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Drug-resistant infectious agents – those that are not killed or inhibited
by antimicrobial compounds – are an increasingly important public health
concern. Tuberculosis, gonorrhea, malaria and childhood ear infections are just
a few of the diseases that have become more difficult to treat due to the
emergence of drug-resistant pathogens. Antimicrobial resistance is becoming a
factor in virtually all hospital-acquired (nosocomial) infections. Many
physicians are concerned that several bacterial infections soon may be
untreatable.
In addition to its adverse effect on public health, antimicrobial resistance
contributes to higher health care costs. Treating resistant infections often
requires the use of more expensive or more toxic drugs and can result in longer
hospital stays for infected patients. The Institute of Medicine, a part of the
National Academy of Sciences, has estimated that the annual cost of treating
antibiotic resistant infections in the United States may be as high as $30
billion.
A key factor in the development of antimicrobial resistance is the ability of
infectious organisms to adapt quickly to new environmental conditions. Microbes
generally are unicellular creatures that, compared with multicellular organisms,
have a small number of genes. Even a single random gene mutation can have a
large impact on their disease-causing properties; and since most microbes
replicate very rapidly, they can evolve rapidly. Thus, a mutation that helps a
microbe survive in the presence of an antibiotic drug will quickly become
predominant throughout the microbial population. Microbes also commonly acquire
genes, including those encoding for resistance, by direct transfer from members
of their own species or from unrelated microbes.
The innate adaptability of microbes is complemented by the widespread and
sometimes inappropriate use of antimicrobials. Ideal conditions for the
emergence of drug-resistant microbes result when drugs are prescribed for the
common cold and other conditions for which they are not indicated or when
individuals do not complete their prescribed treatment regimen. Hospitals also
provide a fertile environment for drug-resistant pathogens. Close contact among
sick patients and extensive use of antimicrobials force pathogens to develop
resistance.
Scope of the problem
Antimicrobial resistance has been recognized since the introduction of
penicillin nearly 50 years ago when penicillin-resistant infections caused by Staphylococcus
aureus rapidly appeared. Today, hospitals worldwide are facing unprecedented
crises from the rapid emergence and dissemination of other microbes resistant to
one or more antimicrobial agents.
- Strains of Staphylococcus aureus resistant to methicillin and other
antibiotics are endemic in hospitals. Infection with methicillin-resistant S.
aureus (MRSA) strains may also be increasing in non-hospital settings. A
limited number of drugs remain effective against these infections. S.
aureus strains with reduced susceptibility to vancomycin have emerged
recently in Japan and the United States. The emergence of vancomycin-resistant
strains would present a serious problem for physicians and patients.
- Increasing reliance on vancomycin has led to the emergence of vancomycin-resistant
enterococci (VRE), bacteria that infect wounds, the urinary tract and other
sites. Until 1989, such resistance had not been reported in U.S. hospitals.
By 1993, however, more than 10 percent of hospital-acquired enterococci
infections reported to the CDC were resistant.
- Streptococcus pneumoniae causes thousands of cases of meningitis
and pneumonia, and 7 million cases of ear infection in the United States
each year. Currently, about 30 percent of S. pneumoniae isolates are
resistant to penicillin, the primary drug used to treat this infection. Many
penicillin-resistant strains are also resistant to other antimicrobial
drugs.
- In sexually transmitted disease clinics that monitor outbreaks of
drug-resistant infections, doctors have found that more than 30 percent of
gonorrhea isolates are resistant to penicillin or tetracycline, or both.
- An estimated 300 to 500 million people worldwide are infected with the
parasites that cause malaria. Resistance to chloroquine, once widely used
and highly effective for preventing and treating malaria, has emerged in
most parts of the world. Resistance to other antimalaria drugs also is
widespread and growing.
- Strains of multidrug-resistant tuberculosis (MDR-TB) have emerged over the
last decade and pose a particular threat to people infected with HIV.
Drug-resistant strains are as contagious as those that are susceptible to
drugs. MDR-TB is more difficult and vastly more expensive to treat, and
patients may remain infectious longer due to inadequate treatment.
- Diarrheal diseases cause almost 3 million deaths a year – mostly in
developing countries, where resistant strains of highly pathogenic bacteria
such as Shigella dysenteriae, Campylobacter, Vibrio
cholerae, Escherichia coli and Salmonella are emerging.
Recent outbreaks of Salmonella food poisoning have occurred in the
United States. A potentially dangerous "superbug" known as Salmonella
typhimurium, resistant to ampicillin, sulfa, streptomycin, tetracycline
and chloramphenicol, has caused illness in Europe, Canada and the United
States.
- Fungal pathogens account for a growing proportion of nosocomial
infections. Fungal diseases such as candidiasis and Pneumocystis carinii
pneumonia are common among AIDS patients, and isolated outbreaks of other
fungal diseases in people with normal immune systems have occurred recently
in the United States. Scientists and clinicians are concerned that the
increasing use of antifungal drugs will lead to drug-resistant fungi. In
fact, recent studies have documented resistance of Candida species to
fluconazole, a drug used widely to treat patients with systemic fungal
diseases.
- Recent years have seen the introduction of powerful new drugs and drug
combinations against HIV. Although treatments that combine new protease
inhibitor drugs with other anti- HIV medications often effectively suppress
HIV production in infected individuals, results from recent clinical studies
suggest that many treatment failures occur due to the development of
resistance by the virus.
NIAID research
Scientists and health professionals agree that decreasing the incidence of
antimicrobial resistance will require improved systems for monitoring outbreaks
of drug-resistant infections and a more judicious use of antimicrobial drugs.
They also recognize the critical role that basic research plays in responding to
this problem. For example, studies of microbial physiology help scientists
understand the biological processes that pathogens use to resist drug treatment.
This knowledge can lead to the development of novel strategies to overcome or
reverse these processes.
Source: National Institutes of Health;
National Institute of Allergy and Infectious
Diseases
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