Resistance to second- and third-line antibiotics is predicted to increase by 70% by 2030 if effective public health measures are not employed (Organisation for Economic Cooperation and Development, 2018). The pandemic has further reinforced what a virus can do when we do not have the know-how or the tools to protect ourselves, and the results could be similar for a wave of everyday microbial infections that also can no longer be as a result of antimicrobial resistance.
One of the main measures that can help to tackle this looming crisis is to reduce the unnecessary and inappropriate use of antibiotics where possible, particularly in primary care where antibiotics are most prescribed. For instance, medications are commonly prescribed for respiratory tract infections, though Stuart et al (2021) note that such intervention has a modest effect on the outcome of the illness. They also highlight that antimicrobials continue to be overprescribed across the country and on a global scale, which has a huge potential impact on the burden to come when resistance to such treatments is at an all-time high. Delayed prescribing therefore appears to be the way forward – perhaps a useful compromise to reassure both the patient and prescriber.
Delayed prescribing
In 2016, the National Institute for Health and Care Excellence (NICE) released a quality statement declaring that prescribers in primary care could use delayed prescribing of antimicrobials where they were uncertain about whether a condition is self-limiting or likely to deteriorate. The rationale for this was that when there is clinical uncertainty, delayed prescribing offers health professionals an alternative to the immediate prescription of antibiotics, which may do more harm than good if the patient becomes resistant following several more prescriptions in similar circumstances (as is often the case for elderly, frail or disabled people in the community suffering chronic conditions that involve frequent symptoms of possible infection).
The concept of delayed prescribing encourages self-management as a first step, while also allowing a person to access antibiotics without another appointment if their condition does go on to worsen. The quality statement therefore recommends that systems be in place for GPs, health centres and pharmacies to allow delayed antimicrobial prescribing in cases of uncertainty regarding whether a condition is self-limiting or is likely to deteriorate.
For commissioners, this meant that clinical commissioning groups and NHS England would allow and monitor the practice in such circumstances of uncertainty over the patient's condition. For patients, this meant that their condition may improve without treatment, but that they would be able to receive a prescription for an antimicrobial, with the agreement they will only go on to use this if their condition worsens (NICE, 2016). This practice is also known as ‘back-up prescribing’, and the patient should always be given clear instructions about when they should use the prescription.
A downside of this approach may be that the patient does not follow the instructions and either through an inability to understand how to judge their symptoms or through anxiety-led actions, seeks and takes the antimicrobials earlier than required. In other cases, if the patient does deteriorate, for some, the question would be that they may delay for too long until they are too unwell to access the antimicrobials, and the many patients who live alone with chronic conditions and perhaps some level of cognitive decline, may be at risk. Therefore, practitioners should always exercise caution when applying the practice of delayed prescribing.
Assessment through research
The British Medical Journal has recently published a systematic review with a meta-analysis of patient data from multiple well-established sources to assess the overall effect of delayed prescribing of antibiotics on average symptom severity in patients with respiratory tract infections in the community, and identify factors that modify this effect. The eligibility criteria for study selection by Stuart et al (2021) involved the use of randomised controlled trials (RCTs) and observational cohort studies in a community setting that allowed comparison between delayed versus no-antibiotic prescribing, as well as delayed versus immediate antibiotic prescribing. The primary outcome was the average symptom severity identified 2-4 days after the first consultation, measured on a seven-item scale ranging from normal to as bad as could be. Secondary outcomes were defined as the duration of illness following the initial consultation, complications resulting in admission to hospital or death, reconsultation with the same or worsening illness, and patient satisfaction rated on a Likert scale.
Stuart et al (2021) identified nine suitable RCTs and four observational studies. In total, 55682 patients were involved. No difference was identified in follow-up symptom severity (seven-point scale) for delayed versus immediate antibiotics or delayed versus no antibiotics. Symptom duration was observed to be slightly longer in those given delayed versus immediate antibiotics (11.4 v 10.9 days), but was found to be similar for delayed versus no antibiotics. Complications that resulted in admission to hospital or death were observed to be lower with delayed versus no antibiotics and delayed versus immediate antibiotics.
The researchers also identified a significant reduction in reconsultation rates, as well as an increase in patient satisfaction for delayed versus no antibiotics. The effect of delayed versus immediate antibiotics and delayed versus no antibiotics was not modified by previous duration of illness, fever, comorbidity, or severity of symptoms. The study also found that in children younger than 5 years, there was a slightly higher follow-up symptom severity with delayed antibiotics than with immediate antibiotics, but no increased severity was observed in the older age group.
Stuart et al (2021) therefore concluded that delayed antibiotic prescribing is a safe and effective strategy for the majority of patients, even for those in higher risk subgroups. They confirmed that delayed prescribing was associated with similar symptom duration as no antibiotic prescribing and is unlikely to lead to poorer symptom control than immediate antibiotic prescribing, which therefore would imply it is a safe strategy. Delayed prescribing could also reduce reconsultation rates, reducing the pressure and strain on limited primary care resources, and is unlikely to be associated with an increase in symptoms or illness duration, except in young children.
Conclusion
Overall, the findings reported by Stuart et al (2021) suggest that delayed antibiotic prescribing is just as effective as no antibiotics for all clinical outcomes, with the exception of increased patient satisfaction, reduced reconsultation and complication rates.
The reason for reduced reconsultation rates is unclear, the authors suggest a possible explanation that if a prescription is delayed, by the time the antibiotic course has finished, symptoms will have had more time to settle and so reconsultation is less likely. Another possibility offered by the authors is that it secondary opportunistic bacterial infections that start following an initial viral illness are more effectively managed by the later start of a delayed prescription.
Delayed antimicrobial prescribing appears to be a safe and effective strategy with minimal risk, which may help to tackle the looming antimicrobial resistance crisis, which may be the next big topic to address on the world health agenda following the current pandemic.