Antibiotic resistance: have we become the dinosaurs?

It's been open warfare for approximately half a century, and the news is not good. All of our troops are engaged, the reserves have been mobilized, and we can still barely contain the enemy. Our towns have been infiltrated. The enemy has established pockets everywhere. We do not know when or where it will strike, but we know it will strike again. We are valiantly fending off the latest massive blow, SARS, and are still reeling from the attack of AIDS. Many of our troops are still engaged with the Ebola virus, and others are battling with the West Nile virus.

The omnipresent enemy is taking all sorts of forms and shapes, attacking us from all fronts, and becoming resistant to several antibiotics. (1-3) Even agents that we thought were subdued are rearing their ugly heads and attacking us with vengeance. Multidrug-resistant tuberculosis is now a reality; (4-6) many Staphylococcus pneumoniae are no longer susceptible to penicillin; (7,8) several are resistant to third-generation cephalosporins; and more than one-third of gonorrhea isolates are resistant to penicillin, tetracycline, or both. (9) Approximately 70% of the bacteria that cause infections in hospitals are resistant to at least one of the antibiotics commonly recommended. (10) Methicillin-resistant Staphylococcus aureus is widespread in many hospitals, (11-13) and vancomycin-resistant pathogens are becoming increasingly prevalent. (14,15) It is estimated that each year in the United States, approximately 2 million patients acquire an infection while in the hospital, and approximately 90,000 die as a result of this infection. (10)

How did we get to this stage, when only 60 years ago we thought we had dealt the final fatal blow to infective agents? As a result of the discovery of penicillin during the Second World War, a new era of confidence in the medical profession was ushered in with the ability to control bacteria and eventually, it was hoped, all infective agents. Many thought that it was only a matter of time before we could totally eliminate all of these nasty little germs. Once we got rid of these lowlife organisms, we could concentrate our efforts on other diseases, such as treating and preventing cancers, cardiovascular diseases, degenerative diseases, and even reverse the effects of aging. Pharmaceutical companies lost interest in developing new antibacterial agents. It was thought that soon there would be no need for them.

However, we underestimated the ability of bacteria to survive and adapt to hostile environments. Being unicellular, they can easily change their genetic configuration, acquire resistant genes or plasmids, and become resistant to antibiotics much more quickly than we can develop new antibiotics. We also have become overconfident and negligent. We have misused antibiotics. About one-half of the approximately 100 million prescriptions written each year for antibiotics are unnecessary. (16) Sadly, this is often so because clinicians are too busy and do not have time to explain to their patients that antibiotics are not needed, or because their patients insist on being prescribed antibiotics. (10,17) We also tend to be too empirical and prescribe antibiotics without first ascertaining the nature of the offending organism. Antibiotics are frequently used prophylactically before many operations. Patients often discontinue or forget to take their antibiotics once they feel better. Worse still, without proper medical consultation, patients may use antibiotics that they had hoarded some time ago. All of these activities enhance the development of antibiotic resistance.

We also have been too quick to adopt the use of antiseptics in various household items such as soaps, detergents, and hand lotions without demanding proof of the efficacy and safety of this practice. (10) At the same time, we have become complacent and often overlook basic hygiene principles, such as frequent and thorough hand washing and the hygienic storage of food.

Finally, we have become too liberal in feeding antibiotics to food-producing animals to prevent infections and enhance their growth. (18-20) Farmers also often treat their entire flock by adding antibiotics to drinking water because the size of their flock precludes testing and treating individual birds. We have sprayed antibiotics as pesticides onto fruit trees and other food-producing plants. (10) In 1999, the National Academy of Sciences established a link between the use of antibiotics in agriculture and antibiotic resistance in humans. (10) Fluoroquinolones were first approved to treat poultry in 1995. Before this date, there were few fluoroquinolone-resistant bacteria, but shortly afterward many such bacteria were found in humans and in poultry. (21)

The U.S. Department of Health and Human Services has developed a detailed action plan to combat antimicrobial resistance. A Public Health Action Plan to Combat Antimicrobial Resistance (22,23) has four major components: surveillance, prevention/control, research, and product development. The National Antimicrobial Resistance Monitoring System (NARMS) (24) was established in 1996. Several guidelines are available to prevent the development of antibiotic resistance. (25-28) Each health care provider has an important role to play if antibiotic resistance is to be curbed and if we do not want to end up like the dinosaurs.

God often visits us,

But most of the time we are not at home.

-Joseph Roux 

References

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2. Stratton CW. Dead bugs don't mutate: Susceptibility issues in the emergence of bacterial resistance. Emerg Infect Dis 2003:9:10-16.

3. Schito GC. Is antimicrobial resistance also subject to globalization? Clin Microbiol Infect 2002;8(Suppl 3):1-8, 33-35.

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9. National Institute of Allergy and Infectious Diseases, National Institutes of Health. Antimicrobial Resistance (NIAID Fact Sheet), Bethesda, MD, U.S. Department of Health and Human Services, June 2000. Available at: http://www.niaid.nih.gov/factsheets/antimicro.htm. Accessed August 6, 2003.

10. Bren L. The battle of the bugs: Fighting antibiotic resistance. FDA Consum 2002 Jul-Aug:36(4):28-34.

11. Oliveira DC, Tomasz A, de Lencastre H. Secrets of success of a human pathogen: Molecular evolution of pandemic clones of methicillin-resistant Staphylococcus aureus. Lancet Infect Dis 2002;2:180-189.

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13. Hiramatsu K, Okuma K, Ma XX, et al. New trends in Staphylococcus aureus infections: Glycopeptide resistance in hospital and methicillin resistance in the community. Curr Opin Infect Dis 2002;15:407-413.

14. Walsh TR, Howe RA. The prevalence and mechanisms of vancomycin resistance in Staphylococcus aureus. Annu Rev Microbiol 2002;56:657 675.

15. Hamilton-Miller JM. Vancomycin-resistant Staphylococcus aureus: A real and present danger? Infection 2002;30:118-124.

16. U.S. Food and Drug Administration. FDA publishes final rule to require labeling about antibiotic resistance (PO3-07). FDA News, Feb 5, 2003. Available at: http://www.fda.gov/bbs/topics/NEWS/2003/NEW00869.html. Accessed August 6,2003.

17. Gonzales R. A 65-year-old woman with acute cough illness and an important engagement. JAMA 2003;289:2701-2708.

18. Butaye P, Devriese LA, Haesebrouck F. Antimicrobial growth promoters used in animal feed: Effects of less well known antibiotics on Grampositive bacteria. Clin Microbiol Rev 2003;16:175-188.

19. van den Bogaard AE, Stobberingh EE. Epidemiology of resistance to antibiotics: Links between animals and humans. Int J Antimicrob Agents 2000;14:327-335.

20. Teale CJ. Antimicrobial resistance and the food chain. J Appl Microbiol 2002;92(Suppl):85S-89S.

21. Bren L. Antibiotic resistance from down on the chicken farm. FDA Consum 2001 Jan-Feb;35(1):10-11.

22. U.S. Department of Health and Human Services. HHS releases action plan to combat antimicrobial resistance (Press Release). Washington, DC, U.S. Department of Health and Human Services, January 18, 2001. Available at:http://www.hhs.gov/news/press/2001pres/20010118b.html. Accessed August 6, 2003.

23. Interagency Task Force on Antimicrobial Resistance. A Public Health Action Plan to Combat Antimicrobial Resistance. Washington, DC, U.S. Department of Health and Human Services. Available at: http://www.cdc.gov/drugresistance/actionplan/aractionplan.pdf. Accessed August 8, 2003.

24. Center for Veterinary Medicine, U.S. Food and Drug Administration. National Antimicrobial Resistance Monitoring System (NARMS). Rockville, MD. Center for Veterinary Medicine, U.S. Food and Drug Administration, U.S. Department of Health and Human Services. Available at: http://www.fda.gov/cvm/INDEX/narms/narms_pg.html. Accessed August 6, 2003.

25. McCracken GH Jr. Clinical practice guidelines for the diagnosis and treatment of respiratory tract infections. Am J Manag Care 2001;7(6 Suppl):S183-S191.

26. Dalhoff K. Worldwide guidelines for respiratory tract infections: Community-acquired pneumonia. Int J Antimicrob Agents 2001;18(Suppl 1):S39-S44.

27. Gross PA, Pujat D. Implementing practice guidelines for appropriate antimicrobial usage: A systematic review. Med Care 2001;39(8 Suppl 2):1155-1169.

28. Al-Ghnaniem R, Benjamin IS, Patel AG. Meta-analysis suggests antibiotic prophylaxis is not warranted in low-risk patients undergoing laparoscopic cholecystectomy. Br J Surg 2003;90:365-366.

Ronald C. Hamdy, MD, FRCP, FACP