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Drug resistance

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Drug resistance is the reduction of effect 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, the 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:

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.

To counter 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 pan-drug resistant strains of Staphylococcus aureus, Klebsiella pneumonia, and Pseudomonas aerginosa, 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 astounding 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 HIV pandemic, 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. In short, the lack of concerted effort by governments and the pharmaceutical industry, together with the innate capacity of microbes to develop resistance at a rate that outpaces development of new drugs, suggests that existing strategies for developing viable, long-term anti-microbial therapies are ultimately doomed to failure. Without alternative strategies, the acquisition of drug resistance by pathogenic microorganisms looms as possibly the single most significant public health threat facing humanity in the coming century.


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