Increasing resistance to antibiotics could lead to more illness and deaths, says the doctor responsible for managing their effectiveness in Wales.
Dr Robin Howe said clinicians and patients must accept they could only be used when they had most benefit.
Each year in Wales there are about 2,000 blood stream infections caused by E.coli, which resulted in death for one in five sufferers, he said.
He is concerned that number will rise if resistance to antibiotics continues.
Since their arrival in the 1940s, antibiotics have been on the frontline of medicine's battle against disease.
But experts are warning that they are becoming increasingly ineffective at a rate that is alarming and irreversible.
Dr Howe, of Public Health Wales, has the task of minimising deaths in Wales that are caused by bugs developing a resistance to antibiotics.
He told the BBC's Sunday Politics Wales programme: "Each year in Wales there are about 2,000 blood stream infections caused by E.coli.
"That's the commonest cause of blood stream infections here and across the UK.
"But it's a very important and serious infection because about one in five of the people who have a blood stream infection with that bug will die.
"And so an increase in those blood stream infections is an extremely serious problem."
Resistance to antibiotics has been increasing in Wales over the past seven years.
There are now superbugs such as MRSA that are immune to the drugs.
The more antibiotics that are used the more likely it is that any bacteria will evolve to build up a resistance to them.
One expert from Cardiff University, Professor Les Baillie, described it as an "arms race" between those developing drugs and the bacteria building resistance.
He said it was a battle that science may be losing.
"I hate to say that we're heading back towards the pre-antibiotics days when treating serious diseases was extremely problematic," he said.
"People are trying to, in the United Kingdom at least, develop strategies of controlling the antibiotics they use.
"So they always have something in reserve. It would be horrendous if we ever came to a situation where there was nothing left in the cupboard."
Prof Baillie and his team are researching whether traditional remedies, including tea and honey, could be the next way to battle the bugs.
Cardiff surgeon Rhidian Morgan-Jones said there were real concerns about what medicine would be like after antibiotics.
"You're going back to the last century where before antibiotics all you had to do was lance boils, drain the puss and put people in bed and rest them. And sometimes you cured them and sometimes you didn't."
All the experts in the field said it was important to educate clinicians and patients to only use antibiotics when they would deliver the maximum benefit.