Multidrug resistance
Encyclopedia
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. Organisms that display multidrug resistance can be pathologic cells, including bacteria
l and neoplastic (tumor
) cells.
Many different bacteria now exhibit multidrug resistance, including staphylococci, enterococci, gonococci, streptococci, salmonella
, Mycobacterium tuberculosis
, and others. In addition, some resistant bacteria are able to transfer copies of DNA
that codes for a mechanism of resistance to other bacteria, thereby conferring resistance to their neighbors, which then are also able to pass on the resistant gene. This process is called horizontal gene transfer
.
To limit the development of antibiotic resistance, one should:
It is argued that government legislation will aid in educating the public on the importance of restrictive use of antibiotics, not only for human clinical use but also for treating animals raised for human consumption.
As an alternative to antibiotics, destroying the resistant bacteria can often still be archeived by using specific bacteriophage
(virus that kill bacteria).
cells also have the ability to become resistant to multiple different drugs, and possess many of the same mechanisms:
Because efflux is a significant contributor for multidrug resistance in cancer cells, current research is aimed at blocking specific efflux mechanisms. Treatment of cancer is complicated by the fact that there is such a variety of different DNA mutations that cause or contribute to tumor formation, as well as myriad mechanisms by which cells resist drugs. There are also certain notable differences between antibiotic drugs and antineoplastic (anticancer) drugs that complicate designing antineoplastic agents. Antibiotics are designed to target sites that are specific and unique to bacteria, thereby harming bacteria without harming host cells. Cancer cells, on the other hand, are altered human cells; therefore they are much more difficult to damage without also damaging healthy cells.
infections are almost uniformly fatal because of their resistance to antifungal agents. (http://www.ncbi.nlm.nih.gov/pubmed/12627286 and http://jcm.asm.org/cgi/content/abstract/41/8/3981 Combatting increasing resistance)
DRUGS
Destroy Rebuild Until God Shows are an American post-hardcore band formed in 2010. They released their debut self-titled album on February 22, 2011.- Formation :...
or chemicals of a wide variety of structure and function targeted at eradicating the organism. Organisms that display multidrug resistance can be pathologic cells, including 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...
l and neoplastic (tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
) cells.
Common MultiDrug-Resistant Organisms (MDROs)
- Vancomycin-Resistant EnterococciVancomycin-Resistant EnterococcusVancomycin-resistant Enterococcus, or vancomycin-resistant enterococci , are bacterial strains of the genus Enterococcus that are resistant to the antibiotic vancomycin. To become VRE, vancomycin-sensitive enterococci typically obtain new DNA in the form of plasmids or transposons which encode...
(VRE) - Methicillin-Resistant StaphylococcusStaphylococcusStaphylococcus is a genus of Gram-positive bacteria. Under the microscope they appear round , and form in grape-like clusters....
aureus (MRSA) - Extended-spectrum ß-lactamse (ESBLs) producing Gram-negative bacteria
- Klebsiella pneumoniae carbapenemase (KPC) producing Gram-negatives
- ImipenemImipenemImipenem is an intravenous β-lactam antibiotic developed in 1980. It has an extremely broad spectrum of activity.Imipenem belongs to the subgroup of carbapenems. It is derived from a compound called thienamycin, which is produced by the bacterium Streptomyces cattleya...
-resistant or MultiDrug-Resistant Organisms AcinetobacterAcinetobacterAcinetobacter [asz−in−ée−toe–back−ter] is a genus of Gram-negative bacteria belonging to the Gammaproteobacteria. Acinetobacter species are non-motile and oxidase-negative, and occur in pairs under magnification....
baumannii - Imipenem-resistant or MultiDrug-Resistant Organisms PseudomonasPseudomonasPseudomonas is a genus of gammaproteobacteria, belonging to the family Pseudomonadaceae containing 191 validly described species.Recently, 16S rRNA sequence analysis has redefined the taxonomy of many bacterial species. As a result, the genus Pseudomonas includes strains formerly classified in the...
aerginosa
Bacterial resistance to antibiotics
Various microorganisms have survived for thousands of years by their being able to adapt to antimicrobial agents. They do so via spontaneous mutation or by DNA transfer. This process enables some bacteria to oppose the assault of certain antibiotics, rendering the antibiotics ineffective. These microorganisms employ several mechanisms in attaining multidrug resistance:- No longer relying on a glycoprotein cell wallCell wallThe cell wall is the tough, usually flexible but sometimes fairly rigid layer that surrounds some types of cells. It is located outside the cell membrane and provides these cells with structural support and protection, and also acts as a filtering mechanism. A major function of the cell wall is to...
- Enzymatic deactivation of antibiotics
- Decreased cell wall permeability to antibiotics
- Altered target sites of antibiotic
- EffluxEfflux (microbiology)Active efflux is a mechanism responsible for extrusion of toxic substances and antibiotics outside the cell; this is considered to be a vital part of xenobiotic metabolism...
mechanisms to remove antibiotics - Increased mutation rateMutation rateIn genetics, the mutation rate is the chance of a mutation occurring in an organism or gene in each generation...
as a stress response
Many different bacteria now exhibit multidrug resistance, including staphylococci, enterococci, gonococci, streptococci, salmonella
Salmonella
Salmonella is a genus of rod-shaped, Gram-negative, non-spore-forming, predominantly motile enterobacteria with diameters around 0.7 to 1.5 µm, lengths from 2 to 5 µm, and flagella which grade in all directions . They are chemoorganotrophs, obtaining their energy from oxidation and reduction...
, Mycobacterium tuberculosis
Mycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...
, and others. In addition, some resistant bacteria are able to transfer copies of DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
that codes for a mechanism of resistance to other bacteria, thereby conferring resistance to their neighbors, which then are also able to pass on the resistant gene. This process is called 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...
.
To limit the development of antibiotic resistance, one should:
- Use antibiotics only for bacterial infections
- Identify the causative organism if possible
- Use the right antibiotic; do not rely on broad-range antibiotics
- Not stop antibiotics as soon as symptoms improve; finish the full course
- Not use antibiotics for most colds, coughs, bronchitis, sinus infections, and eye infections, which are caused by viruses.
It is argued that government legislation will aid in educating the public on the importance of restrictive use of antibiotics, not only for human clinical use but also for treating animals raised for human consumption.
As an alternative to antibiotics, destroying the resistant bacteria can often still be archeived by using 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).
Neoplastic resistance
CancerCancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
cells also have the ability to become resistant to multiple different drugs, and possess many of the same mechanisms:
- Increased efflux of drug (as by P-glycoproteinP-glycoproteinP-glycoprotein 1 also known as multidrug resistance protein 1 or ATP-binding cassette sub-family B member 1 or cluster of differentiation 243 is a glycoprotein that in humans is encoded by the ABCB1 gene...
, multidrug resistance-associated protein, lung resistance-related protein, and breast cancer resistance protein & reproductive cancer resistance protein) - Enzymatic deactivation (i.e., glutathione conjugation)
- Decreased permeability (drugs cannot enter the cell)
- Altered binding-sitesBinding siteIn biochemistry, a binding site is a region on a protein, DNA, or RNA to which specific other molecules and ions—in this context collectively called ligands—form a chemical bond...
- Alternate metabolic pathways (the cancer compensates for the effect of the drug).
Because efflux is a significant contributor for multidrug resistance in cancer cells, current research is aimed at blocking specific efflux mechanisms. Treatment of cancer is complicated by the fact that there is such a variety of different DNA mutations that cause or contribute to tumor formation, as well as myriad mechanisms by which cells resist drugs. There are also certain notable differences between antibiotic drugs and antineoplastic (anticancer) drugs that complicate designing antineoplastic agents. Antibiotics are designed to target sites that are specific and unique to bacteria, thereby harming bacteria without harming host cells. Cancer cells, on the other hand, are altered human cells; therefore they are much more difficult to damage without also damaging healthy cells.
Antifungal resistance
Scedosporium prolificansScedosporium prolificans
Scedosporium prolificans is an emerging opportunist fungus that causes different types of infections in immunocompetent and immunosuppressed people. Originally named Lomentospora prolificans in 1974, it was transferred to the genus Scedosporium in 1991....
infections are almost uniformly fatal because of their resistance to antifungal agents. (http://www.ncbi.nlm.nih.gov/pubmed/12627286 and http://jcm.asm.org/cgi/content/abstract/41/8/3981 Combatting increasing resistance)
See also
- Antibiotic tolerance
- Drug resistanceDrug resistanceDrug resistance is the reduction in effectiveness of a drug such as an antimicrobial or an antineoplastic in curing a disease or condition. When the drug is not intended to kill or inhibit a pathogen, then the term is equivalent to dosage failure or drug tolerance. More commonly, the term is used...
- MDRGN bacteriaMDRGN bacteriaMDRGN bacteria is an abbreviation for multidrug resistant gram-negative bacteria. For hospitalized patients, and especially patients in intensive care units, these bacterial infections pose a serious and rapidly emerging threat....
- Xenobiotic metabolismXenobiotic metabolismXenobiotic metabolism is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organism's normal biochemistry, such as drugs and poisons...
- Multidrug toleranceMultidrug toleranceMultidrug tolerance or antibiotic tolerance is the ability of a disease-causing microorganism to resist killing by antibiotics or other antimicrobials. It is mechanistically distinct from multidrug resistance: It is not caused by mutant microbes, but rather by microbial cells that exist in a...