The warning is from the HSE director general Tony O’Brien who said the bill including "considerable" litigation costs.
Over 100 thousand euro is being spent dealing with a small outbreak at a care facility in Donegal.
The CPE bug represents a "current and future significant threat" to the health and safety of patients that could cost more than €20 million a year to tackle, Mr O'Brien stated in an internal memo, seen by The Irish Times.
"Litigation costs to the health service are likely to be considerable and would certainly exceed the estimated €20 million cost of controlling even a limited number of outbreaks," he wrote.
A number of Irish hospitals are currently battling outbreaks of CPE.
Up to 2 per cent of cases detected so far have been invasive, involving septicaemia, meningitis and deep abscesses. Up to 50 per cent of such cases can be fatal.
Mr O'Brien says expert opinion is that Ireland is still in a position to contain the epidemic but needs to respond urgently.
University Hospital Limerick has spent €4 million on dealing with 60 cases since 2015, while the estimated cost of a small outbreak in a long-term care facility in Co Donegal is €106,000, he said.