Post by LymeEnigma on Jun 14, 2008 10:08:17 GMT -8
Superbug Supremacy
Harmful bacteria are mutating faster and becoming resistant to numerous antibiotics, leading to a possible 'superbug'.
by Alexis Bergen
Bacteriologist Alexander Fleming stumbled upon the first antibiotic almost 80 years ago after discovering that his cultured bacteria were stunted by a yellow-green mold. Another decade passed before a team of Oxford University scientists harnessed the mold’s power and turned it into the life-saving drug known as penicillin.
But antibiotics’ key flaw quickly made itself known.
The Oxford team and Fleming saw that when penicillin was given in insufficient doses, resistant strains of bacteria not only survived the drug’s onslaught, but took hold and thrived. Even today, this flaw remains. The consequences of resistance include the need for more toxic medications, an increase in the duration of illness, risk of medical and surgical complications and even death.
According to the Centers for Disease Control and Prevention (CDC), more than 70 percent of the bacteria that cause infections are resistant to at least one antibiotic used to treat them.
“There is a relative lack of new classes of antibiotics in the drug development pipeline, considering the ever-increasing numbers of antibiotic-resistant bacteria,” says Annie Wong-Beringer, Pharm.D., associate professor of clinical pharmacy at the USC School of Pharmacy. “It’s scary to think about a ‘superbug’ that could be resistant to every antibiotic we have available, which is a definite possibility.”
Part of the challenge scientists face comes from the overuse of antibiotics for the treatment of disease caused by viruses and bacteria and a decline in the interest of the pharmaceutical industry in developing new antibiotics due to a low return on investment, Wong-Beringer says.
Although both bacteria and viruses bring about illness, and both are microscopic invaders of the body, they are very different in the way they cause disease.
Antibiotics that work against bacterial infections, such as strep throat, do not work against viruses, such as those that cause colds. Moreover, antibiotic misuse against a virus is potentially dangerous, says Wong-Beringer.
“Inappropriate antibiotic use may kill beneficial bacteria, opening the door for harmful bacteria to establish themselves in their place. It also may toughen up some bacteria by encouraging them to mutate and develop drug resistance,” she says.
Experts estimate that physicians in the United States write 50 million antibiotic prescriptions a year to treat disease actually caused by viruses. Part of the reason may be patients’ or caregivers’ expectations. Pediatricians prescribe antibiotics 65 percent of the time if they sense that parents expect them but only 12 percent of the time if they sense parents do not expect them, according to a CDC study.
“Physicians and patients equally contribute to this problem,” she says. “Studies show that patients often demand antibiotics, regardless of their illness. Or patients are appropriately prescribed antibiotics for bacterial infections but do not finish their course of treatment, which doesn’t kill all of the bugs.”
To understand how antibiotics work, it helps to understand bacteria basics.
Bacteria are single-celled organisms that are routinely found within the human body—except in the blood and spinal fluid—and outside the body. Many bacteria provide important functions, such as helping with digestion and inhibiting the growth of bacteria that cause disease.
Because the bacterium is such a simple life form, it can evolve easily—and quickly.
“Bacteria quickly develop new traits through mutations that help protect them against antibiotics,” Wong-Beringer says. “The mutated organisms survive and reproduce, passing along the mutation to their offspring. Eventually, antibiotic-resistant bacteria will outnumber the non-resistant ones under the constant pressure of antibiotic use.”
Wong-Beringer is working to discover the mechanism that enables some bacteria to become resistant to multiple antibiotics. Her clinical research has focused on Pseudomonas aeruginosa, a virulent bacterium that is known for its adaptability, its capacity to cause severe illness in susceptible patients and its resistance against numerous drugs.
“Bacteria have efflux pumps that remove toxic substances from within the cells as well as pump out signaling molecules to communicate with other bacteria cells,” she explains. “These pumps protect the bacteria from being destroyed by moving antibiotic drugs from inside to outside of the cell. Once bacteria encounter a specific antibiotic, they mutate and create new forms of bacteria with a greater amount of efflux pumps designed to more efficiently eliminate that particular antibiotic.”
Wong-Beringer explains that one of the signaling molecules produced by P. aeruginosa has a chemical structure similar to a class of antibiotics known as fluoroquinolones, potent drugs commonly prescribed to treat many different types of bacterial infections.
“P. aeruginosa already have a mechanism in place to readily pump out fluoroquinolones and render them ineffective when these drugs are overused,” she says.
In the last five years, Wong-Beringer has observed a sharp increase of fluoroquinolone-resistant P. aeruginosa that also are resistant to other antibiotics. Her research has shown that exposure to fluoroquinolones activates the bacteria’s natural defense mechanism to make more efflux pumps to not only remove the fluoroquinolones but other antibiotic classes as well.
According to the CDC, the prevalence of fluoroquinolone-resistant P. aeruginosa rose from 4 percent to 18 percent in U.S. hospitals in the last decade. Because levels of antibiotic-resistant bacteria have reached an all-time high, Wong-Beringer hopes to educate physicians and patients about the dangers of inappropriate antibiotic use.
“Physicians need to be vigilant about choosing antibiotics to treat bacterial infections as specifically as possible,” she says. “Overuse will encourage bacteria to mutate and become resistant to potentially all existing antibiotics, which will endanger the health and lives of the public.”
Alicia Di Rado contributed to this article.
USC Health Magazine
www.usc.edu/hsc/info/pr/hmm/04fall/superbug.html
Harmful bacteria are mutating faster and becoming resistant to numerous antibiotics, leading to a possible 'superbug'.
by Alexis Bergen
Bacteriologist Alexander Fleming stumbled upon the first antibiotic almost 80 years ago after discovering that his cultured bacteria were stunted by a yellow-green mold. Another decade passed before a team of Oxford University scientists harnessed the mold’s power and turned it into the life-saving drug known as penicillin.
But antibiotics’ key flaw quickly made itself known.
The Oxford team and Fleming saw that when penicillin was given in insufficient doses, resistant strains of bacteria not only survived the drug’s onslaught, but took hold and thrived. Even today, this flaw remains. The consequences of resistance include the need for more toxic medications, an increase in the duration of illness, risk of medical and surgical complications and even death.
According to the Centers for Disease Control and Prevention (CDC), more than 70 percent of the bacteria that cause infections are resistant to at least one antibiotic used to treat them.
“There is a relative lack of new classes of antibiotics in the drug development pipeline, considering the ever-increasing numbers of antibiotic-resistant bacteria,” says Annie Wong-Beringer, Pharm.D., associate professor of clinical pharmacy at the USC School of Pharmacy. “It’s scary to think about a ‘superbug’ that could be resistant to every antibiotic we have available, which is a definite possibility.”
Part of the challenge scientists face comes from the overuse of antibiotics for the treatment of disease caused by viruses and bacteria and a decline in the interest of the pharmaceutical industry in developing new antibiotics due to a low return on investment, Wong-Beringer says.
Although both bacteria and viruses bring about illness, and both are microscopic invaders of the body, they are very different in the way they cause disease.
Antibiotics that work against bacterial infections, such as strep throat, do not work against viruses, such as those that cause colds. Moreover, antibiotic misuse against a virus is potentially dangerous, says Wong-Beringer.
“Inappropriate antibiotic use may kill beneficial bacteria, opening the door for harmful bacteria to establish themselves in their place. It also may toughen up some bacteria by encouraging them to mutate and develop drug resistance,” she says.
Experts estimate that physicians in the United States write 50 million antibiotic prescriptions a year to treat disease actually caused by viruses. Part of the reason may be patients’ or caregivers’ expectations. Pediatricians prescribe antibiotics 65 percent of the time if they sense that parents expect them but only 12 percent of the time if they sense parents do not expect them, according to a CDC study.
“Physicians and patients equally contribute to this problem,” she says. “Studies show that patients often demand antibiotics, regardless of their illness. Or patients are appropriately prescribed antibiotics for bacterial infections but do not finish their course of treatment, which doesn’t kill all of the bugs.”
To understand how antibiotics work, it helps to understand bacteria basics.
Bacteria are single-celled organisms that are routinely found within the human body—except in the blood and spinal fluid—and outside the body. Many bacteria provide important functions, such as helping with digestion and inhibiting the growth of bacteria that cause disease.
Because the bacterium is such a simple life form, it can evolve easily—and quickly.
“Bacteria quickly develop new traits through mutations that help protect them against antibiotics,” Wong-Beringer says. “The mutated organisms survive and reproduce, passing along the mutation to their offspring. Eventually, antibiotic-resistant bacteria will outnumber the non-resistant ones under the constant pressure of antibiotic use.”
Wong-Beringer is working to discover the mechanism that enables some bacteria to become resistant to multiple antibiotics. Her clinical research has focused on Pseudomonas aeruginosa, a virulent bacterium that is known for its adaptability, its capacity to cause severe illness in susceptible patients and its resistance against numerous drugs.
“Bacteria have efflux pumps that remove toxic substances from within the cells as well as pump out signaling molecules to communicate with other bacteria cells,” she explains. “These pumps protect the bacteria from being destroyed by moving antibiotic drugs from inside to outside of the cell. Once bacteria encounter a specific antibiotic, they mutate and create new forms of bacteria with a greater amount of efflux pumps designed to more efficiently eliminate that particular antibiotic.”
Wong-Beringer explains that one of the signaling molecules produced by P. aeruginosa has a chemical structure similar to a class of antibiotics known as fluoroquinolones, potent drugs commonly prescribed to treat many different types of bacterial infections.
“P. aeruginosa already have a mechanism in place to readily pump out fluoroquinolones and render them ineffective when these drugs are overused,” she says.
In the last five years, Wong-Beringer has observed a sharp increase of fluoroquinolone-resistant P. aeruginosa that also are resistant to other antibiotics. Her research has shown that exposure to fluoroquinolones activates the bacteria’s natural defense mechanism to make more efflux pumps to not only remove the fluoroquinolones but other antibiotic classes as well.
According to the CDC, the prevalence of fluoroquinolone-resistant P. aeruginosa rose from 4 percent to 18 percent in U.S. hospitals in the last decade. Because levels of antibiotic-resistant bacteria have reached an all-time high, Wong-Beringer hopes to educate physicians and patients about the dangers of inappropriate antibiotic use.
“Physicians need to be vigilant about choosing antibiotics to treat bacterial infections as specifically as possible,” she says. “Overuse will encourage bacteria to mutate and become resistant to potentially all existing antibiotics, which will endanger the health and lives of the public.”
Alicia Di Rado contributed to this article.
USC Health Magazine
www.usc.edu/hsc/info/pr/hmm/04fall/superbug.html