The UK government is set to allow community pharmacists to issue trimethoprim to women with uncomplicated urinary tract infections, but could wider access to antibiotics worsen antimicrobial resistance? Rod Tucker investigates.
In May 2023, the UK’s Department of Health and Social Care, issued its ‘Delivery plan for recovering access to primary care’. A key driver for the report was the apparent lack of adequate access to primary care services.
The report outlined several innovative solutions for improving access, one of which was to allow pharmacists to supply prescription-only medicines, including antibiotics and antivirals, for the treatment of seven common conditions. One such condition was uncomplicated urinary tract infection (UTI) in women requiring, where appropriate, treatment with trimethoprim.
In a footnote, the report mentioned that this provision would be via patient group directions (PGDs). These written instructions for the supply or administration of medicines to patients in planned circumstances, are commonly used in the UK. In fact, a PGD for the supply of trimethoprim via a PGD is already available in many parts of the UK, thereby enabling self-care access to treatment for an uncomplicated UTI.
Despite the current availability of a trimethoprim PGD, opponents to widening of the access to antibiotics such as trimethoprim, argue that this could ultimately increase antimicrobial resistance. But are these concerns justified and, more importantly, is there evidence that antimicrobial resistance to trimethoprim increases as a result of pharmacy supply?
Pharmacists and the supply of trimethoprim
The idea of supplying trimethoprim without prescription for the treatment of uncomplicated UTIs has been previously explored in the UK. In 2008, the MHRA proposed that trimethoprim should become available for sale in pharmacies without a prescription. However, concerns were raised and by 2010, the potential switch had been halted.
This disquiet arose in part, because of the evidence that resistance to multiple agents is often linked. In other words, the selective pressure of using one antibiotic will often lead to the resistance of other unrelated agents. Moreover, a study in 2019 also found that a history of more than three prescriptions for extended-spectrum penicillins was significantly associated with trimethoprim resistance in E. coli-causing UTIs.
Tackling antimicrobial resistance has become global collaborative, with many countries introducing antimicrobial stewardship programmes. While it is abundantly clear that increased prescribing of antibiotics such as trimethoprim is linked to a greater incidence of trimethoprim-resistant bacteraemia, it is less clear whether the converse is true. That is, do antimicrobial stewardship programmes, which are designed to ensure more appropriate use of antibiotics, actually reduce levels of antibiotic resistance?
Until fairly recently, this was an important unknown. The evidence that these stewardship programmes did in fact lower the incidence of resistant organisms came from the publication of a 2020 study by researchers in Bristol. The findings were very clear: initiatives to reduce antibiotic use were associated with a decrease in levels of resistance. For example, the practice-level odds of resistance to trimethoprim decreased by 4% for every 100 fewer trimethoprim items dispensed per 1,000 patients per annum.
Precisely why the UK government is intent on extending access to an antibiotic is unclear, especially as this approach is incompatible with existing policy. For instance, the report, ‘Tackling Antimicrobial Resistance 2019-2024‘ set a target to reduce UK antimicrobial use in humans by 15% by 2024. Consequently, attempts to increase antibiotic use – as with the pharmacy trimethoprim scheme – would not only thwart this target but potentially increase antimicrobial resistance.
Are PGDs the ideal solution?
As the PGD model is UK specific, how have other countries approached increased access to trimethoprim through pharmacies? The available evidence would suggest that suppling antibiotics through a pharmacy for uncomplicated UTIs, is both safe and of immense value to patients.
For example, a recent Canadian study, although not using trimethoprim, calculated that pharmacy management of uncomplicated UTI’s would be a cost-effective strategy. The same researchers also reported that patients treated by pharmacists had a clinical cure rate of 88.9% and that there were very high levels of satisfaction with the care they received.
In New Zealand, where supplies of trimethoprim for uncomplicated UTIs are available from specially trained pharmacists, such supplies have had little overall effect on antibiotic use. In a follow-up study, researchers found that one year after the introduction of the New Zealand scheme, pharmacist prescribing of trimethoprim accounted for less than 5% of GP prescribing for the drug.
The findings from the latter study go some way towards placating those who believe that more widespread availability of antibiotics would drive up usage and potentially antibiotic resistance. To put the New Zealand study findings into perspective, after the re-classification of chloramphenicol eye drops from prescription to over-the-counter status in the UK, there was a 47.8% increase in total chloramphenicol use. But, despite this huge increase in usage, a 2023 review found that resistance to ocular chloramphenicol ranged from 0 to 74.1%. In addition, the study reassuringly noted how, in the UK, the median estimate of resistance was 13.1% between 2000 and 2020.
There is limited data on the effectiveness of a PGD-based supply of trimethoprim apart from a 2013 study, which found that community pharmacy supply helped to improve patient access to treatment. One notable concern in the study, however, was that the inclusion and exclusion criteria for the supply of the drug were only met in 76% of cases.
Should pharmacists use a diagnostic point of care test?
The use of a PGD for the supply of trimethoprim relies on the women reporting specific symptoms. An alternative strategy is for a pharmacist to undertake a point-of-care diagnostic test in conjunction with symptoms. This was suggested by a group of UK scientists who warned in an open letter to Rishi Sunak, published in The Telegraph, that making trimethoprim available from pharmacies might contribute to the public health crisis and spread of antibiotic resistance.
It seems that concerns over greater access to antibiotics from pharmacies are not just restricted to the UK. In 2020, the Queensland government proposed that pharmacists could supply trimethoprim and this prompted concerns based on data showing how Australia’s rate of trimethoprim resistance in E. coli had increased from an estimated 21-29% in 2014 to 33% in 2017.
Despite these protestations, in 2022, the Queensland government decided to extend the trimethoprim prescribing pilot scheme, a move that was heavily criticised by the Royal Australian College of General Practitioners, whose own research suggested that as many as one in five GPs could have treated patients with complications resulting from their involvement in the pharmacy pilot.
The level of trimethoprim prescribing in the UK fell slightly between 2017 and 2021, according to the latest ‘English surveillance programme for antimicrobial utilisation and resistance‘ report covering 2021/22. However, trimethoprim resistant organisms are still a concern, with a 2022 study of patients with E. coli bacteraemia related to a UTI noting the presence of resistant organisms in 41% of blood culture isolates.
There is no doubt that improving access to trimethoprim from pharmacies is beneficial to women. This is particularly important in the context of the current healthcare climate, with many GPs leaving the profession and patients struggling to get an appointment. But, with clear evidence that reducing antibiotic use also lowers levels of antimicrobial resistance, it seems that concerns over increased resistance may turn out to be correct.
Finally, in an era where tackling antimicrobial resistance has become a global priority, extending the provision of trimethoprim through pharmacies ultimately becomes nothing more than a large and uncontrolled experiment for which the intended benefits may turn out to be significantly outweighed by the ensuing harm to the wider community.