report went on to add that our global GDP would dip by 0.5 percent by 2020 and will end up 1.4 percent smaller by 2030, purely due to the steady march of resistant bacteria.

In 2013, the chief medical officer of the UK, Sally Davies, announced that antimicrobial resistance would be put on the government’s national risk register of civil emergencies, to join the equally serious threats of terrorism, the pandemic flu, and major flooding.

Antimicrobial resistance is a huge problem, but we might finally have the upper hand in this power struggle between man and bug – a new antibiotic called teixobactin, which has been shown to kill a wide range of drug-resistant bacteria in lab mice, including those responsible for tuberculosis and septicaemia, plus Clostridium difficile colitis (C. dif) – the most common gut bug infection.

“Teixobactin kills exceptionally well. It has the ability to rapidly clear infections,” lead researcher and director of the Antimicrobial Discovery Centre at Northeastern University, Kim Lewis, told Ian Sample at The Guardian.

The secret to Teixobactin’s success is that it prevents microbes from being able to construct their cell walls, and holes in your cell walls means certain death. In fact, the antibiotic ended up killing 100 percent of the bacteria it came into contact with, and no survivors means there’s no one to evolve resistance. “That’s an Achilles’ heel for antibiotic attack,” the researcher who discovered this ability, Tanja Schneider from the University of Bonn, told Sample. “It would take so much energy for the cell to modify this, I think it’s unlikely resistance will appear this way.”

As Kelly Servick explains at Science Magazine, resistance usually occurs when a fraction of a population of microbes somehow survives an antibiotic attack because of a particular mutation, and then those mutated bacteria multiply into a separate resistant population.

“My guess is that if resistance is going to develop against Teixobactin, it will take more than 30 years for that to occur,” Lewis told CBS News.

Not only did Teixobactin kill off 100 percent of the bacteria it came into contact with, including Staphylococcus aureus (Staph infection) and Streptococcus pneumoniae (Strep throat), but it cleared these infections without any side-effects.

Which is all great, but perhaps even more exciting is how the antibiotic was discovered. “Most antibiotics are isolated from bacteria or fungi that churn out lethal compounds to keep other microbes at bay,” says Sample at The Guardian. “But scientists have checked only a tiny fraction of bugs for their ability to produce potential antibiotics because 99 percent cannot be grown in laboratories.”

Since the first antibiotic, Penicillin, was discovered by accident in 1928 by Alexander Fleming, scientists haven’t had a particularly efficient way of finding more. But recently, Kim Lewis’s team developed a device they’re calling the iChip, which can culture bacteria in their natural habitat – in this case, dirt. Bacteria are inserted into the device between two permeable sheets and dug into the ground, where the bacteria are free to grow into colonies as they would in the wild, except for the fact that they’re confined to their iChip chambers.

After two weeks, the researchers retrieved their iChip and were able to test the colonies that had grown in their natural habitat. “To do this, they covered the top of the iChip with layers of pathogens,” says Sample. “Bugs that produced natural antibiotics revealed themselves by killing the pathogens above them.”

The team paired up with NovoBiotic, a Massachusetts-based pharmaceuticals start-up, and researchers at the University of Bonn, and screened 10,000 different types of soil bacteria – cultured in the iChip – for antibiotics. They found 25 new antibiotic compounds, teixobactin being the most high-achieving of the lot. They published their results in Nature today.

Servick reports at Science Magazine that Teixobactin was so effective, it also outperformed Vancomycin – the antibiotic we currently rely on to treat methicillin-resistant  Staphylococcus aureus (MRSA) – by a factor of 100. “In mice infected with MRSA, injections of teixobactin led to a 100 percent survival rate at lower doses than vancomycin,” she says.

It’s exciting stuff, but it’s still going to be a while before people can be treated with the antibiotic. Human trials are set to begin in about two years, and if they go well, development for the market will follow.

“Another shortcoming of Teixobactin is that it only works against bacteria that lack outer cell walls, known as Gram-positive bacteria, such as MRSA, Streptococcus and TB,” says Sample at The Guardian. “It doesn’t work against Gram-negative bacteria, which include some of the most worrying antibiotic-resistant pathogens, such as Klebsiella, E. coli and Pseudomonas.”

But hopefully that’s something Lewis’s team’s new iChip method will help solve.

As Mark Woolhouse, professor of infectious disease epidemiology from the University of Edinburgh in the UK, told Sarah Knapton at The Telegraph:

“Any report of a new antibiotic is auspicious, but what most excites me about the paper is the tantalising prospect that this discovery is just the tip of the iceberg. Most antibiotics are natural products derived from microbes in the soil. The ones we have discovered so far come from a tiny subset of the rich diversity of microbes that live there.

Lewis et al. have found a way to look for antibiotics in other kinds of microbe, part of the so-called microbial ‘dark matter’ that is very difficult to study.”

Sources: The Guardian, Science Magazine,  The Telegraph

The above story is reprinted from materials provided by Science Alert.

Clinical Syndromes, Laboratory Diagnosis and Treatment of Orthomyxoviruses

Clinical Syndromes

Depending on the degree of immunity to the infecting strain of virus and other factors, infection may range from asymptomatic to severe. Patients with underlying cardiorespiratory disease, people with immune deficiency (even that associated with pregnancy), the elderly, and smokers are more prone to have a severe case.

After an incubation period of 1 to 4 days, the “flu syndrome” begins with a brief prodrome of malaise and headache lasting a few hours. The prodrome is followed by the abrupt onset of fever, chills, severe myalgias, loss of appetite, weakness and fatigue, sore throat, and usually a nonproductive cough. The fever persists for 3 to 8 days, and unless a complication occurs, recovery is complete within 7 to 10 days. Influenza in young children (under 3 years) resembles other severe respiratory tract infections, causing bronchiolitis, croup, otitis media, vomiting, and abdominal pain, accompanied rarely by febrile convulsions (Table 1). Complications of influenza include bacterial pneumonia, myositis, and Reye syndrome. The central nervous system can also be involved. Influenza B disease is similar to influenza A disease.

Influenza may directly cause pneumonia, but it more commonly promotes a secondary bacterial superinfection that leads to bronchitis or pneumonia. The tissue damage caused by progressive influenza virus infection of alveoli can be extensive, leading to hypoxia and bilateral pneumonia. Secondary bacterial infection usually involves Streptococcus pneumoniae, Haemophilus influenzae, or Staphylococcus aureus. In these infections, sputum usually is produced and becomes purulent.

Although the infection generally is limited to the lung, some strains of influenza can spread to other sites in certain people. For example, myositis (inflammation of muscle) may occur in children. Encephalopathy, although rare, may accompany an acute influenza illness and can be fatal. Postinfluenza encephalitis occurs 2 to 3 weeks after recovery from influenza. It is associated with evidence of inflammation but is rarely fatal.

Reye syndrome is an acute encephalitis that affects children and occurs after a variety of acute febrile viral infections, including varicella and influenza B and A diseases. Children given salicylates (aspirin) are at increased risk for this syndrome. In addition to encephalopathy, hepatic dysfunction is present. The mortality rate may be as high as 40%.

Laboratory Diagnosis

The diagnosis of influenza is usually based on the characteristic symptoms, the season, and the presence of the virus in the community. Laboratory methods that distinguish influenza from other respiratory viruses and identify its type and strain confirm the diagnosis (Table 2).

Influenza viruses are obtained from respiratory secretions. The virus is generally isolated in primary monkey kidney cell cultures or the Madin-Darby canine kidney cell line. Nonspecific cytopathologic effects are often difficult to distinguish but may be noted within as few as 2 days (average, 4 days). Before the cytopathologic effects develop, the addition of guinea pig erythrocytes may reveal hemadsorption (the adherence of these erythrocytes to HA-expressing infected cells). The addition of influenza virus-containing media to erythrocytes promotes the formation of a gel-like aggregate due to hemagglutination. Hemagglutination and hemadsorption are not specific to influenza viruses, however; parainfluenza and other viruses also exhibit these properties.

More rapid techniques detect and identify the influenza genome or antigens of the virus. Rapid antigen assays (less than 30 min) can detect and distinguish influenza A and B. Reverse transcriptase polymerase chain reaction (RT-PCR) using generic influenza primers can be used to detect and distinguish influenza A and B, and more specific primers can be used to distinguish the different strains, such as H5N1. Enzyme immunoassay or immunofluorescence can be used to detect viral antigen in exfoliated cells, respiratory secretions, or cell culture and are more sensitive assays. Immunofluorescence or inhibition of hemadsorption or hemagglutination (hemagglutination inhibition [HI]) with specific antibody can also detect and distinguish different influenza strains. Laboratory studies are primarily used for epidemiologic purposes.

To read more click on this link to the full article: Clinical Syndromes, Laboratory Diagnosis and Treatment of Orthomyxoviruses