Sludge Watch ==> Bacteria Race Ahead of Drugs

[Maureen Reilly]

Sludgewatch Admin:

In their most recent review of the US federal sewage sludge regulations The 
National Academy of Sciences stated that the EPA needs to investigate the 
role of sewage treatment plants in creating and spreading antibiotic 
resistant pathogens.

The EPA has not done such research.

It is increasingly the inescapable monkey on their back.  Hospitals, 
pharmaceutical companies, seniors residences...all empty their 
pharmaceutical wastes into the toilets... in addition to the pharmacueticals 
that enter the wastewater stream after having passed through the digestive 
tract of those taking the medications.

Increasingly the population is dosed with drugs and hormones on a routine 
basis, as opposed to only being medicated when acutely ill.  (think Viagra, 
steriods, hormone replacement, anti depressants, daily aspirin, etc).

The fecal bacteria of about 85 % of the North American population are in a 
digester for at least 15 days ... if not months...where they are in a war of 
all against all for decreasing food sources.  Those that are 'naive' to 
antibiotics are killed off while those that carry antibiotic resistant DNA 
reproduce successfully.  We backwash these successful virulent bacteria into 
the incoming sewage stream further refining the antibiotic resistance 
characteristics of the successful bacteria.

We take these bacteria..most of them we put on food chain lands...for 
grazing cattle and dairy herds to ingest after top dressing pasture lands 
for instance.  Some of them are swept into the lagoons of incoming sewage to 
again replace naive populations of bacteria with those successful antibiotic 
resistance bacteria.

The liquid effluent from the wastewater plant is discharged to lakes and 
rivers and in increasing numbers of communities...into public parks, golf 
courses, and even drinking water acquifers.
Meanwhile the risk of resistant infections is leading hospitals to routinely 
dose surgery patients with vancomycin..one of our few remaining effective 
antibiotics.  So these hospitals will be discharging this valuable remaining 
antibiotic in relatively large doses to the public sewers where it will 
result in more tonnage of vancomycin resistant pathogens to be spread into 
the ecology and sprayed on parks are gardens.  Even tender leafy greens in 
the Salinas Valley are being spray irrigated with sewage treatment plant 
effluent.


Is it any wonder we a seeing an epidemic of community acquired resistant 
infections?

Sewage treatment plants and the propogation and distribution of antibiotic 
resistant bacteria is truly the elephant in the room.  We turn away from 
this issue at our peril.

.........................


http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2008/01/20/MN1234A1.DTL&type=health

San Francisco Chronicle
Bacteria race ahead of drugs
Falling behind: Deadly infections increasingly able to beat antibiotics
Sabin Russell

Sunday, January 20, 2008


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.

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 Angeles.

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 nation.

"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 antibiotics.

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 100 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 huge.

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 exodus.

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 
links.sfgate.com/ZCEJ.



Online resources
A support resource created by MRSA patients is at:

links.sfgate.com/ZCEE

For more information:

links.sfgate.com/ZCBT

links.sfgate.com/ZCBQ

http://sfgate.com/cgi-bin/article.cgi?f=/c/a/2008/01/20/MN1234A1.DTL

This article appeared on page A - 1 of the San Francisco Chronicle