Scientists Studying Bacteria And Antibiotics At The Atomic Level See Potential To Create Antibiotics Less Vulnerable To Resistance

A new understanding of an enzyme important for the transfer of genetic information in bacteria may help scientists improve current antibiotics and also create antibiotics that are less vulnerable to resistance. Researchers used extremely powerful imaging techniques to see, for the first time, exactly what happens between bacteria and antibiotics at the atomic level. They report their findings in two studies in the journal Nature. The work provides the most detailed view yet of an enzyme structure that is key to turning on the genes that make bacteria work, said Irina Artsimovitch, a co-author on both studies and an associate professor of microbiology at Ohio State University. Artsimovitch worked with Dmitry Vassylyev, the lead author of both studies and a professor of biochemistry and molecular biology at the University of Alabama at Birmingham. The two conducted the study with researchers from the University of Alabama at Birmingham , the University of Wisconsin-Madison and the University of Nebraska Medical Center. In the first study, the team found that they could create a detailed image of the elongation complex, a structure formed by RNA polymerase. RNA polymerase is the enzyme responsible for setting gene expression in motion, a process called transcription. Without a properly functioning RNA polymerase, a cell will die. "RNA polymerase spends most of its working hours as the elongation complex," Artsimovitch said. "The complex makes RNA's messages one step at a time, many thousands of times, until its completion. "This structure is important from a physiological point of view, not only for antibiotic design, but also because faults in the complex have been implicated in many diseases such as hereditary cancers." Artsimovitch and her colleagues used the bacterium Thermus thermophilus to run their experiments. While T. thermophilus won't make a human sick, the bacterium is widely used to gather structural information at the molecular level. The researchers first isolated the RNA polymerase from T. thermophilus. They then created an active elongation complex by mixing the enzyme with small molecules of DNA and RNA. This solution hardened into a crystal, which the researchers could then examine using an imaging technique called X-ray crystallography. X-ray crystallography let them create a computerized image showing the minute details of the elongation complex. In the second study, the team learned how the antibiotic streptolydigin blocks transcription. Streptolydigin has been around for several decades and the researchers already knew that this antibiotic stops RNA polymerase activity inside a cell. But they didn't know what controlled this mechanism. "We have to know what we're looking at -- and working with -- before it's possible to make a useful antibiotic," Artsimovitch said. "Now we can. Now we can see where the enzyme and antibiotic make contact at the atomic level." Upon examining the X-ray images, the researchers found that the antibiotic prevented the normal operation of the elongation complex by freezing it in the inactive state. They saw a loop-shaped element that must close every time the elongation complex adds a nucleotide (a building block of DNA or RNA) to the growing RNA chain. This loop must open again to allow the next cycle to happen. If something such as an antibiotic keeps the loop from closing, RNA polymerase can't properly function and stalls. "This loop is a target for antibiotics, including streptolydigin," Artsimovitch said. "If we can design new drugs that will prevent its movements, then we will immediately stop the action of RNA polymerase, and bacteria will die soon thereafter." The team's findings may be applicable to realms outside microbiology and drug discovery. Such a clear picture of the RNA polymerase elongation complex may be useful to a number of research areas, including manipulating the complex to increase the efficiency of bacteria that can harvest biofuels, Artsimovitch said. "We think that this mobile loop is a hot spot for regulating transcription in all living organisms, not only by using antibiotics but also by manipulating cellular factors," she said.

Foreclosure’s building problem

She wasn't an investor. She didn't have a subprime mortgage. But when Jordan Fogal's house became uninhabitable, the 62-year-old grandmother says foreclosure became her best alternative.
Fogal's troubles began when she and her 72-year-old husband, Bob, moved to a new housing development near Houston in 2002. That first night in the new house, the dining room ceiling collapsed. Bob had pulled the plug in the Jacuzzi tub upstairs, and 100 gallons of water came crashing through the ceiling downstairs because the plumbing drains were not connected.
"That was a preview of coming attractions," Fogal says. Later, the roof and windows leaked, the yard flooded, the shower walls started bowing out, the floor in the kitchen started sinking, and mold began to grow all over the house. The smell was terrible, she recalls, and eventually Fogal's doctor ordered her to leave the house because of the dangerous mold levels. A construction company hired by the Fogals estimated that it would take $150,000 to repair everything. "I could afford my mortgage payment, but I couldn't afford $150,000 in repairs," says Fogal, who had a 30-year fixed-rate mortgage at the time. The home — appraised at $408,000 the day the couple bought it — ended up selling for $234,000 at a foreclosure auction.
"All of this time, I was begging the builder to fix these problems," Fogal recalls. But, she says, they only showed up to about 25% of the appointments she made. "That's absolute nonsense," says Tom Thibodeau, president of Tremont Homes and then-president of the Fogal home's builder, Tremont Custom Construction. "We tried everything we could to fix this house, and she refused it. She only wanted us to buy the house back."
The only original problem with the Fogals' house, Thibodeau says, was a roof leak that was neglected and led to a myriad of other problems. "She would like everyone to believe the house was foreclosed on because of the defect," he says. "But by neglect, she let the leak go and other problems manifested from the leak."
More than a subprime problem?Fogal's case is not an isolated incident. Greg Cole, a homeowner in Georgia who runs a gripe site at georgiamoldhome.com, says he is on the brink of foreclosure after dealing with structural problems and leaks that have led to elevated mold levels. He, his wife, and his two children now take antibiotics every day, he says, because of the high level of mycotoxins — a toxin produced by fungi — in their blood. Elizabeth Dziedzic, a Realtor in Orange Park, Fla., says the deficiencies in her home make it impossible to sell for the amount it would take to pay off her mortgage balance. "There are only few events that are as devastating to a family as the loss of the family home to foreclosure," she says. "I guess this would be a price my family will pay for trying to achieve the American dream."
Foreclosures are up 93% from last year, according to Irvine, Calif.-based Web site RealtyTrac. At the same time, questions are arising as to whether construction quality suffered as homebuilders worked at lightning-fast speed to keep up with demand during the housing boom. It has become increasingly common for homeowners across the U.S. to share personal stories about defective construction through Web sites and blogs.
Everything you read says that the rise in foreclosure has to due with subprime lending," says Nancy Seats, president of Homeowners Against Deficient Dwellings, a nonprofit consumer protection group for homeowners dealing with defective construction. "But [defective construction] absolutely has something to due with the rise in foreclosures. There were absolutely investors that pushed up the price of housing, but there is no question that there are home buyers that were taken in and scammed big-time."
Why not just sue your builder when an irreparable problem arises? Homeowners usually don't have the right to. Most new-home sales contracts state that the customer must go through arbitration before they can even think about bringing their complaint to court.

"Wait-And-See" Approach For Treating Ear Infections Substantially Reduces Use Of Antibiotics

For children with acute ear infections seen in an emergency department, giving parents the option of delaying use of antibiotics resulted in significantly lower use of antibiotics compared to parents who received a standard prescription, with little difference in the outcomes for the children, according to a study in the September 13 issue of JAMA. Acute otitis media (AOM; ear infection) is the most common reason for which an antibiotic is prescribed to children. Treatment of AOM accounts for an estimated 15 million antibiotic prescriptions written per year in the United States, according to background information in the article. Untreated AOM has a high rate of natural resolution, with similar rates of complications whether antibiotics are prescribed or withheld. Resistance to antibiotics is a major public health concern worldwide and is associated with the widespread use of antibiotics. David M. Spiro, M.D., M.P.H., formerly of the Yale University School of Medicine, New Haven, Conn., and colleagues conducted a study to determine whether treatment of AOM using a "wait-and-see prescription" (WASP) significantly reduced use of antibiotics compared with a "standard prescription" (SP), and evaluated the effects of this intervention on clinical symptoms and adverse outcomes. Overall, 283 children with AOM aged 6 months to 12 years seen in an emergency department were randomly assigned to receive either a WASP (n = 138) or a SP (n = 145). All patients received ibuprofen and ear analgesic drops for use at home. Phone interviews were conducted after enrollment to determine outcomes. The trial was conducted between July 2004 and July 2005. The researchers found that the WASP significantly reduced the use of antibiotics. Substantially more parents in the WASP group did not fill the antibiotic prescription, compared to the SP group (62 percent vs. 13 percent). There was no statistically significant difference between the groups in the frequency of subsequent fever, otalgia (ear ache), or unscheduled visits for medical care. The patients in the WASP group whose parents filled the prescription reported they did so because of fever (60 percent), otalgia (34 percent), or fussy behavior (6 percent). No serious adverse events were reported for patients in the study. "This randomized controlled trial has provided evidence that the WASP strategy significantly reduces the use of antibiotics in an urban population presenting to an emergency department and may be an alternative to routine treatment of AOM with antibiotics. Wait-and-see prescriptions remain controversial as most pediatricians in the United States have been trained to routinely prescribe antibiotics for AOM and believe that many parents expect a prescription; a small minority of practitioners who care for children routinely use watchful waiting. "The WASP approach may interrupt the cycle of antibiotic prescription, the expectation of parents to immediately treat AOM with an antibiotic, and subsequent medical visits for this illness. The risks of antibiotics, including gastrointestinal symptoms, allergic reactions, and accelerated resistance to bacterial pathogens must be weighed against their benefits for an illness that, for the most part, is self limited. The routine use of WASP for AOM will reduce both the costs and adverse effects associated with antibiotic treatment and should reduce selective pressure for organisms resistant to commonly used antimicrobials," the authors conclude.

Research May Lead To New Classes Of Antibiotics

Scientists have what could be some very bad news for disease-causing bacteria. All three major classes of antibiotics that kill infectious bacteria do so in part by ramping up the production of harmful free radicals, researchers report in Cell a publication of Cell Press. Because those different types of antibiotics each initially hit different targets, it had been believed they worked by independent means. The findings could point the way to new classes of antibiotics and to a common method by which existing antibiotics could be made to stamp out bacteria even better, according to the Boston University researchers. Such advances are particularly critical at a time when, according to the Centers for Disease Control and Prevention, nearly all significant bacterial infections in the world are becoming resistant to the most commonly prescribed antibiotic treatments. "Hydroxyl radicals damage DNA, which turns on the S.O.S. repair response," said James Collins. "Therefore, our findings suggest that if you could shut off the bacteria's repair response, you might make all bactericidal antibiotics more effective and effective at lower doses. You could in essence create a super-Cipro, super-mycins, and so on." Current antimicrobial therapies fall into two general categories: (1) bactericidal drugs, which kill bacteria with almost complete efficiency, and (2) bacteriostatic drugs, which inhibit their growth, allowing the immune system to clear the infection, Collins's group explained. The targets of bactericidal antibiotics are well studied and predominantly fall into three classes: (1) those that hit DNA, (2) those that hit proteins, and (3) those that hit the bacterial cell wall. In contrast, most bacteriostatic drugs work by blocking the function of ribosomes, which are the sites of protein synthesis. While antibiotics' ability to kill bacteria had been attributed solely to those class-specific drug-target interactions, "our understanding of many of the bacterial responses that occur as a consequence of the primary drug-target interaction remains incomplete," the researchers said. Collins and his colleagues recently uncovered some evidence that at least some antibiotics might have some other deadly tricks. They showed that one type of antibiotics, including quinolones, which block DNA's replication and transcription into messenger RNA, also causes a breakdown that leads to the production of free radicals. Moreover, they found that those highly reactive chemicals help finish the bacteria off. In the new study, the researchers wanted to know whether other antibiotics also drive the toxic brew. Indeed, they show, drugs that kill bacteria all do cause a rise in free radicals, and all in the same manner. This is not so for drugs that only stunt bacteria's growth, they report. "The ever-increasing prevalence of antibiotic-resistant strains has made it critical that we develop novel, more effective means of killing bacteria," the researchers concluded. "Our results indicate that targeting bacterial systems that remediate hydroxyl radical damage, including proteins involved in triggering the DNA damage response… is a viable means of potentiating all three major classes of bactericidal drugs. Moreover, pathway analyses and systems biology approaches may uncover druggable targets for stimulating hydroxyl radical formation, which could result in new classes of bactericidal antibiotics."

Industry Provides Antibiotics, Heart Medicines And Painkillers Needed In Lebanon By Its Health Ministry, The WHO And NGOs

In rapid response to urgent medical needs in the Lebanon, the researchbased pharmaceutical industry has donated antibiotics, heart medicines, painkillers and other treatments. Ahead of the international donors' conference in Stockholm to raise funds to help the Lebanon, the International Federation of Pharmaceutical Manufacturers & Associations (IFPMA) today provided an overview of medical aid already furnished by its member companies. IFPMA Director General Dr. Harvey Bale said: "While the wholesale value of medicines donated by pharmaceutical companies for this latest Lebanese emergency is approaching USD 5 million, what is more significant is how quickly these products have been made available and that the donations were to meet the specific emergency demands of the Lebanese Ministry of Health, the World Health Organization and experienced non-governmental organizations operating in the region." Dr Bale continued: "Such a rapid response can only be achieved by working closely with the organizations on the ground, national governments and the WHO. Existing specialized pharmaceutical aid coordination organizations, notably Health Partners International of Canada, International Health Partnerships (UK), Partnerships for Quality Medicine Donations (USA) and TULIPE (France), have played an invaluable role in ensuring the speed and focus of the pharmaceutical industry's recent humanitarian aid effort in the Lebanon." The medicines provided by pharmaceutical companies for emergency use in the Lebanon include anesthetics, antibiotics, anticonvulsants, antidepressants, antidiarrheals, antifungals, antiinflammatories, antiretrovirals, heart medicines (antiarrhythmic, anticoagulant, anticholesterol, antiplatelet and hypertension treatments), laxatives, stomach medicines (beta-blockers and H2- antagonists), painkillers and tranquilizers. The donor companies involved include: AstraZeneca, Bayer, Boehringer Ingelheim, GlaxoSmithKline, Jansen-Cilag, Merck & Co., Novartis, Pfizer, Procter & Gamble, sanofi-aventis and Schering Plough. The International Federation of Pharmaceutical Manufacturers & Associations is the global nonprofit NGO representing the research-based pharmaceutical, biotech and vaccine sectors. Its members comprise 26 leading international companies and 46 national and regional industry associations covering developed and developing countries. The industry's R&D pipeline contains hundreds of new medicines and vaccines being developed to address global disease threats, including cancer, heart disease, HIV/AIDS and malaria. The IFPMA Clinical Trials Portal (http://www.ifpma.org/clinicaltrials) and IFPMA activities in Health Partnerships (http://www.ifpma.org) help make the industry's activities more transparent. The IFPMA strengthens patient safety by improving risk assessment of medicines and combating their counterfeiting. It also provides the secretariat for the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).

Antibiotics Help Combat Dangerous Tropical Disease

An antibiotic which has long been used to fight infections of the respiratory tract and intestine also seems to be able to defeat the dangerous pathogens causing elephantiasis. This is proved by a study carried out by parasitologists from the University of Bonn together with colleagues from Hamburg, Liverpool and Tanzania. Their findings have been published in the prestigious medical journal The Lancet (vol. 365, May 2005). The disease has previously been usually incurable. The disease is triggered off by the bite of an infected mosquito: together with its anticoagulant the mosquito pumps threadworm larvae into its host's body. These gravitate towards the lymph nodes, where they grow into threadworms which may be up to ten centimetres long. The body reacts by producing inflammation which halts the flow of lymphatic fluid. The consequence of this is that arms, legs and genitals swell to monstrous proportions - hence the name elephantiasis. More than 120 million people worldwide are infected with the pathogen wuchereria bancrofti. Adult wuchereria worms have a lifespan of up to five years. During this time they produce millions of offspring, what are known as micro-filariae, each of them smaller than the full stop at the end of this sentence. If the host is bitten again by a mosquito, the micro-filariae are ingested together with the blood. Inside the insect they mature into infectious worm larvae, thereby completing the circle. 'Although the drugs currently in use kill the micro-filariae, they largely leave the adult worms unscathed,' Bonn parasitologist Professor Achim H?f explains. 'Due to the long lifespan of the wuchereria worms, therapy lasts several years, during which time the symptoms continue to persist.' What is more, the drugs may cause severe side-effects. De-worming the roundabout wayYet the threadworm, too, has a sub-tenant, and this may be its Achilles heel, since in each wuchereria worm there are specific bacteria which are absolutely indispensable to the parasite's survival. If these bacteria die, the parasite will also die sooner or later. 'This is why wuchereria is susceptible to antibiotics which are normally used against bacterial infections,' Professor H?f emphasises. One example is doxycyclin, which has been used for decades for infections of the respiratory tract and the gastro-intestinal tract. In their study the medical experts in Tanzania treated 72 male patients for eight weeks with doxycyclin or a placebo. Initially the patients' blood was swarming with micro-filariae: the researchers counted up to 1,300 of them per millilitre of blood. Eight months later they had almost completely disappeared; only in one patient were sporadic micro-filariae still detected. However, the proportion of micro-filariae also dropped in the placebo group - an effect which was probably due to the improved care given the test persons. Unlike the drugs in use up to now the antibiotic also killed off the adult worms. Fourteen months after being treated with doxycyclin the doctors were only able to detect the typical movements of the worms ('the dance of the filariae') on ultrasound in one in five patients. In the placebo group the rate was 89%. In the doxycyclin group the concentration of specific worm proteins in the blood fell by over half. Effective, cheap, few side-effects'The importance of these findings for therapy should not be underestimated,' Professor H?f emphasises. 'The mature worms are after all responsible for such symptoms of the disease as the extreme swelling of the limbs. In the past there was no effective and reliable method of combating them.' The effectiveness of the antibiotic might be even greater than what was measured: 'We cannot exclude the possibility that several patients became re-infected in the months following treatment with doxycyclin. It is therefore quite possible that all the worms were killed and the remaining 20% are the result of re-infection which would no longer occur if infection was effectively prevented. Doxycyclin has been used for many years and has only minor side-effects. However, in young children it may cause irreparable damage to the teeth and slow down growth of the bones. For this reason the antibiotic should not be used during pregnancy, either. For adolescents and adults, however, the drug is harmless. Moreover, it is comparatively cheap. 'Its biggest advantage is that it is already licensed for medical use,' Professor H?f points out. 'Elephantiasis hits the poor most of all. It is therefore not likely that the pharmaceuticals industry will develop completely new drugs.'

Antibiotic Resistant Bacteria In Poultry Could Threaten Human Health

A surprising finding by a team of University of Georgia scientists suggests that curbing the use of antibiotics on poultry farms will do little - if anything - to reduce rates of antibiotic resistant bacteria that have the potential to threaten human health. Dr. Margie Lee, professor in the UGA College of Veterinary Medicine, and her colleagues have found that chickens raised on antibiotic-free farms and even those raised under pristine laboratory conditions have high levels of bacteria that are resistant to common antibiotics. Her findings, published in the March issue of the journal Applied and Environmental Microbiology, suggest that poultry come to the farm harboring resistant bacteria, possibly acquired as they were developing in their eggs. "The resistances don't necessarily come from antibiotic use in the birds that we eat," Lee said, "so banning antibiotic use on the farm isn't going to help. You have to put in some work before that." Lee and her team sampled droppings from more than 140,000 birds under four different conditions: 1.) commercial flocks that had been given antibiotics; 2.) commercial flocks that had not been given antibiotics; 3.) flocks raised in a lab that had been given antibiotics; and 4.) flocks raised in a lab that had not been given antibiotics. The researchers examined levels of antibiotic resistance in normal intestinal bacteria that do not cause human illness and - in a companion study published in May in the same journal - also examined levels of drug resistant campylobacter bacteria, a common foodborne cause of diarrhea, cramping and abdominal pain. They found that even birds raised in the pristine laboratory conditions had levels of antibiotic resistance levels comparable to what was seen on farms that used antibiotics. Even when the levels were lower, Lee adds, they were still well above the reasonable comfort zone for antibiotic resistance - roughly five to 10 percent. Seventy-three percent of the bacteria from one flock in the antibiotic-free commercial group were resistant to the drug oxytetracycline, for example, while 90 percent were resistant to the drug in a commercial flock that used antibiotics. Ninety-seven percent were resistant in the experimental flock that was given antibiotics, while forty-seven percent were resistant in the experimental group that was not given antibiotics. Strikingly, they even found bacteria resistant to streptomycin, a common human antibiotic that is rarely used in poultry and was not used on the farms the researchers studied. Bacteria swap genes relatively easily, and Lee explained that the concern is that drug resistance genes from bacteria that infect poultry could be passed on to bacteria that cause human illness. With these resistance genes, human bacterial illness could become harder to treat. These concerns led the European Union to ban the use of antibiotics for growth promotion in chickens in 2006. In 2005, the U.S. Food and Drug Administration banned the use of the drug Baytril - the brand name for enrofloxacin, a fluoroquinolone antibiotic - in poultry, citing concerns that it could lead to resistance in human antibiotics such as Cipro, also a fluoroquinolone. Several advocacy groups are pushing for a more comprehensive animal antibiotic ban in the United States, but Lee said her research plus the evidence from the Baytril ban suggests that approach won't help. "They banned Baytril in 2005, and if you look at Baytril resistance in campylobacter now it's essentially unchanged," Lee said. In previous studies, Lee has tried to recreate experimentally conditions that should lead to the swapping of resistance genes among bacteria. Lee said these events - known as the horizontal transfer of genes - do occur, but they may not be as common as initially thought. What may be driving the antibiotic resistance that Lee has observed in her studies is what's known as vertical transfer - from parent to child - of bacteria carrying resistance genes. In short, the birds may come to the farm harboring antibiotic resistant bacteria. "This issue of antibiotic resistance is more complicated than once thought," Lee said. "These findings suggest that banning antibiotics at the farm level may not be as effective as assumed. We need further studies to identify which management practice would be effective" Lee stresses that for consumers, the advice on poultry is the same that it's always been. Cook meat thoroughly and use proper food handling and preparation techniques - washing your hands regularly and keeping other foods away from raw chicken, for example - to minimize the risk of illness. "All foods have the potential to contain pathogens - all of them," Lee said. "There's no substitute for good food handling and preparation."

Researchers make gains in understanding antibiotic resistance

Howard Hughes Medical Institute researchers chiseling away at the problem of antibiotic resistance now have a detailed explanation of how the drugs' main cellular target in bacteria evolves to become resistant to some of these medications. The findings are already leading to new experimental antibiotics that are being engineered to circumvent resistance, which is a major worldwide health problem. Led by Thomas A. Steitz, a Howard Hughes Medical Institute investigator at Yale University, and Peter B. Moore, a professor of chemistry at Yale, the research team published its findings in the April 22, 2005, issue of the journal Cell. Steitz and his colleagues studied the structural basis of bacterial resistance to a group of antibiotics that, while chemically quite different, all jam the activity of the protein-making factory in bacteria in much the same way. They studied the MLSBK antibiotics, an acronym for a group of antibiotics which include macrolides, lincosamides, streptogramin B and ketolides. MLSBK antibiotics work by binding to the RNA, near the peptidyltransferase center, of the large subunit of the ribosome. The ribosome is the molecular machine responsible for translating the genetic information on messenger RNA into the long strings of amino acids called polypeptides that are used to build the cell's enzymatic machinery. "These antibiotics are clinically very important, and resistance to such antibiotics is a major health problem," said Steitz. "It is becoming critical to understand the precise structural basis of resistance and even more important to do something about it." Steitz cited, for example, recent statistics published in the journal Nature, stating that hospitals in the United States see some two million cases of antibiotic-resistant infections each year; 90,000 patients die annually from such infections. In their experiments, Steitz and his colleagues used x-ray crystallography to do high-resolution structural analyses of the large ribosomal subunits bound to a number of the MLSBK antibiotics. In this analytical technique, intense beams of x-rays are directed through crystals of proteins. The underlying atomic structure of the proteins is deduced by analyzing the pattern of diffraction of the x-rays. Steitz's group used ribosomal subunits from the primitive archaebacterium Haloarcula marismortui (Hma), which is found in the Dead Sea. They chose Hma ribosomes for their studies because they crystallize well enough to yield high-resolution structural data, but these ribosomes, like those from eukaryotes, are resistant to most MLSBK antibiotics. The researchers analyzed the structure of erythromycin - among the most widely prescribed macrolide antibiotics - bound to a mutated version of the Hma ribosome that corresponds to a form found in pathogenic bacteria. Their studies revealed details of erythromycin binding to the mutant form of the Hma ribosome that do not agree with similar analyses by other researchers, according to Steitz. The studies by Steitz's group yielded new information about the basic chemical principles that underlie binding of the antibiotic to the ribosome, as well as new data about how that mutation confers drug resistance. Steitz and his colleagues also analyzed the structure of five other clinically important antibiotics - azithromycin, telithromycin, clindamycin, and virginiamycin M and virginiamycin S - bound to the large mutated ribosomal subunit. Steitz said these studies provided new details about the nature of drug resistance involving these antibiotics. Furthermore, the studies of the two forms of virginiamycin offer an explanation for how the two forms of that antibiotic work synergistically to kill bacteria. Finally, the researchers used x-ray crystallography to explore at high resolution the structural basis of a particular ribosomal mutation dubbed L22 that confers resistance to macrolides such as erythromycin. In a seeming paradox, said Steitz, this mutation confers resistance, even though the antibiotic still binds to the mutant ribosome. The new structural data indicate that the L22 mutation increases the size of a "tunnel" in the ribosome, through which the growing peptide chain moves during synthesis. This tunnel is normally blocked by macrolide antibiotics. In the mutant form, the tunnel widens, which may explain why macrolide antibiotics are no longer effective. According to Steitz, insights about the ribosomal origins of antibiotic resistance are already being applied to the development of new antibiotics. One company leading the way is Rib-X Pharmaceuticals, which was founded by Steitz and colleagues at Yale. "About half of current antibiotics target the ribosome, and most of them target the large subunit," he said. "So, such advances have the potential for significant clinical impact. The general strategy of Rib-X to overcome resistance is to create new hybrid antibiotics that possess the ability to bind to interact simultaneously with different, nearby sites on the ribosome represented by different classes of antibiotics," he said. "The idea is to take a bit of one antibiotic and tie it to another. So, if resistance arises due to a mutation in one site, there is still another binding site that can be targeted. It's like multiple drug therapies for HIV, in which the drugs attack several sites at once. And if the virus mutates to avoid the effects of one drug, it still gets hit by another. However, in the case of these antibiotics, the binding sites are linked in one molecule. It's like a multi-drug treatment, but in one compound," he said.

Antibiotic Use In Infants Linked To Asthma

New research indicates that children who receive antibiotics before their first birthday are significantly more likely to develop asthma by age 7. The study, published in the June issue of CHEST, the peer-reviewed journal of the American College of Chest Physicians (ACCP), reports that children receiving antibiotics in the first year of life were at greater risk for developing asthma by age 7 than those not receiving antibiotics. The risk for asthma doubled in children receiving antibiotics for nonrespiratory infections, as well as in children who received multiple antibiotic courses and who did not live with a dog during the first year. "Antibiotics are prescribed mostly for respiratory tract infections, yet respiratory symptoms can be a sign of future asthma. This may make it difficult to attribute antibiotic use to asthma development," said lead study author Anita Kozyrskyj, PhD, University of Manitoba, Winnipeg, MB. "Our study reported on antibiotic use in children being treated for nonrespiratory tract infections, which distinguishes the effect of the antibiotic." By using a prescription database, Dr. Kozyrskyj and colleagues from the University of Manitoba and McGill University in Montreal were able to monitor the antibiotic use of 13,116 children from birth to age 7, specifically noting antibiotic use during the first year of life and presence of asthma at 7. The reason for antibiotic use was categorized by lower respiratory tract infection (bronchitis, pneumonia), upper respiratory tract infection (otitis media, sinusitis), and nonrespiratory tract infection (urinary infections, impetigo). Risk and protective factors also were noted, including gender, urban or rural location, neighborhood income, number of siblings at age 7, maternal history of asthma, and pets reported living in the home. Within the study group, 6 percent of children had current asthma at age 7, while 65 percent of children had received at least one antibiotic prescription during the first year of life. Of the prescriptions, 40 percent of children received antibiotics for otitis media, 28 percent for other upper respiratory tract infections, 19 percent for lower respiratory tract infections, and 7 percent for non-respiratory tract infections. Results showed that antibiotic use in the first year was significantly associated with greater odds of asthma at age 7. This likelihood increased with the number of antibiotic courses, with children receiving more than four courses of antibiotics having 1.5 times the risk of asthma compared with children not receiving antibiotics. When researchers compared the reason for antibiotic use, their analysis indicated that asthma at age 7 was almost twice as likely in children receiving an antibiotic for nonrespiratory tract infections compared with children who did not receive antibiotics. Maternal asthma and presence of a dog during the first year of life were both associated with asthma risk. Children who received multiple antibiotic courses and who were born to women without a history of asthma were twice as likely to develop asthma than those not receiving antibiotics. Furthermore, absence of a dog during the birth-year doubled asthma risk among children taking multiple courses of antibiotics. "Dogs bring germs into the home, and it is thought that this exposure is required for the infant's immune system to develop normally. Other research has shown that the presence of a dog in early life protects against the development of asthma," said Dr. Kozyrskyj. "Exposure to germs is lower in the absence of a dog. The administration of an antibiotic may further reduce this exposure and increase the likelihood of asthma development." "Antibiotics are frequently prescribed for young children for both respiratory and nonrespiratory infections," said Mark J. Rosen, MD, FCCP, President of the American College of Chest Physicians. "Understanding the relationship between antibiotic use and asthma can help clinicians make more informed decisions about treatment options for children."

Bacteria Fighter Goes Where Antibiotics Can't

Researchers at the Technion-Israel Institute of Technology have figured out a way to turn one of nature's most powerful microbe fighters into a guided missile that strikes specifically at a common bacteria responsible for serious infections throughout the body.Professor Amram Mor of the Biotechnology and Food Engineering Faculty and his colleagues revamped an antimicrobial peptide, a small molecule made of short chains of amino acids, that attacks Pseudomonas aeruginosa. P aeruginosa is the bacterium behind serious lung infections in people with cystic fibrosis and some types of pneumonia and meningitis, as well as less serious but widespread infections such as "swimmer's ear" and urinary tract infections.The research was reported in the January 26 issue of the journal Chemistry and Biology. Common antibiotic medicines used to treat infections are increasingly thwarted by new strains of drug-resistant bacteria. Unlike most antibiotics, antimicrobial peptides can sidestep such resistance mechanisms and destroy by brute force, often simply ripping a hole in a targeted cell. For this reason, "antimicrobial peptides present an obvious advantage over conventional antibiotics," said Mor.Yet one of the features that makes the peptides so useful their ability to kill a variety of invaders from bacteria to cancer cells makes them hard to deploy as a treatment against specific infections. Their "non-specific" action can also destroy normal red blood cells.The number and order of amino acids in an antimicrobial peptide determines how it recognizes and attacks an invading microbe. Some previous studies have shown that removing amino acids from one end of a peptide can boost its antibacterial properties. However, these shortened peptides are also more deadly to red blood cells.To build a more useful and less toxic antimicrobial peptide, Mor and colleagues removed a few amino acids from one end of a dermaseptin peptide and replaced it with a fatty acid molecule. (Dermaseptins are a well-known family of peptides that destroy a wide range of microbes). The study shows for the first time that a fatty acid can replace part of a shortened peptide, which may lower the costs of manufacturing such peptides, according to the researchers.The change made this particular peptide deadly accurate against P. aeruginosa while leaving other bacteria alone. The new peptide was also 60 times less likely to adhere to red blood cells."Many experts believe that one of the factors that might hamper the commercial use of antimicrobial peptides is their prohibitive cost. Therefore, smaller means cheaper and in this case, more potent," Mor said.Mor said the procedure might be used to create a variety of designer peptides that latch on different microbes, and that his lab will work on repeating the strategy with other peptide chains. The researchers also hope to test these new peptides against infections in animals.The Technion-Israel Institute of Technology is Israel's leading science and technology university. Home to the country's winners of the Nobel Prize in science, it commands a worldwide reputation for its pioneering work in nanotechnology, computer science, biotechnology, water-resource management, materials engineering, aerospace and medicine. The majority of the founders and managers of Israel's high-tech companies are alumni. Based in New York City, the American Technion Society is the leading American organization supporting higher education in Israel, with 17 offices around the country.

Discount Store Publix Begins To Offer Seven No-Cost Prescription Generic Antibiotics

Florida-based Publix Super Markets on Monday began offering 14-day supplies of seven common, generic antibiotics at no cost to customers with a valid prescription, the AP/South Florida Sun-Sentinel reports. There will be no limit on the number of prescriptions a customer may fill. The supermarket chain will offer the no-cost antibiotics at its 684 stores in Florida, Georgia, South Carolina, Alabama and Tennessee (AP/South Florida Sun-Sentinel, 8/6).The move by Publix comes after Wal-Mart Stores last year launched a program that offers 30-day supplies of 291 generic drugs for $4; Target offers a similar program. Michigan-based grocer Meijer in October 2006 began offering eight generic antibiotics at no cost.The antibiotics offered by Publix, which have an average price between $10 and $60, are amoxicillin, cephalexin, sulfamethoxazole/trimethoprim, penicillin VK, ciprofloxacin, ampicillin and erythromycin. The company has declined to disclose how much the program would cost (Bora, St. Petersburg Times, 8/7). Publix said that it will not bill insurers, including Medicare, for the cost of the drugs for customers who have health coverage. The company estimates that antibiotics account for nearly 50% of generic and pediatric prescriptions filled at Publix pharmacies (Dorschner, Miami Herald, 8/6).Publix CEO Charlie Jenkins said, "Frankly, we're interested in building our pharmacy business," adding, "But moreover, we want to help the citizens of our state have affordable health care, and we thought this was just a good start in doing that." Andrew Agwunobi, secretary of Florida's Agency for Health Care Administration, noted that the state has 3.6 million uninsured residents and that many insured residents lack prescription drug coverage. Agwunobi predicted a heavy response to the program, adding, "So I hope (Publix stores) are ready" (AP/South Florida Sun-Sentinel, 8/6). Reprinted with kind permission from . You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.bestdrugsnow.com/antibiotics/. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation.

Creating a permanent chemical bond between antibiotics and titanium, a material used in orthopedic implants

Infections associated with inserting a medical device can be devastating, painful, and cause prolonged disability, costing tens of thousands of dollars. Now, researchers at Jefferson Medical College have found a way to create a permanent chemical bond between antibiotics and titanium, a material used in orthopedic implants. The proof-of-principle study showed that an antibiotic can be connected to the titanium surface in an active form, and can kill bacteria and prevent infection. The work is a critical first step toward developing stable, bacteria-resistant implants to combat infection. "The biggest benefit of this work is to keep the infection from ever starting," says Eric Wickstrom, Ph.D., professor of biochemistry and molecular biology at Jefferson Medical College of Thomas Jefferson University, who in collaboration with Noreen Hickok, Ph.D., associate professor of orthopedic surgery at Jefferson Medical College and Allen Zeiger, Ph.D., professor of biochemistry and molecular biology at Jefferson Medical College, developed the bonding method. Infections associated with orthopedic implants are one of the major causes of implant failure. If bacteria grow on an implant, it can't knit properly with bone. "Our technique puts a bed of antibiotic nails on the surface of the implant," Dr. Wickstrom says. "The first time a bacterium lands on those nails, it dies." The researchers, along with co-authors Binoy Jose, Ph.D., a former postdoctoral fellow now at SK Biopharmaceuticals, and M.D./Ph.D. student Valentin Antoci, Jr., report their results September 23, 2005 in the journal Chemistry and Biology. In the work, the scientists fastened the antibiotic vancomycin to titanium powder. The vancomycin could then immediately kill bacteria sensitive to vancomycin that landed on the titanium. The researchers checked to see if vancomycin was indeed attached to the titanium surface using microscopy. Next, they added a fragment of bacterial cell wall to see if the vancomycin on the powder, or beads, could bind to its natural target. The tests proved that the vancomycin was bound and active. Finally, they added bacteria and showed that titanium beads with vancomycin on the surface killed the bacteria. When the beads were exposed to more bacteria, the vancomycin continued to kill the new infection. The vancomycin was not only chemically bound, but aggressively curtailed re-infection as well. The researchers, led by Irving Shapiro, Ph.D., professor of orthopedic surgery at Jefferson Medical College, and including collaborators at the Rothman Institute at Jefferson and the University of Pennsylvania are supported by a grant from the U.S. Department of Defense to develop techniques to protect titanium surfaces with antibiotics. "The recent results are another step toward our ultimate goal of preventing infections in battlefield fractures and hip and knee implants," Dr. Shapiro says. "This technology bonding antibiotics to the implant surface is analogous to having land mines," says orthopedic surgeon Javad Parvizi, M.D., who treats implant-related infections and works on the project. "Once the organism steps on the surface, the antibiotic mine explodes and kills the bacteria. It holds great promise for our patients." When a hip or knee implant is infected, physicians give extensive antibiotic treatment and the old implant is replaced. The treatment can include cement-containing antibiotics. "The hope is that the drugs in the glue will protect the implant, but that doesn't always work," Dr. Hickok explains. She notes that while they are infrequent, such infections can occur right after surgery from contamination during the operation. Later, infections can start on the implant from a different source in the body, such as a bladder infection or a dental procedure. Dr. Wickstrom says the same approach can be used for other antibiotics and other implants. "There are plastic devices - bladder catheters, implants for kidney dialysis, Hickman tubes, pacemakers - every implant you can think of is a magnet for bacteria," he says. "The idea of having a permanent chemical bond to the metal is a new approach. This can be used for every metal and plastic implant, with every antibiotic." While the current work is proof-of-principle for binding titanium to an antibiotic, the research team has received a new grant for $3 million from the National Institutes of Health for five years to investigate ways of encouraging bone growth on implants bearing permanent antibiotics. "When an infected implant is taken out, it's usually covered with a slimy layer of bacteria," Dr. Hickok explains. "We're moving from just having a bacteria-killing surface to having one that prevents infection while promoting better bone-implant interactions. The idea is to have the implant last for many more years and avoid infection.

Guidelines For Duration Of Antibiotics During Labor Refuted

The intensive and prolonged observation of infants at risk for group B streptococcus (GBS) may not benefit the infant and may heighten parental anxiety, researchers at Yale School of Medicine report in a recent article in Obstetrics & Gynecology.Current Centers for Disease Control and Prevention (CDC) guidelines recommend at least four hours of antibiotics to treat GBS in pregnant women in labor. About 50 percent of women with GBS are unable to receive the full four hours of treatment due to rapid labor and delivery. The CDC considers their newborns "at risk" for GBS and recommends blood tests and 48 hours of observation in the hospital.Researchers from Yale School of Medicine's Departments of Obstetrics, Gynecology & Reproductive Sciences (Ob/Gyn), and Epidemiology and Public Health (EPH) sought evidence to support the CDC guidelines. They conducted a systematic review of all published studies that included the duration of GBS antibiotic treatment of women in the delivery room and the numbers of infants who developed GBS. They calculated risk ratios for GBS colonization or sepsis based on duration of treatment."Neither the pharmacologic literature nor the clinical literature provide evidence to support the current CDC guidelines about duration of antibiotic prophylaxis during labor," said Jessica Illuzzi, M.D., assistant professor in Yale Ob/Gyn who conducted the study with Michael Bracken, the Susan Dwight Bliss Professor of Epidemiology in EPH and Professor of Neurology and Ob/Gyn."The current protocol results in large numbers of low risk newborns undergoing invasive, expensive neonatal testing and prolonged observation, despite the lack of evidence that this group of infants is at higher risk for GBS infection," Illuzzi added.She said the pharmacologic literature reveals that effective levels of antibiotics are detectable in the fetal bloodstream and amniotic fluid as early as five minutes after treatment begins. The risk of neonatal GBS infection is also significantly reduced after one to two hours of treatment."Ultimately, we hope the CDC guidelines will be re-evaluated and revised to reflect the evidence so that resources, invasive testing and prolonged observation are directed to infants truly at risk for GBS disease," said Illuzzi.Future research by Illuzzi and Bracken include a possible prospective study to measure the duration of treatment and the spread of GBS among newborns.

"Super Bug" Scares - Straight Facts About Antibiotic Resistance

With recent news about "super bugs," you may wonder if antibiotics are still effective, and whether they will work for you when you need them. You're not alone - there is a lot of confusion about antibiotics - what they do and don't treat, and why they sometimes stop working. It is important to know that antibiotics are effective only if they are prescribed and taken correctly.Two main types of germs cause most infections - viruses and bacteria. Antibiotics are a type of medicine that can kill or stop the growth of bacteria and help cure the infections they cause. Some people think that antibiotics can be used to treat viral infections, such as a cold or the flu. However, it is very important that you not take an antibiotic for a cold or the flu - doing so can contribute to what experts call "antibiotic resistance." To help you understand when you need to take antibiotics and how you should use them, here are answers to some of the most commonly asked questions about antibiotics and resistance.Q. What is antibiotic resistance?A. Antibiotic resistance is the ability of bacteria to resist the effects of an antibiotic. When this occurs, medications used to treat infections caused by bacteria become less effective or not effective at all. When antibiotics are used incorrectly, such as when they are taken when not needed, bacteria can develop new ways to fight the medicine, and they become resistant to antibiotic medications. This can lead to more visits to the doctor, more medication, higher medical bills or even a visit to the hospital.Q. Do currently available antibiotics still work?A. Yes. There are still many effective antibiotics available. The best antibiotic is the one that kills the bacteria and stops the infection the first time. Antibiotics are most effective when taken as prescribed by your doctor.Q. Can an antibiotic be used to treat the cold or the flu?A. No. Antibiotics only treat illnesses caused by bacteria. Colds and the flu are caused by viruses. Taking antibiotics when you have a virus may cause more harm than good. Your doctor can determine whether your infection is caused by a virus or bacteria.Q. I was prescribed an antibiotic the last time I was sick, so is it safe to assume that I should probably take an antibiotic again?A. No. Often, people become confused about whether they should treat the sniffles, a cough and aches with just rest and fluids, or with an antibiotic. Doctors report that many patients see them to request antibiotics even though antibiotics might not be appropriate. Your doctor will decide if an antibiotic is appropriate for you. DO NOT take leftover antibiotics or an antibiotic that was prescribed for someone else. Taking antibiotics when not needed may increase your risk of getting an infection that resists antibiotic treatment.Q. If I feel better, can I stop taking my antibiotic?A. No. Take your antibiotic exactly as prescribed - and that means finishing the entire course, even if you feel better. Stopping treatment too soon, even if you feel better, also contributes to resistance because the bacteria may be left to grow and multiply. Taking the complete course helps to make the medication effective, allowing it to kill the bacteria causing the infection and reduce the risk of resistance. If you feel worse or experience a side effect while taking an antibiotic, please consult your doctor.Remember, antibiotics are strong medications that can stop infections and save lives. Talk to your doctor about whether or not you need an antibiotic and how to use it correctly.LEVAQUIN® (levofloxacin) is indicated for adults with acute bacterial sinusitis due to Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis.Important Safety InformationThe most common drug-related adverse events in US clinical trials were nausea (1.5%) and diarrhea (1.2%).The safety and efficacy of levofloxacin in pediatric patients, adolescents (under 18), pregnant women, and nursing mothers have not been established. Levofloxacin is contraindicated in persons with a history of hypersensitivity to levofloxacin, quinolone antimicrobial agents, or any other components of this product. Serious and occasionally fatal events, such as hypersensitivity and/or anaphylactic reactions, as well as some of unknown etiology have been reported in patients receiving therapy with quinolones, including levofloxacin. These reactions may occur following the first dose or multiple doses. The drug should be discontinued at the first appearance of a skin rash or any other sign of hypersensitivity.As with other quinolones, levofloxacin should be used with caution in patients with known or suspected central nervous system disorders, peripheral neuropathy, or in patients who have a predisposition to seizures.Tendon ruptures that required surgical repair or resulted in prolonged disability have been reported in patients receiving quinolones, including levofloxacin, during and after therapy. This risk may be increased in patients receiving concomitant corticosteroids, especially the elderly. The quinolone should be discontinued in patients experiencing pain, inflammation, or rupture of a tendon.Some quinolones, including levofloxacin, have been associated with prolongation of the QT interval, infrequent cases of arrhythmia, and rare cases of torsades de pointes. Levofloxacin should be avoided in patients with known risk factors such as prolongation of the QT interval, patients with uncorrected hypokalemia, and patients receiving class IA (quinidine, procainamide), or class III (amiodarone, sotalol) antiarrhythmic agents.Antacids containing magnesium or aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc, or Videx®* (didanosine) chewable/buffered tablets or the pediatric powder for oral solution, should be taken at least 2 hours before or 2 hours after levofloxacin administration.For information on Warnings, Precautions, and additional Adverse Reactions that may occur, regardless of drug relationship, please see full Prescribing Information.

Natural Antibiotics Yield Secrets To Atom-Level Imaging Technique

Frog skin and human lungs hold secrets to developing new antibiotics, and a technique called solid-state NMR spectroscopy is a key to unlocking those secrets. That's the view of University of Michigan researcher Ayyalusamy Ramamoorthy, who will discussed his group's progress toward that goal at the annual meeting of the Biophysical Society in Baltimore, Md. Ramamoorthy's research group is using solid-state NMR to explore the germ-killing properties of natural antibiotics called antimicrobial peptides (AMPs), which are produced by virtually all animals, from insects to frogs to humans. AMPs are the immune system's early line of defense, battling microbes at the first places they try to penetrate: skin, mucous membranes and other surfaces. They're copiously produced in injured or infected frog skin, for instance, and the linings of the human respiratory and gastrointestinal tracts also crank out the short proteins in response to invading pathogens. In addition to fighting bacteria, AMPs attack viruses, fungi and even cancer cells, so drugs designed to mimic them could have widespread medical applications, said Ramamoorthy, who is an associate professor of chemistry and an associate research scientist in the Biophysics Research Division. While researchers have identified hundreds of AMPs in recent years, they're still puzzling over exactly how the peptides wipe out bacteria and other microbes. Unlike conventional antibiotics, which typically inhibit specific bacterial proteins, AMPs get downright physical with invaders, punching holes into their membranes. But they're selectively pugnacious, targeting microbes but leaving healthy host cells alone. "They're like smart bombs," Ramamoorthy said. "We'd like to exploit their properties to design super-smart bombs, but before we can do that, we need to understand how these AMP smart bombs interact with membranes to destroy bacteria. We need to know how they're shaped before, during and after the process of attaching to bacteria and how they attach." Solid-state NMR spectroscopy is an ideal tool for answering such questions because it provides atom-level details of the molecule's structure in the complex and challenging cell membrane environment, Ramamoorthy said. "Just as an MRI produces a detailed image of our internal organs, solid-state NMR spectroscopy is used to construct a detailed image of a peptide or protein and to reveal how it sits in the cell membrane," providing clues for modifications that might make synthetic AMPs even more effective in overcoming ever-increasing bacterial resistance. For instance, rearranging parts of the molecule might make it fit into the membrane better, resulting in greater effectiveness with smaller amounts of AMP. "Our overall mission is to use the kind of basic physical data we obtain from solid-state NMR spectroscopy to help interpret biological functions," Ramamoorthy said. The work is highly interdisciplinary, involving not only Ramamoorthy's lab and several other groups in the Chemistry Department, but also researchers from the College of Engineering, the School of Dentistry, the Medical School and the Biophysics Research Division, as well as collaborators in Canada, Japan, India and the U.S. pharmaceutical companies Genaera Corporation and Eli Lilly and Company. Ramamoorthy was awarded support from the National Institutes of Health and the National Science Foundation, through an NSF Faculty Early Career Development Award. A leader in this area of research, he has organized two major international symposia on the field at the University of Michigan, edited a special issue in the journal BBA-Biomembranes, published a number of papers in leading journals, and brought out a book on NMR Spectroscopy of Biological Solids. Ramamoorthy says that this area of research will grow considerably at U-M from implementing plans to set up a high magnetic field solid-state NMR spectrometer facility and an NIH-funded program.

Reminding Doctors Which Antibiotics To Prescribe Cuts C. Difficile Infection Rates

A study published today in the Journal of Antimicrobial Chemotherapy1 provides the best available evidence that cases of Clostridium difficile infection (CDI) one of the most common and increasing types of hospital-acquired infection can be reduced in hospital wards if doctors prescribe narrow-spectrum antibiotics rather than broad-spectrum agents. Researchers at the Royal Free Hospital in London, which now has the lowest CDI rates of any teaching hospital in the UK, investigated the best way to encourage doctors to make the switch from broad spectrum to narrow spectrum agents. They found that use of a pocket-sized laminated card telling doctors which antibiotics to prescribe combined with feedback on antibiotics use and CDI rates led to a significant drop in prescriptions of broad-spectrum agents, and an accompanying fall in CD infections. The research team, from the Academic Department of Geriatrics, in the Medical School, suggest that both the study and the intervention could be successfully replicated in other hospitals in an attempt to reverse the rapid increase in CDI in the NHS. . This finding is especially important because CDI rates are rising rapidly in the UK and a new more virulent strain has recently been identified2 A 2005 study by the Healthcare Commission3 found that 38% of NHS Trusts did not restrict broad-spectrum antibiotic use, despite the known association between these compounds and CDI. Background Drugs such as cephalosporins-so-called broad-spectrum agents because of their action against many types of bacteria-damage normal intestinal flora in addition to killing disease-causing microbes. This damage gives CD the opportunity to spread in the guts of patients recently treated with antibiotics. Infected patients can develop diarrhoea, colitis, and other conditions associated with intestinal inflammation. Rarely, CD infection can be fatal. By contrast, drugs that target only specific types of bug cause less damage to normal gut bacteria and therefore reduce the likelihood that CD will take hold. In their audit study, Dr Sheldon Stone, of the Academic Department of Geriatrics, Royal Free and University College Medical School, London, and colleagues investigated whether use of feedback to individual doctors about their prescribing habits can improve adherence to a narrow-spectrum antibiotic prescribing policy, thereby reducing CD cases. "National guidelines recommend narrow-spectrum antibiotic policies and suggest a variety of methods to ensure these are implemented, but feedback is not mentioned in national guidelines as a way of addressing prescribing behaviour," says Dr Stone. The team, working at the Royal Free Hospital in London, studied prescribing and CDI rates in three wards for acute care of the elderly where CD was endemic. When the study began, doctors working on the wards had already been told to use less cephalosporin to treat bacterial infections, but this policy had resulted in increased use of another broad-spectrum antibiotic, amoxicillin/clavulanate. To prevent future CDI rises as a result of the increased use of amoxicillin/clavulanate, a new narrow-spectrum policy was implemented as part of the hospital's clinical governance programme at the beginning of July 2001. This policy recommended less use of amoxicillin/clavulanate, increased use of benzyl penicillin, trimethoprim, and amoxicillin, and further restricting cephalosporin use. Dr Stone and colleagues analysed the effectiveness of reinforcing this new policy with a pocket-sized laminated card telling doctors which drugs to use in which circumstances. These instructions were combined with feedback to doctors every 2-3 months on how many courses of each specific drug they had prescribed, and ward rates of CD infection and MRSA. Doctors' prescriptions were compared before the policy change (September 1999-June 2001) and afterwards (July 2001-March 2003). A statistically significant drop in use of both cephalosporin and amoxicillin/clavulanate was observed after the narrow-spectrum policy came into effect. Prescriptions for antibiotics not specified by the policy did not change during this time, suggesting that the feedback and laminated card had had the desired targeted effect. There was also a significant fall in rates of CDI associated with the policy change. "We have shown that introduction of a narrow-spectrum antibiotic policy, reinforced by feedback, was associated with significant changes in targeted antibiotics and a significant reduction in CDI", explains Dr Stone. "National figures for CD and associated diseases showed the Royal Free to have the lowest rates of any teaching hospital. This success is largely being attributed to the antibiotic policies described in the paper", he adds. The authors think their study could be a useful reference for other centres where cephalosporin use is higher than in the Royal Free. Compared with many other hospitals, cephalosporin use was already low at the beginning of the study and the intervention was still highly successful, indicating that even better results could be achieved in institutions where a greater reduction is desirable. Dr Stone and colleagues used an interrupted time series design, which includes a single group of study subjects assessed before an after an intervention (in this case a change to antibiotic prescribing policy). This design includes measurement of many different variables both before and after the intervention, including a set of "control outcomes" that are not expected to change during the course of the study, to reduce the potential contribution of confounding factors to any result. This design means the study provides stronger evidence than previous investigations of similar interventions. "Nearly all previous studies assessing interventions to improve prescribing were poor quality unplanned studies with no control groups or outcomes and inadequate statistical analysis," explains Dr Stone. The authors suggest that wider use of this method to study interventions in other hospitals would enhance the pool of good quality evidence on the best ways to change antibiotic prescribing. It would also enable meaningful comparisons between studies and interventions. The paper is intended to be an example of best practice for reporting such studies. Guidelines laying out minimum requirements for data recording, statistical analysis, and reporting are contained in the consensus statement for infection control studies-labelled the ORION (Outbreak Reports and Intervention studies Of Nosocomial infection) statement-are being published simultaneously in The Lancet Infectious Diseases this month and also the Journal of Antimicrobial Chemotherapy.4 This statement, put together with the aim of improving the quality of research in hospital epidemiology to ensure it is robust enough to influence policy and practice, is intended to be an equivalent to the CONSORT standards and checklist for reporting of randomized controlled trials. Dr Stone says: "The quality of research in infection control must be robust enough to influence policy and practice in the fight against hospital acquired infection. This statement is intended to help produce well designed studies that will aid that fight".

Bayer Donates Antibiotics With A Wholesale Value Of More Than US$ 25 Million To MAP International For Africa And Latin America

Bayer HealthCare has given a donation of Cipro® with a wholesale value of more than US$ 25 million to MAP (Medical Assistance Programs) International. The aid organization will distribute the critically needed antibiotic to clinics and hospitals in Africa and Latin America that are fighting on the front lines in the battle against diseases of poverty where there is little or no access to essential medicines.“The successful and ambitious work of MAP is impressive,” said Dr. Gunnar Riemann, Head of Bayer HealthCare’s Pharmaceuticals Division, following the official signing of the agreement. “We are delighted to be able to contribute to their health programs with our donation.”MAP International President and CEO Michael J. Nyenhuis says the donation of this specific drug is particularly significant in MAP’s work to save lives in impoverished communities.“More than 20,000 people die each day in Africa from preventable diseases,” said Mr. Nyenhuis. “By joining MAP in collaboration, Bayer will help us to save lives in areas of the world where there is little or no access to essential medicines like Cipro®. With many people earning less than the equivalent of US$ 1 a day, life-saving antibiotics are beyond their economic reach. Bayer is helping MAP to bridge this gap in poor countries.”Cipro® (ciprofloxacin) is an antibiotic used to treat certain bacterial infections. Cipro® tablets and suspension are used to treat pneumonia, bronchitis, some types of gonorrhea, bacterial diarrhea, typhoid fever, and bone, joint, skin, prostate, sinus and urinary tract infections.About MAP InternationalMAP International headquartered in Brunswick, Georgia (USA), is one of the fifty largest non-profit organizations. Founded in 1954 as Medical Assistance Programs, MAP International today promotes the total health of impoverished people in over 115 countries. MAP distributes more than US$ 300 million in donated live-saving medicines and health supplies to over 100 countries annually.Bayer HealthCareBayer HealthCare, a subsidiary of Bayer AG, is one of the world’s leading, innovative companies in the health care and medical products industry based in Leverkusen/Germany. In 2005, the Bayer HealthCare subgroup generated sales amounting to some €9.4 billion. Bayer HealthCare employed 33,800 people world-wide in 2005.The company combines the global activities of the divisions Animal Health, Consumer Care, Diabetes Care, Diagnostics and Pharmaceuticals. Since January 1, 2006, the new Pharmaceuticals Division consists of the former Biological Products and Pharmaceuticals Division and now comprises three business units: Hematology/Cardiology, Oncology and Primary Care.Bayer HealthCare’s aim is to discover and manufacture products that will improve human and animal health worldwide. The products enhance well-being and quality of life by diagnosing, preventing and treating diseases.Forward-Looking StatementsThis news release contains forward-looking statements based on current assumptions and forecasts made by Bayer Group management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in our public reports filed with the Frankfurt Stock Exchange and with the U.S. Securities and Exchange Commission (including our Form 20-F).The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

Probiotics May Ease Diarrhea In Children Taking Antibiotics

Probiotics, the "good" bacteria in many dietary supplements, might counteract an unpleasant side effect for children on antibiotics, according to a new systematic review.Antibiotics commonly used to treat children with conditions such as respiratory tract and skin infections can cause antibiotic-associated diarrhea (AAD). Estimates indicate that between 11 percent and 40 percent of children taking antibiotics suffer from AAD.Parents have routinely given children over-the-counter diarrhea medicines, such as Kaopectate or Imodium A-D, but some are turning to other remedies. One alternative has been to give probiotics dietary supplements containing healthy bacteria or yeasts that can help to restore the body's natural balance.The systematic review aimed to assess whether probiotics actually reduce the incidence of AAD in children and if children should take probiotics over common diarrhea medications on a routine basis."Probiotics offer an excellent safety profile in healthy children and seem to be effective in preventing AAD in children," said review co-author Sunita Vohra, M.D. "Public interest in natural health products is high and given how commonly diarrhea occurs in children prescribed antibiotics, we think that many families will be interested in our findings."The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates research in all aspects of health care. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing trials on a topic.AAD occurs when antibiotics disturb the body's natural balance of "good" and "bad" bacteria and thereby interfere with normal digestion. AAD symptoms include frequent watery bowel movements and abdominal cramps. Those with severe cases can suffer from dehydration and electrolyte imbalances.The Cochrane reviewers analyzed 10 studies that tested 1,986 children from birth to 18 years old, who received antibiotics to treat a medical condition along with probiotics to prevent AAD. Children were given between five and 15 days of oral antibiotics such as amoxicillin, cefotaximine and erythromycin.The probiotics given to children included Lactobacillus GG, Lactobacillus sporogenes, Streptococcus thermophilus and Saccharomyces boulardii. Daily doses varied from 20 billion to 40 billion colony-forming units.The studies used various methods to compare children who received probiotics to those who received another type of treatment a placebo, conventional antidiarrheal medications or no treatment at all."Conventional antidiarrheal medications may also be effective, but unless the diarrhea is severe, parents and health care providers are generally averse to prescribing a second medication," said Vohra, associate professor in the department of pediatrics at the University of Alberta in Canada.Results from nine studies found that probiotics reduced the incidence of AAD, and four studies reported that probiotics shortened the average duration of diarrhea symptoms by about three-quarters of a day.Choosing between over-the-counter medicines and probiotics may not be the issue for parents and children in some parts of the world, according to Alfred Bartlett, M.D., a pediatrician and senior advisor for child survival at the U.S. Agency for International Development.Bartlett said his agency's work in numerous countries has shown that replacing fluids to prevent dehydration, providing proper nutrition and administering zinc supplements have proven key to treating diarrhea in children."There's been on-again-off-again talk about probiotics for diarrhea, but the science is not solid enough to make a major program investment in more research," Bartlett said. "In comparison, there have been multiple trials done around the world that have proven fluids, feeding and zinc are effective."Although the Cochrane findings were statistically significant, the reviewers concluded that there was not sufficient evidence to advise physicians to recommend probiotics to prevent AAD routinely. They did reveal, however, that Lactobacillus GG or Saccharomyces boulardii appear to be the most effective. According to Vohra, these supplements will garner more attention in the future."In modern medical school curriculum, physicians have not been taught extensively about many natural health products and probiotics have generally been overlooked," Vohra said. "This is changing, and we are aware of at least some hospitals that now carry probiotics on formulary."

Alternative To Antibiotics May Be More Effective And Less Harmful

Photodynamic therapy (PDT) may be an effective way to treat the bacteria associated with periodontal diseases, and could provide a better option than antibiotics or other mechanical methods for treating periodontal diseases, according to a new study published in the March issue of theJournal of Periodontology. Researchers at São Paulo State University found that using PDT was an effective method to minimize destruction of periodontal tissue which can accompany treatment for periodontal diseases. In a rat population, PDT did minimal damage to periodontal tissues, in comparison to other techniques including scaling and root planing and antibiotic therapy. "We found that PDT is significantly less invasive than other treatments for periodontal diseases," said study author Dr. Valdir Gouveia Garcia, from the Department of Periodontology at São Paulo State University. "It can provide improved dentin hypersensitivity, reduced inflammation of the tissues surrounding the teeth, and allows tissues to repair faster." PDT may be an alternative to antibiotic treatment, which is becoming increasingly important as antibiotic resistance increases. PDT involves two stages; first, a light-sensitive drug is applied to the area. Second, a light or laser is shone on that area. When the light is combined with the drug, phototoxic reactions induce the destruction of bacterial cells. PDT was first approved by the Food and Drug Administration in 1999 to treat pre-cancerous skin lesions of the face or scalp. "This is an exciting finding," said Preston D. Miller, Jr., DDS and President of the American Academy of Periodontology. "PDT may be an effective therapy for the treatment of periodontal diseases. While patients have many options for treating their periodontal diseases, PDT could prove to be a preferable alternative to antibiotic therapy. Unfortunately, long term antibiotic therapy not only decreases the drug's effectiveness, but also may lead to the development of drug resistant organisms. Our Academy supports future research to further define the application of PDT as a means to treat periodontal disease."

Urinary Tract Infections Not Prevented By Antibiotics, Future Infections May Become Antibiotic Resistant

After a first childhood urinary tract infection (UTI), daily antibiotics may not prevent another such infection, and may actually increase the risk that the next urinary tract infection is caused by resistant bacteria, according to a new study in the July 11 issue of the Journal of the American Medical Association. In the first large study of children diagnosed with UTI in a primary care pediatric setting, researchers from The Children's Hospital of Philadelphia reviewed the electronic health records of 74,974 children with at least two clinic visits in The Children's Hospital of Philadelphia's pediatric healthcare network between July 2001 and May 2006. The researchers found that 611 children had a first urinary tract infection and 83 had a recurrent UTI. Children between ages three and five, Caucasians, and those with severe vesicoureteral reflux had the highest risk of recurrent UTI. Receiving a daily dose of preventive antibiotics was not associated with a lower risk of recurrent UTI. "The majority of children with first UTI were female, Caucasian and two through six years old. Most did not have an imaging study performed and did not receive daily antibiotics to prevent infections," said Patrick Conway, M.D. M.Sc., primary investigator of the study. "We found that daily antibiotic treatment was not associated with a decreased risk of recurrent UTIs, but was associated with an increased risk of resistant infections." Currently at Cincinnati Children's Hospital Medical Center, Dr. Conway conducted the research while at The Children's Hospital of Philadelphia and a Robert Wood Johnson Clinical Scholar at the University of Pennsylvania. "More definitive studies, such as clinical trials, are needed to look at this issue." said Ron Keren, M.D., M.P.H., a general pediatrician at The Children's Hospital of Philadelphia and senior author on this study. "But given these findings, it is appropriate for pediatricians to discuss with families the risks and unclear benefits of daily preventive antibiotic treatment after a child has had a first UTI." UTIs are common in children. In fact, of all the children born in one year, 70,000 to 180,000 will have a UTI by age six. The American Academy of Pediatrics (AAP) practice guideline for management of children after a first UTI recommends an imaging study to evaluate the presence and degree of vesicoureteral reflux (VUR), a condition found in approximately 30 to 40 percent of children who have had a UTI. If the child has VUR, daily antibiotic treatment is recommended in an attempt to prevent recurrent UTIs. Vesicoureteral reflux (VUR) occurs when urine in the bladder flows back into the ureters or kidneys during urination. It is thought that a child who has VUR is at risk for developing recurrent kidney infections, which, over time, can cause damage to the kidneys. However, Dr. Conway summarized, "The majority of children have lower grade VUR and this lower grade VUR was not associated with an increased risk of recurrent UTI in our study."