Scientists have tried to bolster the impact of pyrethroids by mixing them with neonicotinoids.
These systemic poisons are the most widely used group of insecticides, especially in agriculture.
They have become controversial in recent years because many scientists believe they are having a detrimental impact on bees and other wildlife.
In this study, the researchers collected populations of bed bugs in Cincinnati and Michigan back in 2012 and exposed them to four different neonicotinoid insecticides.
"The insects produce detoxifying enzymes, and they use them to detoxify and this is one of the mechanisms they might be using to counter the insecticide effect," said Dr Alvaro Romero, the lead author from New Mexico State University, speaking to BBC News.
"In this paper we found that the Jersey city and these other strains have elevated enzymes. This is one piece of evidence that we have that these might have a role, but we need to do more work," he added.
The researchers stress that although they have found significant levels of resistance to neonics in two locations that doesn't mean that bed bugs all over the US and the rest of the world are now immune from chemicals.
But they recognise that there is nothing new coming down the chemical pipeline right now.