A Superbug Nightmare


washhandsA recent blog from the RAND corporation entitled Who killed Mrs. X  cites Sir Alexander Fleming’s warning about the dangers of penicillin resistance when antibiotics are misused and discusses the global threat of antimicrobial resistance. The post warns that it may soon be too dangerous to undergo even routine surgical procedures because of an increased risk of contracting an infection from multiple drug-resistant organisms, for which we do not have a cure.

This is, of course, a critical situation. However, the plan of action outlined by the RAND authors to confront these issues— including: improving personal hygiene, behavior and awareness, incentivizing innovation to develop new drugs, and establishing an international agreement analogous to the WHO Framework Convention on Tobacco Control—appears to blame the victim, shows a bias towards benefiting the pharmaceutical industry, and needs to be stronger, given the extent of the threat to global public health. Below, I discuss some limitations of these proposed solutions, while offering suggestions to address the complexities inherent in solving public health problems.

“1) Improve personal hygiene, behavior and awareness…”

Plumbing, safe water and waste disposal, collectively known as the sanitation revolution, have had the greatest impact in human health history, ahead of antibiotics, anesthesia and vaccines.[1] Yet, regrettably, by 2013, 783 million people still do not have access to clean water and almost 2.5 billion do not have access to adequate sanitation.[2] On the other end of the spectrum, lies the frenzy towards living in a “microbe free” environment, which has led to a market-driven abuse of antibacterial soaps and cleaning supplies, which, while preventing some infections, are further contributing to the problem of bacterial resistance.[3,4]

All of us live in an environment full of microorganisms; however, the overwhelming majority of microorganisms in our skin, mucous membranes, and digestive system are helpful to keep the “bad” bacteria from taking over, and thus maintaining equilibrium in our bodies.  For this reason, the one tried and true solution for the prevention of infections is simply frequent hand washing in all settings, from restaurants to day cares, hospitals, or at home.

The bigger issue here, however, is the hurried and imprudent use of antimicrobials by health care professionals and patients alike.  No doctor or other healthcare provider should prescribe medications to his or her patient on the basis of misguided patient pressure.  Rather doctors and providers must educate the patient, and assert his or her position as a professional. So while it is important to acknowledge that there is a complex set of issues which influence physician behavior, like the uncertainty of the nature of the infection, time-constraints, and the litigious nature of current medical practice, health care professionals must focus more on patient education regarding the appropriate use of medication and the dangers of misuse.

It is important to understand the process by which a person can be treated with antimicrobials. If an infection is suspected, a qualified healthcare provider should assess the patient’s symptoms and underlying risk factors, and prescribe the appropriate antimicrobial, at the right dosage, and for an optimal length of treatment. Then, at an authorized pharmacy, a registered pharmacist fills in the prescription with a certified-quality product, the patient pays (unless provided by the government) for the drugs and finally, the patient has to actually take the medication for the recommended length of therapy (unless there are allergies or any side effects).

Antimicrobial resistance is more likely to develop if there is a misstep in this process, related to factors to do with physicians, pharmacies, patients or quality of products. For example, in the United States (US) alone, it is estimated that about 50% of all antibiotics are prescribed when not needed, or are misused (insufficient dose).[5] These concerns tend to be more severe for people living in poverty, since their living conditions and social determinants of health,[6] place them at a higher risk, not only of contracting infections, but also having access to quality healthcare. Worldwide, some of the major antimicrobial resistance threats include: multiple drug-resistant tuberculosis (MDRTB), methicillin-resistant Staphilococcus Aureus (MRSA) –a hospital-acquired infection, and multiple drug-resistant malaria.[7]

There are a couple of significant contributors to the surge in antimicrobial resistance not mentioned in the blog, notably, the use of antimicrobials in the food industry and hospital-acquired infections.  It is estimated that 80% of the antibiotics sold in the US are used in animals,[8,9] and even in countries with very strong monitoring systems like the US’ Food and Drug Administration (FDA), people could be consuming low dose antibiotics in their everyday milk and dairy products [10], and ingesting antibiotic residue, as well as drug resistant bacteria in meat,[11] fish [12] and poultry.[13]

Furthermore, studies show that up to 75% of the antibiotics used in animals do not get absorbed in the passage through their intestine and end up polluting water sources,[14] thus creating another source of potential antimicrobial resistance.  Use of antimicrobials in animal feed, in some instances the exact same antimicrobials used to treat infections in humans, is also a cause for development of multiple drug-resistant microorganisms or “super microbes”, like the appearance of highly virulent strains of  E.Coli and other bacteria in the food industry, which have subsequently been implicated in deadly disease outbreaks in the United States [15] and elsewhere.[16]

Regarding hospital-acquired infections, microorganisms transmitted through medical devices (from needles to catheters to prosthetic devices) or when germs contaminate wounds, are the subject of heavy scrutiny and concern in the healthcare system, in an effort to prevent and decrease the incidence of hospital-acquired infections.  In the US alone, hospital-acquired infections affect around 2 million people every year, with 23,000 people dying as a direct result of such infections. [17,18] Of particular concern are intensive care units, where patients tend to undergo multiple invasive procedures and can be exposed to virulent organisms.[19]

 2) “Incentivize innovation: “four Ps” partnerships, prices, prizes and patents…'”

This suggested area of action is my main concern. The pharmaceutical industry is among the world’s most lucrative industries, with profit margins significantly above most other industries.[20]

The 10 largest drugs companies control over one-third of this 300 to 400 billion-dollar market, with profit margins of around 30%. Six of these companies are based in the United States and four in Europe. [21]

The pharmaceutical industry already disproportionally benefits from public subsidies, in comparison with most industries, in the form of research and development (R&D), money from governments, work done at universities with public funds,[22] as well as from tax credits (in the US, 34 cents of each dollar spent by the industry is a tax credit). The tag price for R&D for a new drug is a hotly contested issue; from USD $71 million to $2 billion and beyond, [23] and how much of that tag price is paid for by private investment vs. public funds remains unclear.[24]

The line of separation between the two sectors, within existing public/private partnerships is blurry. Many a startup company stems from work performed by researchers who have blossomed under government-sponsored research, which then go on to biotech companies and ultimately are bought by pharmaceutical companies. These companies then sell the product under a patent that protects exclusive production rights and therefore price monopoly, for 20 years, without in many cases having paid for the publicly subsidized research.[25] Asking for more regulation of these partnerships seems appropriate, since clarification of the exact contributions in the partnerships could shed light into the real (lower) cost of new medications, given that the public have already paid once for those medications through taxes, which funded the research in the first place.

Advanced market commitments to purchase medications seem like a good idea, but need to be based on cost and not price negotiations. If the buyer (e.g., the government, insurance company or healthcare corporation) is going to purchase from the pharmaceutical industry all their production of a new antimicrobial (based on historic-need data) for a set number of years, (zero risk marketing for the company), the buyer is going to shop around for the lowest bidder, making sure the quality of the product is up to par, and having a very clear idea of the actual cost of production.

This would still be very good business for the pharmaceutical industry, because of the volume of sale and zero marketing risk. A good tool for this type of market commitments, and for medication purchases in general, is a “drug price observatory” which Brazil has been very successful in implementing.[26] It is a place where any purchase from the pharmaceutical industry is posted online and the actual price of each medication is displayed. Based on this publicized price, other buyers can use the precedent to negotiate down the price, particularly larger players, like governments that provide universal healthcare, and can use their bargaining muscle to benefit the population.

Four_colors_of_pillsRegarding “prizes” to incentivize production, incentives should be in the form of priority research funds available to produce the so called “orphan drugs” for “neglected” diseases. These are drugs that do not come with the profit margin that the pharmaceutical industry is used to (30% of sales), or have a limited potential market, that is, the treatment will only require a single course of medication (like antibiotics) as opposed to a chronic disease which requires medication for life. Or the disease is very rare and consequently there is no economic interest in producing medicine to treat them. In this respect, there may be a need to develop national (or regional) public, or not-for-profit pharmaceutical laboratories to produce such drugs or create a patent pool [27] and have the generic drug industry produce these drugs.

Finally, patents are considered a birthright of pharmaceutical companies and the most cited reason to promote innovation (new patent = increase profits).  However, it seems that patents are increasingly becoming one of the causes of stifled innovation. Any breakthrough, small or important, in developing a new drug is sent to the legal department of the institution, be it in academia or industry, to define if a patent already exists in that pathway, and if so, they issue an order to stop whatever track the research team was pursuing –no matter how promising – because the patent belongs to someone else.[28]

It is a system that destroys collaboration and severely limits innovation. Voluntary patent pools could be an initial step to solve this conundrum. [29] It seems the concept of health as a human right has been replaced with the concept of health (including health care and medicines) as a commodity. This larger, fundamental topic of health as a human right needs to be discussed intensely within individual nations, as well as within the United Nations, in the pursuit of a healthier future for all.

3) “An international agreement…”

The final area of intervention noted in RAND’s blog revolves around establishing a worldwide monitoring system, which I agree is a key recommendation. However, the World Health Organization’s (WHO) tobacco framework  – cited as a sample agreement – seems like a subdued approach to such a pressing need. The WHO needs to take charge of the situation and act firmly in its role as overseer of the health interests of all people, above the economic interests of countries or corporations.  It cannot forget its’ guiding principle – to attain the best possible health for all.

If antibiotic misuse and resistance are considered serious threats, an equally serious solution needs to be set in place. The Word Health Organization needs to lead this effort and actively work with national governments to implement effective guidelines through enforceable mechanisms to confront this global threat:

1)     Establish a worldwide surveillance network. Mandate active antimicrobial resistance surveillance in sentinel hospitals and communities, and establish global WHO emergency support teams to actively control outbreaks.

2)     Monitor quality of antimicrobials through enforcement of good manufacturing practices and pharmaceutical quality assurance and control.

3)     Prohibit pharmaceutical companies from selling antimicrobials to businesses other than those recognized by national legislation within a WHO-designed and approved framework, under the tenets of a global health risk. In many countries, antibiotics can still be obtained over the counter and even in convenience stores.

4)     Ban the sale of antimicrobials that are critical in the pathway of resistance for unregulated use in veterinary medicine, agribusiness models or cleaning supplies industry.

5)     Limit the number and type of antibiotic options for general practice use and relegate second and third line options for specialty care with oversight; and provide feedback on prescribing practices to avoid wrong antimicrobial choice and under-dosage, which are the most common issues.

6)     Promote development and accessibility of tests for resistant bacteria and the development of new antimicrobials through alternative pathways, like mandated patent pools and the establishment of national or regional not-for-profit laboratories.

7)     Engage in aggressive targeted continuing education regarding antibiotic resistance to all stakeholders: healthcare providers, food industry, service industry, schools, government officials, etc., as well as the general population worldwide.

This is a critical global problem that will only get worse the longer we wait.  It is time not only for all of us to take individual responsibility, but in particular for our governments and international bodies to be proactive, aggressive and creative in confronting this rapidly evolving public health crisis.


david-chiribogaDr. Chiriboga obtained his postgraduate training in Preventive Medicine at the University of Massachusetts Medical School and School of Public Health. He designed and implemented a comprehensive healthcare system for the indigenous people in central Ecuador 1988-2001.  He served as Minister of Health in Ecuador (2010-11) where he undertook a major re-structure of the healthcare system of the country. He also served as President of the Health Council for the Union of South American Nations (UNASUR) 2010, bringing key draft resolutions regarding generic medicines and research and development of medicines for neglected diseases, and a proposal for the need to re-structure the World Health Organization, which were approved by the World Health Assembly.  Dr. Chiriboga was the keynote speaker for the European Union Conference in Global Health held in Brussels in 2010. His interests include global health equity, the development of affordable universal health care systems, as well as multisectorial prevention strategies.



Article Sources


[1] http://www.bmj.com/content/334/7585/111.2  BMJ readers choose the “sanitary revolution” as greatest medical advance since 1840 BMJ 2007;334:111.2 (Published 18 January 2007)

[2] http://www.unwater.org/water-cooperation-2013/water-cooperation/facts-and-figures/

[3]   http://cid.oxfordjournals.https://academic.oup.com/cid/article/45/Supplement_2/S137/285530/Consumer-Antibacterial-Soaps-Effective-or-Justorg/content/45/Supplement_2/S137.full.pdf+html Consumer Antibacterial Soaps: Effective or Just Risky? Allison E. Aiello, Elaine L. Larson, and Stuart B. Levy. Clin Infect Dis. (2007) 45 (Supplement 2): S137-S147. doi: 10.1086/519255

[4] https://www.research.gov/research-portal/appmanager/base/desktop;jsessionid=1Bv2R8cbTp0TcGmymSZPnkQpQc5mXh05tHMfgWCL9vn2J2ZlyL0V!-371378653!1342109944?_nfpb=true&_windowLabel=awardSummary_1&_urlType=action&wlpawardSummary_1_id=%2FresearchGov%2FAwardHighlight%2FPublicAffairs%2F23002_DisinfectantExposureIncreasesAntibioticResistance.html&wlpawardSummary_1_action=selectAwardDetail Disinfectant-Induced Antibiotic Resistance: Relevance, Mechanisms and Practical Considerations (Georgia Tech Research Corporation).

[5] http://www.cdc.gov/drugresistance/threat-report-2013/

[6] http://www.who.int/social_determinants/B_132_14-en.pdf World Heath Organization, Executive Board, EB132/14 132nd session. November 2012. Social determinants of health. Report by the Secretariat.

[7] http://www.who.int/mediacentre/factsheets/fs194/en/index.html Antimicrobial resistance Fact sheet N°194, 
Updated May 2013

[8] http://www.fda.gov/ForIndustry/UserFees/AnimalDrugUserFeeActADUFA/ucm236149.htm

[10] http://www.nytimes.com/2011/01/26/business/26milk.html?_r=0 NYT article: F.D.A and Dairy Industry Spar Over Testing of Milk

[11] http://www.fsis.usda.gov/shared/PDF/2010_Red_Book.pdf UNITED STATES National Residue Program for Meat, Poultry, and Egg Products. 2010 RESIDUE SAMPLE RESULTS, United States Department of Agriculture Food Safety and Inspection Service Office of Public Health Science. June 2012

[12] http://www.ncbi.nlm.nih.gov/pubmed/16817922 Cabello FC, Environ Microbiol. 2006 Jul;8(7):1137-44. Heavy use of prophylactic antibiotics in aquaculture: a growing problem for human and animal health and for the environment.

[13] Foodborne Pathog Dis. 2013 Nov;10(11):916-32. doi: 10.1089/fpd.2013.1533. Epub 2013 Aug 20. Human and Avian Extraintestinal Pathogenic Escherichia coli: Infections, Zoonotic Risks, and Antibiotic Resistance Trends.

[14] Chee-Sanford JC, Mackie RI, Koike S, Krapac IG, Lin YF, Yannarell AC, Maxwell S, Aminov RI.J Environ Qual. 2009 Apr 27;38(3):1086-108. doi: 10.2134/jeq2008.0128. Print 2009 May-Jun. Fate and transport of antibiotic residues and antibiotic resistance genes following land application of manure waste

[15] http://www.cdc.gov/ecoli/

[16] http://www.euro.who.int/en/health-topics/disease-prevention/food-safety/outbreaks-of-e.-coli-o104h4-infection. World Health Organization, Europe Regional Office Outbreaks of E. coli O104:H4 infection

[17] http://www.cdc.gov/drugresistance/threat-report-2013/

[18] https://www.cdc.gov/hai/organisms/organisms.html

[19] http://www.who.int/gpsc/country_work/gpsc_ccisc_fact_sheet_en.pdf  World Health Organization. Health care-associated infections FACT SHEET

[20] http://www.cmaj.ca/content/171/12/1451.full CMAJ December 7, 2004 vol. 171 no. 12 doi: 10.1503/cmaj.1041594 Canadian Medical Association Over and above. Excess in the pharmaceutical industry, Marcia Angell.

[21] http://rd.springer.com/article/10.1007/BF03256183?no-access=true World Health Organization. Pharmaceutical industry

[22] http://www.cbo.gov/sites/default/files/cbofiles/ftpdocs/76xx/doc7615/10-02-drugr-d.pdf  Congress of the United States, Congressional Budget Office. CBO Study, October 2006, Research and Development in the Pharmaceutical Industry

[23] Washington, Harriet. Deadly Monopolies: The Shocking Corporate Takeover of Life Itself –and the Consequences for Your Health and Our Medical Future. 2011. 1st Ed. Doubleday.

[24] http://www.cbo.gov/sites/default/files/cbofiles/ftpdocs/76xx/doc7615/10-02-drugr-d.pdf  Congress of the United States, Congressional Budget Office. CBO Study, October 2006, Research and Development in the Pharmaceutical Industry

[25] Goozner, Merril. The $800 Million Pill: The Truth behind the Cost of New Drugs. 2004. University of California Press. Berkley, California

[26] http://www.infarmed.pt/portal/page/portal/INFARMED/ENGLISH

[27] Ellen ‘t Hoen: Pool medical patents, save lives http://www.ted.com/talks/ellen_t_hoen_pool_medical_patents_save_lives.html

[28] http://www.cbo.gov/sites/default/files/cbofiles/ftpdocs/76xx/doc7615/10-02-drugr-d.pdf  Congress of the United States, Congressional Budget Office. CBO Study, October 2006, Research and Development in the Pharmaceutical Industry

[29] Ellen ‘t Hoen: Pool medical patents, save lives http://www.ted.com/talks/ellen_t_hoen_pool_medical_patents_save_lives.html