In a speech on discipline, the Tory leader described the units as the "weakest link in the system" and called for a new approach.
"It's time for the state sector to say that when it comes to these children, we're doing a bad job and you're doing a great job we want to trust you with more resources, longer contracts and more freedom," he said.
He named charities which he said were succeeding with a mixture of discipline, kindness and hard work.
But Rev John Stacy-Marks, director of the Amelia Trust in Wales, says the service his trust offers complements that offered by PRUs.
"A PRU is for those pupils who can stay academically focused," he said. "But a lot of our youngsters find it difficult to focus for any period of time and are more able to work with their hands, which we allow them to do."
In Mr Cameron's own Oxfordshire constituency of Witney, Base 33 takes up to 12 excluded Year 11 pupils at a time. They can study for five good GCSEs as part of an alternative approach to education designed to keep them interested.
Their day begins with a breakfast that allows them to settle before they begin studies which are broken down into small chunks of no more than 30 minutes. Alongside academic lessons, the pupils work towards Duke of Edinburgh awards and do activities such as DJ-ing and fitness training.
Mark Bennett (left), a youth worker at Base 33, believes the centre works better than PRUs for some and would like to see it expand to nearby towns.
"The idea is similar to a PRU," he said. "But we do drop-in sessions and detached youth work as well so the response rate we get can be better.
"We are not just there nine to five. I may be in a police station on Saturday night because a young person I am involved with has been nicked."
But he said: "We are not a replacement for PRUs. Each of us have good bits that the other can use. We need to put our heads together."