Rates of infection remain high across England, the HPA says, and show room for improvement.
MRSA, another infection NHS trusts are attempting to control, was less prominent in the last quarter of last year however.
There were 1,542 cases reported in England from October 2006 to December 2006, down seven per cent on the previous quarter, which saw 1,652 reported cases of bloodstream infections caused by MRSA.
Dr Georgia Duckworth, head of the HPA's healthcare associated infection and antimicrobial resistance department, issued caution on taking quarterly statistics as showing a definite long-term rise or fall in infection rates.
"We are publishing these quarterly figures to give trusts more timely feedback on their individual situation and progress alongside other trusts," she explained.
"However it is important that provisional figures like these are interpreted with caution, as numbers can fluctuate from quarter to quarter. Longer periods are needed to assess whether the trend in the number of infections is rising or falling."
Commenting on the figures, shadow health secretary Andrew Lansley said: "In the last year, Labour have cut 6,000 nursing jobs. It is little wonder that we have seen such a rise in C-diff infections. Today's figures are just the tip of the iceberg, because they do not even include the huge number of infections in people aged under 65.
"In cutting one in every twenty NHS beds in the last two years, Labour have forced bed occupancy rates up to dangerously high levels. The government has badly let down NHS staff and the patients they care for."
In response to the HPA's statistics, the chief nursing officer (CNO) Chris Beasley announced a new raft of measures to tackle C difficile in hospitals.
These include improved surveillance and specialist improvement teams.
"The MRSA target has lead to improved clinical standards and the downward trend in MRSA numbers reflects this. However, even more work is necessary to step-up progress in the remaining year of this target," she said.
"Many trusts that have received help from MRSA improvement teams have seen significant reduction in infection. We are determined to see these national reductions replicated for C difficile."
Click here to run an energy price comparison, and see if you could be paying less for your gas and electricity.