NEW ORLEANS - Fifty million pounds of antibiotics are produced in the United States each year for use in people, animals and plants. Is it any wonder that resistance is a growing problem? Stuart Levy, MD, asked here at the annual meeting of the American Academy of Dermatology.
About 50% of those antibiotics are prescribed for people, 45% for animals, and the rest are used in agriculture, with 300,000 lb of antibiotics being sprayed on fruit trees alone, said Levy, director of the Center for Adaptation Genetics & Drug Resistance at Tuft's University School of Medicine in Boston. Levy is also president of the American Society of Microbiology and president of the Alliance for Prudent Use of Antibiotics.
Add to this inordinate use, the number of antimicrobial soaps and other antibacterial products in the household, and you have a medical crisis, where resistant bacteria are selected out, while weaker and susceptible bacteria die, he explained.
Levy discussed the seriousness of antimicrobial resistance, how people arrived at this point and what can be done to reverse the situation. Levy, who wrote the book The Antibiotic Paradox: How Miracle Drugs Are Destroying the Miracle has been studying resistance for much of his career.
"I was impressed by the versatility that enable bacteria to circumvent antibiotics because we gave the advantage to those rare forms that are not susceptible and had developed resistance," he said.
In hospitals, the big problems come from methicillin-resistant Staphylococcus aureus (MRSA), vancomycin resistant enterococcus and four gram-negative bacteria: Klebsiella, Enterobacter Pseudomonas and Acinetobacter
MRSA caused hospitals to notice that resistance was a problem but the situation has not improved. In fact, it has gotten worse. "The MRSA really now should be called multidrug resistant S. aureus because in hospitals nearly 60% of all methicillin-resistant organisms can only be treated by vancomycin. That gives you an idea how multidrug-resistant the organisms are. You cannot use aminoglycosides or fluoroquinolones," Levy said.
Ten years ago the report of a vancomycin-resistant enterococcus shook everyone up, Levy said. In large part because the enterococcus could pass its resistance gene to other organisms, even among different species. In one laboratory, the enterococcus passed resistance gene to a Staphylococcus
The first report of vancomycin insensitive S. aureus occurred last year in Japan, when a 4-month-old child, who underwent cardiac surgery and developed a post-surgical infection with S. aureus did not respond to vancomycin. The child was finally treated with three-drug therapy, which included an aminoglycoside, and recovered. Since then, five patients have appeared in the United States and Japan with vancomycin insensitive S. aureus They all had MICs above 8, which means a physician would need to deliver much higher doses of vancomycin to treat the organism. "If you cannot deliver that much vancomycin to a patient - and it is not a nontoxic antibiotic - your patient does not survive. Two patients died because vancomycin did not work."
Hospitals were the first place that antibiotic resistance emerged, but resistant organisms are now present in communities. It is in the community that physicians and patients can have the most influence.
"The pneumococcus was the first organism to bring antibiotic resistance to the public's attention since many parents were dealing with children who were going to day care centers and elsewhere and were getting repeated ear infections," Levy said. "While previously parents remembered that the antibiotic made kids better. More recently, the kids did not get better. And in many instances, when the cause was bacteria, the organism was multidrug resistant pneumococcus."
If this organism caused meningitis, physicians would have to resort to combination therapy. "We are no longer in the age where a single antimicrobial will work," Levy said.
"We are in a crisis situation, where any use of antibiotic has to be taken into consideration," Levy said.
"The answer is simple. It is the antibiotic, which is being over-used for many different reasons in the community and the resistance genes that have emerged. If we were not using the antibiotic or we were using it in a more prudent fashion," he admitted, would not be the problem it is today."
He told an interesting story about a medical student who pretended to have a cold and went to see 40 physicians. Of the 40 doctors, 37 diagnosed a viral infection, influenza or URI; three diagnosed serious disease like tuberculosis or a chronic condition. Thirty-seven wrote a prescription for an antibiotic although they diagnosed a viral infection. This same stunt was done by several news organizations for stories, and in each case, a person with a suspected URI received an antibiotic.
And the track record in some developing countries is even worse, because they have eliminated the middleman - the physician. Pharmacies in many developing countries sell antibiotics over the counter like aspirin. Levy said that he went to Santiago, Chile, to lecture about antibiotic resistance and the pharmacy across the street had a sale on antibiotics. Up to 30% off the drug if it was the local generic product. "It was antibiotic week!" he exclaimed. "Whatever you wanted, you could get."
Physicians and patients have become demanding and complacent at the same time. Patients expect and demand antibiotics even for viral infections, and physicians hand them over rather than argue. In many cases, physicians prescribe them over the telephone without even seeing the patient. Levy said this "casual attitude" is dangerous.
"Antibiotics are societal drugs. They are very different from any other medication that we use." he said. Talking to dermatologists, he mentioned an area where they prescribe antibiotics for long periods, namely for acne. In one paper, the researchers showed that giving antibiotics to one patient for acne can have consequences for everyone living in the house. "If you examined the people in the household, their skin flora was drastically changed toward resistance. So, there is a pronounced effect of antibiotic use to society - almost a second-hand smoke effect," he said.
However, it is not just the taking of antibiotics that contributes to the problem, Levy said. It is trying to make the home a sterile environment. "The public has heard that bacteria are dangerous and seemingly out to get you.
So, we are inundated with antimicrobial products," he said. "At the same time this is occurring, the home is becoming a hospital because more hospitalized patients are receiving confined treatment at home."
In the attempt to get rid of bacteria with antibacterial products, people are eliminating the weaker bacteria and allowing the stronger to survive and grow. Again, these bacteria could be multi-resistant. "You cannot sanitize the environment. Bacteria are going to come back. What is unknown is what kinds of bacteria will come back."
Several tactics are being tried to overcome the problem, Levy said. In some cases, shorter courses of antibiotics are being used. Some hospitals are encouraging the cyclic use of antibiotics - changing the formulary to give a breather for drugs that have developed some resistance. Education is playing a role for both patient and prescriber. It is important for patients to understand when antibiotics are used and that they must finish the course and not stop because they feel better. Microbiologists also need a better understanding of bacteria and how they develop and transfer resistance.
Finally, new antibiotics are needed that are not susceptible to resistance. "But no new antibiotic is going to last long unless it is used prudently," Levy warned.
"The underlying message for all of us is that we need to give a break to susceptible bacteria. Let them come back. They are our allies, not our foes. That will only occur when we stop using antibiotics as imprudently as we are now," Levy said.
For more information:
- Levy S. Multidrug resistance: What, where and why? Presented at the 57th annual meeting of the American Academy of Dermatology. March 19-24. New Orleans.
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