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Multidrug resistance




Multidrug resistance is the ability of disease-causing organisms to withstand a wide-variety of structurally and functionally distinct drugs or chemicals that are designed to aid in the eradication of such organisms. These organisms can be pathologic cells, including bacterial and neoplastic (tumor) cells.

Contents

Bacterial resistance to antibiotics

Main article: Antibiotic resistance

Microorganisms have survived for thousands of years by their extreme adaptability when it comes to antimicrobial agents. They do so via spontaneous mutation or by DNA transfer.

Some bacteria have been able to adapt so that certain antibiotics are no longer effective. They have done this via several mechanisms.

  • No longer relying on a glycoprotein cell wall.
  • Enzymatic deactivation of antibiotics
  • Decreased cell wall permeability to antibiotics
  • Altered target sites of antibiotic
  • Efflux mechanisms to remove antibiotics
  • Increased mutation rate as a stress response [1]

Many different bacteria now exhibit multidrug resistance, including staphylococci, enterococci, gonococci, streptococci, salmonella, Mycobacterium tuberculosis and others. Additionally, 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, who then are also able to pass on the resistant gene.

To limit the development of antibiotic resistance:

  • Only use antibiotics for bacterial infections
  • Identify the causative organism if possible
  • Use the right antibiotic; don't rely on broad range antibiotics
  • Don't stop antibiotics as soon as symptoms improve; finish the full course
  • Most colds, coughs, bronchitis, sinus infections, and eye infections are caused by viruses; do not use antibiotics

To help this process governments need to legislate greater restrictions on use of antibiotics, particularly for treating animals such as battery hens.

Neoplastic resistance

Cancer cells also have the ability to become resistant to multiple different drugs, and share many of the same mechanisms:

  • Increased efflux of drug (as by P-glycoprotein, multidrug resistance-associated protein, lung resistance related protein, and breast cancer resistance protein)
  • Enzymatic deactivation (i.e. glutathione conjugation)
  • Decreased permeability (drugs can't enter the cell)
  • Altered binding-sites
  • 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 are such a variety of different DNA mutations that cause or contribute to tumor formation as well as a myriad of 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, and therefore they are much more difficult to damage without also damaging healthy cells.

See also

References

  • Noble: Textbook of Primary Care Medicine, 3rd ed., Mosby, Inc. 2001.
  • Guminski, A. (2002). Scientists and clinicians test their metal-back to the future with platinum compounds. The Lancet Oncology 3(5).
  • Krishan, A. (2000). Monitoring of cellular resistance to cancer chemotherapy. Hematol Oncol Clin North Am. 16(2): 357-72.

^  Gary Stix (April 2006). "An Antibiotic Resistance Fighter". Scientific American 294 (4): 81-83.

 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Multidrug_resistance". A list of authors is available in Wikipedia.
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