Intensive care patients, given a cocktail of antibiotics, have better survival rates

Giving a cocktail of antibiotics to intensive care patients may cut the number who die, say researchers. Dutch researchers writing the Lancet journal suggest that wiping out gut microbes could prevent life-threatening infections from taking hold. Their study found that hospital deaths were cut by a quarter after antibiotic treatments were given. However, there are fears that the technique could foster new strains of dangerous 'superbugs'. The practice of 'selective decontamination' - as the drug treatment is called - has been around for decades, and still practiced in many hospitals around the world. However, there is still fierce debate over the benefits of giving the cocktail of drugs to intensive care patients. Weakened People in these units are unusually vulnerable to infection - not only are they physically weakened by their illness or injury, but they often have 'wounds' - including intravenous lines for the delivery of fluids or drugs. The human gut contains a wide variety of bacteria which could, in theory, cause serious infection if they got into these wounds. The researchers, from the universities of Amsterdam and Utrecht wanted to test the theory that killing the majority of potentially harmful bacteria as soon as the patient arrived in the intensive care unit could reduce the risk of them dying in hospital, or at least reduce the amount of time spent there. On a random basis, they gave 934 patients either normal treatment or a cocktail of three antibiotics and one anti-fungal drug over a period of four days. In the 'decontamination' group, 69 patients died, compared with 107 in the normally-treated group - 15% as opposed to 23%. Hospital stays were shorter for the 'decontamination' group, as were costs associated with drug treatment - perhaps reflecting that these patients did not need to be treated for so many infections. Antibiotic resistance However, there are fears that widespread use of antibiotics might be counterproductive - increasing the risk of drug-resistant strains emerging and causing even greater problems for individual patients, and entire intensive care units. Dr Jonathan Cooke, a member of a Department of Health advisory committee on anti-microbial resistance, said he would be unsure about the merits of the practice becoming widespread in the UK. In recent years, there has been a drive to cut the amount of antibiotics used in hospitals to restrict the emergence of resistant bacteria. 'This is something that has gone in and out of vogue over the years - and I am not sure about it. 'It might yield a benefit to start with - but ultimately make things worse.' Surprisingly, however, patients in the treated group were less likely to become 'colonised' with resistant strains of bacteria such as enterococci and Pseudonomas aeruginosa than those given normal treatment. The authors of the report say that unless the hospital has particular problems with 'superbugs', then the approach could cut death rates in intensive care units.

Antibiotics not necessary for children with simple skin abscess

DALLAS (USA) - Physicians may not need to prescribe antibiotics when treating a common skin infection in children, according to researchers at UT Southwestern Medical Center at Dallas. The findings, which appear in the February issue of The Pediatric Infectious Disease Journal, show draining a skin or soft-tissue abscess - a pus-filled boil - and packing the wound with gauze is adequate therapy for simple skin abscesses. Patients still need to seek medical attention for these boils even though they may not need antibiotics. This traditional treatment is even effective when the antibiotic-resistant, methicillin-resistant Staphylococcus aureus (MRSA) causes the abscess. Children can get these boils from a scratch or prick, even when there are no known signs of a preceding trauma.Antibiotic-resistant bacteria are often thought to be more virulent than their ancestors, said Dr. R. Doug Hardy, assistant professor of internal medicine and pediatrics and the study's senior author. Many physicians now have questions regarding how aggressively to treat these antibiotic-resistant bacteria. 'We were surprised. What we found is that if a physician adequately drains the abscess, it will most likely get better with or without effective antibiotics,' Dr. Hardy said. At the beginning of the study, researchers were simply looking for alternative drugs and treatments for the methicillin-resistant Staphylococcus aureus. Abscesses caused by these bacteria have become extremely common in children.'I think it's good news for physicians. It addresses the dilemma of how to treat these kids,' said Dr. Michael C. Lee, assistant professor of pediatrics and co-lead author of the study. 'We needed a plan, and we needed to know how to deal with it better on a day-to-day basis.'The study is among the first to look at managing an infection caused by antibiotic-resistant bacteria, researchers said. Previous research has focused mainly on identifying antibiotic-resistant bacteria and determining frequency and risk of infections.The prospective study, one of the largest to date on this subject, included 69 children. Patients' average age was 5? years. All children had their abscesses drained through incision, manually or spontaneously. Nearly all were initially treated with ineffective antibiotics before physicians knew whether patients were infected with the resistant bacteria. In 21 children, the prescribed antibiotics were changed on their first follow-up visit to drugs that could kill the resistant bacteria, while in 37 children antibiotics were not adjusted. On further follow-up, researchers found no statistically significant differences with regard to fever or wound tenderness, discharge or size in patients whose antibiotic therapy was changed compared to those whose therapy was not changed to an effective antibiotic. Four patients were hospitalized on the initial follow-up visit because the abscess had either increased or had not improved as physicians expected. One third of the patients with an abscess and cellulitis more than 5 centimeters in diameter were hospitalized. Ineffective antibiotic use from the initial visit did not predict whether a child would need to be hospitalized, according to the study. It is not known if these findings apply to infants.

Antibiotics may not be enough to stop recurrent gastric lymphoma caused by Helicobacter pylori

Research led by Dr. Anne Mueller at Stanford University School of Medicine demonstrates that successful eradication of Helicobacter may not prevent future aggressive gastric lymphoma since resting B cells are left behind. The paper by Mueller et al., "The role of antigenic drive and tumor-infiltrating accessory cells in the pathogenesis of Helicobacter-induced MALT lymphoma," appears in the September issue of The American Journal of Pathology. Helicobacter pylori, a spiral bacterium of the stomach, infects more than half of the world's population. It is now widely accepted that, aside from gastritis and ulcers, H. pylori is also a causative agent of gastric lymphoma, specifically gastric B cell lymphoma of mucosa-associated lymphoid tissue (MALT). While antibiotic treatment eradicates the bacteria and promotes tumor regression, the effects of re-infection on disease are more severe. To address the effects of re-infection and the role of immune cells in disease progression, Dr. Mueller's group used a mouse model of Helicobacter-induced MALT lymphoma that employs H. felis to mimic human disease in the mouse. Mice were infected with H. felis and maintained for 18 months before being assigned to one of three treatment groups: 1) no treatment (primarily infected), 2) antibiotic therapy to eradicate bacteria, or 3) antibiotic therapy followed by re-infection. As expected, low-grade MALT lymphoma occurred in 35% of all infected animals. However, frank MALT lymphoma was more prevalent in re-infected animals (44%) than in primarily infected animals (25%). Transcription profiling identified B cell markers in mice that had been infected at any point in time, even after successful antibiotic treatment, suggesting that resting B cells remain in the gastric mucosa. Lymphoid aggregates of re-infected animals also contained more proliferating cells than those of primarily infected or antibiotic-treated animals (46% vs. 23.2% or 4.8%, respectively). Closer inspection of the lymphoid aggregates revealed that the tumors were indeed derived from B cells and the main antigen-presenting cells were follicular dendritic cells. Finally, follicular dendritic cell numbers were highest in the tumors of re-infected animals followed by primarily infected and then antibiotic-treated animals, thus correlating with severity of gastric lymphoma. Because it is the follicular dendritic cells that present antigen to T cells that in turn activate B cell proliferation, follicular dendritic cells appear to be better indicators of tumor behavior than B cells. Thus, follicular dendritic cells represent an untapped target in the fight against recurrent gastric lymphoma. The significance of the described work is that gastric lymphoma progresses more rapidly upon secondary infection. Because resting B cells are left behind following antibiotic treatment, re-infection by H. pylori promotes the existing B cells to progress quickly into tumors. Therefore, it is important that treated patients be carefully monitored for H. pylori re-infection. Mueller A, O'Rourke J, Chu P, Chu A, Dixon MF, Bouley DM, Lee A, Falkow S: The role of antigenic drive and tumor-infiltrating accessory cells in the pathogenesis of Helicobacter-induced MALT lymphoma. Am J Pathol 2005, 167:797-812Research was supported by the National Institutes of Health (US), the Emmy-Noether-Program of the Deutsche Forschungsgemeinschaft (Germany), and J National Health and Medical Research Council (Australia). The American Journal of Pathology, the official journal of the American Society for Investigative Pathology (ASIP), seeks to publish high-quality original papers on the cellular and molecular mechanisms of disease. The editors accept manuscripts which report important findings on disease pathogenesis or basic biological mechanisms that relate to disease, without preference for a specific method of analysis. High priority is given to studies on human disease and relevant experimental models using cellular, molecular, biological, animal, chemical and immunological approaches in conjunction with morphology.

Antibiotics and baby asthma

Babies given antibiotics are more likely to develop asthma and other allergies, research suggests. Scientist at Henry Ford Hospital in Detroit say doctors should be more cautious about prescribing the drugs to babies under six months. They believe the drugs may interfere with the development of the gut and therefore the immune system. It is known that antibiotics can kill off beneficial bacteria which live in the gut. More than a million UK children have been diagnosed with asthma, and allergy rates in general are rising. Researcher Christine Cole Johnson said: 'I'm not suggesting that children shouldn't receive antibiotics, but I believe we need to be more prudent in prescribing them for children at such an early age.' Dr Johnson's team studied 448 children, whose development was tracked for the first seven years of their life. By the age of seven, children given at least one antibiotic during their first six months were 2.5 times more likely to have developed asthma than those who were not given the drugs at such a young age. Overall, they were 1.5 times more likely to have developed some form of allergy. Children whose mothers had a history of allergies were particularly at risk. Early use of antibiotics in this group doubled their risk of developing an allergy. Breastfeeding Babies who were breastfed for more than four months, and who received antibiotics in their first six months were three times more likely to develop allergies - although they were no more likely to develop asthma. Exposure to pets, however, seemed to have a protective effect. Those given antibiotics who lived in a family with fewer than two pets had 1.7 times the risk of allergies and three times the risk of asthma. However, when a family had two or more pets, the risk was normal. The biggest risk of all - an 11-fold increase - was found among children who were prescribed a broad-spectrum antibiotic, such as penicillin, were breastfed for four months, and did not have any family pets. The researchers also found evidence that the more courses of antibiotics a child received during their first six months, the higher was their risk of developing an allergy. A spokesman for the National Asthma Campaign said research into the area had proved inconclusive. 'Whilst this is an interesting study, further research is needed to understand the complexities of the relationship between these factors.' Details of the research were presented at the European Respiratory Society's annual conference in Vienna.

Natural Antibiotics Yield Secrets To Atom-Level Imaging Technique

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

Prescriptions for antibiotics to prevent anthrax uncommon after the 2001 anthrax attacks

Prescriptions for antibiotics that could be taken in advance to prevent against anthrax were uncommon among concerned patients after September 11, 2001 and the 2001 U.S. anthrax attacks, according to an article in the October 11 issue of The Archives of Internal Medicine, one of the JAMA/Archives journals.According to the article, nationwide, more than 10,000 affected workers and others were given 3.75 million prophylactic antibiotic pills through official dispensing campaigns between October 2001 and January 2002. However, media reports suggest that even more prescriptions were given out by individual physicians. Nathaniel Hupert, M.D., M.P.H., of the Weill Medical College of Cornell University, New York, N.Y., and colleagues reviewed the electronic medical records of outpatient telephone contacts and clinic visits at a large, primary care practice in New York City from September 11 to December 31, 2001 to identify factors associated with prescribing antibiotics to prevent anthrax. There were 30,456 total patient visits (via phone or in person) between September 11 and December 21, 2001. Of these visits, 244 involved patient-initiated discussion about bioterrorism: 92 (0.6 percent) of 14,917 telephone contacts and 152 (1.0 percent) of 15,539 office visits. Average patient volume was higher from October to December in 2001 (221.2 patients per day) compared with the same time period in 2000 (199.1 patients per day). Fifty patients (21 percent of the 244 who discussed bioterrorism with their physician) requested antibiotics or vaccines, and 52 patients (22 percent) received antibiotics: 39 received ciprofloxacin; 12 doxycycline; and 1 received both drugs. "Despite widespread popular concern about bioterrorism and speculation about increased patient requests and physician prescribing of antibiotics for anthrax prophylaxis, only one in five patients who initiated discussion about anthrax or smallpox with physicians at this internal medicine practice in the wake of the 2001 terrorist attacks either requested antibiotics or received them," write the researchers. "While we cannot comment on the New York City population as a whole, our results do not suggest widespread antibiotic abuse in the aftermath of the 2001 terrorist attacks, as measured by patient requests and physician prescribing in this academic outpatient practice," the authors state. "Prescription of antibiotics appropriate for anthrax prophylaxis (i.e., ciprofloxacin, doxycycline, or amoxicillin) was most highly associated with patient requests, followed by report of potential exposure and abnormal findings on physical examination."

Hearing Loss Due To Antibiotics May Be Prevented By Genetically Screening Patients Beforehand

Some patients have a genetic mutation which means they are more at risk of hearing loss after taking antibiotics called aminoglycosides. Experts, writing in the British Medical Journal (BMJ) believe that screening patients for this genetic mutation may prevent this. The writers, Maria Bitner-Glindzicz and Shamima Rahman, the Institute of Child health, London, England, explain that aminoglycosides are valuable antibiotics for such serious infections as complicated urinary tract infections, tuberculosis and septicemia. They are known to potentially cause damage to the ear (otoxicity). However, what isn't well known is that there are people who have an inherited predisposition that makes them extremely sensitive to the effects - they can end up with severe and permanent hearing loss. Approximately 5% of deafness in children in the UK is caused by this mutation, known as m.1555A-G. About 1 in 40,000 people in the UK have this mutation. Studies in other countries have indicated much higher incidences, in New Zealand it is thought to occur in 1 in 206 cases of newborns, and 1 in 1,161 in the USA (also newborns). Families carrying this mutation, even if they never take aminoglycosides, may develop some degree of deafness later in life. A study carried out in Spain found that 27% of families which included two deaf people were positive for this mutation. It was also found that everybody who had this mutation in Spain and took aminoglycosides suffered from hearing loss. A person who had taken aminoglycosides had a 96.5% of becoming deaf by the age of 30 if he/she had been exposed to aminoglycosides, while 38.9% of those who had never taken it became deaf. The authors write that aminoglycosides are a major environmental modifier of the m.1555A-G mutation. The writers ask whether it is cost effective to screen for this mutation before deciding whether to prescribe aminoglycosides. A test in the UK costs approximated £35 ($70). This cost would probably go down considerably if they were carried out in much larger numbers. It costs the NHS £61,000 ($122,000) for every child who becomes deaf (over his/her lifetime), plus about £18,000 ($36,000) in educational costs. US estimates have placed the lifetime cost to society for a child who loses his/her hearing before acquiring language at one million dollars. It is possible to prevent deafness brought on by aminoglycosides in individuals who have this genetic mutation, explain the authors. Doctors who have patients who are deaf are well aware of this mutation. Many doctors, however, do not know about this susceptibility, and many others do not know that mutation testing is available. The authors propose that the true prevalence of this mutation be ascertained for the UK, so that the cost-effectiveness of screening everyone who is prescribed aminoglycosides can be determined. Until this is done, people who are likely to be receiving multiple courses of aminoglycosides should be screened, such as leukemia patients and infants admitted to special care baby units. They conclude that test results should be produced rapidly, and until they appear the patient should be given some other type of antibiotic.