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 bacterial and neoplastic (tumor) cells.

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. It is this very process that enables some bacteria to oppose the assault of certain antibiotics, rendering the antibiotics no longer effective. These microorganisms employ several mechanisms in attaining multidrug resistance:

• 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

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.

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.

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 cannot 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 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 prolificans 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

• Drug resistance
• Xenobiotic metabolism

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.

External links

• BURDEN of Resistance and Disease in European Nations - An EU-Project to estimate the financial burden of antibiotic resistance in European Hospitals

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