Hand-washing was "absolutely crucial" to protect visitors to petting farms, and under-fives "haven't learned how to do it yet", he told the BBC.
Young children were the most likely part of the population to get complications if they get infected, he added.
However the Department of Health said its advice remained the same: that children could pet animals as long as they practised good hand hygiene.
"Direct contact is not what presents the risk, it's what happens afterwards. If you use good hand hygiene and other measures, you hopefully shouldn't get it," a spokesperson said.
"Ill health following a visit to an open farm is unusual, even among children, and these risks need to be balanced against the benefits for a child's education and development that arise from contact with animals."
The spokesman added that current guidance was under review following the E.coli outbreaks last week.
The Health Protection Agency (HPA) said that, while infection risks are reduced by sites being well regulated and run, there would always be some E.coli risk from farm animals and their environment.
Whether to stay away from such attractions is "a decision for parents based on a balance of risks", its advice says.
The HPA's advice, published on its website, also remains unchanged despite Prof Pennington's warning.
But the mother of two young boys who suffered kidney failure following their visit to Godstone Farm in Surrey, said current guidelines were insufficient.
Tracy Mock said: "The guidelines were not clear enough before. We did the hand washing and we were careful about hygiene.
"There was information which told you about E.coli but you didn't really know what it was. You didn't really know it was much more than a stomach ache and you didn't know how serious it was."
However Miranda Stevenson, director of the British & Irish Association of Zoos & Aquariums, said facilities where children handled animals were strictly regulated and there were always either gels or washing facilities available.
"[Handling animals] is so good for the children - one would hate to get to the stage where we had to stop them doing it."
Forty-nine cases of E.coli have been linked to a Surrey farm
World of Country Life, in Exmouth, Devon, voluntarily closed its petting areas and deer train ride following infections in three children who visited the farm last month - although the farm has not been confirmed as the source.
Four people became infected after visiting White Post Farm at Farnsfield, Nottinghamshire, though no direct link has been confirmed there.
A total of 57 cases of E.coli have now been linked to Godstone Farm in Surrey, with its sister farm - Horton Park Children's Farm in Epsom - also closing because of hygiene concerns.
Nine children are being treated in hospital with Godstone Farm-linked infections; one is due to be allowed home later on Saturday, with the others remaining in a stable condition, according to the HPA.
Lab tests have identified the most serious E.coli strain, O157, which can cause serious kidney damage in a small proportion of cases.
There are about 20,000 cases of E.coli reported in England, Wales and Northern Ireland every year but last year just 950 cases in England and Wales were the O157 strain.
Since Prof Pennington made his comments, hundreds of members of the public have e-mailed the BBC News website, with the majority expressing opposition to a ban on the petting of animals.
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