The outbreak was stopped by substantially reducing use of ciprofloxacin and related antibiotics, researchers said.
Inappropriate use and widespread over prescribing of fluoroquinolone antibiotics such as ciprofloxacin allowed Clostridium difficile bugs that were resistant to the drug to thrive, because non-resistant bugs in the gut were killed off by the antibiotic, leaving the way clear for rapid growth of resistant C difficile.
Concerns about hospital "superbugs" which had become resistant to common antibiotics resulted in the announcement of a programme of "deep cleaning" and other infection control measures in the UK's National Health Service (NHS) in 2007.
The restriction of fluoroquinolones resulted in the disappearance in the vast majority of cases of the infections caused by the antibiotic-resistant C difficile, leading to around an 80 per cent fall in the number of these infections.
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In contrast, the smaller number of cases caused by C difficile bugs that were not resistant to fluoroquinolone antibiotics stayed the same.
At the same time, the number of bugs that were transmitted between people in hospitals did not change. This was despite the implementation of comprehensive infection prevention and control measures, like better handwashing and hospital cleaning in this case.
The researchers conclude that ensuring antibiotics are used appropriately is the most important way to control the C difficile superbug.
They note that it is important that good hand hygiene and infection control continues to be practiced to control the spread of other infections.
More than 4,000 C diff bugs also underwent genetic analysis using a technique called whole genome sequencing, to work out which antibiotics each bug was resistant to.
"Alarming increases in UK hospital infections and fatalities caused by C difficile made headline news during the mid-2000s and led to accusations of serious failings in infection control," said Derrick Crook, Professor of Microbiology, University of Oxford.
"These findings are of international importance because other regions such as North America, where fluoroquinolone prescribing remains unrestricted, still suffer from epidemic numbers of C difficile infections," Crook said.