drug resistance

A state in which a patient does not respond to a therapeutic drug. Bacteria may acquire resistance through gene mutation to a particular antibiotic by its overuse or misuse; for example, the first class of antibiotics, the sulphonamides, fell out of use when many common strains of bacteria became resistant. Development of resistance to a range of modern antibiotics, combined with poor living conditions in many inner cities, has led to predictions of new epidemics of infectious diseases such as tuberculosis in the West, which may no longer be curable. Cancer cells may also acquire resistance to drugs which had previously been effective, requiring a change in the course of treatment. Resistance to malarial drugs is a major problem in tropical countries, where malaria causes a million deaths per year. Similarly, insects and other pests acquire resistance to agents (eg DDT) which previously controlled them.

Organisms are said to be drug-resistant when drugs meant to neutralize them have reduced effect. When a drug such as an antibiotic is administered, those which have a genetic resistance to the drug will survive and reproduce, and the new population will be drug-resistant. 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. 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. ~$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. 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.