MRSA Infection

One Big Antibiotic Dose Fights MRSA, Study Says

One Big Antibiotic Dose Fights MRSA, Study Says - WSJ.com.

Targanta's oritavancin has had a troubled history. It was developed by Eli Lilly & Co. in the 1990s, but never reached the market, partly because of concern over side effects. Targanta says it has resolved those issues. It licensed the drug in 2005, applied for approval from the Food and Drug Administration earlier this year, and says it expects a decision in December. Targanta's submission to the FDA was based on a normal dose of 200 milligrams per day, for up to a week. But in the new study, the company compared that treatment against one huge dose of 1,200 milligrams, given all at once in a hospital. Patients were kept in the dark about what group they were in. The results were similar: After three weeks, about 72% of the day-dose patients, and 82% of the one-big-dose patients, saw a cure or significant improvement. Each group only included about 76 patients, meaning the results are preliminary. Targanta says it's working on a bigger, more reliable study.

What Will '09 Bring In MRSA Treatment

What Will '09 Bring In Medicine?, Expert On Likely Directions In Treatment Of Obesity, Cancer, Infections, Brain Diseases, And Aging Skin - CBS News.

More hospital patients die from staph infections than from AIDS each year. But there's a breakthrough in the way hospitals will treat those infections in the future. New prevention and treatment options for the bug known officially as methicillin-resisten staphylococcus aureus have emerged. One is a protective nasal gel (XF-73), designed to kill the microbes early on, upon contact, with every breath. Past anti-MRSA drugs focused on preventing bacteria from spreading or stunting the bacteria's growth. Also, surgeons began experimenting on animals this year with MRSA-fighting stitches coated with a virus that fights the MRSA bug but doesn't affect humans. Each tiny hole for stitches is a potential entry point for MRSA or other stubborn infections, so the idea of fortifying dozens of these sites to prevent chances of future infection is brilliant.

Basilea says superbug drug gets positive opinion

UPDATE 1-Basilea says superbug drug gets positive opinion | Industries | Healthcare | Reuters.

ZURICH, Nov 21 (Reuters) - Basilea Pharmaceutica's (BSLN.S: Quote, Profile, Research, Stock Buzz) MRSA superbug antibiotic ceftobiprole has received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) for the treatment of complicated skin and soft tissue infections, the Swiss biotech company said on Friday. The drug will be marketed under the Zevtera trade name in Europe. Recommendations for marketing approval by the CHMP are usually endorsed by the European Commission within a couple of months. Earlier this month ceftobiprole -- co-developed with Johnson & Johnson's (JNJ.N: Quote, Profile, Research, Stock Buzz) Janssen-Cilag unit -- received approval in Switzerland for the treatment of complicated skin and soft tissue infections including diabetic foot infections.

Arpida Comments On FDA's Anti-infective Drugs Advisory Committee Outcome

Arpida Comments On FDA's Anti-infective Drugs Advisory Committee Outcome.

Arpida (SWX: ARPN) announced that the Anti-infective Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA) has voted 17 to 2 against the approval of intravenous iclaprim, an antibiotic currently in development for the treatment of patients with complicated skin and skin structure infections (cSSSIs), including those caused by methicillin-resistant Staphylococcus aureus (MRSA). Arpida remains confident in the efficacy and safety of intravenous iclaprim and its potential in combating serious resistant infections. Iclaprim has been tested against both vancomycin and linezolid, and in combined Phase III studies that included nearly 1,000 patients with cSSSI, iclaprim has been shown to have high cure rates, exceeding 90 percent in the Per-Protocol population. Iclaprim has demonstrated potent bactericidal (killing) activity against MRSA and an extended range of resistant pathogens, with a well tolerated side-effect profile. Arpida is fully committed to iclaprim's development and will continue to work with the FDA to address any questions related to iclaprim in anticipation of the drug's Prescription Drug User Fee Act (PDUFA) goal date of January 16, 2009.

Project investigating Himalayan oregano as MRSA antibacterial agent

Project investigating Himalayan oregano as MRSA antibacterial agent wins SEED award.

A research team from the University of the West of England, working in partnership with a laboratory in Delhi, a fair trade company, a community-based organisation and an environmental research institute in Himachal Pradesh in the Western Himalaya, have jointly been awarded a 2008 SEED award for their project investigating Himalayan oregano essential oil as an antibacterial agent for MRSA. Anzeige The project is part of an initiative to provide rural communities with sources of income generated from sustainable collection of non-timber forest products in the Kullu District of Himachal Pradesh. Origanum vulgare is a relatively common herb that grows in high altitude meadows throughout the Himalayan region, yet it is perceived by many villagers to have no culinary, medicinal or economic value. In Kullu oregano is often referred to as ‘bekaar gahaas’, or ‘useless grass’; even cows and goats don’t eat it.

High hopes for new MRSA antibiotic

Pharmacy Europe - High hopes for new MRSA antibiotic.

A new antibiotic that shows promise in treating the superbug MRSA and related infections is poised to enter the market after phase III ASSIST trials in the US. Intravenous iclaprim, a novel antibiotic, is reported by manufacturer Arpida to show high clinical cure rates similar to those of the comparator drug, linezolid. The test results were gathered from the ASSIST-1 and ASSIST-2, (Arpida's skin and skin structure infection study) pivotal Phase III studies involving a total of 991 patients. Data from the studies also show that iclaprim exhibited a high eradication rate for MRSA (76.4%), which was comparable to that of linezolid (78.7%).

Chinese plants to yield new drugs?

Link: HighWire Press -- Medline Abstract.

The antimicrobial activity of crude 80% ethanol extracts of 19 medicinal plants collected in Lijiang, the southwest of China, was tested against clinical strains of Methicillin-resistant Staphylococcus aureus (MRSA). All the 19 plants showed anti-MRSA activity with MIC of 1.25-3.07mg/ml. The most active antimicrobial plants were Dendrobenthamia capitata, Elsholtzia rugulosa, Elsholtzia blanda, Geranium strictipes, Polygonum multiflorum and Potentilla fulgens (MIC

Groundbreaking Discovery May Lead to Stronger Antibiotics

Link: Groundbreaking Discovery May Lead to Stronger Antibiotics.

The study led by Bushweller represents the first time scientists have cracked the code required to solve a certain class of membrane protein structure by using nuclear magnetic resonance (NMR) spectroscopy, the preeminent technique for determining the structure of organic compounds.  This novel NMR approach now gives the scientific community a brand new platform for attempting to determine structures of other important membrane proteins. "What this means is that not only did we establish NMR spectroscopy as a potent tool for the characterization of the structure, dynamics and function of integral membrane proteins, but we also discovered that the DsbB enzyme is an exciting potential new target agent for the creation of novel antibiotics," says Bushweller.  "This could give us the roadmap to an entirely new class of antibiotics."

Trius Doses First Patient In Antibacterial Phase 2 Trial

Link: Trius Doses First Patient In Antibacterial Phase 2 Trial - TR-701 Tested For Efficacy In Drug Resistant Skin Infections.

Trius Therapeutics, Inc. announced the initiation of Phase 2 testing of the oral form of its second-generation oxazolidinone antibacterial drug TR- 701. The multicenter trial will test the efficacy, safety and tolerability of once- daily doses of 200, 300 and 400 milligrams of TR-701 in complicated skin and skin structure infections (cSSSI) for five to seven days of treatment. The study follows the recently completed two-part Phase 1 study that tested the safety, tolerability and pharmacokinetics of TR-701 in single and multiple ascending doses for up to 21 days compared with Zyvox® (linezolid), the only marketed drug of the oxazolidinone class. In addition, separate food effect and microdialysis studies measuring the absorption of TR-701 in the presence and absence of food and the tissue penetration of the drug, respectively, have also been completed.

Wyeth's 'Superbug' Antibiotic, Tygacil (tigecycline), Commended For Innovation And Health Benefit

Link: Wyeth's 'Superbug' Antibiotic, Tygacil (tigecycline), Commended For Innovation And Health Benefit.

Wyeth's innovative antibiotic, Tygacil (tigecycline), developed to treat a range of superbugs, has been commended at the 2008 UK Prix Galien. The Prix Galien is the pharmaceutical industry's premier award and is designed to recognise pharmaceutical innovation and the resulting health benefits it produces. The 2008 Prix Galien awards were made last night by Professor Sir Michael Rawlins, Chairman of the National Institute for Health and Clinical Excellence (NICE), who heads the Prix Galien judging panel. Tygacil is the world's first glycylcycline intravenous antibiotic. It has an expanded broad-spectrum antibiotic activity and is the only such agent effective against resistant Gram-negative and Gram-positive organisms including the superbug MRSA- a national and global concern. As such, it offers a significant advance in the treatment of patients at risk of difficult-to-treat bacterial infections and gives doctors the confidence to successfully manage these conditions.

Arpida Completes Enrolment In Phase II "Intravenous-to-Oral" Switch Trial With Oral Iclaprim

Link: Arpida Completes Enrolment In Phase II "Intravenous-to-Oral" Switch Trial With Oral Iclaprim.

Arpida's leading product candidate is intravenous iclaprim, a potent antibacterial that targets severe infections requiring hospital treatment, including those caused by methicillin-resistant Staphylococcus aureus (MRSA). The clinical programme for the first indication, complicated skin and skin structure infections (cSSSI), has been completed. The submission of the NDA to the US FDA was completed in March 2008. The FDA has defined that the Prescription Drug User Fee Act (PDUFA) goal date will be 16 January 2009. Arpida submitted a Marketing Authorisation Application for intravenous iclaprim with EMEA in July 2008. EMEA notified that it had accepted the MAA for review in August 2008.

In vitro activity of retapamulin against Staph

Link: In vitro activity of retapamulin against Staphylococcus aureus isolates resistant to fusidic acid and mupirocin -- Woodford et al. 62 (4): 766 -- Journal of Antimicrobial Chemotherapy.

Results: The S. aureus included 488 (73%) methicillin-resistant isolates (oxacillin MICs >2 mg/L), 336 isolates (51%) resistant to fusidic acid (MICs >1 mg/L) and 254 (38%) with high-level mupirocin resistance (MICs >256 mg/L); 103 (16%) isolates were resistant both to fusidic acid and to high levels of mupirocin. Retapamulin inhibited 663 (99.9%) isolates at ≤0.25 mg/L. A single methicillin-resistant S. aureus isolate, also with high-level mupirocin resistance, required a retapamulin MIC of 2 mg/L, but its reduced susceptibility to retapamulin was not associated with any mutation in ribosomal protein L3. Conclusions: Retapamulin demonstrated excellent activity in vitro against S. aureus isolates, irrespective of their level of resistance to other antibacterials. These results support the EUCAST epidemiological cut-off value for retapamulin of ≤0.5 mg/L against S. aureus.

Antifungal Vaccine holds MRSA promise

Link: The Antifungal Vaccine Derived from the Recombinant N Terminus of Als3p Protects Mice against the Bacterium Staphylococcus aureus -- Spellberg et al. 76 (10): 4574 -- Infection and Immunity.

The rAls3p-N vaccine, but neither tetanus toxoid nor a related Als protein (Als5p), improved the survival of vaccinated mice subsequently infected with multiple clinical isolates of S. aureus, including methicillin-resistant strains. The rAls3p-N vaccine was effective against S. aureus when combined with aluminum hydroxide adjuvant. However, the vaccine did not improve the survival of mice infected with other bacterial pathogens. Vaccinated, infected mice mounted moderated type 1 immune responses. T lymphocyte-deficient mice were more susceptible to S. aureus infection, but B lymphocyte-deficient mice were not. Furthermore, T but not B lymphocytes from vaccinated mice mediated protection in adoptive transfer studies. The passive transfer of immune serum was not protective. These data provide the foundation for cross-kingdom vaccine development against S. aureus and Candida, which collectively cause 200,000 bloodstream infections resulting in ≥40,000 to 50,000 deaths annually in the United States alone.

MRSA Drugs - Where now

Link: British Journal of Pharmacology - Molecular epidemiology of clinically significant antibiotic resistance genes.

In summary, it seems likely that not only will MRSA continue to increase in prevalence in both the community and hospitals, but there will be increasing problems of antimicrobial resistance. This may well be alleviated by the introduction of a number of potent antibiotics that are active against MRSA, such as ceftobiprole (Noel, 2007), tigecycline (Hawkey and Finch, 2007), novel quinolones (Wang et al., 2007), and newer derivatives of glycopeptides such as oritavancin that are not susceptible to vanA-mediated resistance mechanisms (Allen and Nicas, 2003).

MRSA Drugs - Where now

Link: British Journal of Pharmacology - Molecular epidemiology of clinically significant antibiotic resistance genes.

In summary, it seems likely that not only will MRSA continue to increase in prevalence in both the community and hospitals, but there will be increasing problems of antimicrobial resistance. This may well be alleviated by the introduction of a number of potent antibiotics that are active against MRSA, such as ceftobiprole (Noel, 2007), tigecycline (Hawkey and Finch, 2007), novel quinolones (Wang et al., 2007), and newer derivatives of glycopeptides such as oritavancin that are not susceptible to vanA-mediated resistance mechanisms (Allen and Nicas, 2003).

Helix BioMedix Announces U.S. Patent Issuance for Novel Class of Antimicrobial

Link: Helix BioMedix Announces U.S. Patent Issuance for Novel Class of Antimicrobial - MarketWatch.

Helix BioMedix, Inc. (HXBM: helix biomedix inc com new News, chart, profile, more Last: 0.53+0.12+29.27% 9:44am 08/07/2008 Delayed quote data Add to portfolio Analyst Create alert Insider Discuss Financials Sponsored by: HXBM 0.53, +0.12, +29.3%) , a developer of bioactive peptides, today announced that it has been issued U.S. Patent number 7,407,940 by the United States Patent and Trademark Office, which includes the company's lead pre-clinical lipohexapeptide candidates. The patent covers a family of hexapeptide antimicrobial agents, including HB1345, for use as broad spectrum topical anti-infectives. HB1345 will be developed initially for dermatological indications such acne, rosacea and atopic dermatitis. Subsequent clinical applications are anticipated to include prevention of hospital acquired infections, such as those caused by MRSA and other multi-resistant pathogens.

Multi-Tasking Maggots In Superbug Showdown

Link: Multi-Tasking Maggots In Superbug Showdown.

Scientists at Swansea University have discovered a new type of antibiotic in maggot secretions that can tackle up to 12 different strains of MRSA, as well as E. coli and C. difficile. This research was funded by leading charity Action Medical Research, with support from the Rosetrees Trust. The antibiotic, named Seraticin™, is derived from the maggot secretions of the common green bottle fly (Lucilia sericata) and scientists hope to develop it into an injection, pill or ointment. So far, they have purified Seraticin™ and undertaken the study of its structure and the mechanism by which it prevents infection. The next steps will be to complete the identification of the compound and develop a way to synthesise it. It can then be tested on human cells and eventually in clinical trials in order to determine its medical effectiveness and properties as a novel antibiotic.

Researchers Analyze How New Anti-MRSA Antibiotics Function

Link: Researchers Analyze How New Anti-MRSA Antibiotics Function.

Mobashery and his team have been focusing on a unique protein called penicillin-binding protein 2a (PBP 2a) that MRSA carries on its cell membrane. Previous research has shown that PBP 2a performs the critical cell wall cross-linking reaction. Mobashery has previously reported that PBP 2a exists in "closed and open" forms. The open form is needed for the physiological functioning of PBP 2a, but the closed form is responsible for the antibiotic resistance manifestations. When the protein interacts with the cell wall at a specific location on its surface, it opens up to carry out the physiological function. In their latest paper, Mobashery and his team reveal that the new Cerexa antibiotics appear to interact with PBP 2a in a unique way. The antibiotics mimic some of the interactions of the cell wall with PBP 2a, whereby the enzyme is "tricked" to open up as it attempts its physiological function. Once this opening of PBP 2a takes place, its function is inhibited by the novel antibiotics, resulting in bacterial cell death. "Both antibiotics are highly effective in killing MRSA," Mobashery said. "It's a promise that awaits the outcome of the clinical trials."

XOMA Begins Clinical Trial on anti MRSA gel

Link: XOMA Begins Phase 2a Clinical Trial to Evaluate XOMA 629 Topical Gel as a Treatment for the Common Skin Disease, Impetigo - MarketWatch.

n addition to studying XOMA 629 for impetigo, XOMA plans to commence clinical trials in the second half of 2008 for topical eradication of S. aureus, including MSSA and MRSA. MRSA is a growing healthcare threat and caused 94,000 serious infections and 19,000 deaths in 2005, most associated with healthcare settings (Journal of the American Medical Association 2007;298(15):1763-1771). Certain strains of MRSA are resistant to a significant number of antibiotics, and in preclinical in vitro studies XOMA 629 was active against several of these multi-drug resistant strains.

Retapamulin - what potential against MRSA?

Link: In vitro activity of retapamulin against Staphylococcus aureus isolates resistant to fusidic acid and mupirocin -- Woodford et al., 10.1093/jac/dkn266 -- Journal of Antimicrobial Chemotherapy.

Objectives: We determined the in vitro activity of retapamulin, a novel pleuromutilin antibiotic, against 664 Staphylococcus aureus isolates from the UK, including many resistant to fusidic acid and/or highly resistant to mupirocin. Methods: MICs were determined on Mueller–Hinton agar in accordance with the CLSI guidelines. Susceptibility was categorized using CLSI criteria, where available; otherwise the European Committee for Antimicrobial Susceptibility Testing (EUCAST)/BSAC criteria were used (for mupirocin and fusidic acid). Mutations in the rplC gene, which encodes ribosomal protein L3, were sought by PCR and DNA sequencing. Results: The S. aureus included 488 (73%) methicillin-resistant isolates (oxacillin MICs >2 mg/L), 336 isolates (51%) resistant to fusidic acid (MICs >1 mg/L) and 254 (38%) with high-level mupirocin resistance (MICs >256 mg/L); 103 (16%) isolates were resistant both to fusidic acid and to high levels of mupirocin. Retapamulin inhibited 663 (99.9%) isolates at ≤0.25 mg/L. A single methicillin-resistant S. aureus isolate, also with high-level mupirocin resistance, required a retapamulin MIC of 2 mg/L, but its reduced susceptibility to retapamulin was not associated with any mutation in ribosomal protein L3. Conclusions: Retapamulin demonstrated excellent activity in vitro against S. aureus isolates, irrespective of their level of resistance to other antibacterials. These results support the EUCAST epidemiological cut-off value for retapamulin of ≤0.5 mg/L against S. aureus.

Ceftobiprole matches Vancomycin in combating MRSA

Link: HighWire Press -- Medline Abstract.

Ceftobiprole has so far demonstrated a good safety profile in preliminary studies with similar tolerability to comparators. The broad-spectrum activity of ceftobiprole may allow it to be used as monotherapy in situations where a combination of antibacterials might be required. Further clinical studies are needed to determine the efficacy and safety of ceftobiprole and to define its role in patient care.

Ceftaroline trials prove effective against MRSA

Link: Forests Phase III skin infection study meets study end point - Pharmaceutical Business Review.

Forest Laboratories has announced positive results from two globally conducted, multi-center Phase III studies of ceftaroline, a broad-spectrum cephalosporin with activity against gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus and gram negative bacteria, for the treatment of complicated skin and skin structure infections. Print Article Email A Friend Your Comment Post to del.icio.us Digg this Click here to find out more! RELATED ARTICLES     * Forest and Mylan amend Bystolica agreement       28 Feb 2008     * Glenmark receives milestone payment from Forest Labs       6 Feb 2008     * Forest and Daiichi terminate Azor co-promotion agreement       13 May 2008     * FDA issues approvable letter for nebivolol for hypertension       3 Dec 2007     * Caraco wins tentative FDA approval for generic Lexapro       3 Dec 2007 COMPANIES MENTIONED    No companies found WHITE PAPERS No White Papers Available Click here to find out more! The two globally conducted, multi-center, Phase III, randomized, double-blind comparative studies were designed to evaluate the efficacy and safety of ceftaroline compared to vancomycin plus aztreonam. In both the studies, ceftaroline as monotherapy achieved the primary endpoint of non-inferiority versus the combination of vancomycin plus aztreonam. Ceftaroline treated patients had a clinical cure rate of 91.6% compared to a vancomycin plus aztreonam clinical cure rate of 92.7% at test-of-cure visit in the clinically evaluable population across both studies.

Plant extracts could aid MRSA fight

Link: HighWire Press -- Medline Abstract.

Novel therapies are needed to address the public health problem posed by methicillin-resistant STAPHYLOCOCCUS AUREUS (MRSA). In this study, we determined the effects of combinations of antibiotics and plant polyphenols against 20 clinical isolates of MRSA. The IN VITRO activities of 10 antibiotics and 15 natural polyphenols against the isolates were evaluated by determining minimum inhibitory concentrations (MICs). All isolates were susceptible to vancomycin and resistant to rifampicin, while susceptibilities to ciprofloxacin varied. Among the 15 natural polyphenols, kaempferol (3,4',5,7-tetrahydroxyflavone) and quercetin (3,3',4',5,7-pentahydroxyflavone) showed the lowest MICs. In checkerboard assays, combinations of rifampicin and either kaempferol or quercetin acted synergistically or partially synergistically against the clinical MRSA isolates. Rifampicin combined with kaempferol or quercetin exhibited good beta-lactamase inhibitory effects (57.8 % and 75.8 %, respectively) against a representative isolate according to nitrocefin analysis. The study results and ready availability and low toxicity of plant polyphenols warrant further investigations on the therapeutic potential of combination therapies for MRSA infections. FIC:fractional inhibitory concentration MIC:minimum inhibitory concentration MRSA:methicillin-resistant STAPHYLOCOCCUS AUREUS.

Streptomyces could yield anti MRSA drug

Link: HighWire Press -- Medline Abstract.

Fermented culture of Streptomyces fulvissimus was found to secrete an antibacterial protein inhibitory to Micrococcus luteus, Bacillus subtilis, Bacillus cereus and methicillin resistant Staphylococcus aureus (MRSA) strains. The extracellular protein from the fermented culture on concentration revealed a high molecular weight peptide of 63kDa on SDS-PAGE gel and the region on gel displayed inhibitory activity against methicillin resistant Staphylococcus aureus. Bioactivity of the extra cellular protein was non-sensitive to proteinase K, alpha chymotrypsin, protease, EDTA (ethylene diamine tetra acetic acid), PMSF (phenyl methyl sulfonyl fluoride) and DMSO (dimethyl sulfoxide) but partially susceptible to amylase and heat. Glycoprotein nature of the proteinaceous compound was confirmed by periodic acid schiffs (PAS) staining. The secretary protein of S. fulvissimus demonstrated a significant activity against MRSA strain. It could be an important source for developing new drugs to control multidrug resistant gram positive bacteria.

Targeted drug would seek out MRSA

Link: Important First Steps To Creating A Synthetic Copycat Of A Living Cell.

In work published as a 'VIP paper' in the journal Angewandte Chemie International Edition, they show how in the laboratory they have been able to encourage the capsules to 'talk' to natural bacteria cells and transfer molecular information. The breakthrough could have a number of potential medical uses. Among them could be the development of new targeted drug delivery systems, where the capsules would be used to carry drug molecules to attack specific diseased cells in the body, while leaving healthy cells intact, thereby reducing the number of side affects that can be associated with treatments for life-threatening illnesses such as cancer. The technology could also be used as an anti-microbial agent, allowing doctors to destroy harmful bacteria, without attacking other health-promoting bacteria in the body, which could offer a new weapon in the fight against superbugs. Dr Cameron Alexander said: "These are very primitive steps in the lab, and still a long way from a true synthetic counterpart to a biological cell, but we have demonstrated that we can transfer certain molecules from inside the synthetic capsule to the bacteria when they are in physical contact, which is an exciting development.

XF73 routine treatment in six years

Link: British drug which destroys MRSA offers new hope of cure in battle against superbugs | the Daily Mail.

Dr Bill Love, chief executive of Destiny Pharma, said that within six years XF-73 could be being used routinely to cure patients already infected with MRSA, and it might eventually be used against the superbug C. difficile. "If it goes through clinical trials successfully, it really is a completely fundamental breakthrough," he said. "The potential is really quite amazing." Crucially, the compound works in a different-way to antibiotics, many of which simply prevent MRSA from multiplying in the body. XF-73 works by destroying the superbug's cell membrane.

Guarded welcome for superbug 'cure'

Link: Guarded welcome for superbug 'cure' | Society | guardian.co.uk.

In a statement, the company said: "Destiny Pharma has now completed its phase one clinical trials and this result is the latest of many which have shown XF-73's high potential." The firm presented its findings to the European congress on clinical microbiology and infectious diseases in Barcelona last month. A Department of Health spokesman said: "This is interesting research, and we maintain a close watch on these and other emerging findings in the field. "Reducing healthcare-associated infections is a top priority for the NHS, and we are already seeing significant reductions in healthcare-associated MRSA bloodstream infections, with rates down by 30% compared with the same period last year."

XF73 kills 5 MRSA Strains

Link: Drug gives hope in superbug fight - Sunday Sun.

XF-73 destroyed the five most common strains of methicillin-resistant Staphylococcus aureus bacteria (MRSA) in laboratory tests, according to the study. Five of the most common strains of MRSA were tested against the drug and an antibiotic was used as a control. The research was led by Destiny Pharma's chief executive Dr Bill Love.

MRSA cure in 3 years?

Link: icLiverpool - Drug gives hope in superbug fight.

British scientists are working on a new drug which they believe could herald a breakthrough in efforts to cure MRSA. Researchers are carrying out trials of a bactericidal compound, which they claim actually kills bacteria, with a view to developing a product for use in hospitals within three years. Most antibiotics used to treat hospital bugs such as MRSA are bacteriostatic, meaning they prevent the growth of bacteria. Brighton-based pharmaceutical company Destiny Pharma believes its compound - codenamed XF-73 - could hold the key to stamping out the potentially-fatal bug. A study showed that, even after 55 repeat exposures, MRSA bacteria did not develop resistance to the drug - which is applied as a gel into patients' noses - in the same way it does to antibiotics.

UK-based drug company to take up MRSA bug buster fight - Press & Journal

Link: UK-based drug company to take up MRSA bug buster fight - Press & Journal.

A DRUG company is looking to develop groundbreaking new treatments for the potentially deadly hospital superbug MRSA following a breakthrough by a team of north-east researchers. Aberdeen University professor Jorg Feldmann and a team of international scientists discovered earlier this year that a protein released naturally by the human body has the power to starve MRSA of the “food” it needs to spread. It is hoped the protein, calprotectin, can be developed into a treatment which would beat the killer infection. Last night Prof Feldmann, 43, said there has been huge interest in his team’s findings, including inquiries from a UK-based drug company. “We have had contact from a drug company who are interested in developing our research into a drug. “We are applying for some further funding to get more people involved to take the research to the next step and carry out small-scale tests to find out more about our discovery.”

New Antibiotic Class Proves Effective Against MRSA

Link: New Antibiotic Class Proves Effective Against MRSA.

At ECCMID, the annual European Conference on Clinical Microbiology and Infectious Diseases, Cambridge UK-based Phico Therapeutics presented new data on the rapid bactericial activity of its lead compound against MRSA. PT1.2 belongs to a new class of antibacterial proteins called SASPs that act by binding to bacterial DNA and halting replication and gene expression, resulting in rapid cell death. Phico Therapeutics now intends to take PT1.2 into clinical trials using its unique delivery platform technology called SASPject™ According to Phico Therapeutics CEO Dr Heather Fairhead, these results could lead to a major breakthrough in the fight against both hospital- and community-acquired infection. "The study, carried out in conjunction with the UK's Health Protection Agency, showed that SASP was rapidly bactericidal against all 10 different MRSA isolates gathered from across the US. Indeed in the speed of kill assay, SASP caused a >99.9 % drop in viability within 2 mins against the 10^5 culture and a >99.9 % drop in viability within 10 mins against the 10^7 culture. This data gives us the confidence to take PT1.2 into the clinic. Furthermore, our additional SASPjectTM candidates are showing potential against E. coli, and C. difficile with SASPjectTM targeted to other drug resistant bacteria in development."

New antibody to help fight MRSA

Link: Laureate Pharma, Inc. :: Laureate Pharma Announces Manufacturing Agreement With Alopexx Pharmaceuticals, LLC.

Laureate Pharma, Inc., a full-service biopharmaceutical development and protein production company, today announced that it has entered into a cGMP contract manufacturing agreement with Alopexx Pharmaceuticals, LLC. According to the agreement, Laureate will produce Alopexx's mAb F598 antibody under cGMP conditions. This antibody is planned for use in clinical trials, and later for commercial production for the treatment and prevention of Staphylococcus aureus infections. Terms of the manufacturing agreement were not disclosed.

Alligator blood could help fight MRSA

Link: Alligators could help fight MRSA - Telegraph.

Despite their reputation for deadly attacks on humans and pets, alligators are wiggling their way toward a new role as potential lifesavers, says Dr Kermit Murray of Louisiana State University. He tells the spring meeting of the American Chemical Society in New Orleans that proteins in gator blood may provide a source of powerful new antibiotics to help fight superbugs, along with infections associated with diabetic ulcers and severe burns. Their study is the first to explore the antimicrobial activity of alligator blood in detail. "We're very excited about the potential of these alligator blood proteins as both antibacterial and antifungal agents," says co-author Dr Mark Merchant. "There's a real possibility that you could be treated with an alligator blood product one day."

'Healing Clays' Show Promise For Fighting Deadly MRSA

Link: 'Healing Clays' Show Promise For Fighting Deadly MRSA Superbug Infections, Other Diseases.

In the new study, funded by the National Institutes of Health, Willams and her colleagues collected more than 20 different clay samples from around the world to investigate their antibacterial activities. In collaboration with study co-leader Shelley Haydel, Ph.D., a microbiologist with Arizona State, the researchers tested each of the clays against several different bacteria known to cause human diseases. These bacteria include MRSA (methicillin-resistant Staphylococcus aureus), Mycobacterium ulcerans (a microbe related to the tuberculosis bacterium that causes a flesh-eating disease known as Buruli ulcer), as well as E. coli and Salmonella (which cause food poisoning). The researchers identified at least three clays that killed or significantly reduced the growth of these bacteria.

Penicillin Could Be Back In Battle Against Antibiotic Resistant Bugs

Link: Penicillin Could Be Back In Battle Against Antibiotic Resistant Bugs That Kill Millions.

Research led by the University of Warwick has uncovered exactly how the bacterium Streptococcus pneumoniae has become resistant to the antibiotic penicillin. The same research could also open up MRSA to attack by penicillin and help create a library of designer antibiotics to use against a range of other dangerous bacteria. Worldwide Streptococcus pneumoniae causes 5 million fatal pneumonia infections a year in children. In the US it causes 1 million cases a year of pneumococcal pneumonia in the elderly of which up to 7% are fatal.  Penicillin normally acts by preventing the construction of an essential component of the bacterial cell wall: the Peptidoglycan. This component provides a protective mesh around the otherwise fragile bacterial cell, providing the mechanical support and stability required for the integrity and viability of cells of Streptococcus pneumoniae and other bacteria including MRSA. The researchers targeted a protein called MurM that is essential for clinically observed penicillin resistance and has also been linked to changes in the chemical make up of the peptidoglycan that appear in penicillin resistant Streptococcus pneumoniae isolated from patients with pneumococcal infections. The researchers found that MurM acted as an enzyme that was key to the formation of particular structures within the S. pneumoniae peptidoglycan called dipeptide bridges that link together strands of the peptidoglycan mesh that contributes to the bacterial cell wall. The presence of high levels of these dipeptide bridges in the peptidoglycan of Streptococcus pneumoniae is a pre-requisite for high level penicillin resistance.

FDA Says it Has 'Outstanding Issues' With Theravance Skin Antibiotic

Link: FDA Says it Has 'Outstanding Issues' With Theravance Skin Antibiotic - WSJ.com.

The Food and Drug Administration said Monday it still had several "outstanding issues" with a proposed Theravance Inc. antibiotic that is being developed to treat skin infections. The agency had canceled an advisory committee meeting scheduled for Wednesday that was set to evaluate the drug, televancin. The product is being developed with Astellas Pharma Inc. of Tokyo. But the agency said in a statement that the meeting was being canceled to "allow time for the FDA to review and resolve several outstanding issues." The FDA said it would schedule an advisory committee meeting in the future, if needed. Televancin is a once-daily injectable antibiotic that would be used to treat skin infections, including those caused by resistant bacteria like methicillin-resistant staphylococcus aureus, or MRSA.

Superbug on the run

Link: Superbug on the run.

Superbug on the run Anti-MRSA microbe isolated. But researcher cautions a cure is still years and millions of dollars away A Halifax researcher has made promising findings in the fight against one of the superbugs infecting cities and hospitals across Canada. David Jakeman, a scientist at Dalhousie University, has isolated a microbe that appears to battle methicillin-resistant staphylococcus (MRSA), a form of staph infection resistant to most antibiotics. Jakeman said yesterday the results are sufficiently promising that his lab wants to repeat the experiments as well as evaluate other compounds with similar structures. "It's all very preliminary at the moment," he cautioned. "Some of those natural products we've isolated, we've shown they have good activity against MRSA and that's why we're exploring more fully the compounds that these bacteria produce," Jakeman said.

Biotechs toiling on new antibiotics for extra-tough bugs

Link: Biotechs toiling on new antibiotics for extra-tough bugs - Feb. 14, 2008.

"Antibiotics were considered an area that you couldn't make a lot of money in," said Rachel McMinn, an analyst for Cowen and Co., "so Big Pharma made the decision to get out, and biotechs filled that gap," with a pipeline of new treatments. If their products get government approval, she said, they could lead to a multibillion-dollar market. Oritavancin, an antibiotic for skin infections including MRSA, is awaiting decision from the Food and Drug Administration. Its maker, the biotech Targanta Therapeutics (TARG), submitted its approval application on Feb. 11, and the review could be completed this year. Cethromycin from Advanced Life Sciences (ADLS) finished late-stage studies and is on track for FDA submission. The antibiotic has been studied as a guard against pneumonia, but Chief executive Michael Flavin said it could possibly be used for staph infections. Faropenem, from Replidyne (RDYN), is in early-stage tests for MRSA. An antibiotic from privately held Paratek Pharmaceuticals is in early-stage tests for community and hospital infections. And Cubist's (CBST) fast-growing antibiotic Cubicin, which is already on the market, is being tested for a variety of other infections.

Bacterial toxin closes gate on MRSA immune response

Link: Bacterial toxin closes gate on immune response.

Researchers at the University of Pennsylvania School of Medicine have demonstrated that a bacterial toxin from the common bacterium Staphylococcus aureus shuts down the control mechanism of the tunnel, called an ion channel, in immune cell membranes. Shutting down ion channels has long been known to suppress the immune response, and the bacteria may use the toxin to neutralize host defenses against bacteria. The study is published in the February 14 issue of Nature.

Scientists to unleash potent proteins in hospital superbug battle

Link: Scientists to unleash potent proteins in hospital superbug battle - National News, Frontpage - Independent.ie.

A TEAM of researchers at the Royal College of Surgeons is hoping to make a breakthrough in the battle against MRSA and other hospital superbugs. The group, headed by Dr Marc Devocelle, believes it may have discovered how to treat patients with powerful proteins that can kill off resistant strains of superbugs -- without harming humans. The proteins, called host defence peptides, have been identified as a major weapon in the fight against resistant strains of bacteria and cancer cells. However, they are so potent that they could be toxic when affecting the entire body. Dr Devocelle believes he has developed a way of activating them only at the site of infection, where they can kill off MRSA without harming patients. These proteins could also kill bacteria that cause life-threatening bloodstream infections and can be resistant to all available antibiotics (multi-drug resistant bacteria). "During a research programme funded by Science Foundation Ireland, we have designed and developed the drug delivery systems for both MRSA and multi-drug resistant bacteria," he says. "In collaboration with Beaumont Hospital, we have already proved that it can work on some laboratory bacteria and we are currently optimising the drugs to make sure they are active on clinical bacteria, which are far more aggressive.

Immune System Protein Starves Staph Bacteria

Link: Immune System Protein Starves Staph Bacteria.

Calprotectin makes up about half of the internal content of neutrophils, the primary immune cells that respond to a staph infection. The investigators propose that calprotectin is a second weapon neutrophils employ as they wage battle in the abscess. First, neutrophils try to “gobble up” the bacteria. If they fail and die (staph is expert at secreting toxins that kill neutrophils), then they spill their guts, which are filled with metal-binding calprotectin sponges that soak up the metals. “The neutrophil gets the last laugh,” Skaar quipped. “The work is a phenomenal merger of several cutting edge technologies, which collectively allow an unprecedented view of the host-pathogen interface,” said Paul Dunman, PhD, assistant professor of pathology and microbiology at the University of Nebraska Medical Center, and a co-author of the Science paper. “This discovery could lead to a new way to treat staph infections.” The findings suggest that drugs that bind metals – like calprotectin does – would make good antibiotics. “If we can figure out how to make a molecule that transiently binds metals, and that can be targeted to abscesses, I think that would be a great drug,” Skaar said.

Cholestrol Drug May Render Disease-Causing Staph Harmless

Link: New Approach May Render Disease-Causing Staph Harmless.

The multi-institutional team exploited a chemical pathway that allows staph to defend itself against an immune response. The researchers showed that a compound called BPH-652 – originally designed to lower cholesterol – blocks a key enzyme in that pathway, weakening the staph’s defenses and allowing the body’s immune cells to prevail against the infection. A golden-colored pigment (“aureus” means golden in Latin) called a carotenoid gives the S. aureus bacterium its edge. The carotenoid acts as an antioxidant for the bacterium, allowing it to evade attack by the body’s immune cells. By crippling production of the carotenoid, the compound strips the staph of one of its key defenses.

Trius Initiates U.S. Phase I Trial For Its Oxazolidinone Antibacterial Drug, TR-701

Link: Trius Initiates U.S. Phase I Trial For Its Oxazolidinone Antibacterial Drug, TR-701.

Trius Therapeutics, Inc. announced that it initiated its first Phase 1 clinical trial of TR-701, an antibacterial drug candidate intended for treatment of patients with serious Gram-positive bacterial infections, including those caused by MRSA and other drug-resistant strains. The eighty-eight subject single and multiple ascending dose trial will test tolerability, safety and pharmacokinetics of the oral dosage form of the drug and will compare its properties to those of Zyvox�, the only marketed drug in the oxazolidinone class. "In this early clinical trial our goal is to demonstrate the potential of TR-701 to provide patients and clinicians with more convenient dosing and a broader safety margin than the current standard of care," stated Jeffrey Stein, Ph.D., President and CEO of Trius Therapeutics. "TR-701's potential for once-daily dosing, supported by results of prior exploratory human testing in Korea and preclinical animal data, is expected to translate into an increased therapeutic index and thereby provide an important option for the treatment of serious infections caused by drug-resistant bacterial pathogens."

Scientists Strike Blow In Superbugs Struggle

Link: Scientists Strike Blow In Superbugs Struggle.

Micklefield, Smith and colleagues were the first to engineer the biosynthesis of lipopeptide antibiotics of this class back in 2002. They have now developed methodologies for altering the structure of these antibiotics, such as mutating, adding and deleting components. This innovation provides access to thousands of lipopeptide variants that cannot be produced easily in any other way. Dr Micklefield said: "The results from this work are essential in the development of the next generation of lipopeptide antibiotics, which are critical to combat emerging super bugs that have acquired resistance to other antibiotics. "The potent activity of this class of antibiotics against pathogens that are resistant to all current antibiotic treatments makes them one of the most important groups of antibiotics available. "Our work relies on interdisciplinary chemical-biology, spanning chemistry through to molecular genetics. It follows the tradition of pioneering work in natural product biosynthesis and engineering that has come out of the UK."

Decoy Makes Sitting Duck Of Superbugs

Link: Decoy Makes Sitting Duck Of Superbugs.

A DNA-based therapy could slash the development time of new drugs to combat antibiotic resistant superbugs. Scientists from the John Innes Centre have proven that by taking a short stretch of DNA from a bacterium and delivering it with an existing antibiotic they can switch off antibiotic resistance. Together with technology transfer company PBL, the scientists have launched a spin-out company, Procarta Biosystems Ltd, to develop the technology. "The DNA sequence acts as a decoy, disrupting gene expression and blocking resistance", said Dr Michael McArthur from JIC.

Antibiotics to come with built in defender against resistance

Link: Decoy Makes Sitting Duck Of Superbugs.

A DNA-based therapy could slash the development time of new drugs to combat antibiotic resistant superbugs. Scientists from the John Innes Centre have proven that by taking a short stretch of DNA from a bacterium and delivering it with an existing antibiotic they can switch off antibiotic resistance. Together with technology transfer company PBL, the scientists have launched a spin-out company, Procarta Biosystems Ltd, to develop the technology. "The DNA sequence acts as a decoy, disrupting gene expression and blocking resistance", said Dr Michael McArthur from JIC. "We are putting genetic information directly into drugs. This is the first application of a DNA based therapy". The scientists have also patented a way of discovering decoys in bacteria without necessarily having to know the genes involved. This means they can develop effective new drugs against any bacterium within a couple of years and at a fraction of the normal cost.

Daptomycin More Versatile Against MRSA?

Link: Bactericidal Action of Daptomycin Against Stationary-Phase and Nondividing Staphylococcus aureus -- Mascio et al., 10.1128/AAC.00824-07 -- Antimicrobial Agents and Chemotherapy.

Most antibiotics with bactericidal activity require that the bacteria be actively dividing to produce a rapid kill. However, in many infections such as endocarditis, prosthetic joint infections, and infected embedded catheters, the bacteria divide slowly or not at all. Daptomycin is a lipopeptide antibiotic with a distinct mechanism of action that targets the cytoplasmic membrane of gram-positive organisms including Staphylococcus aureus. Daptomycin is rapidly bactericidal against exponentially growing bacteria (3-log reduction in 60 minutes). The objective of this study was to determine if daptomycin is bactericidal against nondividing S. aureus and to quantify the extent of the bactericidal activity. In high-inoculum methicillin-sensitive S. aureus cultures in stationary phase (1010 colony-forming units/ml), daptomycin displayed concentration-dependent bactericidal activity, requiring 32 �g/ml to achieve a 3-log reduction. In a study comparing several antibiotics at 100 �g/ml, daptomycin demonstrated faster bactericidal activity than nafcillin, ciprofloxacin, gentamicin, and vancomycin. In experiments where bacterial cell growth was halted by the metabolic inhibitors carbonyl cyanide m-chlorophenylhydrazone or erythromycin, daptomycin (10 �g/ml) achieved the bactericidal end point (3-log reduction) within 2 hours. In contrast, ciprofloxacin (10 �g/ml) did not produce bactericidal activity. Daptomycin (2 �g/ml) remained bactericidal against cold-arrested S. aureus, which was protected from the actions of ciprofloxacin and nafcillin. The data presented here suggest that, in contrast to that of other classes of antibiotics, the bactericidal activity of daptomycin does not require cell division or active metabolism, most likely as a consequence of its direct action on the bacterial membrane.

Echinomycin could work better than Vancomycin

Link: HighWire Press -- Medline Abstract.

Echinomycin demonstrated higher in vitro activities against MSSA and MRSA strains, exhibiting 2-fold lower MIC(90)s and 4-fold lower MBC(90)s than vancomycin. Additionally, time-kill assay indicated that echinomycin is more potent than vancomycin against MSSA and MRSA strains in the context of MICs and MBCs. Using an in vivo protection model, it was shown that the 50% effective doses of echinomycin were at least 7-fold lower than those of vancomycin. Therefore, echinomycin displayed excellent protection in mice against acute peritoneal infections caused by both MSSA and MRSA strains. Conclusions Collectively, these data indicate that the activity of echinomycin against S. aureus strains is at least equivalent to that of vancomycin, regardless of the methicillin resistance of these strains. These promising activities of echinomycin might justify its potential use against infections with S. aureus strains resistant to vancomycin. This might be the first report to show that echinomycin possesses antipathogenic staphylococcal activity.

Grieving Notts families raise money for superbug research

Link: Grieving Notts families .

Grieving Notts families have raised money for research into superbugs. An appeal was launched in April for mourners to consider cash donations instead of floral tributes at funerals. Scientists at the University of Nottingham hoped families who had lost loved ones to hospital-acquired infections, such as MRSA and clostridium difficile, would help fund their work. The new Centre for Healthcare Associated Infections, opened by actress Leslie Ash earlier this year, needs more than �100,000 a year for projects, such as improving tests to spot the superbugs and finding new drugs to combat them. Six months on, and families have raised �2,400 which Professor Richard James, director of the centre, said was a great start to the fund-raising.

Positive Data On Ceftobiprole

Link: Johnson & Johnson Unit Reveals Positive Data On Ceftobiprole.

Johnson & Johnson's (JNJ) Pharmaceutical Research & Development unit said results from a Phase III trial showed that its investigational antibiotic ceftobiprole was found to clinically cure 86% of patients with diabetic foot infections, including some infections that were caused by methicillin-resistant Staphylococcus aureus (MRSA). The company said the trial, which enrolled 257 patients, showed ceftobiprole was well tolerated in the treatment of complicated skin and skin structure infections, including diabetic foot infections.