The number of deaths involving the hospital bug Clostridium difficile in England and Wales rose by 28% between 2006 and 2007, official figures show.
The Office for National Statistics data reports C. difficile was mentioned on 8,324 death certificates compared to 6,480 in the previous year.
Experts say the increase may partly be due to better reporting of the infection.
However, deaths from the superbug MRSA fell slightly over the same period.
It went down from 1,652 in 2006 to 1,593 in 2007 - the first time the number of MRSA-related deaths has fallen since the ONS began keeping records in 1993.
The government called for more accurate reporting of MRSA and C. difficile on death certificates in 2005.
The following year - 2006-07, the number of cases where C. difficile was mentioned as a factor in a death soared by 72%.
The infection is the underlying cause of death in around half of the cases.
Professor Brian Duerden, the government's inspector of microbiology and infection control, said: "Patients have a right to high quality, safe care.
"We take this very seriously, which is why we have made infection prevention and control a legal requirement and a number one priority for the NHS.
"We have taken significant steps to tackle infections, including C. difficile. These include stringent hand-washing guidance for the NHS, clear guidance on appropriate antibiotic prescribing and the clinical care of patients with C. difficile.
"Cases of MRSA and C. difficile infections are falling and for the first time we are seeing the number of recorded deaths from MRSA falling too.
"However, people who are very ill are vulnerable to infections, not all of which are avoidable.
"We believe the rise in the number of C. difficile cases recorded as a contributing factor on death certificates does not represent a rise in actual deaths, but primarily an increase in awareness and reporting."
The government has said it wants to cut deaths linked to C. difficile by a third by 2010-11.
Professor Dearden said £230m was being invested each year in order to meet that target.
Liberal Democrat health spokesman Norman Lamb said: "These are horrifying statistics. The truth is that these could be avoidable deaths."
There has been a fall in the number of actual cases of C. difficile.
In the over-65s - the main age group affected - the number fell by 9% between 2006 and 2007 to 50,392.