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Overview
The triumph of antibiotics over disease-causing bacteria
is one of modern medicine's greatest success stories. Since these drugs first
became widely used in the World War II era, they have saved countless lives and
blunted serious complications of many feared diseases and infections. After more
than 50 years of widespread use, however, many antibiotics don't pack the same
punch they once did.
Over time, some bacteria have developed ways to
outwit the effects of antibiotics. Widespread use of antibiotics is thought to
have spurred evolutionary changes in bacteria that allow them to survive these
powerful drugs. While antibiotic resistance benefits the microbes, it presents
humans with two big problems: it makes it more difficult to purge infections
from the body; and it heightens the risk of acquiring infections in a hospital.
Diseases such as tuberculosis, gonorrhea, malaria, and childhood ear infections
are now more difficult to treat than they were decades ago. Drug resistance is
an especially difficult problem for hospitals because they harbor critically ill
patients who are more vulnerable to infections than the general population and
therefore require more antibiotics. Heavy use of antibiotics in these patients
hastens the mutations in bacteria that bring about drug resistance.
Unfortunately, this worsens the problem by producing bacteria with greater
ability to survive even our strongest antibiotics. These even stronger
drug-resistant bacteria continue to prey on vulnerable hospital patients.
To help curb this problem, the Centers for Disease Control and
Prevention (CDC) provides hospitals with prevention strategies and educational
materials to reduce antimicrobial resistance in health care settings. According
to CDC statistics
· Nearly two million patients in the United States get an infection in the hospital each year.
· Of those patients, about 90,000 die each year as a result of their infection-up from 13,300 patient deaths in 1992.
· More than 70 percent of the bacteria that cause hospital-acquired infections are resistant to at least one of the drugs most commonly used to treat them.
· Persons infected with drug-resistant organisms are more likely to have longer hospital stays and require treatment with second or third choice drugs that may be less effective, more toxic, and more expensive.
In short, antimicrobial resistance is driving up health care costs,
increasing the severity of disease, and increasing the death rates from certain
infections.
Environment Forces Evolutionary Change
A key
factor in the development of antibiotic resistance is the ability of infectious
organisms to adapt quickly to new environmental conditions. Bacteria are
single-celled creatures that, compared with higher life forms, have small
numbers of genes. Therefore, even a single random gene mutation can greatly
affect their ability to cause disease. And because most microbes reproduce by
dividing every few hours, bacteria can evolve rapidly. A mutation that helps a
microbe survive exposure to an antibiotic drug will quickly become dominant
throughout the microbial population. Microbes also often acquire genes,
including those that code for resistance, from each other.
The advantage
microbes gain from their innate adaptability is augmented by the widespread and
sometimes inappropriate use of antibiotics. A physician, wishing to placate an
insistent patient ill with a cold or other viral condition, sometimes
inappropriately prescribes antibiotics. Also when a patient does not finish
taking a prescription for antibiotics, drug-resistant microbes not killed in the
first days of treatment can proliferate. Hospitals also provide a fertile
environment for drug-resistant germs as close contact among sick patients and
extensive use of antibiotics force bacteria to develop resistance. Another
controversial practice that some believe promotes drug resistance is adding
antibiotics to agricultural feed.
A Growing Problem
For
all these reasons, antibiotic resistance has been a problem for nearly as long
as we've been using antibiotics. Not long after the introduction of penicillin,
a bacterium known as Staphylococcus aureus began developing
penicillin-resistant strains. Today, antibiotic-resistant strains of S.
aureus bacteria as well as various enterococci-bacteria that colonize the
intestines-are common and pose a global health problem in hospitals. More and
more hospital-acquired infections are resistant to the most powerful antibiotics
available, methicillin and vancomycin. These drugs are reserved to treat only
the most intractable infections in order to slow development of resistance to
them.
There are several signs that the problem is increasing:
· Strains of S. aureus resistant to methicillin are endemic in hospitals and are increasing in non-hospital settings such as locker rooms. Since September 2000, outbreaks of methicillin-resistant S. aureus infections have been reported among high school football players and wrestlers in California, Indiana, and Pennsylvania, according to the CDC.
· The first S. aureus infections resistant to vancomycin emerged in the United States in 2002, presenting physicians and patients with a serious problem. In July 2002, the CDC reported that a Michigan patient with diabetes, vascular disease, and chronic kidney failure had developed the first S. aureus infection completely resistant to vancomycin. A similar case was reported in Pennsylvania in September 2002.
· Increasing reliance on vancomycin has led to the emergence of vancomycin-resistant enterococci infections. Prior to 1989, no U.S. hospital had reported any vancomycin resistant enterococci, but over the next decade, such microbes have become common in U.S. hospitals, according to CDC.
· A 2003 study in The New England Journal of Medicine found that the incidence of blood and tissue infections known as sepsis almost tripled from 1979 to 2000.
NIAID Research
The National Institute of Allergy and Infectious
Diseases (NIAID), part of the Department of Health and Human Services' National
Institutes of Health (NIH), funds research, drug screening, and clinical trials
to combat the problem of antimicrobial resistance. It manages a research
portfolio of grants specifically aimed at the problem of antibiotic resistance
among common bacteria responsible for hospital-acquired infections. These grants
fund studies on the basic biology of resistant organisms; applied research on
new diagnostic techniques, therapies, and preventive measures; as well as
studies of how bacteria develop and share resistance genes. Other NIAID-funded
research projects seek to identify natural antimicrobial peptides (small pieces
of protein molecules) that could help stave off drug-resistant infections.
NIAID also funds the Network on Antimicrobial Resistance in
Staphylococcus aureus (NARSA), a multidisciplinary international cadre of
basic scientists, clinical microbiologists, and clinical investigators focused
on combating drug-resistant S. aureus and related staphylococcal
bacterial infections. The network maintains a repository of drug-resistant staph
strains that scientists can request for use in their research. It also provides
an Internet site with scientific presentations and a discussion forum to promote
communication between researchers.
NIAID also supports a number of
networks for clinical trials with the capacity to assess new antimicrobial drugs
and vaccines against other drug-resistant infections. The AIDS Clinical Trials
groups can evaluate drugs that combat the problem of the HIV virus developing
resistance to standard antiretroviral treatments. The Bacteriology and Mycology
Study Group, a network of academic and private research institutes, conducts
clinical trials for improved treatments for fungal infections, particularly in
people with weakened immune systems. In a similar fashion, the Collaborative
Antiviral Study Group, made up of researchers at approximately 50 institutions,
evaluates experimental therapies for viral infections. The Vaccine and Treatment
Evaluation Units are a network of seven U.S. institutions that conduct clinical
research on vaccines and therapeutics to speed development of new vaccines and
therapies.
Other research projects-at NIH or funded by other components
of NIH-are seeking new, molecular-level knowledge on the interactions of
microbes and human cells as well as the tricks microbes use to outwit
antibiotics. Another avenue of research is sleuthing the genomes of
drug-resistant bacteria for vulnerabilities that could be attacked with new or
existing drugs.
Antimicrobial Advances and
Activities
NIAID-funded research grants and activities are yielding
results that will help public health officials hold the line in our fight
against drug-resistant microbes. For example NIAID-funded researchers at the
University of California Berkeley have documented the mechanics of how E.
coli bacteria use pumps in the thin space between their membranes to expel
antibiotic drugs. Their results, reported in the Journal of Bacteriology,
serve as a model for how these molecular pumps work in bacteria responsible for
hospital-acquired infections.
NIAID grantees at the Washington
University School of Medicine in St. Louis have uncovered new information about
how bacteria that cause urinary tract infections manufacture hair-like fibers to
cling to the lining of the bladder. Their findings could lead to new drugs that
would treat urinary tract infections by blocking formation of these protein
fibers. Approximately half of all women experience urinary tract infections, and
20 to 40 percent of those will develop recurrent infections. The results were
reported in the journal Cell.
An NIAID-funded project at The
Institute for Genomic Research recently discovered that small pieces of DNA that
can jump between chromosomes or organisms helped a strain of E. faecalis
bacteria develop resistance to vancomycin. The researchers found that these
"mobile elements" of DNA appear to contain a newly identified vancomycin
resistance segment carrying vancomycin resistance genes. These results were
published in the journal Science.
Partnerships and Interagency
Collaborations
In addition to sponsoring research, NIAID co-chairs
the federal government's Interagency Task Force on Antimicrobial Resistance.
This task force is made up of representatives from NIAID, CDC, the Food and Drug
Administration, the Agency for Healthcare Research and Quality, the Department
of Agriculture, the Department of Defense, the Department of Veterans Affairs,
the Environmental Protection Agency, the Center for Medicaid and Medicare
Services, and the Health Resources and Services Administration. The Task Force
is working on implementing an antimicrobial resistance action plan that reflects
a broad consensus of theses agencies with input from a variety of constituents
and collaborators.
NIAID also co-sponsors the Annual Conference on
Antimicrobial Resistance with the Infectious Disease Society of America and
other government and not-for-profit agencies. The conference updates attendees
on the science, prevention, and control of antimicrobial resistance and provides
a forum for discussion of new methods of treatment and control.