RxPG News : MRSA

New drugs could counter antibiotic resistant hospital infections

Thu, 09 Apr 2009 15:59:11 PST

( from http://www.rxpgnews.com ) Washington, April 9 - Latest research findings that lack of sufficient phosphate in a bacterium could turn it into a killer could help develop new drugs to disarm the antibiotic resistant pathogens that cause serious hospital-acquired infections.

Pseudomonas aeruginosa, a bacteria that is a common cause of lung infections, also infests the intestinal tract of 20 percent of all Americans and 50 percent of hospitalised patients in the US.

It is one of the hundreds of bacteria that colonise the human intestinal tract, usually causing no apparent harm. It might even be beneficial to its host.

However, once the host is weakened by an illness, surgical procedure or immunosuppressive drugs, the bacteria can cause infection, inflammation, sepsis - and death.

Why P. aeruginosa can suddenly turn on its host has eluded researchers - until now. Scientists have long known that after an operation or organ surgery, levels of inorganic phosphate fall.

The study authors, led by scientists of University of Chicago -, hypothesised that phosphate depletion in the stressed intestinal tract signals P. aeruginosa to become lethal.

To test this theory, they let worms - feed on 'lawns' of P. aeruginosa and Escherichia coli grown in both low-phosphate and high-phosphate media.

Only the worms that ate P. aeruginosa with low levels of phosphate died. The researchers dubbed the phenomenon 'Red Death' since unexpected large red spots appeared on the worms before they died, according to an U-C release.

'These findings provide novel insight into the mechanisms by which P. aeruginosa is able to shift from indolent coloniser to a lethal pathogen when present in the intestinal tract of a stressed host,' said Alexander Zaborin, lead author of the study and a research professional at the U-C Department of Surgery.

'It is almost as if the bacterium sense when to strike,' said John Alverdy, study co-author and professor of surgery at the U-C Medical Center. 'That should come as no surprise since the bacteria are smart, having been around for two billion years.'

The study will be published in the April 14 issue of the Proceedings of the National Academies of Science.

High-tech system to cut hospital infections by half

Wed, 12 Nov 2008 13:58:27 PST

( from http://www.rxpgnews.com ) London, Nov 6 - Hospital-based infections continue to be the number-two killer in the US after heart disease.

A new high-tech software programme developed by Tel Aviv University researchers will cut such infections by half.

Yehuda Carmeli professor at the Sackler Faculty of Medicine, Tel Aviv University -, has developed a system for preventing hospital epidemics.

'When a patient comes to the hospital for treatment, the natural barriers that protect them against infection are bypassed,' said Carmeli, also a physician at the TAU Sourasky Medical Centre.

'Intubations, IV lines, catheters and other common hospital procedures expose a patient's most delicate tissues to the world. If a patient is taking immunosuppressants, steroids, or antibiotics, this can be a dangerous cocktail, and infections are just waiting to attack,' he said.

Integrating basic sanitary procedures, his system uses the tools of high-tech communication email alerts, SMSs, and online communication to alert hospital staff of potential threats, according to a TAU release.

'We stopped 45 percent of the primary hospital-borne organisms that attack patients from spreading,' said Carmeli. He recently demonstrated his system at top medical centres at Ohio State University and Philadelphia's Temple University.

Carmeli advised general practitioners to use simple measures. For example, improved hand washing and hygiene techniques, an obvious first line of defence against infection, are not practiced regularly.

He advised nurses to keep an alcohol-based cream solution next to each patient's bed for ease of use. In some cases, visitors and nurses should wear masks and gloves when handling or visiting a patient.

These findings appeared in Antimicrobial Agents and Chemotherapy.

MRSA nasal screening not so important

Thu, 23 Oct 2008 14:19:21 PST

( from http://www.rxpgnews.com ) Three Virginia Commonwealth University epidemiologists are downplaying the value of mandatory universal nasal screening of patients for MRSA, arguing that proven, hospital-wide infection control practices can prevent more of the potentially fatal infections.

In a report published in the November issue of Infection Control and Hospital Epidemiology, the team, composed of internationally acclaimed epidemiologists Richard P. Wenzel, M.D., Gonzalo Bearman, M.D., and Michael B. Edmond, M.D., of the VCU School of Medicine, said "hospitals get more bang for their buck with evidence-based infection control prevention."

Some states, including Pennsylvania, Illinois, California and New Jersey, are mandating nasal screening for methicillin-resistant Staphylococcus aureus, or MRSA, in some hospitalized patients. MRSA is a strain of Staph bacteria that does not respond to penicillin and related antibiotics, but can be treated with other drugs.

"The key safety question today, since it is possible to reduce the total risk of hospital infections by half with a broad-based infection control program, is what is the incremental benefit of a component focusing on a single antibiotic-resistant pathogen?" said Wenzel.

Using epidemiological principles and focusing on deadly bloodstream infections, the team modeled a focused-screening program that was assumed to be effective in reducing MRSA rates by 50 percent and compared it to a hospital-wide program designed to reduce the rates of all infections by half.

According to Wenzel, chair of internal medicine at the VCU School of Medicine and immediate past president of the International Society for Infectious Diseases, MRSA infections cause only 14 percent of hospital infections, and investing huge resources into their control would be less effective than implementing programs that would reduce the burden of all infections by 50 percent.

Also in the model, the MRSA screening was inferior to the general infection control programs, preventing fewer infections, fewer deaths and was also less effective in reducing years of life lost from infections. The MRSA screening tests have false positives – leading to the isolation of patients who are non-MRSA carriers – as well as false negatives – missing some true carriers.

Further, the cost of nasal swabbing tests for all patients in a screening program was estimated to be two to three times that of adding additional infection control nurses for a broad infection control program.

The authors acknowledge that there are some instances in which MRSA screening and topical antibiotic treatment of nares of carriers may add incremental benefit to a hospital wide, evidence-based program. For example, in a patient going for open heart surgery who is a MRSA carrier, a post-operative infection would be devastating.

Wenzel and his colleagues' broad perspective is that a focused screening program would have made more sense in the late 1980s and early 1990s since MRSA was the key in antibiotic-resistant pathogen. However, in the last 15 years hospitals are facing multiple bacteria with broad resistance (Vancomycin-resistant enterococci, imipenam-resistant pseudomonas, totally drug resistant Acinetobacter and others), and efforts need to be broad based with a goal of reducing the overall burden of infections

Transmission of MRSA Linked to Previous Intensive Care Unit Room Occupants

Wed, 11 Oct 2006 05:17:37 PST

( from http://www.rxpgnews.com ) Staying in a room in the intensive care unit previously occupied by a patient with treatment-resistant bacteria may increase the odds of acquiring such bacteria, according to a report in the October 9 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Two particular microorganisms cause significant illness and death in hospitals: methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), according to background information in the article. Researchers previously found that 29 percent of patients who acquire these pathogens develop infections or other complications within 18 months. Floors, beds, gowns, faucets and other hospital room fixtures are persistently contaminated with these bacteria, but it is not known whether levels of the bacteria are high enough to infect additional patients or whether currently mandated cleaning practices are effective in reducing bacterial spread. Although high-risk rooms may exist because of difficult-to-clean design or poor placement of hand hygiene equipment, transmission may be more directly linked to a prior occupant who harbors a resistant organism rather than to a particular room, the authors write.

Susan S. Huang, M.D., M.P.H., Brigham and Womens Hospital and Harvard Medical School, Boston, and colleagues conducted a 20-month study of 8,203 patients who had 11,528 stays in eight ICUs between 2003 and 2005. As part of the hospitals normal protocols, cultures were obtained from all ICU patients when they arrived and every week they stayed to determine the presence of MRSA and VRE.

Upon entering the ICU, 809 patients carried MRSA and 658 carried VRE, leaving 7,629 to screen for the acquisition of MRSA and 7,806 for acquisition of VRE. The average patient age was 61 years, and 58 percent were male. Fourteen percent of these ICU patients stayed in rooms in which the prior occupant had MRSA and 13 percent stayed in rooms in which the prior occupant had VRE. Those who stayed in rooms after patients with one of the types of bacteria were more likely to acquire that type of bacteria than those who stayed in rooms following patients who did not test positive for that bacteria (4.5 percent vs. 2.8 percent for VRE and 3.9 percent vs. 2.9 percent for MRSA). The excess risk associated with an infected prior occupant accounted for 5.1 percent of all new cases of MRSA and 6.8 percent of all new cases of VRE.

This additional risk occurred despite the fact that the room cleaning procedures of the hospital in the study exceed national guidelines, indicating that such guidelines do not prevent transmission of disease-causing bacteria. However, the low overall risk among patients exposed to the bacteria suggests that levels of contamination do not pose a high risk for transmission or that current cleaning methods generally reduce contamination below levels required for transmission, the authors write. Based on our findings, the prevention of one case of acquisition due to room contamination could require more intensive cleaning of 94 rooms vacated by MRSA carriers and of 59 rooms vacated by VRE carriers.

Though the number of cases attributed to previous room occupants was small, this type of transmission could become more common as the prevalence of treatment-resistant bacteria continues to rise. Additional data are needed to determine whether more intensive cleaning practices can reduce the risk further and, if so, whether this is worthwhile in a resource-limited system, the authors conclude.

Study shows rising incidence of CA-MRSA muscle infections

Thu, 07 Sep 2006 00:32:37 PST

( from http://www.rxpgnews.com ) Researchers in Houston, Texas have found two bacterial muscle infections common in tropical countries becoming more frequent occurrences along with the emergence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), according to a study published in the Oct. 15 issue of Clinical Infectious Diseases, now available online.

Staphylococcus aureus, or staph, is a common bacterium found on the skin or in the nose of a quarter to a third of all people. Usually harmless, staph can cause skin infections such as pimples and boils and, less frequently, serious infections of surgical wounds or the bloodstream, and pneumonia. For years, infections caused by Staphylococcus aureus have been treated by inexpensive antibiotics in the penicillin and cephalosporin family.

Some years ago, strains resistant to these drugs, called methicillin-resistant Staphylococcus aureus (MRSA) appeared in hospitalized patients. Recently, however, newer forms of MRSA began to strike healthy people who have not been recently hospitalized or undergone invasive medical procedures. These community-acquired strains appear to be readily transmitted from person to person and can cause serious skin and soft tissue infections as well as invasive infections such as bone or joint infections or pneumonia. Failure by physicians to suspect this kind of drug-resistant staph can lead to treatment with the wrong antibiotic.

Pyomyositis is an acute bacterial infection of skeletal muscle that produces an abscess within the muscle. Myositis is also a muscle infection, but does not form an abscess. The study authors investigated the 45 cases of pyomyositis or myositis in otherwise healthy children who were hospitalized at Texas Children's Hospital from 2000 through 2005. Sixteen of these cases were caused by CA-MRSA and 10 by CA-MSSA (methicillin-susceptible Staphylococcus aureus).

The number of cases increased year by year, from four cases in the first year of the study to a high of 12 cases in the fifth year of the study. The authors also discovered that a specific strain of Staphylococcus aureus known as USA300 was associated with more severe disease. Similarly, staph that carried a group of genes known as PVL were also linked to a more severe illness.

"We're seeing an increasing number of muscle infections that is clearly associated with an increase in MRSA," said lead author Pia Pannaraj, MD. "Physicians need to be aware that this is a possibility and consider initial treatment with an antibiotic that covers MRSA, particularly if they live in a region where methicillin resistance is present."

Acanthamoeba polyphagam acts as an incubator for MRSA

Mon, 03 Apr 2006 06:19:37 PST

( from http://www.rxpgnews.com ) Scientists in the UK have found that a type of amoeba acts as an incubator for MRSA bacteria. As amoebae are often found in healthcare environments this discovery has implications for the infection control strategies adopted by hospitals.

The single cell amoeba, Acanthamoeba polyphagam commonly eats and digests environmental bacteria. It also engulfs pathogens such as MRSA. However, instead of being digested by the amoeba, MRSA survives and replicates whilst inside the amoeba. Prof Michael Brown and colleagues at the University of Bath, found that MRSA in association with amoebae increased in numbers 1000- fold.

The pathogenic bacteria, Legionella, also replicate inside amoebae and are then released into the environment. The released bacteria are less susceptible to biocides and antimicrobials, and are more invasive than the same bacteria which have grown freely. Replication within amoebae may have the same effect on MRSA.

Amoebae, as cysts, are often dispersed by air currents, providing another means of spreading any trapped bacteria.

We need more research into the role of amoeba in the spread of MRSA hospitals should aim to eradicate amoebae as well as the bacteria themselves said Prof Brown of the Department of Pharmacy and Pharmacology, University of Bath.

MRSA infects and replicates in amoebae

Tue, 28 Feb 2006 21:14:37 PST

( from http://www.rxpgnews.com ) The MRSA superbug evades many of the measures introduced to combat its spread by infecting a common single-celled organism found almost everywhere in hospital wards, according to new research published in the journal Environmental Microbiology.

Scientists from the University of Bath have shown that MRSA infects and replicates in a species of amoeba, called Acanthamoeba polyphaga, which is ubiquitous in the environment and can be found on inanimate objects such as vases, sinks and walls.

As amoeba produce cysts to help them spread, this could mean that MRSA maybe able to be blown in the wind between different locations.

Further evidence from research on other pathogens suggests that by infecting amoeba first, MRSA may emerge more virulent and more resistant to antibiotics when it infects humans.

Infection control policies for hospitals should recognise the role played by amoeba in the survival of MRSA, and evaluate control procedures accordingly, said Professor Mike Brown from the Department of Pharmacy and Pharmacology at the University of Bath.

Until now this source of MRSA has been totally unrecognised. This is a non-patient source of replication and given that amoeba and other protozoa are ubiquitous, including in hospitals, they are likely to contribute to the persistence of MRSA in the hospital environment.

Adding to the concern is that amoebal cysts have been shown to trap pathogens and could potentially be dispersed widely by air currents, especially when they are dry.

Replication of MRSA in amoeba and other protozoa raises several important concerns for hospital hygiene.

In laboratory tests, the researchers found that within 24 hours of its introduction, MRSA had infected around 50 per cent of the amoeba in the sample, with 2 per cent heavily infected throughout their cellular content.

Evidence with other pathogens suggests that pathogens that emerge from amoeba are more resistant to antibiotics and more virulent.

This makes matters even more worrying, said Professor Brown.

It is almost as though the amoeba act like a gymnasium; helping MRSA get fitter and become more pathogenic.

In many ways this may reflect how this kind of pathogenic behaviour first evolved. A good example is the bacterium that causes legionnaires disease. Probably it was pathogenic long before humans and other animals arrived on the evolutionary scene. Even today, it has no known animal host.

The most likely reason is that Legionella and many pathogens learned their pathogenicity after sparring with single-celled organisms like amoeba for millions of years. Because our human cells are very similar to these primitive, single-celled organisms, they have acquired the skills to attack us.

For these reasons, such primitive cells are being used to replace animals for many kinds of biological tests.

Effective control of MRSA within healthcare environments requires better understanding of their ecology, said Professor Brown.

We now need to focus on improving our understanding of exactly how MRSA is transmitted, both in hospitals and in the wider environment, to develop control procedures that are effective in all scenarios.

Recently released figures show that infections caused by MRSA rose 5 per cent between 2003 and 2004, and mortality rates increased 15-fold between 1993 and 2002.

The research paper has been published online (see link) and will appear in the June or July print issue of Environmental Microbiology which will be published mid-May or mid-June respectively.

The work was funded by The Lord Dowding Fund for Humane Research and also the UK Department of Health.

Two Million Americans Harbor MRSA Superbug

Thu, 22 Dec 2005 03:49:38 PST

( from http://www.rxpgnews.com ) New research estimates that about 2 million people carry a strain of drug-resistant bacteria in their noses. The research, conducted by the Centers for Disease Control and Prevention (CDC), is the first reliable nationwide estimate of colonization with Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA). It is published in the Jan. 15 issue of The Journal of Infectious Diseases, now available online.

Those colonized with normal strains of staph are at higher risk of infection with the bacterium, which can lead to conditions ranging from mild skin infections to fatal toxic shock syndrome. MRSA causes more difficult-to-treat and, sometimes, more virulent illnesses. MRSA was once primarily a problem in hospitals, but is now a growing problem in communities around the country.

Matthew J. Kuehnert, MD, and colleagues collected samples from nearly 10,000 participants in the 2001-2002 National Health and Nutritional Examination Survey, a representative sample of the U.S. population.

Nearly one-third were found to be colonized with staph. Prevalence was highest among males and children between 6 and 11 years old. MRSA prevalence was 0.8 percent. MRSA was highest among women and those older than 60, but those colonized with strains commonly associated with community-associated MRSA were more likely to be younger and black.

Overall, strains and toxins previously found to be associated with community-associated MRSA were unusual. The genetic diversity of strains was remarkableabout half of isolates, including MRSA strains, had unique molecular fingerprinting patterns, and some fell outside recognized groups.

"There is a lot about staph colonization we don't know, Dr. Kuehnert said. Interestingly, carriage of certain strains do seem to vary by sociodemographics, especially age and race. We need to learn more in order to allow design of new, more effective interventions," he added, including vaccines or antimicrobial treatment. Data from subsequent survey years may determine whether there are ongoing trends in colonization.

In an accompanying editorial, Clarence Buddy Creech II, MD, of Vanderbilt University and colleagues observe that, In light of the increasing frequency of community-associated MRSA infection, new antimicrobials are needed, although an effective vaccine against staph would provide a more permanent solution.

25% Of Hospital MRSA Bacteraemia Occurs In New Arrivals

Sat, 10 Sep 2005 00:09:38 PST

( from http://www.rxpgnews.com ) One in four cases of MRSA blood stream infection in hospital occur in patients who have just arrived from the community. These patients tend to be older and have been in hospital before.

These results, published on bmj.com today, should help to refine infection control policies in UK hospitals.

In the past 10 years, MRSA infection has increased in the United Kingdom. The bacterium can infect many sites; one serious form of infection is that in which blood-stream infection occurs (bacteraemia). A national surveillance scheme counts MRSA bacteraemia by hospital trust, but it has not yet addressed whether cases of MRSA bacteraemia are arriving in hospitals from the community.

Researchers at the University of Oxford analysed methicillin resistant Staphylococcus aureus (MRSA) and methicillin sensitive Staphylococcus aureus (MSSA) bacteraemia in patients on arrival in two Oxfordshire hospitals over a seven year period (1997 to 2003).

At one hospital, patients admitted from the community accounted for 49% of total MSSA cases and 25% of total MRSA cases. The proportion of methicillin resistance among patients admitted with Staphylococcus aureus bacteraemia, rose from 14% in 1997 and 1998 to 26% in 2003.

Most patients (at least 91%) admitted with MRSA bacteraemia had previously been in hospital, half had never had MRSA detected before, and 70% were admitted to emergency medical and surgical services. A similar pattern was observed in the other hospital.

Despite some study limitations, the authors conclude that, of the cases of MRSA bacteraemia detected in hospital, a quarter occurs in patients who have just arrived from the community, and that this proportion is increasing. They call for additional research to be undertaken into the best way to recognise these patients.

Zyvox® More Effective than Vancomycin in Treating Complicated Soft Tissue Infections

Mon, 06 Jun 2005 10:15:38 PST

( from http://www.rxpgnews.com ) Pfizer's antibiotic ZYVOX® (linezolid injection, tablets, and for oral suspension) is more effective than vancomycin for the treatment of complicated skin and soft tissue infections (cSSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA), according to the largest MRSA cSSTIs study to date published in Antimicrobial Agents and Chemotherapy. Of the total study population, including those treated for methicillin-susceptible infections, the number of patients cured with ZYVOX was comparable to those cured with vancomycin.

In addition, patients taking ZYVOX spent up to five fewer days on IV treatment because of its availability as a pill. Available in interchangeable IV and oral formulations, ZYVOX is the only oral medicine approved by the U.S. Food and Drug Administration for MRSA infections.

This study involved 1,180 patients with cSSTIs, 361 of whom had confirmed MRSA infections. MRSA is a serious, multidrug-resistant infection, which is on the rise and can lead to prolonged hospitalization, along with increased morbidity, mortality and cost. Patients in the microbiologically evaluable MRSA subgroup treated with ZYVOX had better microbiologic cure rates: 88.6 percent for ZYVOX patients vs. 66.9 percent for vancomycin patients.

"In this study, ZYVOX was shown to be better than traditional vancomycin therapy in improving outcomes for patients with serious MRSA infections," said Dr. John Weigelt, lead investigator of the study, and professor and vice chairman of the department of surgery at the Medical College of Wisconsin. "These data also reinforce the value of having a pill for patients which may allow patients to leave the hospital sooner on oral therapy."

Because of the oral availability of ZYVOX, patients in the ZYVOX arm had up to five fewer days on IV therapy than patients treated with vancomycin. More than half of study participants ( 52 percent ) treated with ZYVOX began treatment on the oral formulation. The U.S. Centers for Disease Control and Prevention recommends getting the catheters out and using an IV only when essential since these and other invasive devices are a frequent cause of hospital-acquired infections.

Skin and soft tissue infections are a common cause of morbidity in the community and hospital. Those at risk for cSSTIs include surgical patients, patients with diabetes and those who are immunocompromised, such as patients with cancer. These infections are increasingly caused by resistant bacteria such as MRSA. According to a previous study, the rate of MRSA among cSSTI isolates is approximately 30 percent. Thirty years ago, only two percent of hospital-acquired Staph infections in intensive care units were resistant to antibiotics, but today physicians are seeing rates of approximately 60 percent.

"The rapid emergence of MRSA is an increasing public health problem, especially among hospitalized patients where skin and soft tissue infections caused by MRSA can be fatal," said Dr. Weigelt. "ZYVOX has been shown to have excellent skin and tissue penetration which I believe is important when treating complicated SSTIs to ensure the treatment reaches the infection site. ZYVOX is a critical option for patients with risk factors for MRSA, such as an acute illness, a compromised immune system or previous antibiotic use."

Study Results

In the intent-to-treat ( ITT ) population, ZYVOX had clinical cure rates of 92.2 percent vs. 88.5 percent for patients on vancomycin. In the MRSA subgroup ( microbiologically evaluable population ), patients treated with ZYVOX had better microbiologic cure rates of 88.6 percent compared with 66.9 percent for patients on vancomycin. In the ITT population, patients in the ZYVOX group had fewer days of IV therapy than those in the vancomycin group ( 4.0 + 2.6 days vs. 9.0 + 5.3 days, respectively ). The overall mean treatment duration was significantly longer in the ZYVOX group vs. the vancomycin group ( 11.8 + 4.9 days vs. 10.9 + 5.3, respectively ).

Study Background

This randomized, open-label, comparator-controlled, multicenter, multinational study evaluated 1,180 patients' response to treatment with ZYVOX and vancomycin. The most common types of cSSTIs seen in study patients were cellulitis ( spreading infection of the skin and subcutaneous tissues ), a major skin abscess ( pus and infected material build up in the skin ) and an infected surgical incision. Clinical efficacy outcomes ( e.g., cured, failed or indeterminate ) were measured by resolution of the signs and symptoms of infection compared with baseline. Microbiologic cure rates were defined as presumed or documented eradication. The study also compared the mean IV duration of each treatment and the total number of days that patients received antibiotic therapy. Patients who received vancomycin did not have the option to start on or switch to an oral agent because vancomycin is only available intravenously.

Patients were randomly assigned in a 1:1 ratio to receive either IV or oral ZYVOX 600 mg every 12 hours ( 592 patients ) or IV vancomycin 1 g every 12 hours ( 588 patients ) for seven to 14 days. The minimal treatment period was four days, but no longer than 21 days. Of the 592 patients treated with ZYVOX, 308 were started on oral therapy. Test-of-cure assessment was planned to be performed seven days after the end of treatment.

The incidence of drug-related adverse events appeared similar between treatment arms. Most adverse events in both groups were classified as mild to moderate. Drug-related adverse events in the ZYVOX-treated patients were noted more often in the digestive system and in lab tests documenting thrombocytopenia. Rash, anaphylaxis, drug-related allergic reaction and phlebitis were reported more often by patients in the vancomycin treatment group.

About ZYVOX

ZYVOX was initially approved in the United States in April 2000 for the treatment of complicated skin and skin structure infections ( cSSSIs ) and nosocomial pneumonia, including those caused by MRSA. In December 2002, ZYVOX was approved for use in pediatric patients and subsequently received approval for diabetic foot infections in July 2003. Since its introduction, ZYVOX has proven to be an important treatment option for designated infections known or suspected to be caused by MRSA. To date, nearly one million patients worldwide have been treated with ZYVOX for its approved indications.

ZYVOX is indicated in the treatment of the following infections caused by susceptible strains of the designated microorganisms:

-- Complicated skin and skin structure infections, including diabetic foot infections, without concomitant osteomyelitis, caused by Staphylococcus aureus ( methicillin-susceptible and -resistant strains ), Streptococcus pyogenes, or Streptococcus agalactiae. ZYVOX has not been studied in the treatment of decubitus ulcers. Combination therapy may be clinically indicated if the documented or presumptive pathogens include Gram-negative organisms.

-- Nosocomial pneumonia caused by Staphylococcus aureus ( methicillin-susceptible and -resistant strains ) or Streptococcus pneumoniae ( including multidrug-resistant strains [MDRSP]* ). Combination therapy may be clinically indicated if the documented or presumptive pathogens include Gram-negative organisms.

ZYVOX formulations are contraindicated for use in patients who have known hypersensitivity to linezolid or any of the other product components.

Myelosuppression ( including anemia, leukopenia, pancytopenia, and thrombocytopenia ) has been reported in patients receiving linezolid. In cases where the outcome is known, when linezolid was discontinued, the affected hematologic parameters have risen toward pretreatment levels. Complete blood counts should be monitored weekly in patients who receive linezolid, particularly in those who receive linezolid for longer than 2 weeks, those with preexisting myelosuppression, those receiving concomitant drugs that produce bone marrow suppression, or those with a chronic infection who have received previous or concomitant antibiotic therapy. Discontinuation of therapy with linezolid should be considered in patients who develop or have worsening myelosuppression.

Lactic acidosis has been reported with the use of ZYVOX. In reported cases, patients experienced repeated episodes of nausea and vomiting. Patients who develop recurrent nausea or vomiting, unexplained acidosis, or a low bicarbonate level while receiving ZYVOX should receive immediate medical evaluation.

Spontaneous reports of serotonin syndrome associated with co-administration of ZYVOX and serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors ( SSRIs ), have been reported. Patients who are treated with ZYVOX and concomitant serotonergic agents should be closely observed for signs and symptoms of serotonin syndrome ( e.g., cognitive dysfunction, hyperpyrexia, hyperreflexia, incoordination ). If any signs or symptoms occur physicians should consider discontinuation of either one or both agents ( ZYVOX or concomitant serotonergic agents ).

Peripheral and optic neuropathy have been reported in patients treated with ZYVOX, primarily those patients treated for longer than the maximum recommended duration of 28 days. In cases of optic neuropathy that progressed to loss of vision, patients were treated for extended periods beyond the maximum recommended duration. Visual blurring has been reported in some patients treated with ZYVOX for less than 28 days.

If patients experience symptoms of visual impairment, such as changes in visual acuity, changes in color vision, blurred vision, or visual field defect, prompt ophthalmic evaluation is recommended. Visual function should be monitored in all patients taking ZYVOX for extended periods ( =3 months ) and in all patients reporting new visual symptoms regardless of length of therapy with ZYVOX. If peripheral or optic neuropathy occurs, the continued use of ZYVOX in these patients should be weighed against the potential risks.

The most commonly reported adverse events in adults across clinical trials were nausea, headache, and diarrhea.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of ZYVOX and other antibacterial drugs, ZYVOX should be used only to treat or prevent 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 or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

As with nearly all antibacterial agents, pseudomembranous colitis has been reported with ZYVOX. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of ZYVOX.

Patent Issued for Dalbavancin for the Treatment of Complicated Skin and Soft Tissue Infections

Thu, 02 Jun 2005 13:50:38 PST

( from http://www.rxpgnews.com ) Vicuron Pharmaceuticals Inc. (Nasdaq: MICU; Nuovo Mercato) today announced that the United States Patent and Trademark Office issued patent number 6,900,175 entitled "Methods of Administrating Dalbavancin For Treatment Of Bacterial Infections."

The patent, which will expire in December 2023, relates to a novel dosing regimen for dalbavancin. The dalbavancin New Drug Application (NDA) for the treatment of complicated skin and soft tissue infections (cSSTIs) including the most difficult to treat strain of staphylococcus, methicillin-resistant staphylococcus aureus (MRSA) is currently under review with the U.S. Food and Drug Administration (FDA).

About Dalbavancin

Dalbavancin is a novel second-generation lipoglycopeptide agent that belongs to the same class as vancomycin. Vancomycin is one of the few treatments available to hospital patients infected with difficult-to-treat strains of Staphylococcus bacteria, or Staph known as MRSA (methicillin- resistant Staphylococcus aureus) and MRSE (methicillin-resistant Staphylococcus epidermidis). Dalbavancin has been specifically designed as an improved alternative to vancomycin.

Community MRSA is re-emergence of 1950's pandemic

Sun, 03 Apr 2005 11:20:38 PST

( from http://www.rxpgnews.com ) This "re-equipping and re-emergence" of a clone that caused a pandemic 40-50 years ago could mean that community acquired MRSA will spread faster and be more widespread than previously expected, warns an international team of researchers who have been studying the bacteria.

First isolated in Australia and Canada in 1953, type 80/81 penicillin-resistant Staphylococcus aureus bacteria caused skin lesions, sepsis and pneumonia in children and young adults around the world. This pandemic of both hospital and community acquired infections waned throughout the 1960s as the antibiotic meticillin was used to treat these infections.

Now researchers have shown that one of the key clones of community acquired MRSA (CA-MRSA) - infections picked up in public places which are resistant to treatment by powerful meticillin antibiotics - may have evolved from this earlier pandemic-causing strain.

The researchers have sequenced key genes from 80/81 samples isolated between 1955 and 1969 in Australia, England and the USA, and compared them with the same regions in genes from a clone of one of the most common CA MRSAs which has been found in England and Scotland.

They found that these key regions in nearly all of the 80/81 isolates were identical to the CA-MRSA clone, and also that they share the same highly-virulent toxin, called Panton-Valentine leucocidin.

They believe that their findings suggest that this particular CA MRSA clone has evolved from the earlier 80/81 type, developing resistance to meticillin antibiotics over the last 30-40 years, possibly through several intermediate steps.

"At the time of the 1950s pandemic, many doctors thought that these isolates were unusually transmissible and virulent," said Dr Mark Enright from Department of Biology and Biochemistry the University of Bath (UK) who is leading the research.

"We have shown that 80/81 and its souped-up community acquired MRSA descendent share many of the same features, which explains why 1950s pandemic was so successful, but also shows why community acquired MRSA could pose such a serious public health challenge in coming years.

"The community acquired MRSA clone has a toxin and other traits with a proven track record for causing serious diseases in healthier and younger age groups than those currently regarded as at risk. The increased resistance to antibiotics of the community acquired MRSA clone over its 80/81 ancestor mean that there could also be other factors which complicate the treatment of the disease it causes."

Drug-Resistant MRSA a Growing Threat

Fri, 18 Mar 2005 15:25:38 PST

( from http://www.rxpgnews.com ) According to the Centers for Disease Control and Prevention (CDC), MRSA is a type of bacteria that is resistant to a class of antibiotics that include methicillin and other more commonly prescribed variants such as oxacillin, amoxicillin and other penicillin-based drugs. Previously MRSA was seen only in the hospital in patients with underlying diseases or compromised immune systems. Now the organism appears to be common among people everywhere, including those in communal settings such as the military, prisons, daycare facilities, and on athletic teams. The CDC estimates that roughly 130,000 people are hospitalized with MRSA each year.

Infectious diseases researchers at Vanderbilt University Medical Center are noticing a significant increase in the number of infections due to Methicillin-Resistant Staphylococcus Aureus (MRSA) and the number of asymptomatic individuals who harbor the organism in their bodies.

In fact, in a recent analysis of children seen in 2003 at the emergency department of the Monroe Carell Jr. Children's Hospital at Vanderbilt, approximately 60 percent of the skin infections due to the staphylococcus germ were due to MRSA, an organism that can produce a variety of physical manifestations across a spectrum, from the very minor, all the way to causing death. Now a new study done by VUMC researchers confirms a dramatic spread of the organism that is being harbored in the noses of healthy children.

"What this tells us is that we're more likely to find MRSA in this population than we are the typical staphylococcus organism that is susceptible to methicillin," said Buddy Creech, M.D., a fellow in pediatric infectious diseases and the lead investigator on the study. "The problem with this organism is that it seems to behave differently, with a tendency to cause skin abscesses and pneumonia."

MRSA can enter the body through even the smallest opening in the skin and infiltrate the bloodstream. Once MRSA enters the bloodstream the bacteria can cause devastating staph infections.

The organism can be difficult to control because its early symptoms are so benign, and because those who are infected frequently delay seeking medical intervention until the organism has begun to spread.

Creech and colleagues visited one of Nashville's large community pediatric practices, and the Vanderbilt Children's Hospital Outpatient Pediatric Clinic, to swab the noses of 500 otherwise healthy children to collect samples. Three years earlier a similar study had been done in the same practices and Creech wanted to see whether things had changed.

"We were just trying to get a sense of how common MRSA actually is in the community," he said. "We've known for over a half century that staphylococcus likes to live in the nose and that's where it thrives. If it's not in the nose, you probably don't have it. So we went out and collected these samples."

What Creech and colleagues discovered was that 9.2 percent of the children from this sampling were positive for MRSA in their noses. "That's up dramatically from three years ago when only 1 percent had MRSA," he said.

"What we are able to show is that the increasing incidence of this organism is not just an isolated phenomenon among football players, prisoners and others in close communal settings," he said. "These are young healthy children who are coming in for well child visits and they have the resistant organisms in their noses."

Creech says the next mystery to be solved is why MRSA is increasing in healthy people.

"This study tells us there are a lot of children walking around with MRSA who are healthy, but we are also seeing this germ cause infections. What we are trying to understand is why some children go on to develop a serious infection and others don't."

Vanderbilt Children's Hospital has had adolescents in the intensive care units suffering from pneumonia and others with the organism in the bloodstream. MRSA skin abscesses, the typical problem associated with MRSA, and bone infections have also been seen in both the Emergency Department and outpatient clinics. The skin abscesses often require drainage and antibiotics.

"We are yet to understand why some children just have MRSA in their nose, causing no disease, while others are severely ill," he said. Still, Creech says parents should not be alarmed but consult their physician if their child develops skin infections, fever or other signs of illness.

Return of the Staphylococcus aureus "superbug"

Thu, 16 Dec 2004 17:28:38 PST

( from http://www.rxpgnews.com ) Staphylococcus aureus causes a wide variety of diseases including boils and furuncles and more serious diseases such as septicemia and pneumonia, and a debate has long raged about the existence of S. aureus "superbugs" more dangerous strains that may be associated with particularly invasive disease.

In the December 15 issue of the Journal of Clinical Investigation, Damian Melles and colleagues from University Medical Center Rotterdam examined 829 S. aureus strains from healthy donors from the city of Rotterdam. The genetic relatedness of the strains was compared and revealed the existence of 3 major and 2 minor genetic clusters. These clusters corresponded to the predominant genetic groups identified in a similar analysis recently performed in the United Kingdom, indicating that the same clonal lineages of the organism appear to be dominant in 2 distinct geographic locations.

Surprisingly, while the 2003 UK-based study found no evidence of hypervirulent clones or "superbugs" assocated with particularly invasive forms of disease, Melles et al. examined isolates from individuals with bacteriemia, deep-seated abscesses, or impetigo and found clear evidence that some strains of S. aureus are more virulent that others in that they appear more frequently in people with serious S. aureusrelated disease that healthy individuals that simply carry the organism without falling prey to infection.

In an accompanying commentary, Timothy Foster from Trinity College, Dublin, discusses some potential reasons for the discrepancies between the Dutch and UK studies, the growing problem of antibiotic resistance, and reiterates the conclusion that while all strains of S. aureus have the potential to cause infection, some appear to be more virulent that others.