'Drug resistance' is the reduction in effectiveness of a drug in curing a disease or improving a patient's symptoms. 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 in the context of diseases caused by
pathogens.
Pathogens are said to be 'drug-resistant' when
drugs meant to neutralize them have reduced effect. When an organism is resistant to more than one drug, it is said to be
multidrug resistant.
Drug resistance occurs in several classes of pathogens:
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bacteria --
antibiotic resistance
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endoparasites
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viruses --
resistance to antiviral drugs
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fungi
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cancer cells
The most prominent is
antibiotic resistance. Drug resistance is also found in some
tumor cells, which makes it more difficult to use
chemotherapy to attack tumors made of those cells.
Resistance to antiviral drugs also occurs in virus populations, notably
HIV. When a drug is administered, those organisms which have a
genetic resistance to the drug will survive and reproduce, and the new population will be drug-resistant (see
natural selection,
selection pressure).
In the presence of drugs, pathogens have
evolved sophisticated mechanisms to inactivate these compounds (e.g. by pumping out compounds, mutating residues required for the compound to bind, etc.), and they do so at a rate that far exceeds the pace of new development of drugs. Examples include
drug resistant strains of Staphylococcus aureus,
Klebsiella pneumonia, and
Pseudomonas aeruginosa, and
Mycobacterium tuberculosis (TB) among bacterium and
HIV-1 among viruses. Indeed, no new
antibiotics have been developed against TB in thirty years. Efforts to develop new antibiotics by the
pharmaceutical industry by large-scale screens of chemical libraries which inhibit bacterial growth have largely failed, and new
tetracycline and
sulfanilamide analogs will likely engender resistance and will quickly be rendered useless. The resistance problem is compounded further by indiscriminate and inappropriate use of antibiotics and anti-viral compounds without compliance measures or public health policies to reduce disease burden. Finally, with current legislative restrictions, the very high costs associated with clinical trials (e.g. ~$400M to bring new tetracyclines to market for an expected revenue of ~$100M), the failure to control generic sales, and the capacity to generate substantial revenues from medications for chronic illnesses, there is little if any financial incentive for big pharmaceutical companies to even develop new antibiotics, and small biotech companies simply do not have the resources. The search for novel anti-viral compounds has been somewhat more successful and largely motivated by the
AIDS epidemic, but drugs have been developed principally against viral targets, and
mutation rates among viruses still outpaces new development. One positive development has been
vaccines, which are promising for some bacterial and viral illnesses. But vaccines are not successful in all cases (e.g. in young children), and adequate resources have not been made available.
See also
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multidrug resistance
External links
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BURDEN of Resistance and Disease in European Nations - An EU-Project to estimate the financial burden of antibiotic resistance in European Hospitals