Office for National Statistics figures show deaths from MRSA fell by 20% from 364 in 2011 to 292 in 2012.
The number of deaths from MRSA has now fallen by more than 75% since 2008.
There were 1,646 deaths from C. difficile in 2012, down from 2,053 in the previous year.
Both infections have shown large declines over the past five years after being repeatedly targeted by government policies.
The number of deaths from two hospital infections, MRSA and Clostridium difficile, have continued their long-term downward trend, according to figures for England and Wales.