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Bacteria race ahead of drugs/Falling behind: Deadly infections increasingly able

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  • rojony57
    Courtesy of Robert Martin and sfgate.com Drugs used in livestock, chickens coming home to roost!! ... This article was sent to you by someone who found it on
    Message 1 of 1 , Feb 5, 2008
      Courtesy of Robert Martin and sfgate.com

      Drugs used in livestock, chickens coming home to roost!!
      This article was sent to you by someone who found it on SFGate.
      The original article can be found on SFGate.com here:
      Sunday, January 20, 2008 (SF Chronicle)
      Bacteria race ahead of drugs/Falling behind: Deadly infections
      increasingly able to beat antibiotics
      Sabin Russell

      At a busy microbiology lab in San Francisco, bad bugs are brewing
      inside vials of human blood, or sprouting inside petri dishes, all in
      preparation for a battery of tests.
      These tests will tell doctors at UCSF Medical Center which kinds of
      bacteria are infecting their patients, and which antibiotics have the
      best chance to knock those infections down.
      [Podcast: Growing problem of drug-resistant diseases and what you
      can do about it.]

      With disturbing regularity, the list of available options is short,
      and it is getting shorter.
      Dr. Jeff Brooks has been director of the UCSF lab for 29 years, and
      has watched with a mixture of fascination and dread how bacteria once
      tamed by antibiotics evolve rapidly into forms that practically no
      drug can treat.
      "These organisms are very small," he said, "but they are still
      smarter than we are."
      Among the most alarming of these is MRSA, or methicillin-resistant
      Staphylococcus aureus, a bug that used to be confined to vulnerable
      hospital patients, but now is infecting otherwise healthy people in
      schools, gymnasiums and the home.
      As MRSA continues its natural evolution, even more drug-resistant
      strains are emerging. The most aggressive of these is one called USA300.
      Last week, doctors at San Francisco General Hospital reported that
      a variant of that strain, resistant to six important antibiotics
      normally used to treat staph, may be transmitted by sexual contact and
      is spreading among gay men in San Francisco, Boston, New York and Los
      Yet the problem goes far beyond one bug and a handful of drugs.
      Entire classes of mainstay antibiotics are being threatened with
      obsolescence, and bugs far more dangerous than staph are evolving in
      ominous ways.
      "We are on the verge of losing control of the situation,
      particularly in the hospitals," said Dr. Chip Chambers, chief of
      infectious disease at San Francisco General Hospital.
      The reasons for increasing drug resistance are well known:

      - Overuse of antibiotics, which speeds the natural evolution of
      bacteria, promoting new mutant strains resistant to those drugs.

      - Careless prescribing of antibiotics that aren't effective for the
      malady in question, such as a viral infection.
      - Patient demand for antibiotics when they aren't needed.

      Heavy use of antibiotics in poultry and livestock feed, which can
      breed resistance to similar drugs for people.
      Germ strains that interbreed at hospitals, where infection controls
      as simple as hand-washing are lax.

      All this is happening while the supply of new antibiotics from drug
      company laboratories is running dry.
      Since commercial production of penicillin began in the 1940s,
      antibiotics have been the miracle drugs of modern medicine,
      suppressing infectious diseases that have afflicted human beings for
      thousands of years. But today, as a generation of Baby Boomers begins
      to enter a phase of life marked by the ailments of aging, we are
      running out of miracles.
      Top infectious disease doctors are saying that lawmakers and the
      public at large do not realize the grave implications of this trend.
      "Within just a few years, we could be seeing that most of our
      microorganisms are resistant to most of our antibiotics," said Dr.
      Jack Edwards, chief of infectious diseases at Harbor-UCLA Medical Center.
      At Brooks' microbiology laboratory, the evolutionary struggle of
      bacteria versus antibiotics is on display every day. He grabbed a
      clear plastic dish that grew golden-hued MRSA germs taken from a
      patient a few days earlier. Inside were seven paper dots, each
      impregnated with a different drug. If the antibiotic worked, the dot
      had a clear ring around it - a zone where no germs could grow. No ring
      meant the drug had failed. This test was typical. Three drugs worked,
      four had failed.
      The strategy for nearly 70 years has been to stay a step ahead of
      resistance by developing new antibiotics. In the past decade, however,
      major drugmakers have been dropping out of the field. The number of
      new antibiotics in development has plummeted. During the five-year
      period ended in 1987, the FDA licensed 16 novel antibiotics. In the
      most recent five-year period, only five were approved.
      For drugmakers, the economics are simple: An antibiotic can cure an
      infection in a matter of days. There is much more money in finding
      drugs that must be taken for a lifetime.
      Toll of antibiotic resistance
      With antibiotic research lagging, the bugs are catching up, and
      infections are taking a terrible toll. The federal Centers for Disease
      Control and Prevention estimates that each year 99,000 Americans die
      of various bacterial infections that they pick up while hospitalized -
      more than double the number killed every year in automobile accidents.
      Of the 1.7 million hospital-acquired infections that occur each
      year, studies show, 70 percent are resistant to at least one antibiotic.
      Drug-resistant staph is rapidly becoming a major public health
      menace. Last fall, the CDC estimated that MRSA alone has killed 19,000
      Americans. Most of these patients picked up the bug in the hospital,
      but it is now spreading in urban and suburban neighborhoods across the
      "MRSA is killing people. It almost killed me," said Peg McQueary,
      whose life was upended when she nicked her leg with a razor three
      years ago.
      Within days, her leg was grotesquely swollen, red from foot to
      knee. Her husband wheeled her into a Kaiser medical office, where her
      doctor took one look and rushed her to an isolation room.
      She was placed on intravenous vancomycin, a drug reserved for the
      most serious cases of MRSA. Since that frightening week, the
      42-year-old Roseville woman has spent much of her life in and out of
      hospitals, and she's learned just how difficult these infections can
      be to treat. McQueary has burned through drug after drug, but the
      staph keeps coming back.
      She's been hooked up at her home to bags of vancomycin and
      swallowed doses of linezolid, clindamycin and a half a dozen other
      antibiotics with barely pronounceable names and limited effect.
      One of the newest antibiotics, intravenous daptomycin - approved by
      the Food and Drug Administration in 2003 - seems to work the best, but
      it has not prevented recurrences.
      "It's just a struggle to do everyday things," she said. "I am ready
      to scream about it."
      Today, she moderates a Web site, MRSA Resources Support Forum,
      swapping stories with other sufferers. "Giving them a place to vent is
      some sort of healing for me," she said.
      McQueary's travails are becoming an all-too-familiar American
      experience. As bacteria evolve new ways to sidestep antibiotics,
      doctors treating infections find themselves with a dwindling list of
      options. Old-line drugs are losing their punch, while the newer ones
      are both costly and laden with side effects.
      Drugs' weakening grip
      Dr. Joseph Guglielmo, chairman of the Department of Clinical
      Pharmacy at UCSF, closely tracks the effectiveness of dozens of
      antibiotics against different infectious bacteria. Laminated
      color-coded cards called antibiograms are printed up for hospital
      physicians each year. They chart the success rate of each antibiotic
      against at least 12 major pathogens. These charts show how
      antibiotics, like tires slowly leaking air, are losing strength year
      by year.
      As head of the hospital pharmacy, Guglielmo oversees a small
      warehouse at the medical center that stores millions of dollars worth
      of prescription drugs that are used every day to treat patients there.
      Strolling down the aisles that houses bins of antibiotics, he reached
      for a bottle of imipenem, and cradled the little vial in the palm of
      his hand.
      "This one is the last line of defense," he said.
      Imipenem was approved by the FDA in 1985. A powerful member of the
      carbapenem family - the latest in a long line of penicillin-like drugs
      - it is frequently used in hospitals today because it can still defeat
      a wide variety of germs that have outwitted the earlier-generation
      But at a cost of about $60 a day, and with a safety profile that
      includes risk of seizure, it is a "Big Gun" drug that must be used
      carefully. As soon as doctors discover that a lesser antibiotic will
      work, they will stop prescribing imipenem, like soldiers conserving
      their last remaining stores of ammunition.
      Now, there are signs of trouble.
      Imipenem has been the antibiotic of choice for doctors treating
      Klebsiella, a vigorous microbe that causes pneumonia in hospitalized
      patients. But in June 2005, New York City doctors reported in the
      journal Archives of Internal Medicine outbreaks of imipenem-resistant
      Klebsiella. Fifty-nine such cases were logged at just two hospitals.
      The death rate among those whose infections entered their bloodstreams
      was 47 percent.
      Last year, Israeli doctors battled an outbreak of
      carbapenem-resistant Klebsiella that has killed more than 400 patients.
      Cipro's dramatic decline
      The antibiotic Cipro, approved by the Food and Drug Administration
      in 1987, is familiar to millions of Americans because it is widely
      prescribed for pneumonia, urinary tract infections and sexually
      transmitted diseases. It was the drug used to treat victims of the
      anthrax mailings that followed the Sept. 11 attacks.
      Unlike most antibiotics, which originated from natural toxins
      produced by bacteria, Cipro came from tinkering with a chemical
      compound used to fight malaria. The German drug giant Bayer patented
      Cipro's active ingredient in 1983, and it subsequently became the most
      widely sold antibiotic in the world.
      At hospitals across the country, however, clinicians have witnessed
      a remarkable drop-off in the utility of Cipro against more commonly
      encountered germs.
      Antibiograms from the UCSF lab highlight the alarming erosion: As
      recently as 1999, Cipro was effective against 95 percent of specimens
      of E. coli - bacteria responsible for the most common
      hospital-acquired infections in the United States. By 2006, Cipro
      would work against only 60 percent of samples tested.
      The bacterial evolution that has so quickly sapped Cipro has also
      reduced the effectiveness of the entire family of related antibiotics
      called fluoroquinolones - drugs such as Levaquin, Floxin, and Noroxin.
      "If there is ever a group of drugs that has taken a beating, it is
      these," said UCSF pharmacy chief Guglielmo.
      Against Acinetobacter - a bug responsible for rising numbers of
      bloodstream and lung infections in intensive care units, as well as
      among combat casualties in Iraq - Cipro's effectiveness fell from 80
      percent in 1999 to 10 percent just four years later. Cipro has also
      lost ground against Pseudomonas aeruginosa, a common cause of
      pneumonia in hospitalized patients. Nearly 80 percent of the bugs
      tested were susceptible to Cipro in 1999. That fell to 65 percent by 2004.
      At UCSF, doctors carefully monitor the trends in drug resistance
      and modify their prescribing patterns accordingly. As a result, they
      have been able to nudge some of these resistance levels down. Cipro's
      effectiveness against Acinetobacter crept up to 40 percent last year,
      for example, but the overall trend remains alarming.
      Although MRSA infections have been capturing headlines, bugs such
      as Acinetobacter, Klebsiella and Pseudomonas are keeping doctors awake
      at night. They come from a class of pathogens called Gram-negative
      bacteria, which typically have an extra layer of microbial skin to
      ward off antibiotics, and internal pumps that literally drive out
      antibiotics that penetrate.
      Gram-negative infections have always been difficult to treat, and
      few new drugs are in development. Some researchers believe that the
      pipeline for new antibiotics is drying up because it is simply getting
      more difficult to outwit the bugs. "It may be that we've already found
      all the good antibiotics," warned Chambers, San Francisco General
      Hospital's infectious disease chief. "If that is so, then we've really
      got to be careful how we use the ones we have."
      Bacteria's natural evolution
      Terry Hazen, senior scientist at Lawrence Berkeley National
      Laboratory and director of its ecology program, is not at all
      surprised by the tenacity of our bacterial foes. "We are talking about
      3.5 billion years of evolution," he said. "They are the dominant life
      on Earth."
      Bacteria have invaded virtually every ecological niche on the
      planet. Human explorers of extreme environments such as deep wells and
      mines are still finding new bacterial species. "As you go deeper into
      the subsurface, thousands and thousands of feet, you find bacteria
      that have been isolated for millions of years - and you find multiple
      antibiotic resistance," Hazen said.
      In his view, when bacteria develop resistance to modern
      antibiotics, they are merely rolling out old tricks they mastered eons
      ago in their struggle to live in harsh environments in competition
      with similarly resilient species.
      Drug industry economics are also a factor. "It takes a hell of a
      lot of effort to find the next really good drug," said Steven Projan,
      vice president of New Jersey pharmaceutical giant Wyeth Inc.
      The costs of bringing a new drug to market are hotly debated. A
      Tufts University study estimated $802 million; the consumer group
      Public Citizen pegs it at $110 million. Either way, the investment is
      By 1990, according to the Infectious Diseases Society of America,
      half the major drugmakers in Japan and the United States had cut back
      or halted antibiotic research. Since 2000, some of the biggest names
      in pharmaceutical development - Roche, Bristol-Myers Squibb, Abbott
      Laboratories, Eli Lilly, Aventis and Procter & Gamble - had joined the
      By common measures used to gauge the profit potential of new drugs,
      antibiotics fall way behind, Projan explained. For every $100 million
      that a new antibiotic might yield, after projected revenue and
      expenses are tallied, a new cancer drug will generate $300 million. A
      new drug for arthritis, by this same analysis, brings in $1.1 billion.
      Investors have been placing their bets accordingly.
      In 2002, Wyeth had sharply curtailed its own antibiotic drug
      discovery programs. "We tried to get out of the field, but one of the
      reasons we did not get out altogether is we feel we have a public
      responsibility to fund more research," said Projan.
      Wyeth's decision to keep some antibiotic research alive eventually
      paid off. In June 2005, the FDA licensed Tygacil, an intravenous
      antibiotic for complicated skin diseases such as drug-resistant staph
      infection. Only one new antibiotic for oral or intravenous use has won
      FDA approval since.
      Pointing a finger at doctors
      The waning of antibiotics in the arsenal of modern medicine has
      been going on for so long that some doctors fear a kind of complacency
      has set in. Increasingly, the medical profession is pointing a finger
      at itself.
      "We have behaved very badly," said Dr. Louis Rice, a
      Harvard-educated, Columbia-trained specialist in infectious diseases.
      "We have made a lot of stupid choices."
      His words brought a nervous silence to thousands of his colleagues,
      as he delivered a keynote speech in 2006 for the American Society for
      Microbiology's annual conference in San Francisco.
      Rice, a professor at Cleveland's Case Western Reserve University,
      said doctors and drug companies alike are responsible for breeding
      resistance by "the indiscriminate dumping of antibiotics into our
      human patients."
      Drug-resistant germs contaminate the bedrails, the catheter lines,
      the blood pressure cuffs and even the unwashed hands of doctors,
      nurses and orderlies. The germs keep evolving, swapping
      drug-resistance traits with other microbes. He likened American
      intensive-care units - the high-tech enclaves where the most seriously
      ill patients are treated - to "toxic waste dumps."
      Drug companies, he said, have a responsibility to refill the
      nation's depleted medicine chest. He suggested that a tax - similar to
      a Superfund tax placed on polluters to clean up toxic waste sites - be
      imposed on companies that have dropped antibiotic research. It would
      support drugmakers that are still in the game. "Your products that
      you've made billions and billions and billions and billions of dollars
      on have created this problem, and you can't just walk away," he said.
      Rice has stressed that the existing arsenal of antibiotics should
      be used wisely, and that often means sparingly. During a half century
      of antibiotic use, he said, there is scant research on how short a
      course of drugs is actually needed to cure a patient. Instead, doctors
      routinely prescribe a week to 10-day course of drugs recommended by
      manufacturers. If patients are taking antibiotics after their
      infections are truly gone, they are creating conditions that breed
      resistance. Indeed, a Dutch study showed that one kind of pneumonia
      can be treated just as successfully with three days of amoxicillin as
      with the traditional eight.
      Since drug companies cannot be expected to spend money on research
      that could trim sales of their products, federally funded agencies
      such as the National Institutes of Health should do the job, Rice said
      in a recent interview.
      He also took his own specialty to task for failing to protect the
      most important weapons its arsenal. Infectious disease experts at
      hospitals must find the "backbone" to stop other doctors from
      prescribing antibiotics unnecessarily, Rice said. He argued they
      should assert their authority to control antibiotic usage, just as
      cancer specialists have a say in which chemotherapy drugs are
      prescribed by surgeons.
      And all health care professionals, he added, "have to wash their
      damn hands."

      How to get involved
      What: The STARR Act, a bill sponsored by Sen. Sherrod Brown,
      D-Ohio, and Sen. Orrin Hatch, R-Utah, was introduced last fall to
      address the problem of antibiotic-resistant bacteria and to spur
      development of new drugs.
      To learn more: Go to links.sfgate.com/ZCEF.
      Want to tell your representatives in the U.S. Senate or the House
      of Representatives how you stand on the STARR Act?
      Call Sen. Barbara Boxer at her Washington office at (202) 224-3553
      or her San Francisco office at (415) 403-0100, or e-mail her by going
      to links.sfgate.com/ZCEK.
      Call Sen. Dianne Feinstein at her Washington office at (202)
      224-3841 or her San Francisco office at (415) 393-0707, or find her
      e-mail address at links.sfgate.com/ZCEL.
      Contact information for your House representative can be found at

      Online resources
      A support resource created by MRSA patients is at:
      For more information:
      links.sfgate.com/ZCBQ ------
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