Researchers from Cardiff University found antibiotic treatment failure rates rose from 13.9% in 1991 to 15.4% in 2012, a relative increase of more than 12% in 21 years.
They said that given the lack of new antibiotics being developed, the growing ineffectiveness of those used in primary care was 'very worrying indeed'.
The BMJ study, funded by Abbott Healthcare Products, examined failure rates of antibiotics for upper respiratory tract infections (URTIs), lower respiratory tract infections (LRTIs), skin and soft tissue infections, and acute otitis media.
Researchers used surrogate outcomes for treatment failure, including switching drugs after 30 days of treatment and hospitalisation for an infection within 30 days of the first-line prescription.
Between 1991 and 2012, antibiotics were least effective for LRTIs, and the failure rate rose 35% over this time.
Failure rates of trimethoprim for URTIs rose by 40 percentage points, from 29.2% in 1991-95 to 70.1% in 2008-12.
'Clearly this is worrying'
Lead author Professor Craig Currie from Cardiff University’s School of Medicine said the rise in antibiotic treatment failure was linked to an increase in prescriptions.
He said: 'There is a mistaken perception that antibiotic resistance is only a danger for hospitalised patients, but recent antibiotic use in primary care is the single most important risk factor for an infection with a resistant organism. Furthermore, what happens in primary care impacts on hospital care and vice versa.
'Antibiotic resistance in primary care needs to be more closely monitored, which is actually quite difficult given that primary care clinicians seldom report treatment failures.
'The association between antibiotic resistance and antibiotic treatment failure also needs to be further explored. From the general level of feverish debate, it’s not quite the "cliff" we would have imagined, but clearly this is worrying.'