Scientists from the US and Russia studying the treatment of patients with extensively drug-resistant tuberculosis (XDR TB) in Tomsk, Russia, concluded that it was possible to contain the global threat from this highly resistant strain with aggressive treatment that reduces deaths and prevents further transmission. Success is maximized by individually assessing drug susceptibility in each patient, and making sure they follow their individually designed treatment programme which ideally includes at least five drugs to which their particular strain of TB is susceptible.

The research was the work of Dr Salmaan Keshavjee, from the Department of Global Health and Social Medicine at Harvard Medical School in Boston, Massachusetts, and colleagues, and is published in an early online issue of The Lancet.

According to the World Health Organization (WHO), one in three people in the world is infected with dormant TB bacteria. People only get ill when the bacteria become active, which can be as a result of a weakened immune system, such as old age, HIV, and certain medical conditions.

The normal treatment for TB is a course of four standard, or first-line, anti TB drugs. If these are misused or not managed correctly (for instance interruption or failure to complete the course), the result can be that non-resistant TB mutates into multidrug-resistant TB (MDR-TB). This form takes longer to treat with second-line drugs, which cost more and have more side effects.

If the second-line drugs are also misused or mismanaged, then the MDR TB can turn into XDR TB, the most drug-resistant form of the disease. It is therefore important that TB control is managed properly to prevent the rise of resistant forms.

For this retrospective cohort study, Keshavjee and colleagues looked at 608 patients with MDR TB in Tomsk, Russia, who were treated in civilian or prison health centres between 2000 and 2004. Their treatment followed the protocol recommended by WHO.

Drug susceptibility testing (DST) on all patients showed that 4.8 per cent (29 patients) had XDR TB, while the rest has non-XDR TB. Each patient was given an individually designed treatment programme based on the result of their DST and any treatments they had been given before. The aim was to give each patient at least five drugs to which their particular strain of TB was susceptible.

If the doctors could not get hold of five effective drugs for a patient, they considered using drugs to which resistance was known, especially if that patient had no history of exposure to them.

The results showed that treatment failure was more common in XDR TB patients than non-XDR TB patients, (31 versus 9 per cent failure respectively). 48 per cent of XDR TB patients and 67 per cent of non-XDR TB patients were either cured or completed their programme.

Frequency and management of adverse events were the same in both XDR and non-XDR TB patients.

Keshavjee and colleagues concluded that:

“The chronic features of tuberculosis in these patients suggest that extensively drug-resistant tuberculosis may be acquired through previous treatments that include second-line drugs. Aggressive management of this infectious disease is feasible and can prevent high mortality rates and further transmission of drug-resistant strains.”

“48 per cent of patients with XDR tuberculosis — often termed untreatable in press reports — responded favourably to treatment,” they added.

In an accompanying Comment, Dr Helen Cox, of the Macfarlane Burnet Institute for Medical Research and Public Health in Melbourne, Australia, and Médecins Sans Frontières (MSF), Cape Town, South Africa, and Dr Cheryl McDermid, also from MSF, Cape Town, South Africa, said:

“Keshavjee and colleagues have shown that both MDR and XDR tuberculosis can be cured with aggressive treatment, with use of the most effective antituberculosis drugs available.”

“Although we should be cautious in our hope to attain such success rates in settings with a high prevalence of HIV, aggressive treatment is the logical strategy to provide the best chance of cure while avoiding the creation of additional drug resistance,” added Cox and McDermid.

“Treatment of extensively drug-resistant tuberculosis in Tomsk, Russia: a retrospective cohort study.”
Salmaan Keshavjee, Irina Y Gelmanova, Paul E Farmer, Sergey P Mishustin, Aivar K Strelis, Yevgeny G Andreev, Alexander D Pasechnikov, Sidney Atwood, Joia S Mukherjee, Michael L Rich, Jennifer J Furin, Edward A Nardell, Jim Y Kim, Sonya S Shin.
The Lancet, Early Online Publication, 25 August 2008.
DOI:10.1016/S0140-6736(08)61204-0.

Click here for Abstract.

“XDR tuberculosis can be cured with aggressive treatment.”
Helen Cox, Cheryl McDermid.
The Lancet, Early Online Publication, 25 August 2008.
DOI:10.1016/S0140-6736(08)61205-2.

Click here for Abstract.

Sources: The Lancet, WHO.

Written by: Catharine Paddock, PhD
Copyright: Medical News Today

Montana State University scientist Darla Goeres knows that there is more than one way to grow a biofilm, a fact that she uses to make sure that when a product claims it kills “99 percent” of bacteria, it really does the job.

Biofilms are the extremely common communities of bacteria that form on most wet surfaces. They range from the plaque on teeth to the slime on streamside rocks to the sludge that clogs pipes.

Most biofilms are harmless, but some have been linked to ailments such as urinary tract infections, gingivitis and infections around implanted devices like artificial joints and heart valves.

“In the world that I study, everybody’s trying to kill the biofilm,” said Goeres, a research professor in the Department of Chemical and Biological Engineering. “But there’s not a concrete answer for that, and that’s why you need to understand methods.”

Earlier this year, Goeres was awarded a five-year, $1.7 million contract from the Environmental Protection Agency to work on new ways to measure how well antimicrobial products perform against biofilms.

“The EPA contract provides a solid basis of support,” Goeres said. “That’s why we can be one of the few labs in the world that can focus on methods development.”

Goeres works in the Standardized Biofilms Methods Laboratory at MSU’s Center for Biofilm Engineering. There, she develops standards for growing, treating and sampling biofilms.

All biofilms are unique. They are composed of varying numbers of different bacteria, and the conditions under which these bacteria form a biofilm can make a big difference in the resulting slime. So a product designed to kill one biofilm might not work on any others, which makes proving the effectiveness of antibacterial cleaning products tricky.

“Every time a person buys a product with an EPA-approved efficacy claim, such as ‘kills 99 percent of bacteria,’ the public trusts the validity of the process used to prove that claim,” Goeres said.

However, the method a company uses to prove its product’s effectiveness can make a big difference in the test results. Until recently, most methods for testing products involved growing bacteria in a way that’s not consistent with the real world, Goeres said.

“Our goal is to grow bacteria in a way that’s relevant to how the bacteria exist where the product is used,” she said. “That way, we can have more confidence in the product’s actual effectiveness, and so can the public.”

The EPA contract will allow Goeres to hire two additional undergraduate students for her lab, where they will receive training and experience that will help them continue into graduate school or biofilms jobs. The lab normally hires four to six undergraduates each year.

Goeres said her biofilm methods work, which can seem detached from the real world, is ultimately about making sure people can trust the products they’re using to keep their homes clean.

“So many results depend on the process a person uses,” Goeres said. “To have only one way to grow a biofilm isn’t going to cut it.”

—————————-

—————————-

Source: Michael Becker
Montana State University

Self-destruction for a common cause

ETH Zurich biologists, led by Professors Martin Ackermann and Wolf-Dietrich Hardt, in collaboration with Michael Doebeli of the University of British Colombia in Vancouver (CN), have been able to describe how random molecular processes during cell division allow some cells to engage in a self-destructive act to generate a greater common good, thereby improving the situation of the surviving siblings.

Survival strategy

The biologists investigated this unusual biological concept using the pathogenic salmo-nella bacteria as an example. Diseases caused by salmonellae are very unpleasant and even life-threatening. When contaminated food is consumed - for example, egg-based foods or chicken and meat - salmonella bacteria enter the gastro-intestinal tract where it triggers infection. Vomiting and diarrhoea can last for days.

Normally, salmonellae grow poorly in the intestine because they are not competitive with other bacteria of the gut. However, this dynamic changes if salmonellae induce an in-flammatory response, namely diarrhoea, which suppresses the other bacteria. The in-flammation is triggered by salmonellae penetrating into the intestinal tissues. Once inside, salmonellae is killed by the immune system. This in turn creates a conflict: salmo-nellae are either suppressed by the other bacteria in the gut, or die while trying to elimi-nate these competitors.

As Ackermann, Hardt and Doebeli report, salmonellae have found a surprising solution to this conflict. Inside the gut, the samonella bacteria forms two groups that engage in job-sharing. A first group invades the tissue, triggers an inflammation, then dies. A sec-ond group waits inside the gut until the inactivation of the normal intestinal flora gives them an opportunity to strike.This second group then multiplies unhindered.

Random processes and self-sacrifice

What determines whether an individual salmonella bacterium cell self-sacrifices, or whether it will wait and benefit from the sacrifice of others? The two groups are clones of the same genotype, so genetic differences do not play a role. Rather, the difference between the two groups is a result of random molecular processes during cell division. Cellular components are randomly distributed between the two daughter cells with each cell receiving a different amount. The resulting imbalance can be amplified and lead to different properties of the clonal siblings.

In recent years it has been recognized that such random processes in a cell can have a large influence on individual cells. The work by the ETH Zurich researchers reveals a new biological explanation for this phenomenon. The two salmonella phenotypes share their work, with the result being that they achieve what a single phenotype on its own would not be capable of doing. This scenario is fundamentally different from the usual explanations and presupposes that individual phenotypes interact and have an effect on one another. The self-sacrifice of phenotypes may be quite common among pathogenic bacteria, for example, among the pathogens causing diarrhoea after antibiotic treatment (clostridia) or pneumonia (streptococci).

Essential findings

Professor Ackermann says that “Random processes could promote job-sharing in many different types of organisms.” Many bacteria manufacture substances which are toxic to their hosts but which are only released into the host environment if the bacteria sacrifice themselves - if this is the sole method to get the toxin out of the cell. This is why every cell makes a decision: toxin and death or no toxin.

He stresses that it would not have been possible to study this theory so thoroughly with-out the collaboration that took place among the three specialist groups: Professor Hardt’s group specialises in salmonella infections; Professor Doebeli is a mathematician and theoretical biologist; and Professor Ackermann’s group focuses on phenotypic noise.

—————————-

—————————-

Click here to download images.

Literature reference:
Ackermann M et al. Self-destructive cooperation mediated by phenotypic noise; Nature 454, 987-990 (21 August 2008), doi: 10.1038/nature07067

ETH Zurich (Swiss Federal Institute of Technology Zurich) has a student body of 14,000 students from 80 nations. Nearly 360 professors teach mainly in engineering sciences and architecture, system-oriented sciences, mathematics and natural sciences, as well as carry out research that is highly valued worldwide. On a yearly basis, ETH Zurich applies for 80 -100 patents and directly supports the founding of up to 20 spin-off companies. Distinguished by the successes of 21 Nobel laureates, and an active member of the IPCC (Intergovernmental Panel for Climate Control) that was awarded the 2007 Nobel Peace Prize, ETH Zurich is committed to providing its students with unparalleled education and out-standing leadership skills.

Source: Professor Dr. Wolf-Dietrich Hardt
ETH Zurich/Swiss Federal Institute of Technology

PolyMedix, Inc. (OTC BB: PYMX), an emerging biotechnology company developing new therapeutic drug products to treat infectious diseases and acute cardiovascular disorders based on biomimetics, has initiated dosing and commenced a Phase I clinical study in Canada for its defensin mimetic antibiotic compound, PMX-30063. PolyMedix received a notice of no objection from Health Canada for the Company’s Clinical Trial Application (”CTA”) for PMX-30063 in May 2008. PMX-30063 is the first and only defensin mimetic antibiotic compound to enter human clinical trials for systemic use, and represents an entirely new class of antibiotic drugs.

This first Phase I clinical trial will assess the safety of PMX-30063. The protocol for the trial involves a dose-escalation study in healthy volunteers in which each subject will receive a single dose of PMX-30063. The subjects are grouped into different cohorts with different dosage levels which will allow for the study of the effects of increased dosages. PolyMedix expects to enroll a total of thirty to fifty subjects in this clinical trial. Upon successful completion of the first clinical study, PolyMedix plans to initiate a second clinical trial to mimic the expected clinical dosing regimen. The second trial, also to be conducted in healthy volunteers, will involve repeat dosing of two intravenous infusions per day, for up fourteen days. Following these clinical trials, significant additional clinical studies and regulatory submissions will be required to obtain regulatory approval from the FDA and other regulatory bodies before PMX-30063 could be commercially sold.

“The start of the clinical study for PMX-30063 represents a major milestone for PolyMedix, and we believe, for the entire medical community,” said Nicholas Landekic, CEO of PolyMedix. “This novel antibiotic compound signals a fundamental potential breakthrough in treating infectious diseases. PMX-30063 is the first and only small molecule defensin mimetic to commence clinical development for the treatment of systemic infections, and the first and only such compound whose mechanism of action is intended to directly address the major problem of bacterial drug resistance. We are proud to be the first company to bring this completely new type of antibiotic to clinical trials, and to address a major clinical need and market opportunity.”

About PMX-30063

Completely different from other antibiotic compounds currently on the market, PMX-30063 is a synthetic chemical mimic of host defense proteins, one of the oldest and most effective antimicrobial defense systems found in virtually all living creatures. PMX-30063 is the first small molecule mimetic of host defense proteins to enter clinical trials intended to treat systemic infections.

PolyMedix has undertaken in vivo studies in animals and in vitro pre-clinical studies to observe compound efficacy and toxicology attributes, and to evaluate the development of drug resistance. Based on these pre-clinical studies, we believe PMX-30063 has unique properties which sets it apart from traditional antimicrobial molecules and materials, including:

- A novel mechanism of action, the direct biophysical disruption of bacterial cell membranes, that makes development of bacterial resistance unlikely;

- Activity against both Gram-positive and Gram- negative bacteria, and in particular, activity against 146 different strains of Staphylococcus bacteria, including 89 drug-resistant strains of Staph bacteria;

- Bactericidal activity, meaning it kills bacteria directly, rather than simply stopping reproduction (bacteriostatic) as do many current antibiotics;

- Faster acting than many antibiotics; and

- Activity against drug-resistant bacteria, including clinical isolates of multiple vancomycin- and methicillin-resistant strains.

Primitive life forms, such as molds, secrete compounds like penicillin to protect themselves from bacteria. This forms the basis for conventional antibiotics 鈥” compounds which act against biochemical targets or pathways in bacterial cells. Multi-cellular organisms, such as insects, animals, and humans, possess a more complex, first-line immune system defense against bacterial infections: the host defense proteins. Host defense proteins are part of the non-humoral (that is, not involving antibodies) response that keep humans from rapidly succumbing to infections. Biologists have discovered many different classes of natural host-defense peptides. Although these molecules possess a diverse array of structures, their physicochemical properties are similar. All are amphiphilic, meaning they have a combination of positively electrically charged properties, and hydrophobic (water-hating, fat-loving) chemical properties. This amphiphilic structure is believed to be responsible for host defense peptides’ antimicrobial activity and their unique abilities to directly disrupt bacterial cell membranes. Among the most common and well-studied antimicrobial peptides are the defensins, found in humans, the magainins, found in frogs, and the cecropins and melitins, found in insects.

PMX-30063 is designed to mimic the amphiphilic structure of the host defense proteins, but with a completely synthetic, non-peptide, small molecule structure. PMX-30063 directly disrupts bacterial cell membranes; a mechanism shared with the host defense proteins but is unique among known antibiotic drugs. For this reason, we believe that bacterial resistance is less likely to develop with PMX-30063 than has been experienced with many conventional antibiotic drugs. Multiple serial passage experiments conducted by PolyMedix and others on PMX-30063 and related PolyMedix antibiotic compounds also support our view of a lower likelihood of developing resistance.

About PolyMedix, Inc.

PolyMedix is a publicly traded biotechnology company focused on the development of novel drugs and biomaterials for the treatment of infectious diseases and acute cardiovascular disorders. PolyMedix’s compounds are based on biomimetics: non-peptide small molecule drugs that mimic the activity of proteins. The Company’s antibiotic compounds, including PMX-30063 鈥” small molecule mimetics of human host-defense proteins - have a completely different mechanism of action from current antibiotic drugs, a mechanism which is intended to make bacterial resistance unlikely to develop. These compounds are being developed as rapidly acting antibiotics for serious systemic and local infections. The Company plans to continue the development of polymeric formulations as antimicrobial biomaterials, which can be used as additives to paints, plastics, and textiles to create self-sterilizing products and surfaces. The Company’s heptagonist compounds, including PMX-60056, reverse the activity of both heparin and Low Molecular Weight Heparins, with the goal of developing an antagonist drug that is safer and easier to use than currently approved therapy. For more information, please visit PolyMedix on its website at http://www.polymedix.com.

This press release contains forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 that involve risks and that could cause PolyMedix’s actual results and experience to differ materially from anticipated results and expectations expressed in these forward looking statements. PolyMedix has in some cases identified forward-looking statements by using words such as “anticipates,” “believes,” “hopes,” “estimates,” “looks,” “expects,” “plans,” “intends” and similar expression.. Among other things, there can be no assurance that PolyMedix’s compounds will enter or successfully complete clinical testing or be granted regulatory approval to be sold and marketed in the Unites States or elsewhere. A more complete description of these risks, uncertainties and assumptions is included in PolyMedix’s filings with the Securities and Exchange Commission. You should not place undue reliance on any forward-looking statements. PolyMedix undertakes no obligation to release publicly the results of any revisions to any such forward-looking statements that may be made to reflect events or circumstances after the date of this press release or to reflect the occurrence of unanticipated events.

PolyMedix, Inc.

ETH Zurich biologists, led by Professors Martin Ackermann and Wolf-Dietrich Hardt, in collaboration with Michael Doebeli of the University of British Colombia in Vancouver (CN), have been able to describe how random molecular processes during cell division allow some cells to engage in a self-destructive act to generate a greater common good, thereby improving the situation of the surviving siblings.

Survival strategy

The biologists investigated this unusual biological concept using the pathogenic salmo-nella bacteria as an example. Diseases caused by salmonellae are very unpleasant and even life-threatening. When contaminated food is consumed for example, egg-based foods or chicken and meat salmonella bacteria enter the gastro-intestinal tract where it triggers infection. Vomiting and diarrhoea can last for days.

Normally, salmonellae grow poorly in the intestine because they are not competitive with other bacteria of the gut. However, this dynamic changes if salmonellae induce an inflammatory response, namely diarrhoea, which suppresses the other bacteria. The inflammation is triggered by salmonellae penetrating into the intestinal tissues. Once inside, salmonellae is killed by the immune system. This in turn creates a conflict: salmonellae are either suppressed by the other bacteria in the gut, or die while trying to eliminate these competitors.

As Ackermann, Hardt and Doebeli report, salmonellae have found a surprising solution to this conflict. Inside the gut, the samonella bacteria forms two groups that engage in job-sharing. A first group invades the tissue, triggers an inflammation, then dies. A second group waits inside the gut until the inactivation of the normal intestinal flora gives them an opportunity to strike.This second group then multiplies unhindered.

Random processes and self sacrifice

What determines whether an individual salmonella bacterium cell self-sacrifices, or whether it will wait and benefit from the sacrifice of others? The two groups are clones of the same genotype, so genetic differences do not play a role. Rather, the difference between the two groups is a result of random molecular processes during cell division. Cellular components are randomly distributed between the two daughter cells with each cell receiving a different amount. The resulting imbalance can be amplified and lead to different properties of the clonal siblings.

In recent years it has been recognized that such random processes in a cell can have a large influence on individual cells. The work by the ETH Zurich researchers reveals a new biological explanation for this phenomenon. The two salmonella phenotypes share their work, with the result being that they achieve what a single phenotype on its own would not be capable of doing. This scenario is fundamentally different from the usual explanations and presupposes that individual phenotypes interact and have an effect on one another. The self-sacrifice of phenotypes may be quite common among pathogenic bacteria, for example, among the pathogens causing diarrhoea after antibiotic treatment (clostridia) or pneumonia (streptococci).

Essential findings

Professor Ackermann says that “Random processes could promote job-sharing in many different types of organisms.” Many bacteria manufacture substances which are toxic to their hosts but which are only released into the host environment if the bacteria sacrifice themselves - if this is the sole method to get the toxin out of the cell. This is why every cell makes a decision: toxin and death or no toxin.

He stresses that it would not have been possible to study this theory so thoroughly with-out the collaboration that took place among the three specialist groups: Professor Hardt’s group specialises in salmonella infections; Professor Doebeli is a mathematician and theoretical biologist; and Professor Ackermann’s group focuses on phenotypic noise.

ETH ZUERICH
Raemistrasse 101
CH - 8006 Zuerich
http://www.ethz.ch

Mosquitoes are known for transmitting deadly viruses to humans, but theinsects themselves are susceptible to viral infection. According to astudy published in the open-access journal PLoS Pathogens,researchers at Johns Hopkins University have described a virus thatinfects the mosquito best known for transmitting malaria - Anophelesgambiae. Malaria kills over one million people worldwideevery year, and the researchers believe that the infectious mosquitovirus might be used to control malaria by passing on new geneticinformation to A. gambiae.

AgDNV is a densonucleosis virus (densovirus) - a type common tomosquitoes and other insects but not infectious to humans and othervertebrates. The AgDNV virus does not actually harm mosquitoes, butresearchers believe it is highly infectious to larvae and is easilypassed to the adults.

Researcher Jason Rasgon, PhD (Johns Hopkins Bloomberg School of PublicHealth’s Malaria Research Institute) notes that this new finding cameabout while the investigators were actually trying to use Wolbachiabacteria to infect An. gambiae mosquito cells.Co-author Xiaoxia Ren was analyzing the gel used to detect the bacteriawhen an “artifact” that appeared as an unexpected prominent band in thegel was noticed.

Ragson admits that, “Finding artifacts such as this one duringexperiments is not uncommon, but we decided to investigate this onefurther since we kept observing it over and over. When we sequenced it,we were surprised to learn that we had found a new virus.”

The researchers believe that the virus can be altered to kill themosquito or make it incapable of transmitting malaria. In order to testhow much control the authors had over the virus, the altered the AgDNVso that adult mosquitoes presented a harmless green fluorescent proteinthat is spotted using a microscope.

“In theory, we could use this virus to produce a lethal toxin in themosquito or instruct the mosquito to die after 10 days, which is beforeit can transmit the malaria parasite to humans. However, these conceptsare many years away,” concludes Rasgon.

Viral Paratransgenesis in the Malaria Vector Anophelesgambiae
Ren X, Hoiczyk E, Rasgon JL
PLoS Pathogens (2008). 4(8):e1000135.
doi:10.1371/journal.ppat.1000135
ClickHere to View Article

About PLoS Pathogens

PLoS Pathogens (www.plospathogens.org)publishes outstanding original articles that significantly advance theunderstanding of pathogens and how they interact with their hostorganisms. All works published in PLoS Pathogensare openaccess. Everything is immediately available subject only to thecondition that the original authorship and source are properlyattributed. Copyright is retained by the authors. The Public Library ofScience uses the Creative Commons Attribution License.

About the Public Library of Science

The Public Library of Science (PLoS) is a non-profit organizationof scientists and physicians committed to making the world’sscientific and medical literature a freely available public resource.For more information, visit http://www.plos.org

Written by: Peter M Crosta
Copyright: Medical News Today

Sometimes something well-tried can also be innovative: already in Ancient Greece, copper was considered to be very antimicrobial. This ability is now playing an important role in the struggle against dangerous hospital germs. In a worldwide noted field test, a whole hospital ward at the Asklepios Clinic in Wandsbek in Hamburg, Germany, was equipped with door handles, door plates and light switches made of copper. Because the germs are not only transmitted from one hand to another but, in many cases, also by touching door handles and switches. At the moment, scientists at the University Halle-Wittenberg, Germany, are evaluating the samples of the first study phase. As a result, the Asklepios Clinic Wandsbek becomes the pioneer in this clinical research in Europe.

The main opponents are dangerous, antibiotic-resistant bacteria (MRSA), with which more and more patients worldwide fall ill in clinics and nursing homes. Classical sanitary measures are often insufficient to prevent a further spreading. According to the clinic and the involved scientists at the University Halle-Wittenberg, the first study results have shown “significantly less chances of survival” of microbes on copper surfaces, which is why the field test will be continued in the second half of the year. A complete evaluation is expected by early 2009.

Worldwide race against time

“The struggle against high-resistant agents cannot be won with the previous means, such as the use of new antibiotics and intensive disinfection measures. We must break new grounds in order to reduce the potential danger for our patients,” Professor Prof. Dr. med. Jorg Braun, chief physician of the I. Medical Department at the Asklepios Clinic Wandsbek explains the motives for the field test. “Scientific tests performed by several independent working groups have shown beyond doubt that copper surfaces can efficiently kill bacteria and other germs,” Prof. Dr. Dietrich H. Nies, Director of the Institute for Biology at the Martin Luther University Halle-Wittenberg, Germany, also confirms.

With its field test (two times eight weeks with weekly periodic sampling), the Asklepios Clinic Wandsbeck is involved in a worldwide study program. Comparable studies under clinical conditions are planned or are being performed at the same time in Great Britain, South Africa, the US and Japan. In Wandsbek, samples from door handles, door plates and light switches were collected during the last weeks: both from common surfaces, e.g. made of stainless steel, and from surfaces with cooper alloys. Experience has shown that door handles and light switches are the most frequent surfaces of transmission.

50,000 casualties in Europe alone every year

According to serious estimates, more than half a million of such nosocomial infections - i.e. caught in the clinic - occur every year, in German hospitals alone. According to the European Centre for Disease Prevention and Control (ECDC), there are three million cases all over Europe, of which 50,000 are fatal. Antibiotic-resistant germs like MRSA (MRSA stands for Methicillin-resistant Staphylococcus aureus) present a particularly high danger in this context.

In addition to the partly life-threatening danger for the patients, there is also an enormous economic damage which might amount to billions in Germany alone. For the US, there is an estimate by the Center for Disease Control (CDC), according to which nosocomial infections incur costs of more than 4.5 billion US dollars. In Great Britain, the National Health Service (NHS) estimates the additional costs at one billion pounds sterling every year. According to estimates, patients who contract MRSA in the clinic stay in sickbed up to four days longer on average and incur additional costs to the amount of 4,000 Euro, in individual cases even up to 20,000 Euro. The most frequent complications with weakened patients after a MRSA infection include wound infections, pneumonias, blood poisonings, and urinary tract infections.

Research is going full steam ahead worldwide

The tests at the Asklepios Clinic in Hamburg, Germany, were initiated by laboratory tests in which 99.9 percent of the bacteria, including the high hazard MRSA agents, were eliminated within a period of a few minutes up to two hours on copper surfaces. In contrast, the same microbes were able to survive up to three days on stainless steel surfaces. This is why the US Environmental Protection Agency (EPA) has confirmed the antimicrobial effect of copper only recently, in March this year. Current research is closing a scientific gap which has existed for a very long time: “Humanity has had positive experience with the hygienic effect of copper for thousands of years”, says Dr.-Ing. Anton Klassert, Business Manager of the German Copper Institute (DKI). “Against the backdrop of the current problems in the health care system, the DKI has now taken the first steps in order to apply these properties of copper in a modern hospital”, according to the Director of the European Copper Competence Centre “Antimicrobial Properties”.

Visual material and the PowerPoint presentations of the speakers on the topic “Copper & Germs” are available on request.

Asklepios Kliniken
http://www.asklepios.com

A new Chinese study has reported a dramatic spike in rabies infections. The research, published in the open access journal BMC Infectious Diseases, shows that in some provinces of China the number of human rabies cases has jumped dramatically since the new millennium.

Jia-Hai Lu, from the School of Public Health at Sun Yat-Sen University, China, led a team of researchers who studied the rabies trend in China between 1990 and 2007. Lu describes how things have changed in the last eight years “In China, human rabies was largely under control during the years 1990-1996, via nation-wide rabies vaccination programmes. Since the end of the century, however, cases of human rabies have jumped high enough to trigger a warning sign for control and prevention”.

Rabies, an infection of the nervous system, transmitted by animal bites, causes over 50,000 deaths each year around the world. During recent years, most of the research on control of rabies has concentrated on the development of post-exposure prophylaxis (preventative treatment - in this case, preventing the worsening of an infection). According to the researchers, “The use of human and equine rabies immunoglobulins (HRIG/ERIG) has saved the lives of countless patients who would have died if treated with vaccine alone. However, both products are often in short supply worldwide and are virtually unaffordable in developing countries”.

Data from 22,527 human rabies cases from January 1990 to July 2007 were obtained from a surveillance database from the Ministry of Health of China. The authors found that human rabies was under control from 1990 to 1996, when only 159 cases of rabies were reported, but this figure had leapt to 3279 cases in 2007.

The authors found that rabies was most frequently encountered in the south-western and southern territories of China, especially in highly populated areas. Lu said “the four rabies-endemic provinces lacked strictly enforced measures to eliminate dog rabies or an ample supply of modern cell culture rabies vaccines for humans”. Most of the patients were children or teenagers, and most contracted the disease after being bitten by a dog, usually on the head and neck. According to the authors, “In the worst-affected province, Guandong, 62.5% of patients did not receive proper treatment on their wounds, 92.5% did not receive adequate post-exposure vaccination and 91.25% did not receive any anti-rabies immunoglobulin”.

The authors recommend that the current rabies control programme be improved by increasing supervision, improving the interaction between local and national authorities, increasing rabies awareness and altering urban planning and development to balance the interaction between humans and animals.

—————————-

—————————-

Notes:

1. Rabies trend in China (1990-2007) and post-exposure prophylaxis in the Guangdong provinceHan Si, Zhong-Min Guo, Yuan-Tao Hao, Yu-Ge Liu, Ding-Mei Zhang, Shao-Qi Rao and Jia-Hai LuBMC Infectious Diseases (in press)
Article available at the journal website: http://www.biomedcentral.com/bmcinfectdis/
All articles are available free of charge, according to BioMed Central’s open access policy.

2. BMC Infectious Diseases is an open access journal publishing original peer-reviewed research articles in all aspects of the prevention, diagnosis and management of infectious and sexually transmitted diseases in humans, as well as related molecular genetics, pathophysiology, and epidemiology. BMC Infectious Diseases (ISSN 1471-2334) is indexed/tracked/covered by PubMed, MEDLINE, CAS, Scopus, EMBASE, Thomson Scientific (ISI) and Google Scholar.

3. BioMed Central (http://www.biomedcentral.com/) is an independent online publishing house committed to providing immediate access without charge to the peer-reviewed biological and medical research it publishes. This commitment is based on the view that open access to research is essential to the rapid and efficient communication of science.

Source: Graeme Baldwin
BioMed Central

Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD) announced that the U.S. Food and Drug Administration (FDA) requires additional information before it will approve the company’s New Drug Application (NDA) for DORIBAX(TM) (doripenem for injection) for the treatment of hospital-acquired pneumonia, also known as nosocomial pneumonia (NP), including ventilator-associated pneumonia (VAP).

In response to the J&JPRD application seeking approval for DORIBAX for the additional indication of the treatment of NP, including VAP, the FDA issued a Complete Response letter outlining the actions necessary to address outstanding issues.

J&JPRD is reviewing the agency’s letter and will work to resolve any outstanding questions. The NDA for DORIBAX for the treatment of NP, including VAP, was submitted to the FDA in June 2007.

The NDA for DORIBAX for the treatment of NP, including VAP, was the subject of a July 16, 2008 U.S. Food and Drug Administration Anti-Infective Drugs Advisory Committee. Based on data presented from two large nosocomial pneumonia trials, the committee voted that 500 mg of DORIBAX at both the one-hour and four-hour infusion regimens were safe (8-5) and effective (7-6) in the treatment of NP, including VAP. The committee did not agree that the non-inferiority margin for the DORIBAX NP trials was appropriately justified, nor did it agree on the appropriate margin for NP trials in general. J&JPRD is confident in the NP data submitted and will work with the FDA to address the issues raised in the Complete Response letter.

DORIBAX is an intravenous (IV) antibiotic for hospital use, and belongs to a class of antibacterial drugs called carbapenems. Carbapenems are important antibiotics to treat serious — and sometimes life-threatening — infections caused by a broad range of bacteria, which are characterized as Gram-negative and Gram-positive, based on a classification process that is used to identify the specific type of bacteria.

DORIBAX was approved in the U.S. in October 2007 for the treatment of complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI), including pyelonephritis, due to susceptible bacteria, and is marketed by Ortho-McNeil, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc. DORIBAX also is approved in Europe and Russia for cIAI, cUTI and NP, including VAP. Doripenem is licensed from Shionogi & Co., Ltd.

INDICATIONS

DORIBAX is indicated as a single agent for the treatment of: complicated intra-abdominal infections caused by susceptible strains of E. coli, K. pneumoniae, P. aeruginosa, B. caccae, B. fragilis, B. thetaiotaomicron, B. uniformis, B. vulgatus, S. intermedius, S. constellatus or P. micros, and for the treatment of complicated urinary tract infections, including pyelonephritis, caused by susceptible strains of E. coli, including cases with concurrent bacteremia, K. pneumoniae, P. mirabilis, P. aeruginosa, or A. baumannii.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of DORIBAX and other antibacterial drugs, DORIBAX should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting and modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

IMPORTANT SAFETY INFORMATION

DORIBAX is contraindicated in patients with known serious hypersensitivity to doripenem or other carbapenems or in patients who have demonstrated anaphylactic reactions to beta-lactams.

Serious and occasionally fatal hypersensitivity (anaphylactic) and serious skin reactions have been reported in patients receiving beta-lactam antibiotics. These reactions are more likely to occur in individuals with a history of sensitivity to multiple allergens. If an allergic reaction to DORIBAX occurs, discontinue the drug. Serious acute anaphylactic reactions require emergency treatment with epinephrine and other emergency measures, including oxygen, IV fluids, IV antihistamines, corticosteroids, pressor amines and airway management, as clinically indicated.

Carbapenems may reduce serum valproic acid concentrations to subtherapeutic levels, resulting in loss of seizure control. Serum valproic acid concentrations should be monitored frequently after initiating carbapenem therapy. Alternative antibacterial or anticonvulsant therapy should be considered if serum valproic acid concentrations cannot be maintained in the therapeutic range or seizures occur.

Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two (2) months after administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued.

When DORIBAX has been used investigationally via inhalation, pneumonitis has occurred. DORIBAX should not be administered by this route.

Safety and effectiveness in pediatric patients have not been established.

The most common adverse reactions (greater than or equal to 5%) observed in clinical trials were headache, nausea, diarrhea, rash and phlebitis.

Please see the DORIBAX Full Prescribing Information by visiting http://www.DORIBAX.com

Ortho-McNeil, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc., is committed to providing innovative, high-quality prescription medicines and resources in the areas of bacterial infection and cardiovascular disease for healthcare providers and their patients in hospitals and other care facilities. For more information, visit http://www.ortho-mcneil.com.

Johnson & Johnson Pharmaceutical Research & Development, L.L.C., is part of Johnson & Johnson, the world’s most broadly based producer of healthcare products. J&JPRD is headquartered in Raritan, NJ, and has facilities throughout Asia, Europe and the U.S. J&JPRD is leveraging drug discovery and drug development in a variety of therapeutic areas to address unmet medical needs worldwide.

FORWARD LOOKING STATEMENT

(This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from the Company’s expectations and projections. Risks and uncertainties include general industry conditions and competition; economic conditions, such as interest rate and currency exchange rate fluctuations; technological advances and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; domestic and foreign health care reforms and governmental laws and regulations; and trends toward health care cost containment. A further list and description of these risks, uncertainties and other factors can be found in Exhibit 99 of Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 30, 2007. Copies of this Form 10-K, as well as subsequent filings, are available online at http://www.sec.gov, http://www.jnj.com or on request from Johnson & Johnson. The Company does not undertake to update any forward- looking statements as a result of new information or future events or developments.)

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
http://www.jnj.com

View drug information on Doribax.

The US Food and Drug Administration (FDA) has issued a ruling that allows food producers to irradiate spinach and iceberg lettuce to kill foodborne bacteria like E. coli and salmonella that can cause people to become ill. The action is intended to reduce outbreaks of foodborne illnesses, of which there have been several in recent years, including the E. coli outbreak of 2007 where fresh bagged spinach was removed from the shelves.

The FDA said irradiation is safe and does not adversely affect the nutitional value of food, although the agency acknowledged in their announcement, as reported by WebMD, that irradiation of spinach does affect levels of folate and vitamin A.

The Centers for Disease Control and Prevention (CDC) said that irradiation of food is safe and does not make it radioactive. Their position on food irradiation is that it “holds great potential for preventing many important foodborne diseases” and overwhelming scientific evidence shows it does not harm the nutritional value of food, nor does it make food unsafe to eat.

The CDC likens the process to the pasteurization of milk, that is it will be most effective when “coupled to careful sanitation programs” and consumers will only trust food producers if they make the food clean first and then irradiate it to make it safe.

The FDA ruling does not force food producers to irradiate spinach and lettuce, it just allows them to do so.

According to a report in the New York Times, the food industry has welcomed the move. Robert Brackett, the chief scientist at the Grocery Manufacturers Association told the Times:

“This is probably one of the single most significant food safety actions done for fresh produce in many years.”

The Association petitioned the FDA in 2000 to allow food producers to irradiate a range of processed meats, prepared foods, and fruits and vegetables.

But the reaction from consumer groups has not been so warm.

Non profit group Center for Science in the Public Interest (CSPI) said that food irradiation should not be mistaken for a “silver bullet”. They favour an alternative method to control foodborne pathogens, as outlined in a petition they sent to the FDA in 2007. The CSPI would prefer a system based on “common sense” with better regulation of water quality, worker sanitation, manure use and management, and annual auditing by the FDA or a third party.

The CSPI said that the FDA should require that irradiated spinach and lettuce carry a clear label showing the words “treated with irradiation”. This is already required for other irradiation products, which the CSPI said allows consumers to make informed choices.

Other groups have said that irradiation lowers nutritional value and can create unsafe chemicals, as well as ruin taste. Patty Lovera, assistant director of Food and Water Watch called the FDA ruling “a total cop-out”. She told the New York Times that:

“They don’t have the resources, the authority or the political will to really protect consumers from unsafe food.”

But the director of the Office of Food Additive Safety at the FDA, Dr Laura Tarantino said they had not found any serious nutritional or safety changes with irradiated spinach and lettuce. She said they were no less safe than other irradiated foods.

Bracket told WebMD that food irradiation is not new and the FDA has allowed the industry to use it since 1986. For example vegetables and fruit are already irradiated at a lower level to kill insects and mold. This latest move will just make it possible to kill bacteria as well.

Consumers will probably have to pay more for irradiated spinach and lettuce. Brackett said it might be around three to five cents a pound, “which is not all that much to guarantee safety”, he added.

The market for irradiated food is very small, which some experts suggest could be because the labelling puts people off. They think the food is radioactive. The FDA may consider revising the labelling so it is less frightening. Such a move is likely to be opposed by groups like the CSPI.

Click here to learn more about food irradiation (CDC).

Sources: WebMD, CSPI, CDC, New York Times.

Written by: Catharine Paddock, PhD
Copyright: Medical News Today