In 2006 there were 55,681 cases of C difficile reported in patients aged 65 years and above in England, compared to 51,767 cases in 2005.
The infection rates for the last quarter have fallen from 15,335 in January to March 2006 to 12,814 in October to December, but an HPA spokesperson said it was too early to identify this as a trend.
The cases reported are highest in small acute trusts at 2.89 per 1,000 bed days, compared to 2.39 in medium trusts and 2.20 in small trusts.
The HPA has not speculated on why small acute trusts have higher infection rates, but it believes that more frequent reporting will help trusts monitor cases more closely.
The agency would not be drawn on the content of the guidance.
Announcing the upcoming guidance at the NHS Confederation conference on hospital-aquired infection last week, health minister Lord Hunt said: 'Tackling C difficile is of equal importance to combating MRSA. PCTs are now charged with local targets for a significant reduction in C difficile infections.
'There is a strong statutory basis placed on the boards. The emphasis is on supporting boards. But those who don't develop the right approach will find themselves in trouble.'
Healthcare Commission chief executive Anna Walker said that the figures for C difficile will be concerning for patients.
She said: 'We fully recognise that outbreaks of C difficile are not easy to control. But we also know that trusts can minimise the spread of infection by following rigorously established guidance on infection control.'
The Health Act 2006 requires all trusts to observe the provisions of the government's hygiene code, which came into force last October.
For the first time this year, trusts will have to declare whether they believe they have all the necessary measures in place to comply with the code as part of the annual assessment.
The commission has already followed up more than 40 trusts that declared non-compliance against the core standard on the control of infection in 2005-06.