Mohandes 1 Samir Mohandes Dr.

Jerzy Rozenblit HNRS 195I 006-CLQ (79539) 12 November 2010 Infectious Disease and Antibacterial Resistance: Choosing the Lesser of Two Evils Since the discovery of penicillin by Alexander Fleming in 1928, the implementation of antibiotics has irrevocably altered the medical world, changing the both the means and strategies by which doctors have attempted to tackle almost all conceivable varieties of ailments. In fact, it is estimated that penicillin alone has saved at least 200 million lives since 1942, when it was first used in the medical field. (Alexander Fleming). Antibiotics seek to destroy the bacterial cells responsible for infectionsor at least prevent them from multiplying long enough for the bodys white blood cells to get the job doneat minimal or no disturbance to the bodys own cells; they are a selective poison in this sense. In doing so, antibiotic technology has been the driving force behind almost too many medical victories to count. As a result, almost every bacteria-based diseasebe it tuberculosis, meningitis, salmonella, or syphiliscan be treated by the use of antibiotics. The immediate implications of such medical technology seem almost too good to be true: antibiotics represent affordable, widely distributable, highly effective means of combating infection in disease, be it in individuals or across entire populations. Standards of living and life expectancies have skyrocketed worldwide since the inception of antibiotic use, while disease fatality rates have plummeted. Penicillin was even ranked one of the ten most important inventions of all time in a 2010 poll of British consumers, nestled comfortably between the

Mohandes 2 telephone and the iPhone for the number seven spot (some perspective for the morbidly curious: the wheel ranked first, space travel ranked thirty-ninth, sliced bread ranked seventieth, and the cheese grater ranked eighty-eighth) (Britons Vote for the iPhone). Undoubtedly, the advent of antibiotics have left an overwhelmingly positive mark on the modern worldsuch a significant one, in fact, that they have been used too often. And that is where the disaster begins. Less than one decade after penicillins heroic arrival onto the medical scene, an outbreak of Staphylococcus aureus was observed in hospitals all across England. This particular strain of the dreaded staph infection, the leading cause of infections developed in hospitals, proved invulnerable against all administered penicillin. As Otto Cars and Per Nordberg from the Swedish Institute for Infectious Disease Control described it, a striking example of biological evolution had begun: bacterial strains with natural and acquired resistance were being selected as a result of the use of antibiotics (Cars and Nordberg 103). In other words, at some point during the mass reproduction of the Staphylococcus aureus bacteria, a genetic mutation occurred that produced antibiotic-resistant offspring. While the rest of the Staphylococcus aureus bacteria was eradicated by the antibiotics, this particular bacterium was able to survive the penicillin treatments, and had gone on to reproduce again, passing on its antibiotic-resistant genome to the next generation of bacteria, all of which reproduced once more, producing another generation of antibiotic-resistant bacteria, and so on. Exacerbated by the hasty reproductive rates of single-cell bacteria, soon enough there were billions upon billions of antibiotic-resistant Staphylococcus aureus bacteria present, none of which could be treated using existing antibiotics. The Staphylococcus aureus incident in the English hospitals proved only to be a precursor for many more resistance cases to come. In fact, the current pandemic of Methicillinresistant Staphylococcus aureusmore commonly known as MRSAcan be seen as a more

Mohandes 3 dangerous, more contagious, and more resistant evolutionary form of the Staphylococcus aureus bacteria observed in the English hospitals in the 1940s. Cars and Nordberg further describe the magnitude of the MRSA pandemic in a 2005 issue of the International Journal of Risk Safety in Medicine: Since the 1980s the frequency of isolates of MRSA among Staphylococcus aureus has increased from close to zero to nearly 70% in Japan and the Republic of Korea, 30% in Belgium and around 40% in the United Kingdom and the United States. It was discovered that mechanisms of resistance could be spread horizontally between different strains and different bacteria and that, consequently, clones with multiresistant qualities could develop. (Cars and Nordberg 104) As Cars and Nordberg illustrate above, MRSA has experienced significant growth in the last three decades, mostly due to the horizontal spread of resistance mechanisms amongst different strains of the MRSA bacteria. On the most basic level, this is accomplished when individual bacterium swap genetic information. Given the almost unfathomably numerous amount of individual bacterium involved in an infection, it is not unlikely that two antibiotic-resistant bacterium will exchange the genetic information that makes each bacterium resistant to its respective antibiotic. After undergoing this process, both bacteria will be resistant to both antibiotics. Then, each of these will reproduce, and the next generation will be multiresistant in the same way; these might then go on to exchange genetic information with another bacterium resistant to an additional two types of antibiotics, creating a strain resistant to four types of antibiotics, and so on. Such is the case with MRSA; in its current form, it has evolved to become resistant to most traditional types of penicillin and cephalosporin, another common antibiotic. In

Mohandes 4 fact, some of the more severe cases of MRSA can only be treated with colistin, which has been rejected by the medical community due to its toxic side effects (Cars and Nordberg 104). Moreover, the issue of resistance is further aggravated by modern globalization. The increased range and availability of trade and travel has created new opportunities for infectious diseases to gain multiresistant traits that would not have been possible otherwise. Globalizations effects on antibacterial resistance are best demonstrated through the example of the multiresistant bacteria strain Streptococcus pneumonia, which was first identified in Spain. In only a short period of time after the Spanish outbreak, the same strain was found in Argentina, Brazil, Chile, Taiwan, Malaysia, the United States, Mexico, the Phillipines, South Korea, South Africa, and Uruguay (Cars and Nordberg 105). Cars and Nordberg issued the following warning after observing the rapid spread of Streptococcus pneumonia: Such examples underline the fact that no single country can protect itself from the threat of resistant bacteria as pathogens are spreading across international, cultural and ethnic boundaries. Although the effects of antibiotic resistance are more documented in industrialised countries, there is a greater potential for harm in the developing world, where many of the second and third line therapies for drugresistant infections are unavailable and unaffordable. (Cars and Nordberg 105) Cars and Nordberg raise an especially important ethical issue in describing the effects of multiresistant bacteria strains in the third world: does the pervasive overuse or misuse of antibiotics in locations where medical care is relatively accessiblethe United States and the European Union, for instancethat is largely responsible for the development and evolution of multiresistant bacteria strains related to the inability of those in the developing world to treat basic infections with traditional antibiotics? And if so, does this obligate those who have ready

Mohandes 5 access to antibiotics to use them responsibly in a way that minimizes the possibility of resistance development? Dan I. Andersson of the Uppsala University Department of Medical Biochemistry and Microbiology, in an article published in a 2005 issue of the International Journal of Risk Safety in Medicine, agrees: the overuse of broad spectrum agents in respiratory infections and diarrhoeal diseases consequently drives resistance development in pathogenic bacteria as well as in the normal bacterial reservoir of the patient. This makes them potential carriers of resistant microbes that might be dangerous to themselves and to other patients. The reservoir for resistance mechanisms in the gut can be transferred to more virulent pathogens passing through the body and be spread to other individuals. Furthermore, the bacteria that are carrying resistance mechanisms will be lost very slowly, if at all. (Andersson 114) Andersson concludes that overusein this case, the use of antibiotics in cases where they are not absolutely necessarycontributes significantly to the evolution of multiresistant strains of bacteria by exposing pathogens to the antibiotic, giving them a chance to evolve resistance. Thus the medical community is faced with an ultimatum, of sorts: it must choose between the wellbeing of individuals in the present (achieved by using antibiotics indiscriminately to treat diseases and infections as they come) or the possibility of fulfilling the global need for sustainable antibiotic use (achieved by using antibiotics conservatively to treat only severe cases, minimizing the possibility of resistance evolution). In contrast, misuse of antibiotics creates a comparable problem. In the classic scenario of patients failing to complete the prescribed dosages of an antibiotic because they have deemed themselves to be feeling normal: Poor patient compliance with dosage regimens and the use of

Mohandes 6 substandard antibiotics lead to intermittent suboptimal serum concentrations that fail to control bacterial populations and are potentially a risk factor for the development of resistance (Andersson 113). Under such conditions, the infectious bacteria are not completely eradicated, and are again provided with the opportunity to evolve resistance. The problem of antibacterial resistance is similar to that of climate change insofar as in both situations, the damage has been already been done, so to speak; proposed solutions cannot solve to the problem, but can only serve to mitigate the situation or minimize the severity of the consequences. Dan I. Andersson voices his concern his paper, The Ways in which Bacteria Resist Antibiotics: Antibiotic therapy has existed for 60 years and the frequency of resistant bacteria continues to increase exponentially and makes drugs useless in treating infections. Much evidence supports the idea that resistance among bacteria is irreversible. Can the tide be turned, or are we already beyond the point of no return in the build-up of antibiotic-resistant strains? (Andersson 116) Like climate change, antibacterial resistance appears to be irreversible; or, at the very least, clinical evidence supporting the idea of reversibility as it pertains to antibacterial resistance is weak (Andersson 115). In other words, bacterial strains that have evolved resistance will remain resistantthe only means by which to treat them is to develop an antibiotic to which the bacteria have not yet evolved resistance against, in what can be seen as almost a medical arms race. However, in such an arms race, the bacteria have the advantage; currently, it is proliferating resistance at a faster rate than modern medicine can synthesize new antibiotics (Andersson 114). It is clear that a major overhaul in the way that antibiotics are used is necessary. But what measures must be taken? Some experts suggest that antibiotics be issued during an optimal

Mohandes 7 dosage timerecent studies have shown that a three-day treatment for pneumonia is the least likely to provide favorable circumstances for the evolution of resistancebut even so, this remains to be a large knowledge gap for the majority of diseases (Andersson 113). Until such gaps are filled, the consequences of such ignorance must be endured. All things considered, it would seem that on balance, antibiotics have served mankind wellafter all, 200 million lives is a staggeringly convincing totalbut, at the same time, it is impossible to guess whether Alexander Fleming would have continued with his experiments on penicillin had he known that widespread misuse of his miracle drug could have caused such devastating consequences. Only by educating the public and enforcing strict, responsible use of antibiotics can they remain what they were designed to be: a benefactor of mankind.

Mohandes 8 Works Cited Alexander Fleming. New World Encyclopedia. 16 Feb. 2009. Web. 8 Nov. 2010. <http://www.newworldencyclopedia.org/entry/Alexander_Fleming>. Andersson, Dan I. "The Ways in Which Bacteria Resist Antibiotics." International Journal of Risk & Safety in Medicine (2005): 111-16. Print. Britons Vote for the iPhone as Most Important Invention Ahead of Flushing Loo and Space Travel.The Telegraph. 19 May 2010. Web. 10 Nov. 2010. <http://www.telegraph.co.uk/finance/newsbysector/retailandconsumer/7738684/Britonsvote-for-the-iPhone-as-most-important-invention-ahead-of-flushing-loo-and-spacetravel.html>. Cars, Otto, and Pers Nordberg. "Antibiotic Resistance:The Faceless Threat." International Journal of Risk & Safety in Medicine (2005): 103-10. Print. Wish, Valdis. "Hospitals: Breeding The Superbug." Allianz Knowledge Partnersite. Allianz, 22 May 2008. Web. 9 Nov. 2010. <http://knowledge.allianz.com/en/globalissues/safety_security/health_pandemics/hospital _infections_mrsa.html>.