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Tag words: antibiotic, antimicrobial, antibiotic resistance, penicillin, Fleming, methicillin, vancomycin, MRSA, VRE, ESBL, horizontal gene transfer, HGT, antibiotic sensitivity, zone of inhibition.









Kenneth Todar currently teaches Microbiology 100 at the University of Wisconsin-Madison.  His main teaching interest include general microbiology, bacterial diversity, microbial ecology and pathogenic bacteriology.

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Bacterial Resistance to Antibiotics (page 4)

(This chapter has 4 pages)

© Kenneth Todar, PhD

Societal, medical and agricultural practices that lead to antibiotic resistance

In the face of a microbe's inherent ability to develop antibiotic resistance, many societal. medical and agricultural practices contribute to this process, foremost of which are discussed below.

Antibiotics in food and water
Prescription drugs are not the only source of antibiotics in the environment. In the United States, antibiotics can be found in beef cattle, pigs and poultry. The same antibiotics then find their way into municipal water systems when the runoff from housing facilities and feedlots contaminates streams and groundwater. So it's a double hit: we get antibiotics in our food and drinking water, and we meanwhile promote bacterial resistance. Routine feeding of antibiotics to animals is banned in the European Union and many other industrialized countries. Maybe they know something we don't.

Indiscriminate use of antibiotics in agriculture and veterinary practice
The non-therapeutic use of antibiotics in livestock production makes up at least 60 percent of the total antimicrobial production in the United States. Irresponsible use of antibiotics in farm animals can lead to the development of resistance in bacteria associated with the animal or with people who eat the animal. Such resistance can then be passed on to human pathogens by mechanisms of HGT.

Of major concern is the use of antibiotics as feed additives given to farm animals to promote animal growth and to prevent infections (rather than cure infections). The use of an antibiotic in this way contributes to the emergence of antibiotic-resistant pathogens and reduces the effectiveness of the antibiotic to combat human infections.

Antibiotic resistance in genetically modified crops

Antibiotic-resistance genes are used as "markers" in genetically modified crops. The genes are inserted into the plant in early stages of development to in order to detect specific genes of interest . e.g. herbicide-resistant genes or insecticidal toxin genes. The antibiotic-resistance genes have no further role to play, but they are not removed from the final product. This practice has met with criticism because of the potential that the antibiotic-resistance genes could be acquired by microbes in the environment. In some cases these marker genes confer resistance to front-line antibiotics such as the beta-lactams and aminoglycosides.

Inappropriate use of antibiotics in the medical environment
One problem is the casual use of antibiotics in medical situations where they are of no value. This is the fault of both health care workers and patients. Prescribers sometimes thoughtlessly prescribe 'informed' demanding patients with antibiotics. This leads to use of antibiotics in circumstances where they are of not needed, e.g. viral upper respiratory infections such as cold and flu, except when there is serious threat of secondary bacterial infection. Another problem is patient failure to adhere to regimens for prescribed antibiotics.

Patients and doctors need to realize their responsibility when they begin an antibiotic regimen to combat an infectious disease. There are several measures that should be considered.

� Patients should not take antibiotics for which there is no medical value (corollary: doctors should not prescribe  antibiotics for which there is no medical value).

� Patients should adhere to appropriate prescribing guidelines and take antibiotics until they have finished.

� Patients should be give combinations of antibiotics, when necessary, to minimize the development of resistance to a single antibiotic (as in the case of TB).

� Patients need to be given another antibiotic or combination of antibiotics if the first is not working.

Combating antibiotic resistance

The following are recommendations to combat the development of antibiotic resistance in bacteria and other microorganisms.

Search for new antibiotics. To combat the occurrence of resistant bacteria, biotechnology and pharmaceutical companies must constantly research, develop and test new antimicrobials in order to maintain a pool of effective drugs on the market.

Stop the use of antibiotics as growth-promoting substances in farm animals. Of major concern is the use of antibiotics as feed additives given to farm animals to promote animal growth and to prevent infections rather than cure infections. The use of such antibiotics contributes to the emergence of antibiotic-resistant bacteria that threaten human health and decreases the effectiveness of the same antibiotics used to combat human infections.

Use the right antibiotic in an infectious situation as determined by antibiotic sensitivity testing, when possible.

Stop unnecessary antibiotic prescriptions. Unnecessary antibiotic prescriptions have been identified as causes for an enhanced rate of resistance development. Unnecessary prescriptions of antibiotics are made when antibiotics are prescribed for viral infections (antibiotics have no effect on viruses). This gives the opportunity for indigenous bacteria (normal flora) to acquire resistance that can be passed on to pathogens.

Finish antibiotic prescriptions. Unfinished antibiotic prescriptions may leave some bacteria alive or may expose them to sub-inhibitory concentrations of antibiotics for a prolonged period of time. Mycobacterium tuberculosis is a slow growing bacteria which infects the lung and causes tuberculosis. This disease kills more adults than any other infectious disease. Due to the slow growing nature of the infection, treatment programs last for months or even years. This has led to many cases on unfinished prescriptions and 5% of strains now observed are completely resistant to all known treatments and hence incurable.

Several other possible solutions have been proposed or implemented to combat antibiotic resistance.

In the pharmaceutical industry, past and current strategies to combat resistance have not been effective. Pharmaceutical companies are seeking new, less costly strategies to develop antibiotics.

A decrease in the number of prescriptions for antibiotics, especially in small children, is occurring.

Several countries such as the UK have regulations concerning the use of antibiotics in animal feed.

Large scale public health education efforts are underway to stress the importance of finishing prescriptions. Indeed, in many places, failure to finish tuberculosis prescriptions can result in jail time.

Summary

The discovery of antibiotics was a leap in modern medicine. They have been able to stop the growth or kill many different kinds of microorganisms. However, bacteria have proven to be much more innovative and adaptive than we imagined and have developed resistance to antibiotics at an ever increasing pace. Bad practices and mismanagement have only exacerbated the situation. We could soon return to a state of medical health that was as dire as that which occurred prior to antibiotic use. However, with more research, education of the public, and well thought out regulations, the problems
can be solved. Several strategies are currently used to find new antibacterial compounds and new strategies are in development and trial.

Not only is there a problem in finding new antibiotics to fight old diseases (because resistant strains of bacteria have emerged), there is a parallel problem to find new antibiotics to fight new diseases. In the past three decades, many "new" bacterial diseases have been discovered (E. coli O157:H7 gastric ulcers, Lyme disease, toxic shock syndrome, "skin-eating" streptococci). Already broad patterns of resistance exist in these pathogens, and it seems likely that we will soon need new antibiotics to replace the handful that are effective now against these bacteria, especially as resistance begins to emerge among them in the selective environment antibiotic chemotherapy.

It is said that the discovery and use of antibiotics and immunization procedures against infectious disease are two developments in the field of microbiology that have contributed about twenty years to the average life span of humans in developed countries where these practices are employed. While the greater part of this span in time is probably due to vaccination, most of us are either still alive or have family members or friends who are still alive because an antibiotic conquered an infection that otherwise would have killed them. If we want to retain this medical luxury in our society we must be vigilant and proactive We must fully understand how and why antimicrobial agents work, and why they don't work, and realize that we must maintain a stride ahead of microbial pathogens that can only be contained by antibiotic chemotherapy.




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Kenneth Todar has taught microbiology to undergraduate students at The University of Texas, University of Alaska and University of Wisconsin since 1969.

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