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Antimicrobial Drug Resistance (AMDR)

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SECTION ONE: The global threat of AMDR

SECTION ONE: The global threat of AMDR

Specific Learning Objective: Understand the global threats of AMDR, including epidemiology and multidrug resistance.

Defining the Problem 

Bacteria have evolved diverse protective mechanisms to cope with and survive in the ever-changing environment (Russell 1997). In the course of evolution, bacteria have had ample time to recognize harmful substances, developing and sharing defense mechanisms to ensure their own survival. As a result, antibiotics, naturally produced by bacteria, existed long before humans discovered their properties and used them on an unprecedented scale. Humans coexist with many microorganisms, of which only a small subset presents a threat to health.

The 2008 global antibiotic market was estimated at US $24 billion and is projected to reach US $40.3 billion by 2015 (PRWeb 2011). Antibiotic drugs, including antivirals, antihelminthes, and antifungal preparations, are sold for both therapeutic and industrial (agricultural) uses. The rate of antibiotic prescriptions is on the rise in Greece, Croatia, Denmark, and Ireland for both outpatient and inpatient services. A modest downward trend (1998-2005) was reported for Belgium, the Czech Republic, France, Slovakia, Slovenia, Sweden, and the United Kingdom (Monnet and Kristinsson 2008; Meropol et al. 2009), whereas in the United States and Japan, the overall rate for antibiotic use remains high (Higashi and Furuhara 2009). Some experts are concerned that we are entering a critical “postantibiotic era” with a decreasing pipeline of new and effective antibiotics and rising trends in mortality from AMDR (Alanis 2005).

The importance of the AMDR threat has been recently highlighted by the WHO (World Health Organization “Combat antibiotic resistance” 2011) as follows. 

  • Infections caused by resistant microorganisms often fail to respond to conventional treatment, often leading to prolonged illness and greater mortality risk
  • About 440,000 new cases of multidrug-resistant tuberculosis (MDR-TB) emerge annually, causing at least 150,000 deaths
  • Resistance to earlier generations of antimalarial preparations such as chloroquine and sulfadoxine-pyrimethamine is widespread in most malaria-endemic countries
  • Inappropriate and irrational use of antimicrobial drugs does provide a fertile environment for resistant microorganisms to emerge, spread, and persist 

The economic burden of AMDR is estimated to exceed US $38 billion (Tucker 2010). Nearly 7 out of every 1000 hospitalized patients (in economically developing countries) are either infected with or carriers of microorganisms resistant to common antibiotic drugs. In US hospitals, 96,000 patients contract nosocomial infection(s) annually, making such infections one of the 10 leading causes of death, claiming between 16,000 and 19,000 lives each year. The 2000 EU hospital estimates (Kaier et al. 2008) of AMDR infection incidence found that: 

  • Thirty percent to 40% of cases are linked to cross-infection by the hands of healthcare workers (HCW)
  • Twenty percent to 25% of cases are due to selective antimicrobial pressure
  • Twenty percent to 25% of patients suffer from new pathogen introduction

Plasmid provides a mechanism for gene transfer and produces a selective survival advantage for microorganisms in many hostile environments. Plasmids may carry genes that provide resistance to antibiotics.

Factors contributing to AMDR include:

1. Compromised immune system
2. Drugs administered for chronic and/or debilitating diseases
3. Age
4. Nutritional deficiencies
5. Increased gastric pH
6. Bronchopulmonary disorders interfering with sputum clearance
7. Invasive procedures or devices (such as orthopedic prostheses, indwelling catheters, or heart valves)
8. Intensive interventions such as hemodialysis, surgery, or catheterization

Patients receiving antibiotic treatments, especially those who are immunocompromised, can act as foci for emergence and spread of AMDR
The remaining 20% of nosocomial infections are caused by the lack of proper control and oversight of antibiotic prescriptions (Weinstein 2001; Woodward et al. 1987). 

Inappropriate and sometimes careless use of antibiotic drugs in healthcare and agriculture is a major contributing factor to the rise of AMDR. In 2005, the WHO reported that more than 50% of all medicines (including antibiotic drugs) are prescribed, dispensed, or sold inappropriately, with 50% of patients failing to take them correctly (World Health Organization 2010). Although a 17% decline in counterfeit antibiotics was reported between 2009 and 2010, this class of medications still remains the second largest counterfeit therapeutic category (Pharmaceutical Security Institute 2011). 

Countries that implemented policies on the appropriate use of antibiotics observed a positive impact on infections caused by AMDR (Awad et al. 2007; Isturiz and Carbon 2000; Berild et al. 2008; Tünger et al. 2000). However, between 2003 and 2005, only 26% of all countries adopted a national strategy and less than half implemented public awareness and education programs (Khor 2005). This lack of action is of concern since many medical and surgical procedures might be at risk for AMDR complications, including death. 

In the fall of 2008 the World Medical Association (WMA) updated its 1996 resolution on microbial resistance, in response to the risk of an emerging AMDR pandemic (World Medical Association 2011). This action was sponsored by the American Medical Association. The School of Public Policy at George Mason University contributed to the peer review and update of the proposed resolution. World Health Day 2011 was marked on April 7, 2011, by focusing on antimicrobial resistance, including drug resistance issues related to HIV/AIDS (World Health Organization “World Health Day 2011” 2011). Professional societies continue to update guidelines on the prevention and treatment of infections caused by AMDR pathogens.


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Table of Contents

SECTION ONE: The global threat of AMDR
SECTION TWO: Understanding AMDR
    1. Etiology and Epidemiology
    2. Incidence and Prevalence of Microbial Resistance
    3. Major AMDR Pathogens
       a. Acinetobacter baumanii
       b. Clostridium difficile
       c. Escherichia coli
       d. HIV/AIDS and Sexually Transmitted Infection
       e. Influenza virus
       f. Malaria (Plasmodium)
       g. Methicillin-resistant Staphylococcus aureus (MRSA)
       h. Streptococcus pneumoniae
       i. Tuberculosis and MDR-TB
       j. Vancomycin-Resistant Enterococcus (VRE)
SECTION THREE: Control and Prevention of AMDR
    1. Implications of Microbial Resistance
    2. Infections and Chronic Diseases
    3. Policies and Best Practices
       a. Antimicrobial Drug Stewardship
       b. Surveillance
       c. Environmental Decontamination
       d. Infection Control
       e. Patient Education
    4. Antibiotic Development Pipeline
SECTION FOUR: Conclusions
Test Questions
Program Evaluation
Self Assessment

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