Home      Discussion      Topics      Dictionary      Almanac
Signup       Login
Drug resistance

Drug resistance

Discussion
Ask a question about 'Drug resistance'
Start a new discussion about 'Drug resistance'
Answer questions from other users
Full Discussion Forum
 
Encyclopedia
Drug resistance is the reduction in effectiveness of a drug such as an antimicrobial
Antimicrobial
An anti-microbial is a substance that kills or inhibits the growth of microorganisms such as bacteria, fungi, or protozoans. Antimicrobial drugs either kill microbes or prevent the growth of microbes...

 or an antineoplastic in curing a disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...

 or condition. When the drug is not intended to kill or inhibit a pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...

, then the term is equivalent to dosage failure or drug tolerance. More commonly, the term is used in the context of resistance acquired by pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...

s. When an organism is resistant to more than one drug, it is said to be multidrug-resistant
Multidrug resistance
Multiple drug resistance or Multidrug resistance is a condition enabling a disease-causing organism to resist distinct drugs or chemicals of a wide variety of structure and function targeted at eradicating the organism...

.

Introduction


Drug or toxin or chemical resistance is a consequence of evolution
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...

 and is a response to pressures imposed on any living organism. Individual organisms vary in their sensitivity to the drug used and some with greater fitness
Fitness (biology)
Fitness is a central idea in evolutionary theory. It can be defined either with respect to a genotype or to a phenotype in a given environment...

 may be capable of surviving drug treatment. Drug-resistant traits are accordingly inherited by subsequent offspring, resulting in a population that is more drug-resistant. Unless the drug used makes sexual reproduction or cell-division
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...

 or horizontal gene transfer
Horizontal gene transfer
Horizontal gene transfer , also lateral gene transfer , is any process in which an organism incorporates genetic material from another organism without being the offspring of that organism...

 impossible in the entire target population, resistance to the drug will inevitably follow. This can be seen in cancerous tumours where some cells may develop resistance to the drugs used in chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

. A quicker process of sharing resistance exists among single-celled organisms, and is termed horizontal gene transfer in which there is a direct exchange of genes, particularly in the biofilm
Biofilm
A biofilm is an aggregate of microorganisms in which cells adhere to each other on a surface. These adherent cells are frequently embedded within a self-produced matrix of extracellular polymeric substance...

 state. A similar asexual method is used by fungi and is termed parasexuality. Examples of drug-resistant strains are to be found in microorganisms such as bacteria and viruses, parasites both endo- and ecto-, plants, fungi, arthropods, mammals, birds, reptiles, fish and amphibians.

In the domestic environment, drug-resistant strains of organism may arise from seemingly safe activities such as the use of bleach
Bleach
Bleach refers to a number of chemicals that remove color, whiten, or disinfect, often via oxidation. Common chemical bleaches include household chlorine bleach , lye, oxygen bleach , and bleaching powder...

, tooth-brushing and mouthwashing, the use of antibiotics, disinfectants and detergents, shampoos and soaps, particularly antibacterial soaps, hand-washing, surface sprays, application of deodorants, sunblocks and any cosmetic or health-care product, insecticides and dips. The chemicals contained in these preparations, besides harming beneficial organisms, may intentionally or inadvertently target organisms that have the potential to develop resistance and thereby become increasingly problematic.

"Drug resistance develops naturally, but careless practices in drug supply and use are hastening it unnecessarily." - Center for Global Development

"The overuse of antibacterial cleaning products in the home may be producing strains of multi-antibiotic-resistant bacteria." - Better Health Channel - Australian Government

"The use and misuse of antimicrobials in human medicine and animal husbandry over the past 70 years has led to a relentless rise in the number and types of microorganisms resistant to these medicines - leading to death, increased suffering and disability, and higher healthcare costs." - World Health Organisation 2010

"Deaths from acute respiratory infections, diarrhoeal diseases, measles
Measles
Measles, also known as rubeola or morbilli, is an infection of the respiratory system caused by a virus, specifically a paramyxovirus of the genus Morbillivirus. Morbilliviruses, like other paramyxoviruses, are enveloped, single-stranded, negative-sense RNA viruses...

, AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...

, malaria
Malaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...

 and tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...

 account for more than 85% of the mortality from infection worldwide. Resistance to first-line drugs in most of the pathogens causing these diseases ranges from zero to almost 100%. In some instances resistance to second- and thirdline agents is seriously compromising treatment outcome. Added to this is the significant global burden of resistant hospital-acquired infections, the emerging problems of antiviral resistance and the increasing problems of drug resistance in the neglected parasitic diseases of poor and marginalized populations." - WHO Global Strategy for Containment of Antimicrobial Resistance 2010

Mechanisms


The four main mechanisms by which microorganisms exhibit resistance to antimicrobials are:
  1. Drug inactivation or modification: e.g., enzymatic deactivation of Penicillin G
    Penicillin
    Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....

     in some penicillin-resistant bacteria through the production of β-lactamases.
  2. Alteration of target site: e.g., alteration of PBP — the binding target site of penicillins — in MRSA and other penicillin-resistant bacteria.
  3. Alteration of metabolic pathway: e.g., some sulfonamide-resistant bacteria do not require para-aminobenzoic acid (PABA), an important precursor for the synthesis of folic acid
    Folic acid
    Folic acid and folate , as well as pteroyl-L-glutamic acid, pteroyl-L-glutamate, and pteroylmonoglutamic acid are forms of the water-soluble vitamin B9...

     and nucleic acids in bacteria inhibited by sulfonamides. Instead, like mammalian cells, they turn to utilizing preformed folic acid.
  4. Reduced drug accumulation: by decreasing drug permeability
    Semipermeable membrane
    A semipermeable membrane, also termed a selectively permeable membrane, a partially permeable membrane or a differentially permeable membrane, is a membrane that will allow certain molecules or ions to pass through it by diffusion and occasionally specialized "facilitated diffusion".The rate of...

     and/or increasing active efflux (pumping out) of the drugs across the cell surface.

Metabolic price


Biological cost or metabolic price is a measure of the increased energy metabolism required to achieve a function.

Drug resistance has a high metabolic price, in pathogens for which this concept is relevant (bacteria, endoparasites, and tumor cells.) In viruses, an equivalent "cost" is genomic complexity.

Treatment


The chances of drug resistance can sometimes be minimised by using multiple drugs simultaneously. This works because individual mutations can be independent and may tackle only one drug at a time; if the individuals are still killed by the other drugs, then the mutations cannot persist. This was used successfully in tuberculosis. However, cross resistance where mutations confer resistance to two or more treatments can be problematic.

For antibiotic resistance
Antibiotic resistance
Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...

, which represents a widespread problem nowadays, destroying the resistant bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

 can be achieved by phage therapy
Phage therapy
Phage therapy is the therapeutic use of bacteriophages to treat pathogenic bacterial infections. Although extensively used and developed mainly in former Soviet Union countries circa 1920, this method of therapy is still being tested for treatment of a variety of bacterial and poly-microbial...

, in which specific bacteriophage
Bacteriophage
A bacteriophage is any one of a number of viruses that infect bacteria. They do this by injecting genetic material, which they carry enclosed in an outer protein capsid...

 (virus that kill bacteria) are being used.

See also

  • multidrug resistance
    Multidrug resistance
    Multiple drug resistance or Multidrug resistance is a condition enabling a disease-causing organism to resist distinct drugs or chemicals of a wide variety of structure and function targeted at eradicating the organism...

  • antibiotic resistance
    Antibiotic resistance
    Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...

  • mass drug administration
    Mass drug administration
    The administration of drugs to whole populations irrespective of disease status is referred to as mass drug administration . This article describes the administration of antimalarial drugs to whole populations an intervention which has been used as a malaria-control measure for more than 70 years...

  • pharmacoepidemiology
    Pharmacoepidemiology
    Pharmacoepidemiology is the study of the use of and the effects of drugs in large numbers of people.To accomplish this study, pharmacoepidemiology borrows from both pharmacology and epidemiology. Thus, pharmacoepidemiology is the bridge between both pharmacology and epidemiology...


External links