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KSR Number: KSRA34105

Delayed antibiotic prescriptions for respiratory infections

  • Cochrane Database Syst Rev 2017, 9, CD004417, 10.1002/14651858.CD004417.pub5
  • Full report

Risk of Bias Assessment

Overall summary: Low risk of bias in the review

Bottom Line

Current evidence suggests that pain and malaise may be increased in patients with respiratory infections who take delayed versus immediate antibiotics. However, delaying antibiotics was reported to reduce antibiotic use compared to immediate antibiotics and did not result in a substantial change in patient satisfaction. The review was considered to be at low methodological risk of bias. More well designed studies are needed to further support these findings, with a particular focus on measuring antibiotic resistance outcomes.

Risk of Bias Assessment

Overall summary Low risk of bias in the review

Low

All domains were considered at low concern.

A. Did the interpretation of findings address all of the concerns identified in Domains 1 to 4? Probably yes
B. Was the relevance of identified studies to the review's research question appropriately considered? Probably yes
C. Did the reviewers avoid emphasizing results on the basis of their statistical significance? Probably yes
Risk of bias in the review Low

Details of Review

Number of studies 11
Number of participants 3555
Last search date 2017
Review type Intervention
Objective To evaluate the effects of advising a delayed prescription of antibiotics on clinical outcomes, antibiotic use, antibiotic resistance and patient satisfaction for respiratory tract infections.
Population Adults and children diagnosed with respiratory tract infections (RTIs).
Interventions Delayed antibiotic use (defined as a strategy involving the use or the advice to use antibiotics more than 48 hours after the initial consultation).
Comparator Immediate antibiotics (defined as the immediate use of a prescription of oral antibiotics given at the initial consultation) or no antibiotics (defined as no prescription of antibiotics at the initial consultation).
Outcome Primary outcomes: Clinical outcomes for sore throat, acute otitis media, bronchitis (a cough), common cold symptoms (pain, malaise, fever, cough and rhinorrhoea), antibiotic use, patient satisfaction and antibiotic resistance.

Secondary outcomes: Adverse effects of antibiotics, complications of disease, reconsultation and the use of other therapies such as simple analgesia, e.g. paracetamol and ibuprofen.
Study design Randomised controlled trials (RCTs).

Results

In terms of clinical outcomes, pooled analysis reported an increase in pain for delayed antibiotics versus immediate antibiotics (standardised mean difference [SMD] 0.35, 95% confidence interval [CI] 0.13 to 0.57; 2 studies, n=327 participants). Similarly, pooled analysis reported an increase in malaise for delayed antibiotics versus immediate antibiotics (SMD 0.29, 95% CI 0.09 to 0.48; 2 studies, n=398 participants). Pooled analysis reported a numerical reduction in the odds of fever for delayed antibiotics versus immediate antibiotics (odds ratio [OR] 0.86, 95% CI 0.54 to 1.38; 2 studies, n=394 participants). Four studies compared clinical outcomes for delayed antibiotics versus no antibiotics. Three of four studies reported no evidence of a difference in clinical outcome (sore throat, otitis media or cough) for delayed antibiotics versus no antibiotics. One of four studies reported an improvement in pain, fever and cough duration but no evidence of a difference in nasal mucosity for delayed antibiotics versus no antibiotics.

In terms of antibiotic use, pooled analysis reported that the odds of using antibiotics were reduced for delayed versus immediate antibiotics (OR 0.04; 95% CI 0.03 to 0.05; 7 studies, n=1963 participants). Pooled analysis reported an increase in antibiotic use for delayed antibiotics versus no antibiotics (OR 2.55, 95% CI 1.59 to 4.08; 4 studies, n=1241 participants).

In terms of patient satisfaction, pooled analysis reported that the odds of patient satisfaction were numerically reduced for delayed versus immediate antibiotics (OR 0.65, 95% CI 0.39 to 1.10; 6 studies, n=1633 participants). Pooled analysis reported that the odds of patient satisfaction were numerically increased for delayed antibiotics versus no antibiotics (OR 1.49, 95% CI 1.08 to 2.06; 4 studies. n=1235 participants).

In terms of reconsultation rates, pooled analysis reported no difference in the odds of patients requiring another consultation for delayed versus immediate antibiotics (OR 1.04, 95% CI 0.55 to 1.98; 2 studies, n=379 participants).

In terms of adverse effects, four studies reported on diarrhoea outcomes. Two of the four studies reported that results favoured delayed antibiotics compared to immediate antibiotics; and two of the four studies reported no evidence of a difference for delayed antibiotics compared to immediate antibiotics. Pooled analysis reported no difference in the odds of rash for delayed antibiotics versus immediate antibiotics (OR 1.03, 95% CI 0.54 to 1.97; 2 studies, n=680 participants).

Full Risk of Bias Assessment

The research objective was clearly stated and appropriate inclusion criteria were defined. No restrictions were reported based on study characteristics. Restrictions were applied based on date; however, this was considered appropriate since this was an update review.

1.1 Did the review adhere to pre-defined objectives and eligibility criteria? Probably yes
1.2 Were the eligibility criteria appropriate for the review question? Probably yes
1.3 Were eligibility criteria unambiguous? Probably yes
1.4 Were all restrictions in eligibility criteria based on study characteristics appropriate (e.g. date, sample size, study quality, outcomes measured)? Probably yes
1.5 Were any restrictions in eligibility criteria based on sources of information appropriate (e.g. publication status or format, language, availability of data)? Probably yes
Concerns regarding specification of study eligibility criteria Low

The studies were identified by searching CENTRAL (which included the Cochrane acute respiratory infection group’s specialised register), Ovid MEDLINE InProcess & Other Non-Indexed Citations, Ovid MEDLINE Daily and Ovid MEDLINE, Ovid EMBASE Classic+EMBASE, EBSCO CINAHL Plus, Web of Science, the World Health Organisation (WHO) International Clinical Trials Registry Platform and ClinicalTrials.gov. The reference lists of all primary studies and review articles were searched to identify additional studies. The search strategy was reported in full and appeared to be adequate. No restrictions were reported based on publication format or language. Restrictions were applied based on date; however, this was considered appropriate since this was an update review. Two (title/abstract screening) or three (full text screening) reviewers were independently involved in the study selection process and any disagreements were resolved through discussion or by consulting a third reviewer.

2.1 Did the search include an appropriate range of databases/electronic sources for published and unpublished reports? Yes
2.2 Were methods additional to database searching used to identify relevant reports? Yes
2.3 Were the terms and structure of the search strategy likely to retrieve as many eligible studies as possible? Yes
2.4 Were restrictions based on date, publication format, or language appropriate? Probably yes
2.5 Were efforts made to minimise error in selection of studies? Yes
Concerns regarding methods used to identify and/or select studies Low

Two reviewers were independently involved in the data extraction process, and any disagreements were resolved by discussion or through the intervention of a third reviewer. Sufficient individual study characteristics appear to have been extracted to allow the interpretation of results. Relevant study results appear to have been extracted. Methodological quality was assessed using the Cochrane risk of bias tool for randomised controlled trials. Two reviewers were independently involved in the risk of bias assessment, and any disagreements were resolved by discussion or through the intervention of a third reviewer.

3.1 Were efforts made to minimise error in data collection? Yes
3.2 Were sufficient study characteristics considered for both review authors and readers to be able to interpret the results? Probably yes
3.3 Were all relevant study results collected for use in the synthesis? Probably yes
3.4 Was risk of bias (or methodological quality) formally assessed using appropriate criteria? Yes
3.5 Were efforts made to minimise error in risk of bias assessment? Yes
Concerns regarding methods used to collect data and appraise studies Low

The synthesis appeared to include all relevant studies. The method of analysis was explained and appeared to be appropriate. Meta-analysis was performed for homogeneous results, and a narrative synthesis was performed where this was not possible. Heterogeneity was assessed and found to be moderate or high for some outcomes; subgroup analyses were performed to address this heterogeneity. A sensitivity analysis was performed to check the robustness of the study results. Publication bias could not be assessed due to the small number of included studies; this was considered appropriate. The quality of the individual studies was considered in the synthesis.

4.1 Did the synthesis include all studies that it should? Probably yes
4.2 Were all pre-defined analyses reported or departures explained? Probably yes
4.3 Was the synthesis appropriate given the degree of similarity in the research questions, study designs and outcomes across included studies? Probably yes
4.4 Was between-study variation minimal or addressed in the synthesis? Probably yes
4.5 Were the findings robust, e.g. as demonstrated through funnel plot or sensitivity analyses? Probably yes
4.6 Were biases in primary studies minimal or addressed in the synthesis? Yes
Concerns regarding synthesis and findings Low

Abstract

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 favo