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.
Overall summary Low risk of bias in the review
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|
|Number of studies||11|
|Number of participants||3555|
|Last search date||2017|
|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).|
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).
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|