"We saw reports on drugs in three new classes of antimicrobials," said Steven Projan, a member of the program committee for the Interscience Conference on Antimicrobial Agents and Chemotherapy.

"That's impressive," Projan told United Press International. "If we could get that many new attacks on these microbes every year we would really be doing well. But the fact is that while we have a steady rate of drugs coming into the pipeline, the resistance rates of these microbes keeps rising."

Projan, vice president for biological technologies at Wyeth Research in Cambridge, Mass., co-chaired the popular ICAAC session at which researchers described:

-- A new anti-viral that targets Hepatitis C infection. Researchers at Viropharma of Exton, Pa., and Wyeth said their drug HCV-796 has moved ahead so quickly that the potential treatment for a major cause of liver failure has entered Phase 2b human testing.

"Currently," Projan said, "about 20 percent to 30 percent of patients treated for Hepatitis C infection with interferon and ribavirin can be cured. We think that if HCV-796 proves successful we could add that drug to the mix and possibly improve cure rates to more than 50 percent."

-- A new agent aimed at preventing infections caused when bacterial and other microbes colonize catheters and other devices used in long-term treatment of patients.

"Infections resulting from the use of medical devices are still the number one cause of nosocomial (hospital-acquired) illness in the United States," said Paul Savage of Brigham Young University in Provo, Utah, who presented data on the antimicrobial molecule CSA-13, a ceragenin that selectively seeks out and compromises the bacterial membrane.

Projan said that the ceragenins represent one of the new attacks on bacteria and may prevent infections from biofilms that collect on medical devices.

-- A new type of agent that attacks the fatty acid biosynthesis of the bacteria -- an essential process for the microbe.

Nachum Kaplan, vice president of microbiology at Affinium Pharmaceuticals Inc. in Toronto, demonstrated that the company's API-1252 was highly effective in laboratory tests of combating deadly methicillin-resistant Staphylococcus aureus and even rare but extremely dangerous vancomycin-resistant S. aureus strains.

"We expect to begin human testing of API-1252 in 2007," Kaplan said.

"We need more drugs that can fight staph," Peter Appelbaum, director of clinical microbiology at the Milton S. Hershey Medical Center in Hershey, Pa., told UPI. "This drug looks promising."

Of the drugs discussed Wednesday at ICAAC, Projan said he was especially impressed by AR-709, a new diaminopyrimidine being developed by Arpida Ltd. in Muenchenstein, Switzerland.

Stephen Hawser, director of biology at Arpida, explained that the drug candidate "appeared to overcome resistance in streptococci that occurred in macrolides, quinolones and penicillins. We feel this molecule can overcome all forms of resistance."

"This drug could be very important," Projan told UPI. "Streptococci cause skin infections, pneumonia, otitis media -- ear infections -- and are the organism also known as the flesh-eating bacteria."

Hawser said the drug was designed to disrupt the mechanism in bacteria known as microbial dihydrofolate reductase. By attacking that action selectively, the drug only destroys the bacteria and therefore has favorable toxicity. He said human clinical trials with the drug are now under way.

Projan said that even though many of the drugs look promising, the road from early human trials and pre-human trials to a marketable agent is slow and fraught with complications. He said that he would not expect any of the drugs described in the ICAAC session to be approved for at least five years.

The ICAAC meeting, which began Wednesday in San Francisco, continues through Saturday. It is expected to draw in the neighborhood of 16,000 doctors, researchers and allied healthcare professionals.

earlier related report
Develop Antibiotics Or Pay The Price
Researchers decried Thursday a lack of research that can fight an epidemic of microbes that have gained resistance against virtually everything that doctors have in their pharmaceutical arsenal. In fact, some are even suggesting that drug companies who refuse to rise to the new microbial challenge should face a financial penalty.

"Pharmaceutical companies have made billions of dollars turning human beings into toxic waste dumps," charged Louis Rice, chief of medicine services at the Louis Stokes Veterans Affairs Medical Center in Cleveland, at an infectious disease meeting sponsored by the American Society for Microbiology.

Rice said that the overuse of antibiotics due in part to over-prescribing by medical professionals has created biologically resistant microbes that cannot be killed off by drugs now available -- especially for bugs known as Gram-negative pathogens.

While the Gram-negative bugs were not considered as important or as dangerous as so-called Gram-positive bugs such as staphylococci or streptococci, he said that 25 percent of infections with klebsiella -- which causes pneumonia, urinary-tract infections and wound infections -- do not respond to anything clinicians can thrown at it.

"I don't blame the pharmaceutical companies for resistant bacteria any more than I blame doctors for overprescribing the drugs," Rice said. "But the pharmaceutical companies made so much money developing the antibiotics they have a responsibility to contribute financially to finding treatments."

Yet there is a dwindling number of pharmaceutical companies that are willing to commit funds to developing drugs to overcome resistance, he said, noting that many companies are merging or are leaving the development arena.

To those companies that shy away from the challenge, Rice suggested they should be taxed to finance the work of other companies willing to find the compounds needed to treat patients with the antibiotic-created resistant pathogens.

Rice also suggested that studies -- probably under the aegis of the National Institutes of Health -- should undertake studies to determine whether it is really necessary for people to take antibiotics for full courses of treatment. He pointed out that the recommendations for taking drugs for a full course was based on clinical trials with set timeframes, not on whether a person was feeling better.

He said that taking antibiotics longer than necessary only contributes to creating more powerful, resistant bugs.

"Gram-negative bacteria have a thicker cell wall that prevents drugs from penetrating and killing it," Karen Bush, distinguished research fellow at Johnson & Johnson Pharmaceutical Research and Development in Raritan, N.J., told United Press International at the 46th annual Interscience Conference on Antimicrobial Agents and Chemotherapy in San Francisco.

"There are now multi-drug resistant acinetobacter strains -- including those brought back to the U.S. from troops and personnel in Iraq -- that don't respond to any classical treatment," Bush said during a news briefing.

Jeffrey Edwards, a consultant to pharmaceutical companies from Flintshire, Wales, United Kingdom, said, "It's a real challenge to find a wide spectrum Gram-negative antibiotic."

In another news briefing at ICAAC, a meeting that has attracted 16,000 scientists, researchers and allied healthcare providers, doctors looked at treatments for fungal infections -- illnesses that emerged among patients with suppressed immune systems or who are treated for extended times in intensive care units, attached to various devices and catheters.

"We now have a number of ways of treating these patients," said Elias Anaissie, professor of medicine at the University of Arkansas for Medical Sciences in Little Rock. For years the mainstay of fungal infection treatment was use of toxic, intravenous amphotericin B. Since then, equally effective but more convenient oral medications have been approved.

"Now the question is whether we can treat those patients by combining medicines in these groups," he told UPI. The problem is that, what looks good in test tube doesn't necessarily work in patients, and what looks good may work in treating one infection but not another.

The need for clinical trials in this area, said Johan Mouton, professor of medicine at Canisius Wilhelmina Hospital, Nijmegen, the Netherlands, has intensified because there are more patients now who are at risk of these infections: Transplant patients, cancer patients, AIDS patients and long-term trauma patients.

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