Paper Resistance Is Futile: The Dilemma of Antibiotic-Resistance Has man pinned the arm behind the back of Mother Nature? Have humans finally won this terrible pathogenic onslaught? Apparently not the Era of Epidemics has risen once again, and it looks as if humans are being bumped off the top of the food chain. Bacteria are mutating into antibiotic-resistant monsters. One of the main reasons why this is is because of the mass antibiotic misuse that increases the chance of bacterial DNA mutation. Bacteria, like all living things, must adapt to survive. DNA mutation is often a mechanism for adaptation. Our misunderstanding and ignorant use of this miracle drug diminishes the miracle and results in the outburst of anti-microbial invulnerability. What humans need is not another miracle drug, but knowledge on the prevention of antibiotic misuse. First, what are antibiotics? Antibiotics are chemical agents created by certain organisms, such as fungi or molds, which are capable of destroying or inhibiting the growth of bacteria. They act by interfering with the nucleic acid synthesis, peptidoglycan synthesis, protein synthesis, or the membrane integrity within the bacterial cell.[2] The prokaryotic bacterial cell does not have a nucleus, however; its genes are composed mainly of two elements: chromosomes and plasmids. Plasmids are circular pieces of genetic material that replicate complementary to the chromosome, and are often the carrier of mutated genes that bestow resistance to antibiotics.[3] Bacterial proliferation depends greatly on DNA and RNA synthesis. One of the enzymes involved in bacterial DNA replication is DNA gyrase. When DNA is being transcripted and replicated, the helix must be unzipped in order to be read, and it cannot bear any kinks or loops, lest it should be severely damaged or even broken by the tension of the twist and thus, cannot be read and transcripted. DNA gyrase relaxes the coiled strands and smoothes out the strand by breaking down the bond and releasing enzymes to relax the nick.[4] As we can see, DNA gyrase is essential to DNA replication. Some antimicrobial agents, such as Quinolone, inhibit bacterial DNA gyrase, rendering the chromosome unable to transcript and replicate.[1] Another target to attack is ribosomal RNA. Streptomycin, for example, prevents the initiation of protein synthesis, and causes the misreading of proteins being translated.[4] But when antibiotics are misused, a bacterium s genetic make-up will often mutate and cause the cell to become resistant to one or many types of antibiotics. When an antibiotic is used inappropriately, the bacteria that do not die will be trained to withstand that chemical. Or, when a single mutant bacterium survives the bactericide, it will multiply rapidly into a colony. There are three ways bacteria spread in such a swift and effective manner. One way is by conjugation, a means by which bacteria mate and distribute their genetic material. Its process is similar to that in the passing of a computer virus or STDs. In conjugation, a fine filament of protein called a pilus reaches to another bacteria and pulls them together. The donor duplicates its plasmids and passes it to the recipient so that both now carry the same copy of DNA, and become donors of the new resistant strain as they continue to multiply and colonize.[8] Another alternative is transduction, which resembles a mosquito in the passing of a disease. Bacterial viruses called bacteriophages inject its DNA into a bacterium where it can both lyse and destroy the cell, or reside in the chromosome. If it resides, the phage DNA matures within the cell, possibly carrying pieces of the bacteria s mutant chromosome.[8] Finally, there is transformation, involving mutated antibiotic-resistance genes hidden in entities called transposons. A transposon is analogous to head lice; they are smaller pieces of mobile DNA sequences capable of transferring themselves from one piece of DNA chromosome to another recipient. These transposons may also be picked up by a bacteriophage, but unlike plasmids, transposons alone cannot replicate, and must be sustained within a plasmid or chromosome.[8] Perhaps most ominous, some strains of Mycobacterium tuberculosis, have become resistant to a series of antibiotics.[11] So now just having enough money to buy antibiotics no longer guarantees a cure. Tuberculosis was once highly responsive to antibiotics. But this is no longer the case; the organism has become multi-resistant and more difficult to treat. Last-ditch antibiotics such as Vancomycin have also bred resistance, which is appearing more frequently in certain strains of enterococcus, a common gut bacterium. Enteroccocci usually do not cause life-threatening disease, but the gene for the resistance may spread to more deadly organisms like Staphylococcus aureus.[10] In 1992, 17 percent of the national cases of tuberculosis had erupted around New York City.[11] According to the World Health Organization, tuberculosis afflicts 7.5 million people, killing as many as 2.5 million people each year.[12] As the leading cause of death among infectious diseases, tuberculosis is particularly severe in AIDS patients, those who can’t afford medical care, and patients who disobey doctors.[10] Hundreds of misinformed people believe that antibiotics are the cure-all pill, taking the antibiotic without prescription for even the most trivial ailments such as a sore throat or the common cold. It must be stressed that antibiotics are used only to kill bacteria; a virus, which the antibiotic will not harm, causes the common cold. People are taking the medicine ineffectively and are merely setting themselves up for the breeding of antibiotic resistant bacteria. In Third-World countries, antibiotics are provided to treat vast amounts of people, but when in short supply, small amounts are given to reserve them for those who are in real need. Insufficient amounts and dosages cannot kill the entire infection, and not only are the people left to suffer, misuse is training the bacteria to become several times more resistant than before.[2] When a patient obtains a certain amount of antibiotic, the person must follow directions and never fall short on taking each and every pill as prescribed. It is best to avoid taking a particular antibiotic over a period of weeks or months; if an infection does not surrender to one antibiotic, then the patient should use two, three, or four simultaneously. Otherwise, the drug may select bacteria with resistance to different kinds of antibiotics. There are many incidences of multi-drug resistance in bacteria, but the most notorious was the triumph of Staph. Even though Penicillin was found to combat Staphylococcus back in 1947, within a decade the organism became resistant, and until recently, Vancomycin, the newest drug on the market, was the only cure for Penicillin-resistant Staphylococcus. It was soon discovered that Staphylococcus aureus, a rare strain of Staphylococcus, may be completely resistant to Vancomycin, and the numbers if infection will no doubt increase.[12] Staphylococcus is just one step away from total resistance; its infections are the cause of 13% of the nation s two million hospitalized infections each year. 260,000 people occupying our hospitals are because of this terrible infection; of these 260,000 infections, 60,000 to 80,000 people die each year; thus, 200 people each day (or 8 people every hour) die of a Staphylococcus infection.[12] If Staphylococcus becomes completely resistant to Vancomycin, death rates could approach even higher perhaps to that of the pre-antibiotic era. Antibiotics are vastly misused in agriculture and in para-veterinarial purposes. Streptomycin is sprayed onto fruits and vegetables as pest control. Antibiotics are added to animal feeds including dog and cat food as growth enhancers, which amount to four or five times more antibiotics than the amount used in the medical treatment of disease in animals.[2] As a result, the animals bacterial flora will certainly be comprised of antibiotic-resistant organisms, which are commonly excreted in their feces. Humans who are in constant contact with these animals will acquire the resistant bacteria and spread them among other people. In the past, animal products such as milk and meat are easily contaminated with Salmonella typhimurium, a bacterium known to be resistant to ampicillin, carbenicillin, tetracycline, streptomycin, and sulfisoxzole.[1] It is best to be assured that perishable products have undergone thorough pasteurization. Another major factor of bacterial resistance to antibiotics is during drug therapy, so it is very important that patients who have a serious contagion be quarantined, since outbreaks disperse quite efficiently throughout the hospital. This is because wards are overcrowded, and the intensive care units lack adequate isolation facilities for infected patients. Patients may also have a feeble lung, an open wound or burn, or an infected urinary bladder catheter, which allow the bacteria to enter at ease. The improper disposal or exposure to hazardous wastes because of poor hygiene and techniques will also create a problem, as well as patients who take an ample spectrum of antibiotics by self-medication, because the antibiotic may unknowingly serve as a mutagen for the bacteria. These situations must be prevented, for they can all lead to the spread of microorganisms. A more simple way to prevent the spread of most pathogens is to practice proper hygiene, such as washing hands with plenty of soap. Under normal circumstances, antibacterial soaps kill a much greater amount of bacteria than regular soap, though a statistical difference between two agents won t necessarily signify that one will be more effective than the other in clinical practice. In surgery for instance, the doctor must wash his hands twice or even three times in a very thorough manner, using clinical bactericidal soap, and then must douse his hands in an alcohol and iodine solution.[7] Alcohol is more actively effective than soap, for all soaps are weak antiseptics, which, after use, are incapable of self-sterilization. Some bacteria are even known to grow in disinfectant solutions, which thrive and become resistant to antibiotics. The solutions must have high levels of active ingredient or preservatives in order to avoid bacterial survival. Still, these non-irritant detergents are widely available and are able to cleanse a great amount of dirt from the skin, and it is a highly recommended procedure, which can significantly reduce the spread of harmful organisms.[6] Even though the knowledge of antibiotic resistant bacteria continues to rise, the relative numbers of cases in medical misuse will most likely increase as well. And though many more antibiotics are being created, the persistent bacteria proceed to resistant to all of them, especially in drug therapy. These super-bacteria are capable of spreading through communities at large. Though 40 million pounds of antibiotics are made annually in the US [2], new antibiotics are getting harder to find. One research approach involves the creation of drugs that inhibit the multiplication of plasmids, disabling bacterial resistance elements. The problem with this approach is that resistant genes may also reside in a transposon, thus curing of a plasmid cannot assure the deletion of the gene.[3] One solution to this would be to develop compounds that interfere with the replication of transposons.[1] In another approach, scientists have found certain insect and frog skins to bear substances called magainins, which have an antibiotic-like effect.[3] Even in our own white blood cells particularly the neutrophils have defensins fighting for fungi, virus, and bacteria.[8] Unfortunately, not only are these substances extremely scarce, they are also made of proteins and may be recognized as a foreign substance to our immune system, and therefore be removed. Again, these substances may also select mutants resistant to them. Everyone should be concerned, or at least informed about the existence of antibiotic resistance. Not only concern, but valid information of the way antibiotics work and of the consequences of relying too much on a good thing, for the majority of antibacterial resistant organisms arise from the abuse and prolonged use of antibiotics selecting bacteria with mutated resistant genes. New and effective antibiotics are getting harder and harder to find. However, most antibiotics, even old ones, can and do have some effective uses today. The important thing is for these valuable drugs to be used widely and in a very proper manner, so as to limit the chances of natural selection of resistant strains. Prevention can be as simple as practicing proper hygiene, avoiding long-term use of a single antibiotic, the quarantine of contagious hospital patients, limiting the use of antibiotics only to medical uses, distributing the antibiotics at sufficient amounts, and merely following the directions of your doctor. As a final word of precaution, man should never assume that he could completely harness Mother Nature. As Ian Malcom says in Michael Crichton s novel, Jurassic Park, Life finds a way. Works Cited 1. Microbial Survival in the Environment. E. Mitscherlich and E.H. Marth Springer-Verlag. Berlin, Heidelberg, New York, Tokyo 1984 2. The Antibiotic Paradox: How Miracle Drugs Are Destroying the Miracle. Stuart B. Levy, MD. Plenium Press, New York and London 1992 3. Gootz, T.D. 1990. Discovery and Development of New Antimicrobial Agents. Clinical Microbiology Reviews vol. 3; pp. 13-31 4. Understanding Antibacterial Action and Resistance; Second Edition. A.D. Russell and I. Chopin. Ellis Horwood, London and New York 1996 5. Carpentier, B. and Cerf, O. 1993. Biofilms and Their Consequences with Particular Reference to Hygiene in Food Industry. Journal of Applied Bacteriology vol. 75; pp. 499-511 6. Disinfectants: Their Use and Evaluation of Effectiveness. C.H. Collins, M.C. Allwood, Sally F. Bloomfeild, A. Fox. Academic Press, Condon, New York 1981 7. Handbook of Disinfectants and Antiseptics. Joseph M. Asanzi. Marall Drekker, Inc., New York, Basel, Hong Kong 1996 8. The Control of Antibiotic Resistant Bacteria. Stuart Harris and Harris. Academic Press, London and New York, 1982 9. Jurassic Park. Michael Crichton. Ballantine Books, New York, NY, 1993; p. 322 10. http://news3.news.wisc.edu/038badbugs/index.html funded by NISE AltaVista Search Engine: antibiotic resistance 11. http://www.accu.nl/ewi-enare/enare AltaVista Search Engine: antibiotic resistance 12. http://www.healthsci.tufts.edu/labs/Sblevy/home.html AltaVista Search Engine: antibiotic resistance 343
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