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Antimicrobial (Drug) Resistance |
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Translating Basic Knowledge Scientific discovery begins with basic research in the laboratory at “the bench”. In order to improve human health, however, these discoveries must be translated into practical applications that reach the patients “bedside.” NIAID-supported research in antimicrobial research helps facilitate this translation of basic research discoveries from “bench-to-bedside."
Faster diagnosticsWithout ways to rapidly diagnose an infection or a microbe’s susceptibility to antimicrobial drugs, healthcare providers may reach for a broad-acting drug that they hope will kill whatever the patient has. However, the practice of using broad-spectrum drugs first, before the specific microbe is identified, can accelerate the emergence of drug-resistant strains. To improve diagnostics, NIAID supports
- Research aimed at speeding development of techniques to rapidly detect the microbes most often responsible for life-threatening sepsis and community-acquired pneumonia. Sepsis is a severe illness caused by overwhelming infection of the bloodstream by toxin-producing bacteria.
- A new program will assist in development of rapid diagnostics for a number of healthcare-associated bacterial infections that are showing signs of increased drug resistance. The microbes targeted in this program include Clostridium difficile, Pseudomonas, Acinetobacter, Enterobacter, and Klebsiella.
Proper dosageAlong with accurate diagnosis, doctors need to prescribe the proper dose of a drug—one that is effective, but that limits the microbe’s odds of developing resistance following prolonged or excessive exposure to the drug. Best dosage requires a clear understanding of how the antimicrobial is broken down in the human body and how the drug affects the body (the drug’s pharmacokinetics and pharmacodynamics, respectively). To improve dosage recommendations, NIAID is supporting research proposals that incorporate drug dynamics and kinetics into studies aimed at preventing antimicrobial resistance.
NIAID is also supporting efforts to collect data on the dynamics and kinetics of older antibiotics for which best dosage information is not available. As situations arise where commonly used antibiotics are no longer effective, doctors are resorting to some of the older antibiotics, such as colistin. Though resistance to colistin is still low, doctors had stopped using colistin because it was known to cause kidney damage. Now, however, colistin is used more frequently to treat antibiotic-resistant infections in people undergoing dialysis. NIAID is supporting a clinical study to determine the best dosage for colistin in these patients.
New DrugsIn recent years, the number of new antimicrobials cannot keep up with the rise of antimicrobial-resistant microbes. NIAID has a substantial research program to spur development of new drugs against disease-causing viruses, bacteria, parasites, and fungi.
NIAID supports university-based scientists and researchers at biotechnology companies who are exploring new ways to treat infections with substances that make it difficult for microbes to develop resistance. For example, researchers are studying both bacteriophages (bacteria-killing viruses) and small protein molecules that have natural antibacterial properties for their infection-fighting potentials.
Other NIAID-supported efforts to develop new or improved drugs include:
- Work on compounds that inhibit bacterial proteins called multiple adaptational response (MAR) proteins, which bacteria use to develop resistance to drugs. Inhibiting MAR proteins would render bacteria extremely sensitive to antimicrobial agents.
- Research on new broad-spectrum antibiotics, including one to fight complicated skin infections and another that is now being tested as a treatment for community-acquired pneumonia.
Clinical Trials: Data to Guide Treatment DecisionsThe selection of antimicrobial-resistant microbes can be reduced if we minimize the unnecessary use of these drugs. Well-designed clinical trials provide the data necessary to guide healthcare providers in their treatment decisions. This research will lead to better healthcare practices and more refined therapeutic approaches, such as shorter treatment duration, or alternative therapies that do not require prescribed antimicrobials to minimize the emergence of antimicrobial resistance. Examples of NIAID-supported clinical trials include the following:
- Antibiotics are commonly prescribed for children with acute ear infections (acute otitis media or AOM), despite the fact that many ear infections are viral—not bacterial, and thus not susceptible to antibiotics. Because a clinical trial had never been conducted to verify the effectiveness of prescribing antibiotics to treat AOM, NIAID is currently sponsoring a trial to compare how long it takes for AOM to resolve in children who receive standard antibiotic treatment versus children who do not receive treatment.
- Skin and soft tissue infections caused by strains of community-associated MRSA (CA-MRSA), are a growing concern, but little is known about how to best treat uncomplicated forms of the infection. NIAID supports two clinical trials that are addressing the question of whether oral “first-line” antibiotics that are no longer under patent can effectively treat CA-MRSA. If so, doctors could use those drugs and avoid unnecessary use of last-resort antibiotics, which are critical for the treatment of hospital-acquired MRSA.
- Rates of drug-resistant infections are higher in the intensive care unit (ICU) than elsewhere in hospitals. Currently, ICU patients typically receive antibiotics for 8 days or longer, but there is no documented evidence that this treatment length is effective. It is well known, however, that long durations of antibiotic use contribute to the development of antimicrobial resistance. NIAID investigators are conducting a trial to compare the effectiveness of the standard treatment to a short-course therapy of 3 days.
Vaccines Against Drug-Resistant MicrobesThe need for new drugs would be lessened if bacterial or other infections could be prevented with a vaccine. NIAID-supported researchers have successfully tested an experimental vaccine against Staphylococcus aureus—the most common hospital-associated bacterial infection—in a mouse model. Importantly, there are indications the vaccine might work even against strains of antibiotic-resistant bacteria.
An NIAID-supported researcher who was testing an experimental vaccine in mice against the fungal infection caused by Candida albicans discovered that the vaccine also appeared to protect the animals against Staphylococcus aureus. The discovery raises the possibility of developing a single vaccine against multiple microbes.
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