Archives for category: antibiotics

microbes

From Harvard Gazette:

In 2002, a new kind of bacterial infection was detected in the United States. It was caused by a common bug, Staphylococcus aureus, but with a troubling new twist. It was resistant to the drug that typically offered the last line of treatment, when other remedies failed.

The appearance of vancomycin-resistant Staphylococcus aureus, dubbed VRSA, sent shock waves through the medical and public health communities. For years, vancomycin was the physicians’ ace in the hole, used to treat infections that didn’t respond to other drugs, in particular methicillin-resistant Staphylococcus aureus, known as MRSA.

In 2009, Harvard scientists teamed up to tackle the challenge posed by growing antibiotic resistance, creating a program bringing together researchers to examine the problem of antibiotic resistance, with a specific focus on VRSA, MRSA, and vancomycin-resistant enterococcus, or VRE.

Michael Gilmore, who organized the Harvard-wide Program on Antibiotic Resistance and whose lab in May announced it had decoded the genome of the 12 known VRSA strains in the United States, said the group is taking a diversified approach to meet the challenge of antibiotic resistance.

The group has seven main investigators who communicate and meet regularly, sharing notes and brainstorming fresh approaches to combat antibiotic-resistant bacteria.

Members of the group include Gilmore, the Sir William Osler Professor of Ophthalmology at Harvard Medical School (HMS) and Harvard-affiliated Massachusetts Eye and Ear Infirmary; Richard Losick, the Maria Moors Cabot Professor of Biology in the Faculty of Arts and Sciences (FAS); Fred Ausubel, professor of genetics at HMS and Harvard-affiliated Massachusetts General Hospital (MGH); Eleftherios Mylonakis, formerly at MGH and now contributing from Brown University; Suzanne Walker, professor of microbiology and immunobiology at HMS and an affiliate of the FAS Department of Chemistry and Chemical Biology; Roberto Kolter, professor of microbiology and immunobiology at HMS; and David Hooper, professor of medicine at HMS and MGH.

Of the three bacteria types the group is studying, MRSA is the most widespread, making up 30 percent of bacterial infections contracted outside of hospitals. It is deadly, having killed 18,000 per year since 2005, and is resistant to all of the commonly used antibiotics, including penicillin, amoxicillin, and methicillin. Vancomycin is typically reserved to fight MRSA and has to be carefully administered in a hospital, Gilmore said.

One difficulty in fighting antibiotic resistance is that the pace of new drug discovery has slowed, and so new drugs to which bacteria could not yet be resistant are few, Gilmore said. Antibiotics are often isolated from new strains of bacteria taken from the environment. The problem, Gilmore said, is that pharmaceutical companies have already scoured the easily accessible locations and are now extending into extreme environments in search of novel compounds.

These compounds are often the result of the chemical warfare that bacteria wage on each other. But only about 1 percent of bacteria found in the wild can be grown in the lab, Gilmore said, making the other 99 percent too difficult to use as sources of new medicines. Though efforts are under way to create strains that can live in the lab — or to transplant their DNA into bacteria like E. coli that grow readily in laboratory conditions — the process remains slow and difficult, Gilmore said.

The problems in dealing with drug-resistant bacterial strains aren’t just biological, however. Economics also comes into play, Gilmore said.

Drug companies have slowed their own research into new antibiotics because it is more economical to focus efforts on drugs for long-term conditions, Gilmore said. Compared with statins, used for a lifetime by patients to control high cholesterol, a new antibiotic makes less economic sense. Such a drug has similar development costs but will be used just for a few weeks until a patient is cured. A replacement for last-line drugs like VRSA, used only in the most intractable cases, would bring in even less money.

That’s why, Gilmore said, it’s important that academic scientists do a lot of the groundwork and initial discovery no longer being done by pharmaceutical companies.

For Losick, that means collaborating with Kolter in working on biofilms to find new ways to fight a physical structure that appears to protect the bacteria from antibiotics. When bacteria form biofilms, Losick said, they become more resistant to antibiotics, so research into how to prevent biofilms from forming or how to disperse them can provide an alternative way to fight bacteria. Today, Losick said, if a biofilm forms on an implant, like a hip replacement, there are few good ways to fight it, and the implant often has to come out.

“Staphylococcus aureus is an important public health threat. The idea is to develop fresh strategies for controlling it,” Losick said. “I think we all feel very pleased on how the program is progressing.”

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From Science:

Pharmaceuticals in drinking water: it’s a made-for-TV topic that can stir up public outcry faster than you can say “barely detectable residues.”

With little data on how much excreted and dumped medicines are in the environment, and even less showing a cause-effect relationship between an active ingredient and an adverse effect, researchers, health and environmental agencies, and water-quality regulators have been playing hot potato with the question for decades. But now it’s getting serious attention from the European Commission and some pharmaceutical companies. A conference convened with the University of Verona met at the Royal Society of Medicine here on Monday to discuss whether increased monitoring of medicines’ effects on the environment, or “ecopharmacovigilance,” warrants more intense scrutiny, and what, if anything, can be done to green an increasingly drug-dependent world.

“Pharmaceuticals are new pollutants,” said Yves Levi of the University of Paris-Sud. What makes them different, he said, is that the whole point of a drug is to have a very targeted effect from the lowest dose possible. Doctors and pharmacists should keep in mind the potential for unintended exposure, said Christian Daughton of the U.S. Environmental Protection Agency, comparing drug waste in water to doctors prescribing a cocktail of unknown medications to healthy people at random.

Weighing the benefit of expensive water cleanup procedures is tough to do when you don’t know much about the risk of environmental exposure. Only a few studies have shown cause-effect relationships. For instance, wide use of the animal growth promoter avoparcin, which chemically resembles vancomycin, is believed to have enabled the evolution of vancomycin-resistant enterococci, which can cause intestinal infections. And in several rivers around the world, endocrine disruptors such as ethinyl estradiol (EE2), the main component in most oral birth control pills, have been linked to the feminization of male fish. (Some research questions whether this has any effect on the fishes’ ability to reproduce, however.) No studies have shown any effects on human health or on developing fetuses, potentially the biggest causes for concern.

While some governments have been concerned, E.U. leaders have not seen pharmaceutical pollution as a priority in the past. Right now, the European Commission requires an environmental risk assessment to be performed prior to drug approval. For veterinary products, approval can be denied based on environmental hazard (although this has never happened). Human medicinal product approval cannot be denied for this reason.

But Sweden, for one, is taking the issue seriously. Over the past decade, Sweden has begun monitoring the environment for approved pharmaceuticals and instituted a national classification system that ranks drugs based on their possible toxic effects and potential to build up, or bioaccumulate, in the tissues of organisms. The government disseminates this information to doctors and pharmacies (state-owned in Sweden) to encourage environmentally sound decisions. At the conference, Åke Wennmalm of the consulting agency Sustainpharma in Stockholm presented part of a new, expanded classification system that analyzes the environmental impacts of a drug—where data are available—as it travels through manufacturing, disposal, and human waste. But Sweden does not set threshold limits for any drug.

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From The Independent:

Our last line of defence against bacterial infections is fast becoming weakened by a growing number of deadly strains that are resistant to even the strongest antibiotics, according to new figures given to The Independent on Sunday by the Health Protection Agency (HPA).

The disturbing statistics reveal an explosion in cases of super-resistant strain of bacteria such as E.coli and Klebsiella pneumoniae, a cause of pneumonia and urinary tract infections, in less than five years.

Until 2008, there were fewer than five cases a year in the UK of bugs resistant to carbapenem, our most effective intravenous (IV) antibiotic. New statistics reveal how there have been 386 cases already this year, in what the HPA has called a “global public health concern”. Doctors are particularly concerned because carbapenems are often the last hope for hospital patients suffering from pneumonia and blood infections that other antibiotics have failed to treat. Such cases were unknown in the UK before 2003.

Years of over-prescribing antibiotics, bought over the counter in some countries, and their intensive use in animals, enabling resistant bacteria to enter the food chain, are among the factors behind the global spread. According to the latest figures from the World Health Organisation, some 25,000 people a year die of antibiotic-resistant infections in the European Union.

In a statement issued during a WHO conference in Baku, Azerbaijan, last week, the organisation warned that doctors and scientists throughout Europe fear the “reckless use of antibiotics” risks a “return to a pre-antibiotic era where simple infections do not respond to treatment, and routine operations and interventions become life-threatening.”

More than 50 countries signed up to a European action plan on antibiotic resistance, unveiled at the conference, which includes recommendations for greater surveillance of antibiotic resistance, stricter controls over the use of antibiotics, and improved infection control in hospitals and clinics.

“We know that now is the time to act. Antibiotic resistance is reaching unprecedented levels, and new antibiotics are not going to arrive quickly enough,” said Zsuzsanna Jakab, the WHO Regional Director for Europe. “There are now superbugs that do not respond to any drug,” she added.

Dr Alan Johnson, a clinical scientist and expert in antibiotic resistance at the HPA, warned delegates at its annual conference last week that the problem is making some infections harder and in some, cases, virtually impossible, to treat.

Speaking to the IoS, he said: “We’ve had a problem of antibiotic resistance for as long as we’ve had antibiotics. The big problem at the moment is, for certain types of bacteria, we are seeing problems of resistance emerging and we don’t actually have any new antibiotics in the pipeline to deal with them.”

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From Los Angeles Times:

We’ve all heard that the overuse of antibiotics is making them less effective and fueling the rise of dangerous drug-resistant bacteria. But did you know it may also be fueling the rise of obesity, diabetes, allergies and asthma?

So says Dr. Martin Blaser, microbiologist and infectious disease specialist at New York University Langone Medical Center who studies the myriad bacteria that live on and in our bodies. He explains his theory in a commentary published in Thursday’s edition of the journal Nature.

In recent years, scientists have developed a growing appreciation for the “microbiome,” the collection of mostly useful bacteria that help us digest food, metabolize key nutrients and ward off invading pathogens. Investigators have cataloged thousands of these organisms through the National Institutes of Health’s Human Microbiome Project, begun in 2008.

Blaser is interested in why so many bacteria have colonized the human body for so long – the simple fact that they have strongly suggests that they serve some useful purpose. But these bacteria have come under attack in the last 80 or so years thanks to the development of antibiotics. The drugs certainly deserve some of the credit for extending the U.S. lifespan, Blaser notes – a baby born today can expect to live 78 years, 15 years longer than a baby born in 1940. But in many respects, an antibiotic targets a particular disease the way a nuclear bomb targets a criminal, causing much collateral damage to things you’d rather not destroy.

“Antibiotics kill the bacteria we do want, as well as those we don’t,” Blaser writes. “Sometimes, our friendly flora never fully recover.”

And that can leave us more susceptible to various kinds of diseases, especially considering that the typical American is exposed to 10 to 20 antibiotics during childhood alone. Blaser points out that the rise (let along overuse) of antibiotics coincides with dramatic increases in the prevalence of allergies, asthma, Type 1 diabetes, obesity and inflammatory bowel disease. That isn’t proof that the two are related, but it’s a question worth exploring, he says.

Take the case of Helicobacter pylori. As Blaser explains, this bacterium was “the dominant microbe in the stomachs of almost all people” in the early 1900s. But 100 years later, it is found in less than 6% of American, Swedish and German kids. One likely reason is that a single course of amoxicillin or another antibiotic to treat an ear or respiratory infection can wipe out H. pylori 20% to 50% of the time.

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From New York Times:

The maker of Dial Complete hand soap says that it kills more germs than any other brand. But is it safe?

That question has federal regulators, consumer advocates and soap manufacturers locked in a battle over the active ingredient in Dial Complete and many other antibacterial soaps, a chemical known as triclosan.

The Food and Drug Administration is reviewing the safety of the chemical, which was created more than 40 years ago as a surgical scrub for hospitals. Triclosan is now in a range of consumer products, including soaps, kitchen cutting boards and even a best-selling toothpaste, Colgate Total. It is so prevalent that a survey by the Centers for Disease Control and Prevention found the chemical present in the urine of 75 percent of Americans over the age of 5.

Several studies have shown that triclosan may alter hormone regulation in laboratory animals or cause antibiotic resistance, and some consumer groups and members of Congress want it banned in antiseptic products like hand soap. The F.D.A. has already said that soap with triclosan is no more effective than washing with ordinary soap and water, a finding that manufacturers dispute.

The F.D.A. was to announce the results of its review several months ago, but now says the timing is uncertain and unlikely until next year. The Environmental Protection Agency is also looking into the safety of triclosan.

The outcome of the federal inquiries poses a significant risk to the makers of antimicrobial and antibacterial hand soaps, which represent about half of the $750 million market for liquid hand soaps in the United States, according to the market research firm Kline & Company.

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From Chicago Tribune:

Trace amounts of sex hormones, prescription drugs, flame retardants and herbicides are being detected in treated drinking water pumped to more than 7 million people in Chicago and its suburbs.

In the latest round of testing prompted by a 2008 Tribune investigation, city officials discovered that more than two dozen pharmaceutical drugs and other unregulated chemicals pass through Chicago’s massive treatment plants.

Little is known about potential health effects from drinking drug-contaminated water, but scientists and regulators increasingly are concerned about long-term exposure, even at very low levels.

“We need to start addressing the cumulative effects that these low-dose exposures could be having on people,” said Thomas Burke, associate dean of the Johns Hopkins Bloomberg School of Public Health.

“There are no quick solutions,” said Burke, who chaired a National Academy of Sciences committee that called for a dramatic overhaul of the way the U.S. regulates toxic chemicals. “But we need a new approach that is more responsive to emerging science.”

Like other cities, Chicago must notify the public if its drinking water contains regulated contaminants, including lead, pesticides and harmful bacteria. There is no such requirement if pharmaceuticals and other unregulated substances are detected.

Annual water quality reports mailed last month to people in Chicago and the suburbs noted that the city is testing for substances that aren’t on the U.S. Environmental Protection Agency’s list of regulated contaminants. A list of results obtained by the Tribune is dated April 11 but wasn’t posted on the city’s website until after the newspaper asked for it last week.

City officials were prompted to start testing for the substances after the Tribune found trace amounts of pharmaceuticals, residue from personal care products and unregulated industrial chemicals in local tap water. Substances found in the city’s latest tests include the sex hormones testosterone and progesterone; gemfibrozil, a prescription cholesterol-fighting drug; and DEET, the active ingredient in bug spray.

The tests also found perfluorooctane sulfonate, an ingredient in Scotchgard stain-fighting coatings; bisphenol A, a hormone-like plastics additive; and tris (2-butoxyethyl) phosphate, a flame retardant chemical.

“Our very awareness of trace amounts of these chemicals comes in large part because we are aggressively conducting research on water quality and safety,” said Tom LaPorte, a spokesman for the Chicago Department of Water Management.

Drugs end up in drinking water after people take medicines and residue passes through their bodies down the toilet. Conventional sewage and water treatment filters out some of the substances, or at least reduces the concentrations, but studies have found that small amounts still get through.

Although treated sewage from the Chicago area drains away from Lake Michigan, more than 300 other cities discharge treated waste and untreated sewage overflows into the lake and its tributaries, according to the EPA.

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From Mother Jones:

Here is a document the USDA doesn’t want you to see. It’s what the agency calls a “technical review”—nothing more than a USDA-contracted researcher’s simple, blunt summary of recent academic findings on the growing problem of antibiotic-resistant infections and their link with factory animal farms. The topic is a serious one. A single antibiotic-resistant pathogen, MRSA—just one of many now circulating among Americans—now claims more lives each year than AIDS.

Back in June, the USDA put the review up on its National Agricultural Library website. Soon after, a Dow Jones story quoted a USDA official who declared it to be based on “reputed, scientific, peer-reviewed, and scholarly journals.” She added that the report should not be seen as a “representation of the official position of USDA.” That’s fair enough—the review was designed to sum up the state of science on antibiotic resistance and factory farms, not the USDA’s position on the matter.

But around the same time, the agency added an odd disclaimer to the top of the document: “This review has not been peer reviewed. The views expressed in this publication do not necessarily reflect the views of the United States Department of Agriculture.” And last Friday, the document (original link) vanished without comment from the agency’s website. The only way to see the document now is through the above-linked cached version supplied to me by the Union of Concerned Scientists.

What gives? Why is the USDA suppressing a review that assembles research from “reputed, scientific, peer-reviewed, and scholarly journals”?

To understand the USDA’s quashing of a report it had earlier commissioned, published, and praised, you first have to understand a key aspect of industrial-scale meat production. You see, keeping animals alive and growing fast under cramped, unsanitary conditions is tricky business. One of the industry’s tried-and-true tactics is low-level, daily doses of antibiotics. The practice helps keep infections down, at least in the short term, and, for reasons no one really understands, it pushes animals to fatten to slaughter weight faster.

Altogether, the US meat industry uses 29 million pounds of antibiotics every year. To put that number in perspective, consider that we humans in the United States—in all of our prescription fill-ups and hospital stays combined—use just over 7 million pounds per year. Thus the vast bulk of antibiotics consumed in this country, some 80 percent, goes to factory animal farms.

For years, scientists have worried that the industry’s reliance on antibiotics was contributing to the growing problem of antibiotic resistance. The European Union took action to curtail routine antibiotic use on farms in 2006 (taking Sweden’s lead, which had banned the practice 20 years before).

But here in the United States, the regulatory approach has been completely laissez-faire—and the meat industry would like to keep it that way. The industry claims that even though antibiotic-resistant bacteria have been found both in confined animals and supermarket meat, there’s simply no evidence that livestock strains are jumping to the human population.

Here is where we get back to that now-you-see-it, now-you-don’t USDA research summary, which reads like a heavily footnoted rebuttal to the industry line. Assembled by Vaishali Dharmarha, a research assistant at the University of Maryland, the report summarizes research from 63 academic papers and government studies. Here are few of her findings:

• “Use and misuse of antimicrobial drugs in food animal production and human medicine is the main factor accelerating antimicrobial resistance.”

• “[F]ood animals, when exposed to antimicrobial agents, may serve as a significant reservoir of resistant bacteria that can transmit to humans through the food supply.”

• “Several studies conducted by the Centers for Disease Control and Prevention (CDC) on antimicrobial-resistant Salmonella showed that [antibiotic resistance] in Salmonella strains was most likely due to the antimicrobial use in food animals, and that most infections caused by resistant strains are acquired from the consumption of contaminated food.”

• “Farmers and farm workers may get exposed to resistant bacteria by handling animals, feed, and manure. These exposures are of significant concern to public health, as they can transfer the resistant bacteria to family and community members, particularly through person-to-person contacts.”

• “Resistant bacteria can also spread from intensive food animal production area to outside boundaries through contact between food animals and animals in the external environment. Insects, flies, houseflies, rodents, and wild birds play an important role in this mode of transmission. They are particularly attracted to animal wastes and feed sources from where they carry the resistant bacteria to several locations outside the animal production facility.”

Naturally, such assertions didn’t please the meat industry—and the fact that they were backed up by dozens of peer-reviewed science papers no doubt only sharpened the sting. In the trade paper National Hog Farmer, a National Pork Producers Council official lashed out. Perhaps lacking factual ammunition, the official resorted to an attack on the researchers’ credentials: “We find it very disappointing that a research assistant at a university, who is not an Agricultural Research Service scientist, can develop and post such a review without it going through an agency or peer review process.”

Well, the pork producers can rest a bit easier. The researcher, Dharmarha, has been silenced. Not only has her report been erased from the USDA site, but she has been forbidden to talk to media.

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