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Gonorrhea Becoming More Resistant to One Antibiotic: CDC

One of several antibiotic treatment options for the sexually transmitted disease gonorrhea seems to be losing its effectiveness, U.S. health officials warn in a new report.HealthDay news image

The U.S. Centers for Disease Control and Prevention’s latest tracking suggests that although resistance to the antibiotic treatment cefixime went down between 2011 and 2013, it started to creep back up in 2014.

The good news is that cefixime isn’t usually the first drug of choice for treating gonorrhea infections. The CDC’s most recent guidelines for gonorrhea treatment (issued in 2012) recommend only using cefixime when the preferred option — ceftriaxone-based combination therapy — isn’t available. And the CDC’s new report doesn’t indicate any recent waning in the effectiveness of that combination therapy.

Still, indications of antibiotic resistance among any gonorrhea treatment is considered troubling, the study authors said.

“It is essential to continue monitoring antimicrobial susceptibility and track patterns of resistance among the antibiotics currently used to treat gonorrhea,” said study lead author Dr. Robert Kirkcaldy, an epidemiologist in the CDC’s division of STD prevention in Atlanta.

“Recent increases in cefixime resistance show our work is far from over,” he said.

The study findings are published as a research letter in the Nov. 3 issue of the Journal of the American Medical Association.

The CDC noted that gonorrhea is spread during unprotected vaginal, anal or oral sex. The sexually transmitted infection is particularly common among youth and young adults between the ages of 15 and 24.

Many people have no symptoms when infected. When symptoms do occur, they may include a painful or burning sensation when urinating; painful, swollen testicles and discolored discharge from the penis among men. In women, symptoms may include increased vaginal discharge and vaginal bleeding between periods. Rectal infections may spark soreness, itching, bleeding, discharge, and painful bowel movements, the CDC said.

If gonorrhea goes untreated, “serious health complications” can result, Kirkcaldy said. Those can include chronic pelvic pain, infertility and life-threatening ectopic pregnancy — an abnormal pregnancy that occurs outside of the uterus. In rare cases, gonorrhea can spread to your blood or joints, causing a potentially life-threatening infection, the CDC warned.

But when identified, antibiotics can provide an effective cure for those with gonorrhea.

The new CDC study looked at treatment outcomes among male gonorrhea patients who had been treated at public clinics across the United States between 2006 and 2014.

More than 51,000 samples were gathered across 34 cities. About one-third were collected in the western United States and one-third collected in the South. A little more than a quarter of the samples were drawn from men who either identified as gay or bisexual, the study said.

The investigators found that the CDC’s 2012 shift away from recommending cefixime and toward ceftriaxone-based combination therapy had a profound impact: while the combination therapy had been given to less than 9 percent of the patients in 2006, that figure shot up to nearly 97 percent by 2014.

Alongside that shift, the team found that cefixime-resistance went up from 0.1 percent in 2006 to 1.4 percent in 2011, and then back down to 0.4 percent in 2013. But by 2014 resistance trended upward to 0.8 percent, the research revealed.

What does this mean? “Trends of cefixime susceptibility have historically been a precursor to trends in ceftriaxone,” said Kirkcaldy. “So it’s important to continue monitoring cefixime to be able to anticipate what might happen with other drugs in the future.”

Dr. Kirsten Bibbins-Domingo, co-vice chair of the U.S. Preventive Services Task Force in Rockville, Md., emphasized the importance of routine screening.

“The task force recommends screening for gonorrhea in sexually active women age 24 years or younger, and in older women who are at increased risk for infection,” she said.

The task force doesn’t advocate for or against screening for men, saying more research is needed to prove effectiveness. However, Kirkcaldy said that the “CDC recommends an annual gonorrhea screening for high-risk sexually active women and for sexually active gay, bisexual, and other men who have sex with men.”

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Scents may affect how appealing tobacco is- Pleasant scents hook people on tobacco; and smelling stinky scents during sleep might help smokers quit

spearmint

WASHINGTON, D.C. — The minty flavor added to menthol cigarettes might make it even harder for smokers to quit, new research shows.

Most smokers know they should quit. Unfortunately, the nicotine in tobacco is addictive. That makes quitting really hard. Scientists have known that it’s even harder for people who light up menthol cigarettes.

The question has been why, notes Brandon Henderson. He’s a neuroscientist in Pasadena at the California Institute of Technology, or Caltech.

The answer, his team now finds, may have a lot to do with how menthol boosts the effect of nicotine on the brain. Repeated exposure to nicotine leads the brain to make more nicotine receptors — docking stations for the chemical on cells. These nicotinic receptors are proteins. And their role is to impact the brain’s pathways for a chemical known as dopamine (DOPE-uh-meen). Dopamine transmits signals in the brain. Some of those signals turn on centers that convey feelings of pleasure and rewards. Indeed, this feel-good chemical helps make smoking rewarding — and addictive.

To see how menthol might affect this system, Henderson and his Caltech teammates worked with special lab mice. One type of nicotinic receptor in the mice glows cherry red under fluorescent light. Another type glows bright green.

The researchers exposed these mice to menthol. (This chemical occurs naturally in spearmint and peppermint.) Then the experts focused in on a part of the midbrain. It’s known as the ventral tegmental area, or VTA. The VTA plays a role in emotion, motivation and addiction.

Mice exposed to menthol had more of both types of nicotinic receptors than did unexposed mice. The increase was similar to that produced by nicotine, the scientists found.

“This goes to show that menthol is not simply an inert flavoring in cigarettes,” says Henderson. “It has some effects in the brain.” Henderson presented his team’s results here on November 16 at the annual meeting of the Society for Neuroscience.

“The most significant finding from Dr. Henderson’s study is that chronic exposure to menthol can change the number of receptors for nicotine in the brain to a similar extent that nicotine can,” says Marina Picciotto. A neuroscientist at Yale University in New Haven, Conn., she did not work on the new study.

“Menthol may increase the addictive properties of nicotine at the molecular level,” Picciotto concludes. Still, she cautions, scientists need to see if that molecular action affects behavior. And to be sure menthol works the same way in people, she says, “We need more information from human subjects.”

Yolks yoke in folks who smoke

Results from a second study presented at the meeting suggest that adding a foul odor to cigarette smoke could help people cut back on smoking. But the idea may work best if people sleep through the stinky experience.

Anat Arzi is a neuroscientist at the Weizmann Institute of Science in Rehovot, Israel.  Earlier, she and other researchers had shown that people can learn to link some experiences as they sleep.

Arzi now wondered whether that type of learning might influence waking behaviors, such as smoking. To find out, she and other scientists exposed groups of smokers to different odors. One stinky stew mixed together the stench of cigarette smoke and rotten eggs. Another paired the smells of smoke and rotten fish.

Researchers told everyone participating in the study that the experience might help them stop or cut back on smoking. But only those smokers who smelled the foul combos while awake knew what just what the experiment involved.

Other smokers smelled those odors only while they slept. Unlike loud noises or bright lights, odors seldom wake people up.

inhaling stinky smells while sleeping

Some volunteers in a study in Israel were exposed to a mix of foul odors and cigarette smoke during different stages of sleep. These tests showed that stinky sleep smells might help people cut back on smoking.

COURTESY OF MICHAEL COOPER.

One group smelled the nasty smells during Stage 2 sleep. That’s the type that occurs most of the night. Others experienced it during rapid eye movement (REM) sleep. Most dreams occur during REM sleep. The study also included control groups — people who slept while no smells scented the air.

Over the following week, people in each group tracked how much they smoked. People exposed to noxious smells during Stage 2 sleep smoked significantly less than before.

“The reduction was around 30 percent,” Arzi reported. That group smoked significantly fewer cigarettes on each day during the week, too.

In contrast, people treated during REM sleep smoked significantly less on only two of the next seven days. So here, the effect did not seem to last all week. And the group that had been awake when exposed to the odors? They showed no change in their smoking habits.

“In other words, sleep learning can influence later awake behavior,” Arzi concludes. The Journal of Neuroscience published the study by Arzi and her colleagues in November.

“The most significant finding of Dr. Arzi’s study is that pairing a nasty odor with the smell of a cigarette can reduce the amount of smoking for several days — and that this only happens during sleep,” says Picciotto, the Yale neuroscientist.

Arzi’s study paired odors for just one night. It then tracked smoking for only one week afterward. A next step, says Picciotto. “would be to see how long the effect lasts.”

That’s important, because tobacco addiction is a major health problem. In the United States alone, cigarette smoking leads to roughly one in five early deaths each year. That statistic comes from the National Institute on Drug Abuse in Rockville, Md. What’s more, it notes, roughly 85 percent of smokers fail when they try to stop on their own.

For that reason, scientists need to learn all they can about causes and treatments for tobacco addiction. The new studies on smoking and smelly substances could one day help all of us breathe easier.

Power Words

addiction  The uncontrolled use of a habit-forming drug or uncontrolled and unhealthy habit (such as video game playing or phone texting). It results from an illness triggered by brain changes that occur after using some drugs or engaging in some extremely pleasurable activities. Persons with an addiction will feel a compelling need to use a drug (which can be alcohol, the nicotine in tobacco, a prescription drug or an illegal chemical such as cocaine or heroin), even when the user knows that doing so risks severe health or legal consequences. (For instance, even though 35 million Americans try to quit smoking each year, fewer than 15 out of 100 succeed. Most begin smoking again within a week, according to the National Institute on Drug Abuse.)

chronic  A condition, such as an illness (or its symptoms, including pain), that lasts for a long time.

control     A part of an experiment where nothing changes. The control is essential to scientific experiments. It shows that any new effect must be due to only the part of the test that a researcher has altered. For example, if scientists were testing different types of fertilizer in a garden, they would want one section of to remain unfertilized, as the control. Its area would show how plants in this garden grow under normal conditions. And that give scientists something against which they can compare their experimental data.

dopamine  A neurotransmitter, this chemical helps transmit signals in the brain.

fluorescent  Capable of absorbing and reemitting light. That reemitted light is known as a fluorescence.

inert   Inactive or having no chemical or physical effects.

neuroscience  Science that deals with the structure or function of the brain and other parts of the nervous system. Researchers in this field are known as neuroscientists.

neurotransmitter  A chemical substance that is released at the end of a nerve fiber. It transfers an impulse to another nerve, a muscle cell or some other structure.

nicotine  A colorless, oily chemical produced in tobacco and certain other plants. It creates the ‘buzz’ effect associated with smoking. It also is highly addictive, making it hard for smokers to give us their use of cigarettes. The chemical is also a poison, sometimes used as a pesticide to kill insects and even some invasive snakes or frogs.

nicotinic receptors   A group of brain proteins that affects the signaling of dopamine. Repeated exposure to nicotine leads to more of these receptors in particular areas of the brain.

REM sleep    A period of sleep that takes its name for the rapid eye movement, or REM, that occurs. People dream during REM sleep, but their bodies can’t move. In non-REM sleep, breathing and brain activity slow, but people can still move about.

ventral tegmental area  Part of the midbrain. It plays an important role in thinking, motivation, emotions and addiction.


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First Global Drug Resistance Overview Paints Grim Picture

WHO asked its member states to provide information on resistance in nine microbe-drug combinations. Many countries provided information for fewer than five or said they had no national data available

WHO

Uncharted territory. WHO asked its member states to provide information on resistance in nine microbe-drug combinations. Many countries provided information for fewer than five or said they had no national data available; white spots indicate countries that did not submit data at all.

The World Health Organization (WHO) presented its first-ever global attempt to assess the spread of drug resistance today—and the results are sobering. Antimicrobial resistance “threatens the achievements of modern medicine,” warns the study, which shows that high rates of resistance occur in most parts of the world.

“Without urgent, coordinated action by many stakeholders, the world is headed for a post-antibiotic era, in which common infections and minor injuries which have been treatable for decades can once again kill,” wrote Keiji Fukuda, WHO’s assistant director-general for health security, in a press statement.

The study presents some data on drugs against influenza, HIV, tuberculosis, and malaria, but it focuses on seven common bacteria and nine classes of drugs used to treat them—for instance, fluoroquinolones to treat Escherichia coli, which can cause urinary tract or bloodstream infections. WHO asked its 194 member states to contribute information on how common resistances to these drugs are and how they survey them; 129 countries provided information, but only 114 of those could provide data for at least one of the nine combinations of pathogen and drug.

The report finds high rates of resistance for some of the bacteria almost everywhere. For instance, nations in all six WHO regions report that more than half of Klebsiella pneumoniaeisolates have acquired resistance to third-generation cephalosporins, an important class of antibiotics. That leaves only one class of drugs, the carbapenems, to treat severe infections with the bacterium, which causes pneumonia as well as bloodstream and urinary tract infections. But even resistance against these drugs of last resort is now cropping up around the world.

For gonorrhea, which infects more than 1 million people every day, third-generation cephalosporins are the last resort. But treatment failure has already been confirmed in Austria, Australia, Canada, France, Japan, Norway, South Africa, Slovenia, Sweden, and the United Kingdom.

And other countries may have the same problem without knowing it. The report warns that many countries do not even manage to monitor resistances adequately and that surveillance, where it happens, is neither coordinated nor harmonized. “I think it’s scary how bad the antibiotic surveillance is, given the seriousness of the problem,” says Andrew Read, who directs the Center for Infectious Disease Dynamics at Pennsylvania State University, University Park.

It is not the first time that WHO has highlighted the problem. In 2000, then–director-general Gro Harlem Brundtland called the increase in antibiotic resistances a “global crisis.” The following year, she issued a major report on the topic, which also called for better surveillance. The report came out on 11 September, however, and garnered little attention.

The new report confirms what doctors around the world are experiencing daily. “We see horrendous rates of antibiotic resistance wherever we look in our field operations, including children admitted to nutritional centres in Niger, and people in our surgical and trauma units in Jordan,” said Jennifer Cohn, medical director of the Access Campaign at Doctors Without Borders, in a written statement issued today. “Ultimately, WHO’s report should be a wake-up call to governments to introduce incentives for industry to develop new, affordable antibiotics that do not rely on patents and high prices and are adapted to the needs of developing countries.”

Petra Gastmeier, head of the Institute for Hygiene and Environmental Medicine at Charité University Medicine Berlin, says the study is an important step in tackling the problem. Maps in the report show which countries provide good data on resistances and which ones are lagging. “That may stimulate some of those countries to finally do something about their surveillance,” Gastmeier says.

But the report falls short when it comes to what should be done about resistance itself, Read says. “Avoiding infections in the first place is of course critical, and so is drug discovery,” he writes—but more research on how to best use drugs is also needed. “The science of resistance management is in its infancy.”


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FDA OKs Quick-Acting Antidote for Prescription Painkiller Overdose

People suffering a potentially fatal narcotic overdose now can receive lifesaving treatment from folks around them, using a new device just approved by the U.S. Food and Drug Administration.

Evzio is a hand-held auto injector that delivers a single dose of the drug naloxone into the muscle or beneath the skin. The injector can be carried in a pocket or stored in a medicine cabinet and is meant as an emergency treatment for people who have suffered a known or suspected overdose of powerful pain drugs called opioids.

Opioids include prescription narcotic painkillers such as Oxycontin, Vicodin and Percocet — all of which have shown increasing rates of abuse in recent years.

They also include the illicit drug heroin, which has increased in popularity and recently led to the death of actor Philip Seymour Hoffman.

The Obama administration is urging all local police and fire departments to equip their officers and vehicles with Evzio, Michael Botticelli, acting director of the White House Office of National Drug Control Policy, said at a Thursday news conference.

Family members and friends of people who are struggling with narcotics addiction or are taking opioids for a medical condition also will be able to equip themselves with Evzio, just by getting a prescription from their physician.

“A family member of someone at risk for opioid overdose could receive a prescription,” said Dr. Douglas Throckmorton, deputy director for regulatory programs at the FDA’s Center for Drug Evaluation and Research. “Physicians can prescribe to anyone concerned about the risks of possible opioid overdose.”

The product is built to be simple and easy-to-use for lay people, FDA Commissioner Dr. Margaret Hamburg said at the news conference.

Naloxone rapidly reverses the effects of overdose and is the standard treatment in such cases. However, current naloxone drugs have to be injected with a needle and their use is typically limited to trained medical personnel, the FDA explained.

Once the device is turned on, it provides verbal instructions on how to deliver the medication, similar to how an automatic heart defibrillator works.

“There was a great emphasis on making it very user-friendly, both the labeling information and the device itself,” Hamburg said.

She added that “the last instruction the device gives is to call 911, because this product is not a substitute for emergency care.”

The product’s simplicity is partially aimed at encouraging police officers to equip and use Evzio, Botticelli said. Officers have been reluctant to administer naloxone injections, and also have been slow to adopt nasal inhalant forms of the medication because overdose treatment is an off-label use, the health officials said.

“We know that the men and women in law enforcement believe that saving a life is more important than making an arrest,” Botticelli said.

More than 16,000 people die each year due to opioid-related overdoses, according to the FDA. Drug overdose deaths — driven largely by prescription drug overdose deaths — are now the leading cause of injury death in the United States, surpassing motor vehicle crashes.

The FDA fast-tracked the approval of Evzio, turning the application around in just 15 weeks, Throckmorton said.

The agency noted that repeat doses may be needed because naloxone may not work as long as opioids. Also, people who receive a shot of Evzio may experience “severe opioid withdrawal,” the agency added.

There are dangers with quick withdrawal from “opioid depression,” the FDA said, with symptoms such as nausea, vomiting, sweating and accelerated heart rate, as well as a risk for spikes in blood pressure, seizures and even cardiac arrest.

Obama administration officials took pains to place the approval of Evzio in the context of other efforts that are being taken to rein in prescription drug abuse, including:

  • Counseling physicians and pharmacists on ways to detect “doctor-shopping” and patients with a drug problem.
  • Advancing development of new non-opioid pain medications.
  • Further restricting the prescription of medications containing hydrocodone by rescheduling them from Schedule III to Schedule II.

Federal officials are tackling this issue while also weighing the needs of people who rely on these pain medications, said U.S. Department of Health and Human Services Secretary Kathleen Sebelius.

“When addressing the opioid problem, it is important we consider those who rely upon and appropriately use their medication,” Sebelius said.

SOURCES: April 3, 2014, news release, U.S. Food and Drug Administration; April 3, 2014, news conference, with Michael Botticelli, acting director of the White House Office of National Drug Control Policy, Douglas Throckmorton, M.D., deputy director for regulatory programs, FDA’s Center for Drug Evaluation and Research, Margaret Hamburg, M.D., commissioner, U.S. Food and Drug Administration, Kathleen Sebelius, secretary, U.S. Department of Health and Human


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First test to predict Alzheimer’s years in advance

The death of nerve cells makes the brains of people with Alzheimer's disease (left) smaller than those of people showing no signs of dementia (right) <i>(Image: Pasieka/Science Photo Library)</i>

The death of nerve cells makes the brains of people with Alzheimer’s disease (left) smaller than those of people showing no signs of dementia (right) 

The world’s first blood test to predict Alzheimer’s disease before symptoms occur has been developed. The test identifies 10 chemicals in the blood associated with the disease two to three years before symptoms start, but it might be able to predict Alzheimer’s decades earlier.

Globally, 35 million people are living with Alzheimer’s. It is characterised by a toxic build up of amyloid and tau proteins in the brain, which destroys the neurons. Several blood tests can diagnose the disease, but until now, none has had the sensitivity to predict its onset.

Howard Federoff at Georgetown University in Washington DC and his colleagues studied 525 people aged 70 and over for five years. The group showed no signs of mental impairment at the start of the study. Each year, the team performed a detailed cognitive examination and took blood samples from all the participants. During this time, 28 people developed Alzheimer’s or mild cognitive impairment, thought to be the earliest noticeable sign of dementia, including Alzheimer’s disease.

An analysis of the participants’ blood highlighted 10 metabolites that were depleted in those with mild cognitive impairment who went on to get Alzheimer’s compared with those who didn’t. In subsequent trials, the team showed these chemicals could predict who would go on to get Alzheimer’s within the next three years with up to 96 per cent accuracy.

Decades of warning?

The 10 metabolites play a key role in supporting cell membranes, maintaining neurons or sustaining energy processes. “We think the decrease in these chemicals reflects the breakdown of neural populations in the brain,” says team member Mark Mapstone at the University of Rochester Medical Center in New York.

Once verified in a larger group, the test should provide a cheap and quick way of predicting Alzheimer’s. Mapstone says that it may even be able to predict the disease much earlier, because the brain changes associated with Alzheimer’s begin many years before symptoms occur. “These metabolic changes might occur 10 or 20 years earlier – that would give us a real head start on predicting the disease,” he says.

The team is hoping to investigate this by looking back at other dementia studies in which blood has been taken over decades and seeing whether the chemical changes can be detected that early, says Federoff.

The group also analysed the full genome sequence of all of the participants in the study. That work has yet to be published, but Federoff says the changes in genes over the five years of the study are even more powerful than the metabolites at predicting who will develop dementia. “The gene changes are linked to the metabolite changes, so we’re hoping to put all this together to provide a more complete description of the underlying pathology of the disease,” he says. “What’s most exciting is that we know the function of all the affected genes so if we can intercept these changes, they might make good candidates for new drugs.”

Knowledge is power

But with no treatments available, would anyone want to take these tests?

Mapstone says yes. “In my experience, the majority of people are very interested to know whether they will get Alzheimer’s. They believe that knowledge is power – particularly when it comes to your own health. We may not have any therapy yet but there are things we can do – we can get our financial and legal affairs in order, plan for future care, and inform family members.”

If the test could predict the disease 20 years before symptoms appear, the implications are huge, he says. “Imagine what you would do in your early 40s to slow the onset of the disease. You could eat the right foodsavoid head trauma or do more exercise.”

“In the short term, I think some people would want to know and some wouldn’t,” says Tracy Young-Pearse, a neurologist at Harvard Medical School. However, if treatments are developed that are only effective before neurons have started dying in large numbers, then it will be an easy decision to choose to take the blood test, she says.

Meanwhile, the new test will be valuable for drug discovery efforts, she says. Years of failed drugs trials have shown that you have to catch the disease early to have any influence.

Three studies starting this year hope to do just that. One will test anti-amyloid drugs on healthy people with a rare mutation that gives them early onset Alzheimer’s by age 45 (see “Testing a drug for the memory curse“).

The second will take advantage of a chemical developed last year that can be injected into the body and which accumulates in tau tangles. It will allow researchers to track the progression of tau in the living brain.

A third trial will investigate whether anti-amyloid drugs can prevent Alzheimer’s in older people who don’t yet have memory problems but do have amyloid building up in their brain.

“If an even earlier pre-clinical population could be identified with this blood test, it could be game changing,” says Young-Pearse.

Journal reference: Nature Medicine, DOI: 10.1038/nm.3466