April 2004
The Problem of Antibiotic ResistanceOverview 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
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:
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. The NARSA Web site is available at http://www.narsa.net. 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. More details on these and other related projects can be found on the NIAID Web site at http://www.niaid.nih.gov/dmid/antimicrob. 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
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. The plan is available online at http://www.cdc.gov/drugresistance/actionplan/index.htm. 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. Related Information Other federal agencies are involved in combating the problem of drug-resistant microbes. See the links below for more information. Centers for Disease Control and Prevention Food and Drug Administration National Library of Medicine Medline database Public Health Action Plan to Combat Antimicrobial Resistance
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