As many as one in five prescriptions for antibiotics written by GPs may be "inappropriate", health officials have said.
Public Health England (PHE) warned that using antibiotics when they are not needed "threatens their long-term effectiveness" as it published new research estimating that 20% of all antibiotic prescriptions written in primary care in England are inappropriate.
It said that to align with ambitions to cut levels of inappropriate prescribing in half, prescribing rates should reduce by 10% in the next two years.
Health experts have previously warned that resistance to antimicrobial drugs could cause a bigger threat to mankind than cancer.
In recent years, the UK has led a drive to raise global awareness of the threat posed to modern medicine by antimicrobial resistance.
Around 700,000 people around the world die annually due to drug-resistant infections including tuberculosis (TB), HIV and malaria.
If no action is taken, it has been estimated that drug-resistant infections will kill 10 million people a year by 2050.
The new research articles, published in a supplement to the Journal of Antimicrobial Chemotherapy, found that antibiotic prescribing rates varied substantially between GP practices, which the authors said means that there is potential to reduce prescribing in at least some practices.
They found that the majority of antibiotic prescriptions in English primary care were for infections of the respiratory and urinary tracts - but in almost one-third of all prescriptions no clinical justification was documented.
PHE medical director Professor Paul Cosford said: "Using antibiotics when you don't need them threatens their long term effectiveness and we all have a part to play to ensure they continue to help us, our families and communities in the future.
"This publication highlights the role GPs can play and I urge all practices to look at ways they can reduce their inappropriate prescribing levels to help make sure the antibiotics that save lives today can save lives tomorrow."
Health Secretary, Jeremy Hunt said: "Drug-resistant infections are one of the biggest threats to modern medicine and inappropriate prescribing of antibiotics is only exacerbating this problem.
"We are leading the world in our response -- since 2012, antibiotics prescribing in England is down by 5% and we've invested more than £615 million at home and abroad in research, development and surveillance. But we need to go further and faster otherwise we risk a world where superbugs kill more people a year than cancer and routine operations become too dangerous."
Professor Helen Stokes-Lampard, chairwoman of the Royal College of GPs, said: "Today's figures are extremely disappointing but they must not be used as an excuse for criticising GPs who are working their hardest to reduce antibiotic prescribing, whilst grappling with countless other workload pressures and a shortage of GPs.
"If GPs do prescribe antibiotics, it is because, in their expert opinion, they are the most appropriate treatment available, given the unique circumstances of the patients before us. However we are still coming under considerable pressure from some patients who need to understand that antibiotics are not a 'catch all' for every illness.
"Antibiotics are excellent drugs when used appropriately, and for many bacterial infections there is no alternative.
"But antimicrobial resistance is now a major global health threat and responsibility for tackling this does not lie solely at the door of GPs - the whole of society must play its part."