DiversityNursing Blog

By Catharine Paddock PhD

The rise of drug-resistant bacteria - such as MRSA - is making it increasingly difficult to control even common infections like pneumonia or urinary tract infections with standard antibiotics. After repeated exposure, the bugs mutate into strains that are immune to the drugs that once killed them.

There is clearly a desperate need for new drugs to fight these superbugs. But there is also another option - to extend the useful life of a drug. Now, researchers have developed a computer algorithm that can help in this area.

Imagine the war against a superbug as a chess game, with each move that your opponent makes being a mutation in the superbug that makes it more drug-resistant. 

To stand a good chance of winning, it helps to anticipate your opponent's most likely counter-moves.

Now, a team of researchers - including members from Duke University in Durham, NC - has developed a computer algorithm that stands a good chance of beating a superbug at its own game.

The software - called OSPREY - predicts the most likely mutations that a bug develops in response to a new drug before the drug is even given to patients.

Writing in the Proceedings of the National Academy of Sciences, the team describes how they tested OSPREY with the superbug MRSA (methicillin-resistant Staphylococcus aureus). 

The researchers programmed the algorithm to identify the genetic changes that MRSA would have to undergo in order to become resistant to a promising new class of experimental drug. And when they exposed MRSA to the new drugs, they found some of the genetic changes the software had predicted actually arose.

"This gives us a window into the future to see what bacteria will do to evade drugs that we design before a drug is deployed," says author Bruce Donald, a professor of computer science and biochemistry at Duke.

The team hopes the approach they are developing will give drug designers a head start in the race against superbugs, as co-author and Duke graduate student Pablo Gainza-Cirauqui explains:

"If we can somehow predict how bacteria might respond to a particular drug ahead of time, we can change the drug, or plan for the next one, or rule out therapies that are unlikely to remain effective for long."

Resistant forms of Staphylococcus aureus now kill 11,000 people in the US every year - more than HIV. In 1975, around 2% of infections caused by the bacterium were resistant to treatment - rising to 29% in 1991 - and now the proportion is 55%.

Depending on the drug, it can take up to 20 years for resistant strains to emerge. Sometimes it only takes 1 year.

Ability to anticipate new mutations beats searching 'libraries' of known mutations

The team believes approaches like OSPREY beat the current method where scientists have to look up "libraries" of previously observed resistance mutations - an approach that is not necessarily satisfactory for predicting future mutations. Prof. Donald explains:

"With a new drug, there is always the possibility that the organism will develop different mutations that had never been seen before. This is what really worries physicians."

OSPREY - which stands for Open Source Protein REdesign for You - is based on a protein design algorithm. It identifies changes to DNA sequences in the bacteria that would enable the resulting protein to block the drug while still being able to work normally.

The team tested OSPREY with a new class of drugs called propargyl-linked antifolates that attack a bacterial enzyme called dihydrofolate reductase (DHFR), used for building DNA and other tasks. The drugs - still to be tested in humans - are showing promise as a new treatment for MRSA infections.

Using OSPREY, the team came up with a ranked list of possible mutations. They picked out four - none of which had been seen before.

One predicted mutation reduced drug effectiveness by 58%

When they treated MRSA with the new drugs, they found more than half of the bacteria that survived carried the mutation they predicted would give the organism the greatest amount of resistance: a tiny change in the bacterial DNA that reduced the effectiveness of the new drugs by 58%.

"The fact that we actually found the new predicted mutations in bacteria is very exciting," Prof. Donald says, adding that the approach could be expanded to anticipate the bug's responses more than one move ahead:

"We might even be able to coax a pathogen into developing mutations that enable it to evade one drug, but that then make it particularly susceptible to a second drug, like a one-two punch."

The team is now enhancing OSPREY to predict resistance mutations to drugs designed to treat E. coli and Enterococcus infections.

They believe OSPREY will be useful for predicting drug resistance in cancer, HIV, flu and other diseases where culturing resistant strains is harder than it is with bacteria.

Prof. Donald and colleagues are developing OSPREY in open source format so it is freely available for any researcher to use.

In September 2014, Medical News Today learned about a study that showed how an  old drug may lead to a potential new class of antibiotics . The study showed that lamotrigine - currently used as an anticonvulsant - can inhibit the assembly of ribosomes in bacteria.

Source: www.medicalnewstoday.com

Use of "antibiograms" in skilled nursing facilities could improve antibiotic effectiveness and help address problems with antibiotic resistance that are becoming a national crisis, researchers conclude in a new study.

Antibiograms are tools that aid health care practitioners in prescribing antibiotics in local populations, such as a hospital, nursing home or the community. They are based on information from microbiology laboratory tests and provide information on how likely a certain antibiotic is to effectively treat a particular infection.

The recent research, published by researchers from Oregon State University in Infection Control and Hospital Epidemiology, pointed out that 85 percent of antibiotic prescriptions in the skilled nursing facility residents who were studied were made "empirically," or without culture data to help determine what drug, if any, would be effective.

Of those prescriptions, 65 percent were found to be inappropriate, in that they were unlikely to effectively treat the target infection.

By contrast, use of antibiograms in one facility improved appropriate prescribing by 40 percent, although due to small sample sizes the improvement was not statistically significant.

"When we're only prescribing an appropriate antibiotic 35 percent of the time, that's clearly a problem," said Jon Furuno, lead author on the study and an associate professor in the Oregon State University/Oregon Health & Science University College of Pharmacy.

"Wider use of antibiograms won't solve this problem, but in combination with other approaches, such as better dose and therapy monitoring, and limiting use of certain drugs, we should be able to be more effective," Furuno said.

"And it's essential we do more to address the issues of antibiotic resistance," he said. "We're not keeping up with this problem. Pretty soon, there won't be anything left in the medical cabinet that works for certain infections."

In September, President Obama called antibiotic resistant infections "a serious threat to public health and the economy," and outlined a new national initiative to address the issue. The Centers for Disease Control and Prevention has concluded that the problem is associated with an additional 23,000 deaths and 2 million illnesses each year in the U.S., as well as up to $55 billion in direct health care costs and lost productivity.

Antibiograms may literally be pocket-sized documents that outline which antibiotics in a local setting are most likely to be effective. They are often used in hospitals but less so in other health care settings, researchers say. There are opportunities to increase their use in nursing homes but also in large medical clinics and other local health care facilities for outpatient treatment. The recent study was based on analysis of 839 resident and patient records from skilled nursing and acute care facilities.

"Antibiograms help support appropriate and prudent antibiotic use," said Jessina McGregor, also an associate professor in the OSU/OHSU College of Pharmacy, and lead author on another recent publication on evaluating antimicrobial programs.

"Improved antimicrobial prescriptions can help save lives, but they also benefit more than just an individual patient," McGregor said. "The judicious use of antibiotics helps everyone in a community by slowing the spread of drug-resistant genes. It's an issue that each person should be aware of and consider."

Multi-drug resistant organisms, such as methicillin-resistant Staphylococcus aureus, or MRSA, and other bacterial attacks that are being called "superinfections" have become a major issue.

Improved antibiotic treatment using a range of tactics, researchers say, could ultimately reduce morbidity, save money and lives, and improve patients' quality of life.

Source: www.medicalnewstoday.com

By Maureen Salamon

 Pediatricians prescribe antibiotics about twice as often as they're actually needed for children with ear and throat infections, a new study indicates.

More than 11 million antibiotic prescriptions written each year for children and teens may be unnecessary, according to researchers from University of Washington and Seattle Children's Hospital. This excess antibiotic use not only fails to eradicate children's viral illnesses, researchers said, but supports the dangerous evolution of bacteria toward antibiotic resistance.

"I think it's well-known that we prescribers overprescribe antibiotics, and our intent was to put a number on how often we're doing that," said study author Dr. Matthew Kronman, an assistant professor of infectious diseases at Seattle Children's Hospital.

"But as we found out, there's really been no change in this [situation] over the last decade," added Kronman. "And we don't have easily available tools in the real-world setting to discriminate between infections caused by bacteria or viruses."

The study was published online on Sept. 15 in the journal Pediatrics.

Antibiotics, drugs that kill bacteria or stop them from reproducing, are effective only for bacterial infections, not viruses. But because doctors have few ways of distinguishing between viral or bacterial infections, antibiotics are often a default treatment.

To determine antibiotic prescribing rates, Kronman and his colleagues analyzed a group of English-language studies published between 2000 and 2011 and data on children 18 and younger who were examined in outpatient clinics.

Based on the prevalence of bacteria in ear and throat infections and the introduction of a pneumococcal vaccine that prevents many bacterial infections, the researchers estimated that about 27 percent of U.S. children with infections of the ear, sinus area, throat or upper respiratory tract had illnesses caused by bacteria.

But antibiotics were prescribed for nearly 57 percent of doctors' visits for these infections, the study found.

"I thought it was really a clever study, actually, to get a sense of the burden of bacterial disease and what the antibiotic usage is," said Dr. Jason Newland, medical director of patient safety and system reliability, and associate professor of pediatrics at University of Missouri-Kansas City School of Medicine.

Newland, former director of the Antimicrobial Stewardship Program at Children's Mercy Hospital and Clinics in Kansas City, cited the 2013 "threat report" by the U.S. Centers for Disease Control and Prevention that indicated 23,000 Americans die each year due to antibiotic-resistant infections.

"We all know when we use antibiotics that we increase the chance of resistance because bacteria evolve," he said. "We need to use them well and not in such excess doses. We have to do way better."

A rapid strep test is currently available to distinguish between bacterial or viral throat infections. But other than that test, physicians have no other clinical tools to tell the cause of most upper respiratory infections, according to background information in the study. Kronman said he hopes the new research will not only help encourage the development of more such tools, but also spur clinicians to think more critically about prescribing antibiotics unless clearly needed.

Kronman added that prior research indicates that parents -- who often pressure pediatricians into prescribing antibiotics -- respond to alternate suggestions to alleviate their children's upper respiratory symptoms, such as using acetaminophen and humidifiers, instead of doctors simply saying they won't prescribe antibiotics.

"We have to take this [problem] on as a society," Newland said. "The reality is that the excess, unnecessary use of antibiotics is really putting us at great risk of not having these antibiotics [work] in the future."

Source: http://healthyliving.msn.com