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Antimicrobial resistance and health care-associated infections: combating this global threat, part 1.


Over the last two decades, multiple factors have led to a dramatic worldwide increase in infections caused by antimicrobial-resistant and nosocomial pathogens. (1,2) Antimicrobial (drug) resistance is the ability of bacteria, viruses, parasites and other microorganisms to change and cause an antimicrobial agent (drug) to be ineffective against the resistant organism and is one of the most significant factors that has led to an alarming increase in the number and types of drug resistant infections. (1,2) This phenomenon affects all classes of antimicrobials including antibiotics, antivirals, antifungals and antimalarials. (1)

Highly resistant organisms account for a large percentage of hospital-acquired infections. (1,2) One particularly worrisome organism, methiciflin-resistant Staphylococcus aureus (MRSA), kills approximately 19,000 Americans every year: more than the combined death toll from emphysema, HIV/AIDS, Parkinson's disease and homicide. (1-4) The World Health Organization (WHO) estimates that about 440,000 new cases of multidrug-resistant tuberculosis (MDR-TB) emerge annually, causing at least 150,000 deaths and extensively drug resistance (XDR) TB cases (resistant to most and sometimes all anti-tubercular drugs) are reported in 64 countries. (1)

This pattern of increased resistance is not limited to bacteria. Viruses, fungi and parasitic organisms are all developing resistance to first-and in many cases even second- and third-line drug therapies. (1) For example, resistance to earlier generation antimalarial medicines such as chloroquine and sulfadoxine-pyrimethamine is widespread in most malaria-endemic countries. (1) Infections from these emerging resistant organisms are increasing in number and becoming very difficult--in some instances impossible--to treat. (1-3) Global trade and the ease of international travel facilitate the spread of resistant microorganisms to virtually any part of the world, rendering standard treatment regimens less and less effective. If these resistant infections persist, they can readily spread to others; resistant infections cost much more to treat and result in much higher rates of morbidity and mortality. (1-3)

WHO, the Centers for Disease Control and Prevention (CDC), and the Infectious Disease Society of America (IDSA) recognize drug-resistant microrganisms as among the greatest threats to human health worldwide. (1-5) Each year, WHO celebrates its founding by sponsoring a World Health Day that focuses on a health topic of global importance. World Health Day, April 2011 was devoted to combating antimicrobial resistance. WHO stated:

* Most of us live longer and healthier lives today, partly because powerful and effective medicines, known as antimicrobials, are available to treat infectious diseases. Until the discovery and availability of antimicrobials in the 1940s, people died needlessly from infectious diseases. Today, none of us can imagine living in a world without antimicrobials.



* We are now on the brink of losing this precious arsenal of medicines. The use and misuse of antimicrobials in human medicine and animal husbandry over the past 70 years have increased the number and types of microorganisms resistant to these medicines, causing deaths, greater suffering and disability and higher health-care costs.

* If this phenomenon continues unchecked, many infectious diseases risk becoming uncontrollable and could derail progress made towards reaching the health related United Nations Millennium Development Goals for 2015. Furthermore, the growth of global trade and travel allows resistant organisms to spread worldwide within hours. (6)

If measures are not put into place to combat the spread of antimicrobial resistance, we could find health care returning to the pre-antibiotic era.

Causes of Antimicrobial Resistance

The emergence and dissemination of antimicrobial resistant organisms are complex and multifactorial. However, four recognized and significant factors play major roles in the development of antimicrobial resistance:

(1.) Adaptability of the organisms and natural biological changes (mutation);

(2.) Indiscriminate/inappropriate use of antibiotic/antimicrobial agents in all health care settings;

(3.) Overuse and/or misuse of antibiotics in farming/animal husbandry and;

(4.) Noncompliance with infection control practices. (1-3,7,8)

Microorganisms are constantly changing, and development of drug resistance is a natural evolutionary phenomenon. Organisms can develop resistance by mutation (biological evolution) or acquire genes (gene transfer) from other organisms that confer resistance. (1-3,7,8) When exposed to an antimicrobial drug, the more susceptible microorganisms are killed. The resistant organisms are not. (1-3,7,8) The small number that carry resistance survive, and in the continued presence of that particular antimicrobial, as the non-resistant organisms are killed, selective pressure changes the composition of the entire microbial population to predominately resistant. (1-3,7,8) These surviving resistant organisms thrive and are able to pass on resistance to their progeny. (1-3,7,8)

Additionally, new patterns and pathways of resistance are constantly emerging that facilitate the development and spread of resistant organisms. (1-3,7,8) Multiple-drug resistant organisms are increasingly encountered in both hospital and community settings. (1-3,7,8) One of the most significant factors in the development of antimicrobial resistance has been the indiscriminate and inappropriate use of antibiotics. (1-3,7,8) The inappropriate use of antimicrobials puts selective pressure on organisms, encouraging resistant microbes to thrive and driving the development of drug resistance. (1-3,7,8)

Overuse, underuse and misuse of antimicrobials over many decades have created significant and persistent selective pressure for the development of antimicrobial resistance throughout the world. (1-3,7,8) Antibiotics are all too often inappropriately prescribed for colds and other viral infections for which they are not indicated and are therefore ineffectual. In other instances, patients do not take prescribed dosage for the entire course of treatment, facilitating the development of resistant strains. Inappropriate antimicrobial medications are prescribed to or taken by the patient (self-medication without prescription).

Today's Internet-driven marketplace has been a perfect avenue for the sale of bootleg or counterfeit pharmaceuticals. These preparations often lack quality control in drug production facilities, resulting in insufficiently potent and/or poor quality drugs. (1) The Food and Drug Administration (FDA) regulates the U.S. pharmaceutical industry; however, there is little or no regulation in many countries. Numerous drugs of all types, including antimicrobials, are available on the Internet, and their quality and content are in some instances questionable. (1)

Antimicrobial drugs, including antibiotics, antifungals and antiviral agents must be prescribed only when indicated and in the proper formulation and dosage. Patients should be advised to take their antimicrobial drugs for the full course of treatment, even if symptoms resolve before the course of therapy is completed.

The use and misuse of antimicrobials in human medicine and animal husbandry over the past 70 years have increased the number and types of microorganisms resistant to these medicines.

Animal husbandry is another source of drug resistance. (1-3,7,8) Subtherapeutic doses of antibiotics are used in animals for promoting growth or preventing diseases. This can result in resistant microorganisms that may be transmissible to humans. (1-3,7,8) Over 50 percent of the antibiotics produced in the U.S. are used in animals, most of which are neither indicated nor appropriately dosed.

Poor infection prevention/infection control amplifies and perpetuates drug resistance. Health care workers (HCWs) are notoriously noncompliant with recommended infection control practices. Poor infection prevention and control can increase the spread of drug-resistant infections. Hospitalized patients are among the main reservoirs of resistant microorganisms. Similarly, infected patients become carriers of resistant microorganisms and reservoirs of infection in their communities. A recent online survey of 5,446 HCWs reveals noncompliance with basic infection control practices associated with the use of syringes, needles, multiple-dose vials, single-use vials and flush solutions.9 The study showed that:

* Nearly 1 percent of respondents admitted to sometimes or always reusing a syringe for more than one patient after only changing the needle

* Six percent of respondents admitted to sometimes or always using single-dose/single-use vials for multiple patients

* Fifteen percent of respondents reported using the same syringe to re-enter a multiple-dose vial numerous times; of this group, about 7 percent reported saving these multiple-dose vials for use with other patients

* Nine percent of respondents sometimes or always use a common bag or bottle of IV solution as a source of flushes and drug diluents for multiple patients (9)

Clearly, improvement in compliance with standard precautions and safe injection practices is warranted.

Antimicrobial Resistance in 2011

Some of the most significant resistant organisms causing infections in 2011 are listed in the box. Tuberculosis is becoming more and more difficult and expensive to treat. (XDR) TB is documented in at least 64 countries, and the number of cases is increasing. While HIV has been successfully managed in most developed countries, the success of antiretroviral therapy depends on strict adherence with the drug regimens prescribed. As HIV is capable of developing resistance very rapidly, and as the use of antiretroviral therapy (ART) expands to other parts of the world, emergence of HIV resistance could become problematic. This problem is exacerbated when inappropriate ART drugs are used and/or patients do not adhere to the ART regimen.

MRSA infections are becoming rampant in both health care settings and the community. Infections from multiple drug-resistant E.coli, K. pneumonia, Shigella and Enterobacter sp. are increasing at an alarming rate and are extremely difficult to treat. Just recently, ceftriaxone-resistant Neisseria gonorrhoeae has been reported in Japan. (10) Since ceftriaxone is the first-line treatment for gonorrhea around the world, there is great concern that gonorrhea may become more difficult or impossible to treat.

This is the first article in a two-part series. The next article will examine specific new threats and consider whether we will return to the pre-antibiotic era.


(1.) World Health Organization. Antimicrobial resistance fact sheet 194, February 2011. Available at:

(2.) Infectious Diseases Society of America. Combating antimicrobial resistance: policy recommendations to save lives. Clin Inf Dis. 2011; 52(S5): S397-S428. Available at: full.pdf.

(3.) Centers for Disease Control and Prevention. Antibiotic/antimicrobial resistance. Available at:

(4.) Klevens RM, Morrison MA, Nadle J, et al. Invasive methicillin resistant Staphylococcus aureus infections in the United States. J Am Med Assoc. 2007; 298: 1763-71.

(5.) Walker B, Barrett S, Polasky S, et al. Environment. Looming global scale failures and missing institutions. Science. 2009; 325:1345-6.

(6.) World Health Organization. World Health Day 2011 brochure. Available at:

(7.) Centers for Disease Control and Prevention (CDC). Recommended immunization schedules for persons aged 0 -18 years - United States, 2008. MMWR Morb Mortal Wkly Rep. January 11, 2008; 57(01);Q-1-Q-4. Available at:

(8.) Centers for Disease Control and Prevention. Antibiotic/antimicrobial resistance. September 24, 2007. Available at:

(9.) Pugliese G, Gosnell C, Bartley JM, Robinson S. Injection practices among clinicians in United States health care settings. Am J Infect Control. 2010; 38: 789-98.

(10.) Ohnishi M, Saika T, Hoshina S, et al. Ceftriaxone-resistant Neisseria gonorrhoeae, Japan. Emerg Infect Dis. 2011; Jan. Available at:

RELATED ARTICLE: Antimicrobial resistant organisms: 2011

Tuberculosis (TB):

* 440,000 new multidrug resistance (MDR) TB cases annually;

* Extensively drug resistance (XDR) TB cases reported in 64 countries so far


* With expanded use of antiretroviral therapy (ART), resistance is a concern,

* Especially when inappropriate drugs are used; and/or patient not adherent to ART regimen.

Methicillin-resistant Staphylococcus aureus (MRSA):

* Lethal infections in hospital settings becoming increasingly frequent

MDR E.coli, K. pneumoniae and Enterobacter sp.:

* Infections are on the rise

* New beta-lactamase, NDM-1, is causing alarm

Neisseria gonorrheae and Shigella:

* Becoming increasingly resistant to drugs

By Louis G. DePaola, DOS, MS, and Jacquelyn L. Fried, RDH, MS

Louis G. DePaola, DDS, MS, is a professor in the Department of Oncology and Diagnostic Sciences, Dental School, University of Maryland, Baltimore. He received his DDS in 1975, completed a master's degree in oral biology, is a diplomate of the American Board of Oral Medicine and the American College of Dentists and has a certificate in prosthodontics. He is an international lecturer and executive director of Biosafety and Continuous Quality Improvement, Dental School, University of Maryland, Baltimore. Active in research, he has authored and co-authored of over 130 journal articles, book chapters and abstracts and serves as a consultant to the American Dental Association and numerous other professional groups and private industry.

Jacquelyn L. Fried, RDH, MS, received her Bachelor of Arts in political science and her Certificate in Dental Hygiene from Ohio State University. She also holds a Master of Science in Dental Hygiene from Old Dominion University. She is associate professor and director of the Dental Hygiene Program in the Department of Health Promotion and Policy at the University of Maryland Dental School. She has been in dental hygiene education for almost 30 years. She has been involved with clinical, research, didactic and community activities related to tobacco. She currently serves as principal investigator for a tobacco training grant funded by the State of Maryland. An active member of the American Dental Hygienists' Association, Fried is widely published and has authored numerous manuscripts and book chapters. She teaches both didactically and clinically and has received student awards for her teaching abilities.
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Title Annotation:infection control
Author:DePaola, Louis G.; Fried, Jacquelyn L.
Geographic Code:1USA
Date:Sep 1, 2011
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