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The Evolution of Antibiotic-Resistant Bacteria

Since antibiotics, such as penicillin, became widely available in the 1940s, they have been called miracle drugs. They have been able to eliminate bacteria without significantly harming the other cells of the host. Now with each passing year, bacteria that are immune to antibiotics have become more and more common. This turn of events presents us with an alarming problem. Strains of bacteria that are resistant to all prescribed antibiotics are beginning to appear. As a result, diseases such as tuberculosis and penicillin-resistant gonorrhea are reemerging on a worldwide scale (1).

Resistance first appears in a population of bacteria through conditions that favor its selection. When an antibiotic attacks a group of bacteria, cells that are highly susceptible to the medicine will die. On the other hand, cells that have some resistance from the start or acquire it later may survive. At the same time, when antibiotics attack disease-causing bacteria, they also attack benign bacteria. This process eliminates drug-susceptible bacteria and favors bacteria that are resistant.

Two things happen, populations of non-resistant and harmless bacteria are diminished, and because of the reduction of competition from these harmless and/or susceptible bacteria, resistant forms of disease-causing bacteria proliferate. As the resistant forms of the bacteria proliferate, there is more opportunity for genetic or chromosomal mutation (spontaneous DNA mutation (1)) or transformation, that comes about either through a form of microbial sex (1) or through the transference of plasmids, small circles of DNA (1), which allow bacteria to interchange genes with ease.

Sometimes genes can also be transformed by viruses that can extract a gene from one bacterial cell and inject it into another (3). In this last situation, resistant genes become embedded in small units of DNA, called transpons, which can easily move into other DNA molecules. Making matters worse, many bacteria have specialized transpons called integrons, which act like flypaper when catching new genes (3). These mutations, no matter what process that has led to their occurrence, block the action of antibiotics by interfering with their mechanism of action (1). Currently, antibiotics attack bacteria through one of two mechanisms.

In both mechanisms the antibiotic enters the microbe and interferes with production of the components needed to form new bacterial cells. Some antibiotics act on the cell membrane, causing increased permeability and leakage of cell contents. Other antibiotics interfere with protein synthesis in cells. They block one or more of the steps involved in the transformation of nucleic acids into proteins. Any mutation that would prevent the action of antibiotics, but not at the same time provide a selective advantage to the bacteria, would be one that interfered with the bacterias ability to reproduce.

If this were to occur, then any selective advantage would be negated by the cells inability to take advantage of the diminished competition caused by the death of susceptible bacteria. This would be likely to occur in reaction to an antibiotic that interfered with protein synthesis, since it would also impact on the chain of reactions that occurs in the transformation of DNA to ribosomes and RNA and eventually the proteins necessary for the fission or reproductive process to occur. If one were able to control all the variables, there is no reason to believe that certain bacteria would be more likely to mutate to resistant forms than others.

It is normally not the type of organism that dictates its propensity towards mutation. This is normally dictated by the variables or changes in the bacterias immediate environment. The advantages of using multiple antibiotics in combination are as follows: for broad coverage in a very sick patient who has an infection of unknown etiology, to prevent the emergence of resistance, and if the two or more drugs in combination achieve a greater effect than simply adding their effects together (4).

In all cases, the use of multiple antibiotics does increase the risk of toxicity, in the individual who is the recipient of the therapy, and should be used tentatively and carefully. It has been shown, that exact adherence to a prescribed drug regimen plays a huge role in the prevention of antibiotic-resistant bacteria (1 & 2). The sporadic use of antibiotics provides the optimum setting for resistant strains of bacteria (1) because it creates the ideal environment for the selection of these strains.

That is, an environment where the particular bacterial strain is never eliminated but just weakened enough to selectively mutate. In theory, therefore, there is some justification for physicians not prescribing medications to patients they deem to be at high risk of non-compliance with a drug regimen. This is especially true in the case of HIV positive patients, who are extremely susceptible to a broad range of opportunistic bacteria and viral infections.

Non-compliance with the drug regimen not only endangers the individual not complying, but other patients that could eventually benefit from the use of those specific drugs. Genetic mutations in bacteria occur readily. So readily, that frequently, bacteria will gain a defense against an antibiotic by taking up resistant genes from other bacterial cells in the vicinity of and outside the body. Therefore, a resistance built up by one individual may be passed along and endanger the lives of many individuals. The only problem inherent, in denying patients deemed unreliable access to certain drugs, is in the word deemed itself.

Although there have been studies, and it is reasonable to assume that intravenous drug users would be more likely not to follow a prescribed drug regimen, or any regimen, can we deny treatment to a patient just because he or she is an intravenous drug user. Even amongst this population, there must be some people who will follow a prescribed drug regimen. If the criteria for physicians is that denying the few will benefit the many, there is some justification for this course of action as a societal prerogative.

Many of the same drugs prescribed for human therapy are widely used in animal husbandry and agriculture. More than 40% of the antibiotics manufactured in the U. S. are given to animals (3). Although some of that amount is used to treat or prevent infection, most is mixed with feed to promote weight gain and growth. In this use, amounts of antibiotics too small to combat infections are delivered over long periods of time. Long-term exposure to low doses of antibiotics is the perfect formula for selecting bacteria for drug resistance.

The animals then pass these resistant microbes to caretakers and people who prepare and consume undercooked meat. On the other hand, if the use of antibiotics in animal feed were curtailed then the cost of meat would inevitably rise. In my opinion, the rise of the price of meat does not concern me as much as the exposure, of any segment of the population, to resistant strains of bacteria. In the case of the weight of animals, regulators should give more weight to public health. Telling people how long and at what temperature to cook meat is just not enough.

There must be some regulation as to the use of antibiotics as a product enhancer. As most people know, it normally costs pharmaceutical companies a huge amount of money to develop and bring a new drug to the market. The only way to recoup this investment is the widespread prescription and subsequent use of these drugs. This is just the scenario that leads to overuse and the eventual obsolescence of this very same drug. Furthermore, many of the same drugs are available over-the-counter in developing and third world countries, making them even more accessible and subsequently overused.

From the perspective of the pharmaceutical companies, both the obsolescence and overuse scenarios are not economically desirable. Since, in most of the industrialized nations, the bulk of the development and marketing of new drugs is left to private enterprise, this ambiguity will continue to exist. On the other hand, regulators could make it less expensive to bring a new drug to market, or the government could underwrite some of the costs of this development. As a result, this would diminish the underlying reasons for this ambiguity, which is driven by the need to recoup investment and make a profit for shareholders.

All of this leads to the conclusion, that there is overuse and even abuse of antibiotics. Awareness and knowledge among patients and physicians are the most important steps in ending this abuse. People must be made to recognize that most bacteria are natural and useful. In fact, bacteria often protect us from disease, because they compete with and limit the proliferation of pathogenic bacteria. People should also be made aware of the fact that although antibiotics are needed to control bacterial infections they can have undesirable effects on total microbial ecology (2).

They produce long-lasting change in the kinds and proportions of various bacteria- both in the antibiotic-resistant and antibiotic-susceptible kinds. This is true not only in the specific individual being treated but in the environment and society as well. Antibiotics should be used only when they are needed and should not be administered for suspected viral infections. Knowledge is a powerful thing; therefore, if I know the limitations of antibiotics I would not request them if they had no application to my illness.

After all, being sick and having a bacterial infection is not one and the same thing. I would certainly forego therapy that had no possible application to my specific illness. As to the issue of a waiting period before antibiotic therapy is initiated, unless the etiology of the illness is immediately recognizable and determinable, I think a waiting period is a good idea. On the other hand, some effort should be made by physicians and laboratories to isolate the cause of the illness before a week or two passes.

Maybe there should be some emphasis on the development of quicker and more precise analytical tools. The time has come to recognize bacterial resistance as a global problem. Reversal of the trend towards antibiotic resistance requires a broad awareness of the consequences of antibiotic overuse. The perspective must go beyond curing bacterial disease right now (3). This understanding must extend to the need to preserve microbial communities that are susceptible to antibiotics, so they will always be able to out-compete resistant strains.

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