Drug-resistant TB

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New TB treatment works...

Aggressive TB treatment 'success'
Sunday, 24 August 2008 - Tuberculosis which is resistant to many treatments can be overcome with aggressive therapy, research suggests.

Extensively drug-resistant TB is associated with high rates of mortality and is thought to account for at least 7% of cases of the infection worldwide. Despite fears that it is untreatable, researchers have shown a cure is possible with a combination of at least five drugs, The Lancet reported.

UK experts said it was good news but would require a lot of resources. Multi-drug resistant (MDR) TB, of which there are around 50 to 70 cases every year in the UK, is resistant to the most commonly used treatments isoniazid and rifampin. "It's a very important paper showing it's possible to deal with XDR-TB", Dr John Moore-Gillon

But in extensively resistant (XDR) TB, at least two of the second-line treatments are also worthless. Some experts have speculated that XDR-TB is effectively untreatable and there were grave concerns after reports of 52 deaths in 16 days in South Africa after an outbreak among patients with HIV.

Tailored treatment

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TB snafu in San Francisco...

Hundreds Of Babies At Risk In TB Scare
Aug. 27, 2008 - S.F. Hospital Informs 960 Mothers That Former Postpartum Unit Employee Was Infected

Kaiser Permanente is telling 960 mothers that they and their babies may have been exposed to a San Francisco maternity ward worker diagnosed with active tuberculosis. Kaiser announced it had started notifying patients Tuesday about the worker formerly employed in the postpartum unit of its San Francisco Medical Center.

The part-time employee worked at Kaiser from March 10 to August 10 and no longer works for the organization. Kaiser learned of the employee's diagnosis last week and said the medical center followed all appropriate screening procedures when hiring the employee.

"We feel that this is a low-risk exposure, but we want to be aggressive about identifying any potential contacts," Dr. Stephen Parodi, chief of infectious diseases for Kaiser Permanente in Northern California, told the San Francisco Chronicle. Dr. Parodi said the infection risk for patients was low and that the worker had a common strain of TB that responds well to antibiotics.

Hundreds Of Babies At Risk In TB Scare, S.F. Hospital Informs 960 Mothers That Former Postpartum Unit Employee Was Infected - CBS News

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New TB defense...

A New Class of Antibiotics Could Offer Hope Against TB
Friday, Oct. 17, 2008 - Eighty years after the discovery of penicillin, researchers say they are on the verge of developing a new class of antibiotics.

Publishing in the Oct. 17 issue of the journal Cell, scientists at Rutgers University describe a group of antibiotic compounds, first isolated decades ago from naturally occurring antibacterial substances in soil. Among them, researchers say, is a compound called myxopyronin that shows great promise. It has been synthesized in the lab and shown to be safe in animal trials, and although the drug hasn't been tested in humans yet, cell-based experiments suggest that it is potent enough to kill a wide range of stubborn bugs, including drug-resistant strains of tuberculosis and the deadly type of staph known as MRSA.

The Rutgers research reflects a much-needed, if slow, renewal of scientific interest in antibiotics development. The last two decades of the 20th century saw nearly zero progress, and in those years several disease-causing bacteria evolved resistance to commonly used drugs. Researchers at the Centers for Disease Control and Prevention found that more than 40% of staph infections in the U.S. in 2006 were MRSA — a bug that now kills more Americans a year than AIDS. Today, the first line of treatment against MRSA is vancomycin, a formidable antibiotic that has been around since the 1950s and is otherwise typically considered a drug of last resort. In the developing world, health workers report a proliferation of XDR (extensively drug-resistant) and MDR (multidrug-resistant) tuberculosis, against which the current first-line antibiotics, rifamycins, developed in the 1960s, have also become useless.

"I would say that most of the American public believe that bacterial infections were conquered with the discovery of penicillin and streptomycin and that the dawn of the antibiotic age meant the end of bacterial infection as an important threat," says Richard Ebright, a Howard Hughes Medical Institute investigator at Rutgers and a co-author on the study. What has happened instead, says Zhenkun Ma, head of research at the Global Alliance for TB Drug Development, who was not involved in the new study, is that "we use really old drugs to fight a very new disease. TB evolves every day." So do all other bacteria. Increasingly, the old arsenal of antibiotics is losing power. Ebright hopes myxopyronin will be especially useful in the battle against drug-resistant tuberculosis, a disease for which clinicians have never had a perfect therapy. The success of TB treatment depends on the destruction of active and dormant bacteria to prevent relapse — something that few existing antibiotics have been able to do. One way to kill a dormant cell is to target biochemical processes that continue even in latency — there aren't many of those. But myxopyronin works by interfering with the enzyme RNA polymerase, which controls gene transcription in cells and is necessary for cell survival, dormant or not.

Rifamycins, the main drugs currently used to treat tuberculosis, attack the same RNA polymerase target, but at a different site. That means the old drugs and the new drugs "should not have cross-resistance," says Ma. Any new drugs will work against bacteria that have developed resistance to current drugs, but won't interfere with the way the current drugs work. Armed with a new biochemical understanding of how myxopyronin functions, along with detailed models of its behavior inside bacterial cells, researchers say drug development is feasible at last. Ebright says the drug could be in clinical human trials within five years. "What has not been possible previously was design of new derivatives ," says Ebright. "It's now possible to make new derivatives that are expressly designed to...have higher potency."

A New Class of Antibiotics Could Offer Hope Against TB - TIME

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More accurate TB test developed...

New TB blood test more accurate than skin test
Mon., Oct. 20, 2008 - ELISpot is 1.5 times better at spotting carriers of disease, researcher says

A new blood test will allow doctors more accurately to pinpoint patients likely to develop the symptoms of tuberculosis, researchers said on Monday. Traditional testing for the disease involves injecting the subject with components of the TB bacterium; a resultant swelling of the skin can signal dormant tuberculosis. Such skin tests are prone to false positives — people wrongly identified as needing treatment — and, conversely, can sometimes wrongly show TB carriers to be free of the infection.

A new blood test known as ELISpot is 1.5 times better at spotting tuberculosis carriers, said Ajit Lalvani, a researcher at Imperial College London. "On a global level, when you stack up those numbers, that is going to make a huge difference," Lalvani, whose findings were published in the Annals of Internal Medicine, said in a telephone interview.

Tuberculosis is an infectious bacterial disease which typically attacks the lungs and affects about 9.2 million more people each year, killing an estimated 1.7 million. Many of its victims are in developing countries whose cash-strapped heath systems have limited means of screening for the disease.

The emergence and spread of drug-resistant germs makes treating tuberculosis more difficult and could make the disease even deadlier in the future. Lalvani and his team studied 908 healthy children in Turkey exposed to tuberculosis in their homes. A little over half tested positive for latent TB using the two tests.

More New TB blood test more accurate than skin test - Infectious diseases - MSNBC.com

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Drug-resistant bacteria...

Hospitals use more antibiotics despite concerns
Mon., Nov. 10, 2008 WASHINGTON - Experts worry bacteria will become resistant to existing drugs

Use of antibiotics at U.S. hospitals is rising despite concerns about fueling bacterial resistance, with Wyeth's Zosyn and the older drug vancomycin driving the trend, researchers said. Use of antibiotics at a group of U.S. academic medical centers rose 7 percent from 2002 to 2006, Ronald Polk of Virginia Commonwealth University and colleagues reported in the journal Archives of Internal Medicine on Monday. "We know from past experience that when we start using any antimicrobial drug excessively, that resistance to that drug eventually appears," Polk said in a telephone interview.

"Given the fact that there are very few new antimicrobial drugs being discovered, the message is that we really need to learn how to use the available drugs better." The researchers tracked data on anti-bacterial drugs at 22 hospitals around the United States over the full five years. In 2006, based on information from 35 such university teaching hospitals, the researchers found that 64 percent of patients were given at least one dose of an antibiotic. As doctors prescribe more antibiotics, experts are alarmed that drugs that once killed the germs no longer do so, meaning an illness may last longer and be more likely to be fatal.

Health care costs also rise when infections defy standard antibiotics. Resistance to drugs can render them useless. Use of Wyeth's Zosyn, also called piperacillin-tazobactam, rose 84 percent from 2002 to 2006 at the hospitals studied, while use of vancomycin rose 43 percent, the researchers said. Both drugs are given to treat numerous bacterial infections. Aside from those two, other antibiotic use was stable. While over-use of antibiotics is a major concern of public health experts, documentation of the problem at U.S. hospitals has been difficult to come by. Polk said the findings at these hospitals probably reflect trends across the United States.

More Hospitals use more antibiotics despite concerns - Infectious diseases