The discovery of a large number of slow-growing Mycobacterium tuberculosis bacteria, which cause tuberculosis (TB), in the lungs of TB patients could be an important step forward in the design of new anti-TB drugs. Until now it was thought that M. tuberculosis bacteria in the lungs of TB patients were rapidly multiplying. However recent research by Dr Simon Waddell and colleagues from St George's University of London and the University of Leicester, using gene chips to look at how TB bacteria behave in different environments, revealed that the tuberculosis bacteria in the sputum (phlegm coughed from the lungs) of TB patients resemble bacteria that are growing very slowly or hardly at all. This has caused concern, as slowly growing bacteria are non-responsive to treatment with isoniazid, one of the main antibiotics used to treat TB. This may be the reason why it takes six months to treat pulmonary TB successfully, whereas most bacterial infections are treated in days. This prolonged treatment often leads people to stop taking their medicines early or only to take them intermittently, which can cause relapses and the emergence of antibiotic resistance.

Bacterial resistance to antibiotics is one of medicine's most vexing challenges. In a study described in Nature Chemical Biology, researchers from Albert Einstein College of Medicine of Yeshiva University are developing a new generation of antibiotic compounds that do not provoke bacterial resistance. The compounds work against two notorious microbes: Vibrio cholerae, which causes cholera; and E. coli 0157:H7, the food contaminant that each year in the U.S. causes approximately 110,000 illnesses and 50 deaths. Most antibiotics initially work extremely well, killing more than 99.9% of microbes they target. But through mutation and the selection pressure exerted by the antibiotic, a few bacterial cells inevitably manage to survive, repopulate the bacterial community, and flourish as antibiotic-resistant strains. Vern L. Schramm, Ph.D., professor and Ruth Merns Chair of Biochemistry at Einstein and senior author of the paper, hypothesized that antibiotics that could reduce the infective functions of bacteria, but not kill them, would minimize the risk that resistance would later develop. Dr. Schramm's collaborators at Industrial Research Ltd. earlier reported transition state analogues of an enzyme that interferes with "quorum sensing" — the process by which bacteria communicate with each other by producing and detecting signaling molecules known as autoinducers. These autoinducers coordinate bacterial gene expression and regulate processes — including virulence — that benefit the microbial community. Previous studies had shown that bacterial strains defective in quorum sensing cause less-serious infections. Rather than killing Vibrio cholerae and E. coli 0157:H7, the researchers aimed to disrupt their ability to communicate via quorum sensing. Their target: A bacterial enzyme, MTAN, that is directly involved in synthesizing the autoinducers crucial to quorum sensing. Their plan: Design a substrate to which MTAN would bind much more tightly than to its natural substrate — so tightly, in fact, that the substrate analog permanently "locks up" MTAN and inhibits it from fueling quorum sensing.

Untreatable cases of extensively drug-resistant tuberculosis (XDR-TB) could be tackled with a combination of two existing drugs — one of which was developed over 30 years ago. Laboratory studies, published in Science last week (27 February), showed that a combination of the drugs meropenem and clavulanate inhibited the growth of 13 separate strains of XDR-TB. They also inhibited the growth of drug-susceptible laboratory strains and those that mimic the 'latent' state of TB — an inactive phase of TB which is difficult to treat. The researchers, from the US National Institute of Allergy and Infectious Diseases and the US-based Albert Einstein College of Medicine, are optimistic that if the results are reproduced in humans, an effective XDR-TB treatment could be produced in a relatively short time. Meropenem belongs to a class of antibiotics called b-lactams. These widely-used drugs have never proved useful in TB treatment as Mycobacterium tuberculosis possesses an enzyme that breaks them down. But clavulanate inhibits the enzyme, allowing meropenem to kill M. tuberculosis when the two are used in combination.

Scientists might have found a way to deal drug-resistant tuberculosis a one-two punch using two old, safe antibiotics _ and studies in ill patients could begin later this year. TB is one of the world's oldest killers, and the lung disease still claims the lives of more than 1.5 million people globally every year. The bacteria that cause TB are fast becoming impervious to many treatments, drug resistance that is seen worldwide but is a particular problem in parts of Asia and Africa. While typically the TB doesn't respond to two top treatments, an emerging threat is so-called extensively drug-resistant disease, or XDR-TB, that is virtually untreatable by remaining options. So researchers are frantically hunting new approaches, including taking a fresh look at some old drugs. TB bacteria contain a certain enzyme that renders the penicillin family of antibiotics drugs useless. "It chews them up and spits them out and they never get to see their target," explained biochemist John Blanchard of the Albert Einstein School of Medicine. But there are different antibiotics that can block that enzyme, called beta-lactamase. One, named clavulanate, has long been sold as part of the two-drug Augmentin combination that's widely used for various children's infections. So Blanchard's team tested whether administering clavulanate might make TB vulnerable to other antibiotics _ and found a combination that in laboratory tests blocked the growth of 13 different drug-resistant TB strains. The combo: Clavulanate to drop TB's shield, plus a long-sold injected antibiotic _ meropenem, part of that penicillin-style family _ that then attacks the bacteria.

Children are picking up more stubborn staph infections that don’t respond to common antibiotics, and the proportion their of ear, nose and throat infections resistant to standard drug treatment increased dramatically over a six-year period, a new study has found. Methicillin-resistant Staphylococcus aureus infections, known as MRSA, accounted for 28.1 percent of children’s head and neck staph infections in 2006, up from just 11.8 percent in 2001, according to researchers at Emory University in Atlanta. It once was rare for an ear, nose and throat doctor to see MRSA infections, noted Dr. Steven E. Sobol, the paper’s senior author and director of pediatric otolaryngology at Emory University School of Medicine. “That was the impetus for the study,” he said.