A combination of pesticide and non-pesticide approaches is one of the best eradication methods for managing a bedbug infestation. Historically effective pesticides include pyrethroids, malathion, and dichlorvos; however their use raises concerns of the negative health effects they have on humans. In addition, bedbugs have a significantly increased resistance to pesticides. It is also recommended to use mechanical approaches, such as heat wrapping or treating the mattresses and vacuuming up the bedbugs themselves. Although carbamate insecticide propoxur has proven to be highly toxic towards bedbugs, the Environmental Protection Agency (EPA) has not officially approved the chemicals for indoor use due to its potentially toxic effect on children after chronic exposure.

Pesticides such as DDT, organophosphates, and pyrethroid are starting to become less effective due to their growing resistance rate. As a result, the use of synthetic pyrethroid and the pryrrole insecticide chlorfenapyr has become a growing interest. Insect growth regulators may also be used, such as hydroprene (or Gentrol). Bedbugs found in Arkansas are reported to be highly resistant to DDT, while studies conducted in Africa show that DDT causes the bedbugs to be more active and productive. Infestations sampled across the United States proved to be one thousand times more resistant to pyrethroids compared to laboratory bedbugs. Due to nerve cell mutations, bedbugs in New York City are 264 times more resistant to deltamethrin than the bedbugs in Florida.

By using a mitochondrial DNA marker within a population genetics study of bedbugs throughout the United States, Australia, and Canada, evidence was found to support high levels of genetic variation with the species. However, no genetic variations were observed within the nuclear RNA marker. As a result of insecticide control during the 1940's and 1950's, many expected the bedbug populations to undergo a genetic bottleneck effect, however that was not the case. A genetic bottleneck, or population bottleneck, is an evolutionary occurrence in which a significant percentage of a species or population is killed off and ultimately prevented from reproducing.

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