NIHR Signal A strategy of 'delayed antibiotic prescribing' for respiratory infections may reduce antibiotic use

Published on 19 December 2017

Delaying antibiotic prescribing made little difference to most symptoms of respiratory infection. It reduced antibiotic use and did not affect patient satisfaction compared with immediate prescribing of antibiotics.

Increasing antibiotic resistance is a global health concern. Many people don’t realise that viruses cause most respiratory infections and that antibiotics won’t help. The strategy allows some time for symptoms to improve naturally.

This review of the latest evidence on delayed prescribing for self-limiting respiratory infections is in line with current guidance. On the whole delaying antibiotics made little difference to symptoms compared with immediate use although certain symptoms, like malaise and fever in sore throat, might last a bit longer.

The 11 studies differed widely by patient populations, delay strategies, antibiotics given and settings. This makes it difficult to draw firm conclusions on where delayed prescribing is most appropriate.

Nevertheless delaying antibiotics seems a worthwhile strategy to reduce antibiotic use.

A strategy of 'delayed antibiotic prescribing' for respiratory infections may reduce antibiotic use

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Why was this study needed?

Antibiotic use is rising in England, which is driving an increase in resistant bacteria. Between 2011 and 2015, antibiotic use increased by 6.5%. It’s estimated that one in five people expect to receive antibiotics when they go to the doctor.

Strategies to reduce antibiotic use are urgently needed to prevent a situation where serious infections can no longer be treated, and even standard surgical procedures become hazardous. Otherwise, it’s estimated that antibiotic resistance may account for 10 million deaths worldwide each year by 2050.

Delayed antibiotic use involves prescribing antibiotics, but advising people not to use them unless symptoms worsen ('patient-led delay'), or asking them to collect a prescription at a later date if they are getting no better. This strategy could educate the public while giving a sense of security to both patients and practitioners.

This Cochrane update adds one trial to the last 2013 review.

What did this study do?

The review included 11 randomised controlled trials involving 3,555 people with respiratory tract infections. Most studies compared delayed with immediate antibiotics, though four compared advice on a delayed prescription with no prescription.

Five studies included children only, two adults only, and four mixed populations. Six were conducted in primary care, three in paediatric clinics and two in the emergency department. Studies came from the UK, New Zealand, US, Spain and Jordan.

Delayed prescribing involved advice to use antibiotics only if symptoms worsen (or to return for a prescription) after more than 48 hours. Studies varied considerably by patient population, treatment protocol and follow-up time. These differences precluded meta-analysis for most outcomes.

Trials were of moderate quality for the main outcomes. The most likely sources of bias were that study personnel were aware which group participants were allocated to, either at time of randomisation or data collection.

What did it find?

  • Delayed prescription reduced antibiotic use. Thirty-five people per 100 used antibiotics in the delayed group compared with 93 per 100 in the immediate group (odds ratio [OR] 0.04, 95% confidence interval [CI] 0.03 to 0.05; seven studies, 1,963 people). Antibiotic use was higher in the delayed group for studies where the comparison was with a no-antibiotic group (four studies, 1,241 people).
  • Five studies (1,573 people) looked at sore throat. Three showed no difference in pain between delayed and immediate antibiotics, while two found increased pain or pain duration with delayed use. Two studies found that delaying antibiotics increased fever on day three (by a mean 0.53 degrees C, 95% CI 0.31 to 0.74). Another study also found malaise was more common in the delayed group on day three. There was no difference in symptoms in two studies comparing delayed with no antibiotics.
  • Three studies (830 people) looked at middle ear infection. Two compared delayed with immediate antibiotics with conflicting results. One study found no difference in pain and fever on days four to six; the other again found that more children in the delayed group reported malaise on day three. One study found no difference in pain or fever between the delayed and no antibiotics.
  • Three studies (1,402 people) found no difference in cough (bronchitis) between delayed, immediate and no-antibiotic groups. One person in the no-antibiotic group developed pneumonia. For the common cold, two studies (534 people) showed no difference in symptoms between delayed and immediate groups. One study (405 people) showed an advantage of delayed over no antibiotics for reducing pain, fever and cough duration.
  • There were similar levels of patient satisfaction between the delayed and immediate groups (OR 0.65, 95% CI 0.39 to 1.10; six studies, 1,633 people). Satisfaction was, however, better in the delayed group compared with the no-antibiotics group (OR 1.49, 95% CI 1.8 to 2.06; four studies, 1,234 people).

What does current guidance say on this issue?

NICE guidance recommends advising people with self‑limiting conditions such as common cold and sore throat about self-management and the adverse effects of overusing antibiotics.

NICE recommends using a delayed strategy as an alternative to immediate prescribing if there is uncertainty whether a condition is self-limiting or the person is likely to deteriorate. This still encourages self-management but allows a person to access antibiotics without another appointment if their symptoms get worse.

What are the implications?

Most respiratory infections are self-limiting, and complications are unlikely. A delayed prescribing strategy seems an effective approach to tackle overuse of antibiotics. It could also reassure patients who may have concerns about managing without antibiotics.

The variety of studies makes it difficult to establish in which settings (e.g. general practice or hospitals) and for which patient groups delayed prescribing could be used safely and most effectively.

It is possible that the delayed prescription strategy reinforces a belief that antibiotics might be needed and this theory was not tested here.

Continuing to educate people that antibiotics aren’t likely to make a difference to their symptoms, with advice to return if symptoms get worse, still seems an essential part of care.

Citation and Funding

Spurling GKP, Del Mar CB, Dooley L, et al. Delayed antibiotic prescriptions for respiratory infections. Cochrane Database Syst Rev. 2017;(9):CD004417.

The Cochrane Acute Respiratory Infections Group is supported by The National Health and Research Council (NHMRC) of Australia, Cochrane Australia, Bond University, University of Queensland, General Practice Education and Training, Australia and previously by NIHR infrastructure funding.

Bibliography

NHS Choices. Respiratory tract infections. London: Department of Health; updated 2015.

NICE. Antibiotic stewardship. QS121. London: National Institute for Health and Care Excellence; 2016.

NICE. Respiratory (self-limiting): prescribing antibiotics. CG69. London: National Institute for Health and Care Excellence; 2008.

Public Health England. Guidance: Health matters: antimicrobial resistance. London: Public Health England; 2015.

Public Health England. Management and treatment of common infections. Antibiotic guidance for primary care: for consultation and local adaptation. London: Public Health England; 2017.

Why was this study needed?

Antibiotic use is rising in England, which is driving an increase in resistant bacteria. Between 2011 and 2015, antibiotic use increased by 6.5%. It’s estimated that one in five people expect to receive antibiotics when they go to the doctor.

Strategies to reduce antibiotic use are urgently needed to prevent a situation where serious infections can no longer be treated, and even standard surgical procedures become hazardous. Otherwise, it’s estimated that antibiotic resistance may account for 10 million deaths worldwide each year by 2050.

Delayed antibiotic use involves prescribing antibiotics, but advising people not to use them unless symptoms worsen ('patient-led delay'), or asking them to collect a prescription at a later date if they are getting no better. This strategy could educate the public while giving a sense of security to both patients and practitioners.

This Cochrane update adds one trial to the last 2013 review.

What did this study do?

The review included 11 randomised controlled trials involving 3,555 people with respiratory tract infections. Most studies compared delayed with immediate antibiotics, though four compared advice on a delayed prescription with no prescription.

Five studies included children only, two adults only, and four mixed populations. Six were conducted in primary care, three in paediatric clinics and two in the emergency department. Studies came from the UK, New Zealand, US, Spain and Jordan.

Delayed prescribing involved advice to use antibiotics only if symptoms worsen (or to return for a prescription) after more than 48 hours. Studies varied considerably by patient population, treatment protocol and follow-up time. These differences precluded meta-analysis for most outcomes.

Trials were of moderate quality for the main outcomes. The most likely sources of bias were that study personnel were aware which group participants were allocated to, either at time of randomisation or data collection.

What did it find?

  • Delayed prescription reduced antibiotic use. Thirty-five people per 100 used antibiotics in the delayed group compared with 93 per 100 in the immediate group (odds ratio [OR] 0.04, 95% confidence interval [CI] 0.03 to 0.05; seven studies, 1,963 people). Antibiotic use was higher in the delayed group for studies where the comparison was with a no-antibiotic group (four studies, 1,241 people).
  • Five studies (1,573 people) looked at sore throat. Three showed no difference in pain between delayed and immediate antibiotics, while two found increased pain or pain duration with delayed use. Two studies found that delaying antibiotics increased fever on day three (by a mean 0.53 degrees C, 95% CI 0.31 to 0.74). Another study also found malaise was more common in the delayed group on day three. There was no difference in symptoms in two studies comparing delayed with no antibiotics.
  • Three studies (830 people) looked at middle ear infection. Two compared delayed with immediate antibiotics with conflicting results. One study found no difference in pain and fever on days four to six; the other again found that more children in the delayed group reported malaise on day three. One study found no difference in pain or fever between the delayed and no antibiotics.
  • Three studies (1,402 people) found no difference in cough (bronchitis) between delayed, immediate and no-antibiotic groups. One person in the no-antibiotic group developed pneumonia. For the common cold, two studies (534 people) showed no difference in symptoms between delayed and immediate groups. One study (405 people) showed an advantage of delayed over no antibiotics for reducing pain, fever and cough duration.
  • There were similar levels of patient satisfaction between the delayed and immediate groups (OR 0.65, 95% CI 0.39 to 1.10; six studies, 1,633 people). Satisfaction was, however, better in the delayed group compared with the no-antibiotics group (OR 1.49, 95% CI 1.8 to 2.06; four studies, 1,234 people).

What does current guidance say on this issue?

NICE guidance recommends advising people with self‑limiting conditions such as common cold and sore throat about self-management and the adverse effects of overusing antibiotics.

NICE recommends using a delayed strategy as an alternative to immediate prescribing if there is uncertainty whether a condition is self-limiting or the person is likely to deteriorate. This still encourages self-management but allows a person to access antibiotics without another appointment if their symptoms get worse.

What are the implications?

Most respiratory infections are self-limiting, and complications are unlikely. A delayed prescribing strategy seems an effective approach to tackle overuse of antibiotics. It could also reassure patients who may have concerns about managing without antibiotics.

The variety of studies makes it difficult to establish in which settings (e.g. general practice or hospitals) and for which patient groups delayed prescribing could be used safely and most effectively.

It is possible that the delayed prescription strategy reinforces a belief that antibiotics might be needed and this theory was not tested here.

Continuing to educate people that antibiotics aren’t likely to make a difference to their symptoms, with advice to return if symptoms get worse, still seems an essential part of care.

Citation and Funding

Spurling GKP, Del Mar CB, Dooley L, et al. Delayed antibiotic prescriptions for respiratory infections. Cochrane Database Syst Rev. 2017;(9):CD004417.

The Cochrane Acute Respiratory Infections Group is supported by The National Health and Research Council (NHMRC) of Australia, Cochrane Australia, Bond University, University of Queensland, General Practice Education and Training, Australia and previously by NIHR infrastructure funding.

Bibliography

NHS Choices. Respiratory tract infections. London: Department of Health; updated 2015.

NICE. Antibiotic stewardship. QS121. London: National Institute for Health and Care Excellence; 2016.

NICE. Respiratory (self-limiting): prescribing antibiotics. CG69. London: National Institute for Health and Care Excellence; 2008.

Public Health England. Guidance: Health matters: antimicrobial resistance. London: Public Health England; 2015.

Public Health England. Management and treatment of common infections. Antibiotic guidance for primary care: for consultation and local adaptation. London: Public Health England; 2017.

Delayed antibiotic prescriptions for respiratory infections

Published on 8 September 2017

Spurling, G. K.,Del Mar, C. B.,Dooley, L.,Foxlee, R.,Farley, R.

Cochrane Database Syst Rev Volume 9 , 2017

BACKGROUND: Concerns exist regarding antibiotic prescribing for respiratory tract infections (RTIs) owing to adverse reactions, cost, and antibacterial resistance. One proposed strategy to reduce antibiotic prescribing is to provide prescriptions, but to advise delay in antibiotic use with the expectation that symptoms will resolve first. This is an update of a Cochrane Review originally published in 2007, and updated in 2010 and 2013. OBJECTIVES: To evaluate the effects on clinical outcomes, antibiotic use, antibiotic resistance, and patient satisfaction of advising a delayed prescription of antibiotics in respiratory tract infections. SEARCH METHODS: For this 2017 update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 4, 2017), which includes the Cochrane Acute Respiratory Infection Group's Specialised Register; Ovid MEDLINE (2013 to 25 May 2017); Ovid Embase (2013 to 2017 Week 21); EBSCO CINAHL Plus (1984 to 25 May 2017); Web of Science (2013 to 25 May 2017); WHO International Clinical Trials Registry Platform (1 September 2017); and ClinicalTrials.gov (1 September 2017). SELECTION CRITERIA: Randomised controlled trials involving participants of all ages defined as having an RTI, where delayed antibiotics were compared to immediate antibiotics or no antibiotics. We defined a delayed antibiotic as advice to delay the filling of an antibiotic prescription by at least 48 hours. We considered all RTIs regardless of whether antibiotics were recommended or not. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Three review authors independently extracted and collated data. We assessed the risk of bias of all included trials. We contacted trial authors to obtain missing information. MAIN RESULTS: For this 2017 update we added one new trial involving 405 participants with uncomplicated acute respiratory infection. Overall, this review included 11 studies with a total of 3555 participants. These 11 studies involved acute respiratory infections including acute otitis media (three studies), streptococcal pharyngitis (three studies), cough (two studies), sore throat (one study), common cold (one study), and a variety of RTIs (one study). Five studies involved only children, two only adults, and four included both adults and children. Six studies were conducted in a primary care setting, three in paediatric clinics, and two in emergency departments.Studies were well reported, and appeared to be of moderate quality. Randomisation was not adequately described in two trials. Four trials blinded the outcomes assessor, and three included blinding of participants and doctors. We conducted meta-analysis for antibiotic use and patient satisfaction.We found no differences among delayed, immediate, and no prescribed antibiotics for clinical outcomes in the three studies that recruited participants with cough. For the outcome of fever with sore throat, three of the five studies favoured immediate antibiotics, and two found no difference. For the outcome of pain related to sore throat, two studies favoured immediate antibiotics, and three found no difference. One study compared delayed antibiotics with no antibiotic for sore throat, and found no difference in clinical outcomes.Three studies included participants with acute otitis media. Of the two studies with an immediate antibiotic arm, one study found no difference for fever, and the other study favoured immediate antibiotics for pain and malaise severity on Day 3. One study including participants with acute otitis media compared delayed antibiotics with no antibiotics and found no difference for pain and fever on Day 3.Two studies recruited participants with common cold. Neither study found differences for clinical outcomes between delayed and immediate antibiotic groups. One study favoured delayed antibiotics over no antibiotics for pain, fever, and cough duration (moderate quality evidence for all clinical outcomes - GRADE assessment).There were either no differences for adverse effects or results favoured delayed antibiotics over immediate antibiotics (low quality evidence - to GRADE assessment) with no significant differences in complication rates. Delayed antibiotics resulted in a significant reduction in antibiotic use compared to immediate antibiotics prescription (odds ratio (OR) 0.04, 95% confidence interval (CI) 0.03 to 0.05). However, a delayed antibiotic was more likely to result in reported antibiotic use than no antibiotics (OR 2.55, 95% CI 1.59 to 4.08) (moderate quality evidence - GRADE assessment).Patient satisfaction favoured delayed over no antibiotics (OR 1.49, 95% CI 1.08 to 2.06). There was no significant difference in patient satisfaction between delayed antibiotics and immediate antibiotics (OR 0.65, 95% CI 0.39 to 1.10) (moderate quality evidence - GRADE assessment).None of the included studies evaluated antibiotic resistance. AUTHORS' CONCLUSIONS: For many clinical outcomes, there were no differences between prescribing strategies. Symptoms for acute otitis media and sore throat were modestly improved by immediate antibiotics compared with delayed antibiotics. There were no differences in complication rates. Delaying prescribing did not result in significantly different levels of patient satisfaction compared with immediate provision of antibiotics (86% versus 91%) (moderate quality evidence). However, delay was favoured over no antibiotics (87% versus 82%). Delayed antibiotics achieved lower rates of antibiotic use compared to immediate antibiotics (31% versus 93%) (moderate quality evidence). The strategy of no antibiotics further reduced antibiotic use compared to delaying prescription for antibiotics (14% versus 28%). Delayed antibiotics for people with acute respiratory infection reduced antibiotic use compared to immediate antibiotics, but was not shown to be different to no antibiotics in terms of symptom control and disease complications. Where clinicians feel it is safe not to prescribe antibiotics immediately for people with respiratory infections, no antibiotics with advice to return if symptoms do not resolve is likely to result in the least antibiotic use while maintaining similar patient satisfaction and clinical outcomes to delaying prescription of antibiotics. Where clinicians are not confident in using a no antibiotic strategy, a delayed antibiotics strategy may be an acceptable compromise in place of immediate prescribing to significantly reduce unnecessary antibiotic use for RTIs, and thereby reduce antibiotic resistance, while maintaining patient safety and satisfaction levels.Editorial note: As a living systematic review, this review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

Expert commentary

It is essential that we reduce the unnecessary use of antibiotics to slow the progress of antibiotic resistance, but it is a difficult decision for individual doctors to deny them to patients who may feel they are needed. Delayed prescriptions could be a safe compromise for some acute respiratory infections in the community.

Through the use of delayed prescriptions, both doctors and patients can learn to recognise the situations where antibiotics aren’t needed. Avoiding antibiotics completely in such cases must remain our ultimate goal.

Dr Meera Chand, Consultant Microbiologist,  Guy’s & St Thomas’ Hospitals NHS Foundation Trust; National Infection Service, Public Health England