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Perfect Drugs: Reaction/Reflection Pieces

Want Cipro[1] prescriptions?

by

Tharaphi Than

Escalating Demands for Cipros

Cipro is one of only three antibiotics approved to treat anthrax, and it is a drug that has been used for over a decade to treat a variety of serious infections. It has now become the first antimicrobial approved in the United States to protect people against a possible biological weapon.[2] After the recent series of anthrax attacks, many primary care physicians in the United States are under intense public pressure to provide Cipro prescriptions. In fact, the numbers of such prescriptions jumped by 50% in the first month after the Sept. 11 attacks, and nearly tripled in New York City. Also, since some drug companies have made it possible to buy Cipro online without prescriptions, its sales have been skyrocketing in the United States.[3] Why are people so anxious to take antibiotics even before they contract a disease? Can antibiotics be effective if taken prophylactically, as a preventive? Given that antibiotic resistance is one of the world's most pressing public health problems, as virtually all important bacterial infections in the United States and throughout the world are becoming increasingly resistant to antibiotics, we must ask to what extent the prophylactic use of antibiotics may cause problems for humans.[4] People should be aware of the threats posed by antibiotic resistance and start thinking through the consequences of taking antibiotics offhandedly. In this paper, I will give a brief history of antibiotics and discuss how bacteria have developed resistance over time, and the underlying reasons for their resistance. At this time in human history, when people in the United States as well as across the world feel most vulnerable to bioterrorism, their prophylactic use of antibiotics might increase the rate of antibiotic resistance, and more than ever, a global solution is called for to slow down the rate of increase of such resistance, if not to stop it entirely.

Origin of antibiotics

An antibiotic is generally defined as a type of antimicrobial agent made from a mold or a bacterium, a substance that kills, or slows the growth of, other microbes, specifically bacteria. Antibiotics are regarded as a medical treasure, perhaps the most important therapeutic discovery in the history of medicine. From penicillin, which was discovered by Alexander Fleming in 1928, to the most recent antibiotic on the market, Zylox, a variety of antibiotics for different bacteria have been developed, and people in every corner of the world have been using them. They first appeared as over-the-counter drugs, but free access led to their use for diseases not responsive to antibiotics. As Fleming warned, the misuse of drugs arose, forcing lawmakers to change antibiotics from over-the-counter to prescription drugs.[5]

Antibiotics are generally active only against bacteria and not against fungi, protozoa or viruses. They are widely used for bacterial infections and diseases, from ear infections to urinary tract infections, but they have no effect on viral infections, such as sore throat, the common cold, or bronchitis. The reason is that antibiotics act against physiological and biochemical pathways that are specific to bacteria, and not to viruses, since viruses have different biochemical pathways.[6]

Bacteria have a thick layer of cell wall made up of protein to resist heat, moisture, and acids. They also have genes, or blueprints to reproduce, which are made up of DNA. Antibiotics fight bacteria by attacking the cell wall, the genes, or the proteins.[7] Viruses cause infections that go away on their own, and antibiotics have no effect on them.

How do bacteria develop resistance?

Antibiotic resistance occurs when bacteria change in some way that reduces or eliminates the effectiveness of drugs, chemicals, or other agents designed to cure or prevent infections. Resistance is a property of bacteria that is developed through mutation, which is a change in the DNA sequence. Mutations that confer resistance modify or eliminate a target, and they occur spontaneously in bacterial DNA. For example, bacterial structures can change by mutation so that antibiotics cannot be taken up, or bacteria produce enzymes that counteract the effect of antibiotics.[8]

Under optimal temperature, pH, and nutrients compositions in a habitat, one resistant bacterium can reproduce itself in less than an hour. Thus, in a matter of hours, thousands of copies of the original bacterium, all having received the resistant gene, can emerge.[9] Also, through some kinds of contact such as conjugation, transposition, transduction, and transformation, bacteria residing in very different places can easily pick up antibiotic resistance genes.[10] Examples of clinically important microbes that are rapidly developing resistance to available antimicrobials include bacteria that cause pneumonia; ear infections; meningitis; skin, bone, lung, and bloodstream infections; urinary tract infections; food-borne infections; and infections transmitted in a health care setting. Up to 30% of bacteria S. pneumoniae, which cause pneumonia, ear infections and meningitis, are no longer susceptible to penicillin, and multi-drug resistance has become common.[11] In the United States, over the past 5 years, the rate of penicillin resistance has increased by more than 300%, and the rate of cefotaxime resistance has increased by more than 1000%. The only remaining antibiotic that is effective against all pneumococci is vancomycin.[12]

And of course, the use of antibiotics selects bacteria with antibiotic resistant genes for survival so that increasing the use of antibiotics will lead to an increase in the reproduction of resistant bacteria.[13] Due to the overuse, misuse and abuse of antibiotics, well-known illnesses once thought to be under control are re-emerging. There has been a general resurgence of infectious diseases throughout the world, including significant outbreaks of cholera, malaria, yellow fever, dengue, and diphtheria.[14] Yet treatments have grown increasingly ineffective owing to the speed with which mutant organisms develop resistance. In India, the past five years have seen 20% of typhoid isolates become resistant to ciprofloxacin, a relatively recent and expensive third-line drug, and around 15,000 people die every year from that disease, against which no antibiotic is now effective.[15]

Antibiotic resistance threatens to emerge as a devastating, nearly uncontrollable health problem worldwide. Multi drug-resistant tuberculosis (MDR-TB) is no longer confined to any one country or to those co-infected with HIV, but has appeared in every country. TB kills two million people each year, and pathologies of multi-drug resistant TB (MDR-TB) have been identified in Eastern Europe, Africa, Asia, and Latin America. MDR-TB is among the most worrisome elements of the pandemic of antibiotic resistance, because TB patients who fail treatment have a high risk of death.[16] Because of the evolution of resistance, drugs for TB, which used to cost as little as US$ 20 must now be replaced with drugs a hundred times more expensive. Other diseases are likewise growing increasingly impervious.[17] One fifth of deaths worldwide are due to infections, according to the Centers for Disease Control, and with increasing bacterial resistance, the cost of addressing new and old infectious diseases will be enormous.

Contributing factors to antibiotic resistance

The over-prescribing of antibiotics is one of the main reasons contributing to antibiotic resistance. In providing health care, doctors sometimes prescribe antibiotics for viral infections, but those drugs are wasted, since antibiotics have no effects on viruses. A recent study has revealed that of the 150 million prescriptions written in the United States in 1999, about one third should have never been written.[18] According to Dr. Jeffry A. Linder of Massachusetts General Hospital and Dr. Randall S. Strafford of Stanford University, in 2,244 visits to the doctor examined in the study, 73% of patients were given antibiotics, 68% of which were the non-recommended ones. Just 5% to 17% of adults suffering from sore throats have bacterial infections that require antibiotics,[19] and some bacterial diseases will clear up in the same amount of time with or without antibiotics. But when sufferers see their primary care doctors, a new study reports, almost three-quarters of them will be given drugs right away.[20]

Due to the fact that doctors over-prescribe antibiotics, antibiotics are sometimes referred to as the "drugs of fear," because they can be used to mitigate the physicians' fear of failing to provide patients with the very best care. Patients, especially parents of sick children, have a fear of the unknown, and they expect a rapid cure. Those fears and expectations are fostered by exaggerated stories in the news media of dread diseases and new miracle cures. Pharmaceutical advertisements and sales representatives also encourage a wide spectrum of coverage.[21]

The introduction of Health Maintenance Organizations (HMOs) also affects the medical practices of doctors. Even though the goal of HMOs is to lower the health care costs while at the same time providing good care, this system encourages the overuse of antibiotics, since doctors are paid less money per patient, and are under pressure to see more patients. Writing a prescription right away or giving one on telephone saves the doctor's time, and in those ways, they are able to see more patients. In addition, most parents now have prescription plans as part of their HMOs, and these plans make antibiotics (even expensive ones) very affordable, again escalating the use of antibiotics.[22] Patients, however, often fail to complete the course of antibiotic treatment, which allows bacteria more easily to develop resistance against the prescribed antibiotic.

Misuse of antibiotics caused by poverty and inadequate access to drugs is another factor increasing the resistance rate. A lack of the resources by governments in developing countries needed to provide the poor with adequate infrastructure such as drainage systems, sanitation, and a good health care system exacerbates the outbreak of infectious diseases. The urban migration, immigration, and widespread travel encourage the increasing prevalence of diseases, and there also can occur exchange of antibiotic resistant strains of bacteria between people when such diseases are not properly cured.[23] Like trade and commerce, bacteria have taken advantage of globalization, and now they reach communities across the globe, from California to tiny atolls in mid-Pacific.

Not only does living in infectious-diseases-prone habitats speed up the rate of antibiotic resistance, but so also does having no choice over antibiotics and no knowledge of their proper use. In many African, Asian, and Latin American countries, antibiotics are readily available on demand from hospitals, pharmacies, patent medicine stalls, roadside stalls, and hawkers.[24] Due to inadequate supplies and facilities at government hospitals and drugstores, people choose to self-medicate, and this practice gives drug vendors an opportunity to promote sales and sometimes treatments, using multiple combinations of drugs. As well, substandard antibiotics have often been detected in these countries, and the poor have often had to use expired or counterfeit drugs when they cannot afford the cost of recommended ones. The misuses of antibiotics I have mentioned create health problems in relation to antibiotic resistance, increasing the costs of health care and also increasing burdens of poverty.

In addition, antibiotics are widely misused in agriculture. They are not only given to stimulate animal growth, but they are also even injected into some plants to control bacterial infections.[25] A broad range of animals receive antibiotics; half of the antibiotics (by weight) used in the United States are used for animals. For example, the poultry industry once used penicillin and tetracycline universally for growth promotion. As well, around 10% of cows in a dairy suffer from Mastitis on a given day, and antibiotics, like ciprofloxacin, are used to treat infections in such quantities that they often prevent milk from being potable for a week.[26] Stanford University microbiologist Stanley Falkow has said that roughly half of the estimated one million metric tons of tetracycline and other antibiotics in the biosphere have entered through the food supply.[27] The antibiotic resistance genes selected in livestock can be transferred through food-borne bacteria or other means to the human intestine, and thus have been linked to drug-resistant infections in people, and even to a number of deaths.

Are there any solutions to problems posed by antibiotic resistance?

Life is, overall, a struggle to main a balance between cost and benefit. Antibiotics were at first clearly beneficial to life, since many people could enjoy longer lives because of them. Yet bacteria soon started developing resistance to antibiotics, and in this way antibiotics carry a price, which is life itself, since many people have died every day of once preventable bacterial infections. So the question is who is winning the contest-bacteria or antibiotics? The situation is such that antibiotic resistant bacteria are now outgrowing antibiotic-susceptible bacteria. Only if we can do something in our use of antibiotics will antibiotic resistance bacteria become a smaller proportion of the total population.[28]

"If nothing is done in this decade to tackle the problem, the window of opportunity may be closed forever," says the World Health Organization (WHO). The effect of antimicrobial resistance, the report emphasizes, "is that it can reduce the curative power of once life-saving medicines to that of a sugar pill".[29] In other words, if we cannot slow the current rate of antibiotic resistance, the victory of humans over the bacterial world will be turned over to superpower resistant bacteria.

The development of new drugs nowadays often seems "something," according to the WHO statement, since it is the most effective strategy to fight against antibiotic resistant strains. However, strains resistant to the new antibiotics are likely to develop eventually. Therefore, a more long-term solution includes the more prudent use of the antibiotics currently available. In terms of long term strategies, the following needs should be addressed. Awareness should be raised among the general public so that people can use antibiotics wisely. Educational campaigns on the use and abuse of antibiotics should be run, targeting heath workers, vendors, and consumers. Global institutions such as the United Nations, World Health Organization, and other non-governmental organization should provide money to government and local communities for educational campaigns. Given enough money, time, and other resources, education, which is the most important element through which to bring about a change in the behavior of people, can be successfully implemented in many countries.

But education campaigns will not be effective if global communities fail to address the underlying issues concerning infectious diseases, such as declining economics, and the same factor leading the misuse of antibiotics, such as inadequate facilities and services that governments provide to the public. Alleviating poverty to raise the living standard of the poor is another priority we must address in attacking the antibiotic resistance problem. Countries are not separated any more, and rich and poor countries alike should address the issues of poverty together. Governments everywhere should improve their primary health care systems, provide better sanitation systems, and improve education in general so that people can make more informed decisions. Centralized control over the use of drugs also needs to be implemented and poor countries need help and facilitation through global institutions. Trying to address the issue of antibiotic resistance is like addressing the problem of global warming. Individual efforts to stop the rate of warming will not solve the problem. We share this Earth, and we must come together to protect our earth from overheating by greenhouse gases. To do so, each and everyone of us needs to change our lifestyles in consuming energy, and only a collective movement across nations can bring any solution. Likewise, we literally share bacteria, and one person's change in behavior using antibiotics will not stop the problem. Competing with each other to stockpile cipros will not help us fight against anthrax. But coming together to change our practices using antibiotics will, in the long run, help us more effectively fight all diseases.

Acknowledgement

I would like to thank Kevin Crim in writing lab for his help in editing.

Works Cited

[1] A trademark used for the drug ciprofloxacin, an oral antibiotic, which is used against serious bacterial infections of the skin or respiratory tract of urinary tract or bones or joints back

[2] "FDA, U.S. Department of Health and Human Services Food and Drug Administration." Hypertext created by clb 2000-OCT-17. retrieved on November 20 2001 back

[3] "Lexis-Nexis: Academic Universe." Oransky, Ivan. Antibiotic overuse can silence medicine's big guns. USA TODAY November 15, 2001, Thursday. Retrieved on November 19, 2001. back

[4] [5] "Center for Disease Control" Emerging Infectious Diseases Retrieved on October 15 2001. back

[6]Levy, Stuart B.. 1992. "The Antibiotic Paradox: How Miracle Drugs Are Destroying the Miracle." Plenum Press, New York. pp: 40 back

[7] [8] [9]Offit, Paul A.. "Breaking The Antibiotic Habit." New York : John Wiley & Sons, Inc. (US).back

[10] Levy, Stuart B.. 1992. "The Antibiotic Paradox: How Miracle Drugs Are Destroying the Miracle." Plenum Press, New York. pp:83 back

[11]U.S. Congress, Office of Technology Assessment. 1995. "Impacts of Antibiotic-Resistant Bacteria.", OTA-H-629 (Washington, DC: U.S. Government Printing Office). back

[12] Center for Disease Control. Target Area Booklet: Addressing the Problem of Antimicrobial Resistance Retrieved on November 21, 2001. back

[13] U.S. Congress, Office of Technology Assessment. 1995. "Impacts of Antibiotic-Resistant Bacteria.", OTA-H-629 (Washington, DC: U.S. Government Printing Office). pp: 45 back

[14] Office of Science and Technology Policy. Global Microbial Threats in the 1990s Retrieved on October 19, 2001. back

[15] "When Germ Becomes Supreme." Financial Times Information, June 3, 2001. back

[16] Levy, Stuart B.. 1992. "The Antibiotic Paradox: How Miracle Drugs Are Destroying the Miracle." Plenum Press, New York. back

[17] The World Health Organization. "Overcoming Antimicrobial Resistance: World Health Report on Infectious Diseases 2000." Retrieved on October 19, 2001. back

[18] Saint John Times Globe back

[19] [20] Nagourney, Eric. "Vital Signs: Consequences: A Regimen for Resistance." The New York Times. September 18, 2001. back

[21] Kim, J.H., and H.A. Galis. 1989. "Observations on spiraling empiricism: Its causes, allure, and perils, with particular reference to antibiotic therapy." American Journal of Medicine. 87: 201-206 back

[22] Offit, Paul A.. "Breaking The Antibiotic Habit." New York : John Wiley & Sons, Inc. (US). pp:142 24 back

[23] [24] Okeke, I.N., Lamikanra, A., and Edelman, R. "Socioeconomic and Behavioral Factors Leading to Acquired Bacterial Resistance to Antibiotics in Developing Countries." Emerging Infectious Diseases, Vol. 5, No. 1, January-February 1999, pp: 18-27 back

[25] Levy, S. B., 1992. "The Antibiotic Paradox." Plenum Press: New York.back

[26] "When Germ Becomes Supreme." Financial Times Information, June 3, 2001. back

[27] Mlot, Christine. "Antidotes for antibiotic use on the farm." BioScience v. 50 no11 (Nov. 2000) p. 955-60 back

[28] U.S. Congress, Office of Technology Assessment. 1995. "Impacts of Antibiotic-Resistant Bacteria." OTA-H-629 (Washington, DC: U.S. Government Printing Office) pp:45 back

[29] Datta Anirudha. "Drug resistant bacteria, killer at large." The Hindu. July 26, 2001 back

If you have any questions or comments, email Tharaphi Than.