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Delayed antibiotics for respiratory infections

  1. Geoffrey KP Spurling1,*,
  2. Chris B Del Mar2,
  3. Liz Dooley3,
  4. Ruth Foxlee4,
  5. Rebecca Farley1

Editorial Group: Cochrane Acute Respiratory Infections Group

Published Online: 30 APR 2013

Assessed as up-to-date: 28 FEB 2013

DOI: 10.1002/14651858.CD004417.pub4


How to Cite

Spurling GKP, Del Mar CB, Dooley L, Foxlee R, Farley R. Delayed antibiotics for respiratory infections. Cochrane Database of Systematic Reviews 2013, Issue 4. Art. No.: CD004417. DOI: 10.1002/14651858.CD004417.pub4.

Author Information

  1. 1

    University of Queensland, Discipline of General Practice, Herston, Queensland, Australia

  2. 2

    Bond University, Centre for Research in Evidence-Based Practice (CREBP), Gold Coast, Queensland, Australia

  3. 3

    Bond University, Faculty of Health Sciences and Medicine, Gold Coast, Queensland, Australia

  4. 4

    University of York, Department of Health Sciences, York, UK

*Geoffrey KP Spurling, Discipline of General Practice, University of Queensland, Level 8, Health Sciences Building 16/910, Royal Brisbane and Women's Hospital, Herston, Queensland, 4029, Australia. g.spurling@uq.edu.au. geoffspurling@optusnet.com.au.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 30 APR 2013

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Background

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms
 

Description of the condition

The use of antibiotics for acute respiratory tract infections (ARTIs) is controversial. Empirical evidence suggests that antibiotics have only a modest benefit in acute otitis media (AOM) (Venekamp 2013), pharyngitis (Spinks 2011) and acute bronchitis (Smith 2011) and no effect in the common cold (Arroll 2010). Any benefits have to be weighed up against common adverse reactions (including rash, abdominal pain, diarrhoea and vomiting) and cost (Berman 1997; Niemela 1999). Over-prescribing may also contribute to community bacterial resistance to antibiotics (Arason 1996; Brook 1998; Verkatesum 1995).

 

Description of the intervention

There has been interest in strategies to reduce antibiotic prescribing for ARTIs. One of these strategies is to advise patients to 'delay' filling their script and only to fill it if their symptoms persist or deteriorate. Delayed antibiotics are advocated as a means of demonstrating to patients that antibiotics are not always necessary, without making them feel under-serviced (Arroll 2002b). Two ways of using this strategy have been deployed: giving the patient the antibiotic (with instructions not to use unless there is deterioration); and making the prescription available at the clinic reception (to be picked up in the event of deterioration).

 

How the intervention might work

Delaying antibiotics may provide a feeling of safety for both patient and clinician should an illness deteriorate. This intervention then provides the safety of having a prescription of antibiotics available, yet an educational way of experiencing whether the illness resolves spontaneously without their use.

A systematic review showed that using delayed antibiotics in ARTIs significantly reduces antibiotic prescribing (Arroll 2003a). The reduction ranges from a risk ratio (RR) of 0.77 (95% confidence interval (CI) 0.73 to 0.81) (Dowell 2001) to RR 0.25 (95% CI 0.19 to 0.34) (Little 1997).

 

Why it is important to do this review

The delayed antibiotic strategy has also been advocated more recently as a safety net for avoiding rare but important complications of initially uncomplicated ARTIs (Little 2005b). The same authors also advocated delayed antibiotics for reducing antibiotic use, allowing adequate control of symptoms, while providing high levels of patient satisfaction (Little 2005b).

This review asks specifically what effect delayed antibiotics have on clinical outcomes of ARTIs compared to immediate antibiotics and no antibiotics. This review also evaluates the available data on antibiotic use, patient satisfaction and antibiotic resistance for the three prescribing strategies of delayed antibiotics, immediate antibiotics and no antibiotics. This is an update of a Cochrane Review originally published in 2007 (Spurling 2007), with an updated version published in 2010 (Spurling 2010).

 

Objectives

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms

To evaluate the use of delayed antibiotics compared to immediate or no antibiotics as a prescribing strategy for ARTIs. We aimed to evaluate clinical outcomes including duration and severity measures for pain, malaise, fever, cough and rhinorrhoea in sore throat, AOM, bronchitis (cough) and the common cold. We also aimed to evaluate the outcomes of antibiotic use, patient satisfaction, antibiotic resistance and re-consultation rates and use of alternative therapies.

 

Methods

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms
 

Criteria for considering studies for this review

 

Types of studies

Randomised controlled trials (RCTs) studying the treatment of ARTIs with delayed antibiotics versus immediate or no antibiotics. Open randomised trials were accepted.

 

Types of participants

Patients of all ages defined as having ARTIs.

 

Types of interventions

  1. 'Delayed antibiotic use' was defined as a strategy involving the use of or advice to use antibiotics more than 48 hours after the initial consultation.
  2. 'Immediate antibiotic use' was defined as the immediate use of a prescription of oral antibiotics given at the initial consultation.
  3. 'No antibiotic use' was defined as no prescription of antibiotics at the initial consultation.

 

Types of outcome measures

 

Primary outcomes

We compared delayed antibiotics with immediate antibiotics and delayed antibiotics with no antibiotics where data were available.

  1. Clinical outcomes for sore throat, AOM, bronchitis (cough) and common cold (we included duration and severity measures for the following symptoms: pain, malaise, fever, cough and rhinorrhoea)
  2. Antibiotic use
  3. Patient satisfaction (where patient satisfaction is measured on a four to six-point Likert scale; we defined satisfaction as including both satisfied and very satisfied)
  4. Antibiotic resistance

 

Secondary outcomes

  1. Adverse effects of antibiotics
  2. Complications of disease
  3. Re-consultation
  4. Use of alternative therapies

 

Search methods for identification of studies

 

Electronic searches

For this updated review we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 2), which includes the Acute Respiratory Infection Group's Specialised Register; Ovid MEDLINE (January 1966 to February Week 3 2013); Ovid MEDLINE In-Process & Other Non-Indexed Citations (28 February 2013); EMBASE (1990 to 2013 Week 08); Science Citation Index - Web of Science (2007 to May 2012) and EBSCO CINAHL (1982 to 28 February 2013).

In the original version of this review MEDLINE was searched using the following keywords and MeSH terms in conjunction with the highly sensitive search strategy designed by The Cochrane Collaboration for identifying randomised controlled trials (Dickersin 1994). For this update we applied no trial filters. We used the MEDLINE search strategy to search CENTRAL (Appendix 1) and adapted this to search EMBASE (Appendix 2) and CINAHL (Appendix 3).

Ovid MEDLINE

1     exp Respiratory Tract Infections/ (114895)
2     (upper respiratory tract infection$ or urti).mp. (2482)
3     exp Otitis Media/ (8289)
4     otitis media.mp. (10100)
5     exp Pharyngitis/ (4870)
6     pharyngitis.mp. (3733)
7     exp Tonsillitis/ (2065)
8     tonsillitis.mp. (2423)
9     exp Common Cold/ (1492)
10     common cold.mp. (2207)
11     exp Bronchitis/ (8275)
12     bronchitis.mp. (8027)
13     exp Sinusitis/ (8071)
14     sinusitis.mp. (10465)
15     sore throat$.mp. (2080)
16     or/1-15 (133707)
17     exp Anti-Bacterial Agents/ (215537)
18     antibiotic$.mp. (127408)
19     or/17-18 (278179)
20     (delay$ adj15 prescri$).mp. (474)
21     and/16,19-20 (55)

There were no language or date of publication restrictions in any of the electronic database searches.

 

Searching other resources

We scanned abstracts from the search results to identify trials that loosely met the inclusion criteria. We checked references of all relevant retrieved trials to identify any other articles.

 

Data collection and analysis

 

Selection of studies

In the original publication of this review, we scanned abstracts from the initial search results to identify trials that loosely met the inclusion criteria. We checked references of all relevant retrieved trials to identify any other articles. Three review authors (RFo, LD, CDM) independently reviewed the full-text articles of the retrieved trials.

In the 2010 update, one further study was found to meet the inclusion criteria (Chao 2008) and two review authors (LD, CDM) independently assessed the methodological quality of the new included study that met the inclusion criteria at that time (Chao 2008).

Similarly, in this updated review (2013), three authors (RFo, GS, RFa) scanned abstracts from the updated searches to identify trials that met the inclusion criteria, checking the references of all retrieved trials to identify other articles. Three review authors (LD, CDM, RFa) independently reviewed the full-text articles of the retrieved trials and applied the inclusion criteria.

We identified two papers, Little 2006 and Moore 2009, as reporting longer-term outcomes from previously included studies (Little 2001; Little 2005a).

 

Data extraction and management

In the initial publication of this review, three review authors (RFo, LD and CDM) independently extracted data for each study trial to be included. We extracted data in a blinded manner (that is, without the knowledge of the study results, the names of the authors, institutions or journal of publication). We extracted additional data from graphs of the published articles of El-Daher 1991 and Pichichero 1987 on fever severity and symptom scores.

In this most recent update (2013), two review authors (LD, CDM) independently extracted data from the two new included papers. We contacted the authors of Little 2006 to obtain original data for the outcomes of earache at three months and one year that had been reported as odds ratios (ORs) in the published trial. The complete data were unavailable and there was some inconsistency between what was provided and the published numbers. These results have been included in the text of this review, in the form of the published ORs.

 

Assessment of risk of bias in included studies

In the first publication of this review three review authors (RFo, LD, CDM) independently assessed the quality of each of the study trials that met the inclusion criteria. We resolved disagreements by consensus. Assessment was blinded (that is, without the knowledge of the study results, the names of the authors, institutions or journal of publication).

We rated the quality of each eligible RCT according to the 'Risk of bias' tool available in RevMan 5.2 and criteria set out in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We assessed methodological quality under the headings of allocation, blinding, incomplete outcome data, selective reporting and other potential sources of bias.

Two review authors (LD, CDM) independently assessed the methodological quality of the trial included in the 2010 update.

We resolved disagreements by discussion.

 

Measures of treatment effect

We analysed data using RevMan 5.2. We expressed continuous data comparisons using mean differences (MD) where there was one study or standardised MD where more than one study used different measurement scales. We expressed dichotomous data using odds ratios (OR). We pooled data into clinical outcomes where multiple trial results for the same clinical presentation existed and there was no heterogeneity.

 

Unit of analysis issues

The units of analysis for each outcome are the individual research participants.

 

Dealing with missing data

Six studies included an intention-to-treat (ITT) analysis. Three other studies described their minimal drop-out rates. One study (El-Daher 1991) did not discuss the drop-out rate, though it was small.

 

Assessment of heterogeneity

We did not undertake a meta-analysis for most clinical outcomes owing to multiple analyses with only one or two study results. We pooled results where satisfactorily low I2 statistic and non-significant Chi2 test results were found. We did not undertake a meta-analysis for antibiotic use owing to the heterogeneity of the included study results, likely owing to different antibiotic indications for different clinical presentations.

 

Assessment of reporting biases

Two studies collected data on clinical outcomes yet did not report them in detail (Dowell 2001; Gerber 1990). In both cases, the studies reported that there was no difference between control and intervention groups.

 

Data synthesis

Most of the data in this review are reported as a narrative synthesis describing outcome measures. As indicated previously, we pooled results where satisfactorily low I2 statistic and non-significant Chi2 test results were found. We undertook a meta-analysis for the outcomes of fever for sore throat and patient satisfaction.

 

Subgroup analysis and investigation of heterogeneity

Subgroup analyses were considered for all outcomes and included year of publication, clinical presentation, differences in the intervention and risk of bias.

We describe in the results section the two subgroup analyses that showed differences in outcomes. We explored heterogeneity of antibiotic use in delayed antibiotic arms further with analysis of different methods of the delay strategy. We explored heterogeneity of patients satisfaction further with respect to blinding of outcome assessor and patient.

 

Results

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms
 

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies.

 

Results of the search

Searches conducted for this review have resulted in 244 articles being identified by electronic searching; 28 were retrieved for more detailed evaluation and 17 studies have been formally evaluated.

Five studies were excluded and are described in the Excluded studies section. Two studies identified in this 2013 update reported longer-term outcomes from previously included studies (Little 2006; Moore 2009) and while their data have been added to this review, they are considered part of the original included studies.

Ten trials were eligible for inclusion. They included 1159 participants in their delayed antibiotic arm, with 1067 participants in the immediate antibiotic arm of nine trials and 465 participants in the no antibiotic arm of three trials.

In this most recent update (2013), following removal of duplicated studies, searches resulted in the identification of 77 articles (out of the 244 previously mentioned). Five articles were retrieved for further evaluation (out of 28). Three studies were excluded (out of a total of five) because they were not randomised. The remaining two reported longer-term outcomes from previously included studies (Little 2006; Moore 2009) and while their data have been added to this review, they are considered part of the original included studies. Therefore, there are no more included studies as a result of this 2013 update.

 

Included studies

Nine trials compared immediate antibiotics with delayed antibiotics. Four of these trials investigated acute pharyngitis/sore throat; two with AOM; two with cough and one dealt with the common cold. Early studies of sore throat (El-Daher 1991; Gerber 1990; Pichichero 1987) were designed as efficacy trials to identify the rate of relapse of group A beta-haemolytic streptococcus (GABHS) throat in immediate versus delayed antibiotic groups. Subsequent trials (Arroll 2002a; Dowell 2001; Little 1997; Little 2001; Spiro 2006) comparing delayed antibiotics and immediate antibiotics were conducted with a view to evaluate the use of delayed antibiotics to reduce the use of antibiotics for upper respiratory tract infections (RTIs).

Three studies compared the prescribing strategy of no antibiotics with delayed antibiotics (Chao 2008; Little 1997; Little 2005a). These three trials investigated the presentations of sore throat (Little 1997), cough (Little 2005a) and AOM (Chao 2008). This last trial (Chao 2008) also asked patients in the no antibiotic arm to return if their symptoms had not resolved.

 

Excluded studies

Since the first publication of this review, five trials have been excluded. One because it used a before-and-after study design (Cates 1999) and four because they were not randomised.

 

Risk of bias in included studies

Summaries of the bias in included studies are provided in Figure 1 and Figure 2.

 FigureFigure 1. Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
 FigureFigure 2. Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

 

Allocation

Eight included studies were adequately randomised using random number tables or computer-generated randomisation. In two studies the method of randomisation was not described (El-Daher 1991; Little 1997). Only four trials described adequate allocation concealment using opaque envelopes (Arroll 2002a; Little 2001; Little 2005a; Spiro 2006)

 

Blinding

Three studies attempted to blind the patient and the doctor without mentioning the outcome assessor (Arroll 2002a; El-Daher 1991; Pichichero 1987). In one study patients were told only that they would be given one of two sets of instructions about taking antibiotics for their colds. Participants read an information sheet and then completed a consent form. Thus, patients were blinded to what the other group would take (Arroll 2002a). Two studies used placebo tablets to blind patients (El-Daher 1991; Pichichero 1987). Seven studies attempted to blind some or all aspects of the study; that is, the patients, the doctor and the outcome assessor. For four studies (Chao 2008; Dowell 2001; Little 2005a; Spiro 2006), the outcomes assessor was blinded but not the patient or the care giver. For the remaining three studies no blinding was undertaken (Gerber 1990; Little 1997; Little 2001).

 

Incomplete outcome data

Only one trial (El-Daher 1991) had incomplete outcome data and did not adequately address it.

 

Selective reporting

Only one trial (Gerber 1990) reported collecting important information (in this case related to clinical outcomes) without fully reporting it.

 

Other potential sources of bias

No other sources of bias were identified.

 

Effects of interventions

For most outcomes meta-analyses were not possible: some studies did not describe their data in sufficient detail and others were too heterogeneous to safely allow meta-analysis. Therefore, few forest plots have more than one study.  Table 1 summarises the statistical outcomes available for each study. However, for patient satisfaction, data were available and homogenous, so pooled results using a random-effects model are presented. For sore throat, two trials with minimal heterogeneity have been pooled for the outcome of fever severity on day three.

Results are outlined under the headings of clinical outcomes, antibiotic use and patient satisfaction in order to reflect the important clinical considerations relevant to the strategy of prescribing delayed antibiotics. The strategy of delayed antibiotics is compared to the strategies of immediate antibiotics and no antibiotics, depending on the available data. For each illness category there is at least one RCT (for example, common cold) with a maximum of four (sore throat). Given the low numbers of trials for each illness category, conclusions for illness categories need to be treated with caution. The multiplicity of comparisons for the clinical outcomes stratified by illness, makes a type I error more likely. However, clinical outcomes are stratified by illness owing to known differences in the effect of antibiotics on different types of respiratory infections. Antibiotic use and patient satisfaction data have been presented without this stratification as they are less likely to be affected by illness type and to show more clearly the effect of prescribing strategies.

 

Clinical outcomes

See  Table 1.

 

Sore throat

Four included studies examined sore throat (El-Daher 1991; Gerber 1990; Little 1997; Pichichero 1987).

 
Delayed antibiotics versus immediate antibiotics

Pain was reduced on day three in the immediate antibiotic group compared to delayed antibiotics in one study ( Analysis 1.1). Pain was not significantly different between delayed and immediate antibiotic groups in three studies (Gerber 1990; Little 1997; Pichichero 1987).

Malaise was reduced on day three in the immediate antibiotic group compared to delayed antibiotics in one study ( Analysis 2.1) and no difference was found in the other study measuring this outcome ( Analysis 2.2).

Fever severity on day three was reduced with immediate antibiotics compared to delayed antibiotics in two studies (pooled results odds ratio (OR) 0.53; 95% confidence interval (CI) 0.31 to 0.74) ( Analysis 3.1). The number of days with fever was reduced in the immediate antibiotic group of Little 1997 and there was no difference found in the fourth study (Gerber 1990).

 
Delayed antibiotics versus no antibiotics

One study examining sore throat compared the prescribing strategy of delayed antibiotics with no antibiotics (Little 1997). This study found no difference in any clinical outcome between these two prescribing strategies.

 
Complications

Data on complications of sore throat such as rheumatic fever, post-streptococcal glomerulonephritis and peri-tonsillar abscess were not reported in any of the four studies looking at sore throat for the three prescribing strategies of immediate, delayed and no antibiotics.

 

Acute otitis media (AOM)

Three included trials examined AOM (Chao 2008; Little 2001; Spiro 2006).

 
Delayed antibiotics versus immediate antibiotics

Pain and malaise were greater using delayed antibiotics compared to immediate antibiotics in one study measuring these outcomes on day three ( Analysis 4.1). One study examined clinical outcomes on days four to six and found no difference ( Analysis 5.1).

Other proxies for malaise outcomes reported by Little 2001 included last day of crying, which favoured the immediate antibiotic group by approximately 16 hours in children with AOM (0.69 days; 95% CI 0.31 to 0.07). In the same study, just over half a spoon of paracetamol a day less was used in the immediate antibiotic group (0.59; 95% CI 0.25 to 0.93). On day one there were no significant differences between immediate and delayed antibiotic groups in symptom outcome measures and by day seven there was no difference between immediate and delayed antibiotic groups (Little 2001).

Further analysis of earache from one trial (Little 2001) found the delayed prescribing strategy did not significantly increase risk of earache at three months (OR 0.89; 95% CI 0.48 to 1.65) or one year (OR 1.03; 95% CI 0.60 to 1.78) (Little 2006).

 
Delayed antibiotics versus no antibiotics

Only one study compared delayed antibiotics with no antibiotics with no significant difference for pain or fever on day three ( Analysis 8.1;  Analysis 9.1). This trial also advised participants in the no antibiotic arm to re-present in two to three days if symptoms did not resolve.

 
Complications

Data on complications of AOM such as mastoiditis, rheumatic fever and post-streptococcal glomerulonephritis were not reported in any of the three studies looking at AOM for the prescribing strategies of immediate and delayed antibiotics. However, Spiro 2006 and Chao 2008 noted that there were no serious adverse events for participants in the study.

 

Bronchitis (cough)

Two studies examined the prescribing strategies of immediate versus delayed antibiotics for the clinical presentation of cough (Dowell 2001; Little 2005a) and neither found any difference in clinical outcomes, including fever and cough.

 
Complications

Little 2005a also looked at delayed antibiotics versus no antibiotics and found no difference in clinical outcomes between the two prescribing strategies. One patient in the no antibiotic group (out of 273) of this study developed pneumonia and recovered with antibiotics in hospital.

Dowell 2001 did not report on complications in the immediate and delayed antibiotic groups.

 

Common cold

One study looked at immediate antibiotics versus delayed antibiotics (Arroll 2002a) and found no difference between the two prescribing strategies for the clinical outcomes of fever, cough, pain and malaise ( Analysis 10.1;  Analysis 11.4;  Analysis 12.1).

 

Antibiotic use

See  Table 1.

 
Delayed antibiotics

The three studies included in this systematic review published prior to 1992 examined the concern that immediate antibiotics for streptococcal pharyngitis might impair the body's immune response and predispose the patient to a relapse of pharyngitis. Compliance in both immediate and delayed antibiotic groups was close to 100%. Six of the included studies published after 1992 were conducted to evaluate the role of delayed antibiotics as a way of reducing antibiotic use for respiratory infections compared to immediate antibiotics. All six studies found that antibiotic use was significantly reduced in the delayed antibiotic group compared to the immediate antibiotic group. There were significant differences in the way antibiotics were delayed which may have resulted in the marked heterogeneity of this result. Of the seven studies published after 1991, four had the delayed script kept at reception to be picked up (Dowell 2001; Little 1997; Little 2001; Little 2005a) and in three, the script was issued to patients with instructions to delay (Arroll 2002a; Chao 2008; Spiro 2006). For the delayed arms of the four studies where the script was left at reception, antibiotics were used in 28% of cases (173/618) compared with antibiotics being used in 40% of cases (122/305) where antibiotics were issued to patients with instructions to delay.

Overall, the seven trials post 1992 providing a delayed antibiotic arm found 295 prescriptions filled out of 923 participants (32.0%).

 
Immediate antibiotics

Six trials published post 1992 provided immediate antibiotic arms examining this outcome resulting in 790 participants filling prescriptions out of 847 participants (93.3%) ( Analysis 13.1).

 
No antibiotics

Three studies compared delayed antibiotics with no antibiotics. Little 1997 found that there was less antibiotic use with the no antibiotic strategy compared to delayed antibiotics. Little 2005a found no differences. Chao 2008 is the most recent and only study conducted comparing delayed antibiotics only with no antibiotics and also found that fewer antibiotics were prescribed in the no antibiotic group ( Analysis 15.1).

Overall, 65 patients filled scripts out of 466 participants (13.9%).

 

Patient satisfaction

See  Table 1.

 
Delayed antibiotics versus immediate antibiotics

( Analysis 16.1)

Patient satisfaction has been measured in five out of seven studies evaluating the prescribing strategy of delayed antibiotics since 1992 (Arroll 2002a; Dowell 2001; Little 1997; Little 2001; Little 2005a). Two of these studies indicated that study participants were more satisfied with the strategy of immediate antibiotics than delayed antibiotics (Little 2001; Little 2005a). There was no difference found in the other three studies (Arroll 2002a; Dowell 2001; Little 1997). The pooled result for this outcome with these five studies was an odds ratio (OR) of 0.52 (95% CI 0.35 to 0.76) favouring immediate antibiotics. Fixed- and random-effects analyses gave similar results. A breakdown of the trials by blinding gave two trials (Dowell 2001; Little 2005a) which blinded the outcome assessor and one blinded the patient and the doctor (Arroll 2002a) to give an odds ratio for all three studies of 0.62 (95% CI 0.38 to 1.01). The two completely unblinded trials (Little 1997; Little 2001) give an OR of 0.42 (95% CI 0.22 to 0.78). Overall 92% of the participants in the immediate antibiotics arms were satisfied versus 87% in the delayed arms.

 
Delayed antibiotics versus no antibiotics

( Analysis 17.1)

Three studies examined patient satisfaction comparing the prescribing strategies of delayed antibiotics and no antibiotics (Chao 2008; Little 1997; Little 2005a). While there was no difference in patient satisfaction for any of these studies, the pooled result for these three studies was an odds ratio of 1.44 (95% CI 0.99 to 2.10) showing no statistically significant difference. Fixed- and random-effects analyses gave similar results. A breakdown of the trials by blinding gave two trials (Chao 2008; Little 2005a) which blinded the outcome assessor to give an odds ratio for these two trials of 1.42 (95% CI 0.92 to 2.19). The one completely unblinded trial (Little 1997) gave an odds ratio of 1.49 (95% CI 0.70 to 3.19). In the delayed antibiotic arm 413 of the participants were satisfied or very satisfied out of 473 participants (87.3%) compared to 387 out of 465 participants in the no antibiotics group (83.2%).

 

Adverse effects of antibiotics

Adverse effects are considered under different clinical headings owing to differences in antibiotic prescribing recommendations for each condition. This is likely to have contributed to the heterogeneity evident in the forest plots for these outcomes preventing pooling of results. Adverse results are presented graphically for delayed versus immediate antibiotics ( Analysis 17.1;  Analysis 17.2;  Analysis 17.3;  Analysis 18.4) and delayed versus no antibiotics ( Analysis 18.1;  Analysis 18.2;  Analysis 18.3;  Analysis 18.4).

 

Sore throat

 
Delayed antibiotics versus immediate antibiotics

One study (Little 1997) found no difference for diarrhoea, vomiting, rash and stomach ache. El-Daher 1991 found more vomiting in the delayed group compared to the immediate antibiotics.

 
Delayed antibiotics versus no antibiotics

One study (Little 1997) found no difference for diarrhoea, vomiting, rash and stomach ache.

 

AOM

 
Delayed antibiotics versus immediate antibiotics

Little 2001 and Spiro 2006 found reduced diarrhoea in the delayed antibiotic group. Spiro 2006 did not find any difference between delayed and immediate antibiotics for vomiting and Little 2001 found no difference for the outcome of rash.

 
Delayed antibiotics versus no antibiotics

There were no adverse events in either group reported by Chao 2008.

 

Bronchitis (cough)

 
Delayed antibiotics versus immediate antibiotics

Little 2005a found no difference for adverse effects.

 
Delayed antibiotics versus no antibiotics

Little 2005a found no difference for adverse effects.

 

Common cold

 
Delayed antibiotics versus immediate antibiotics

There was no significant difference between the groups for diarrhoea, a potential adverse effect of antibiotics (Arroll 2002a).

 

Re-consultation rates

Re-consultation rates were the same between delayed and immediate antibiotic groups in two studies ( Analysis 19.1). Subsequent consultation rates in the 12 months (excluding the first month) were also the same between delayed and immediate antibiotic groups in one study (Little 2001). Participants with sore throat in one study were more likely to intend to consult again if they received immediate antibiotics compared to delayed antibiotics (Little 1997).

 

Discussion

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms
 

Summary of main results

Small differences were found between prescribing strategies for clinical outcomes with immediate antibiotics most likely to show benefit over delayed antibiotics in participants with sore throat and acute otitis media (AOM). All strategies appear to have similar safety with no advantage found for delayed antibiotics over no antibiotics for disease complications. Delay and no antibiotic strategies dramatically reduce the use of antibiotics for acute respiratory tract infections (ARTIs) compared to immediate antibiotics. The least antibiotic use was in the no antibiotic group followed by delay and then immediate. The number needed to treat to prevent one antibiotic prescription using the delay strategy is 1.6 compared to immediate antibiotics. The number needed to treat to prevent one antibiotic prescription using a no antibiotic strategy compared to delay is 5.6. Patient satisfaction was highest in the immediate antibiotic group with 92.2% being satisfied or very satisfied with the consultation. The delay and no groups had similar quite high satisfaction rates at 87.3% and 83.2%, respectively. These high satisfaction results may reflect patient involvement in studies where their treating physicians are more thorough in their explanations than usual (Hawthorne effect) (French 1950; Levitt 2011). Results for satisfaction may not be as high in routine general practice.

 

Overall completeness and applicability of evidence

Studies comparing delayed and immediate antibiotics have been performed for two different motives. The studies of Pichichero 1987, Gerber 1990 and El-Daher 1991 were concerned that immediate antibiotics for streptococcal pharyngitis might impair the body's immune response and predispose the patient to a relapse of pharyngitis. These studies are useful for determining the effect of delayed versus immediate antibiotics on the clinical course of suspected streptococcal pharyngitis. Six of the remaining studies were conducted to determine if the strategy of delayed antibiotics reduces the number of prescriptions filled for upper ARTIs (Arroll 2002a; Dowell 2001; Little 1997; Little 2001) while maintaining patient safety and satisfaction. The most recent study may indicate evolution in prescribing habits as it was the first to drop the immediate antibiotic arm (Chao 2008).

Useful data were collected for many symptom outcomes in all studies but were not always reported in a way that could be analysed. This problem was partially overcome by obtaining raw data from some trial authors. The seven studies conducted after 1992 all reported useful data on antibiotic use and six on patient satisfaction.

There are only three trials comparing delayed antibiotics with no antibiotics.

 

Quality of the evidence

All but one trial (El-Daher 1991) were adequately randomised and accounted for incomplete data. El-Daher 1991 did find large differences for clinical outcomes for sore throat in favour of immediate antibiotics compared to delayed antibiotics.

This intervention does not lend itself to blinding. However, three trials attempted to blind patients and doctors (Arroll 2002a; El-Daher 1991; Pichichero 1987). For four studies (Chao 2008; Dowell 2001; Little 2005a; Spiro 2006), the outcomes assessor was blinded but not the patient nor the care giver.

Otherwise, studies were well reported and appeared to be high quality.

 

Potential biases in the review process

Heterogeneity of randomised controlled trials (RCTs) is one limitation of this review. Heterogeneity may have resulted from variable clinical presentations, differences in delay method, differences in antibiotic use and quality of included studies. Potential for type I error is another limitation of this review given the large number of reported outcome results. For example, multiple outcome measures are reported for the clinical outcomes comparing delayed and immediate antibiotic groups.

 

Agreements and disagreements with other studies or reviews

Findings for certain clinical outcomes in our review might have been anticipated. Systematic reviews on antibiotics for sore throat and AOM found that their time of greatest benefit for symptoms is apparent at days three or four after treatment has started (Spinks 2011; Venekamp 2013). Thus delaying antibiotics by 48 hours or more would overshoot this zenith. Nor is it surprising that we found more adverse reactions to antibiotics from immediate antibiotics in line with known adverse events from comparison RCTs with no antibiotics.

The greatest difference in clinical outcomes was found in the only trial of delayed antibiotics conducted in a low socio-economic environment, favouring immediate antibiotics over delay (El-Daher 1991). This trial was also the least methodologically sound but it highlighted that concerns expressed about delayed antibiotics for children, the elderly (Datta 2008) and those with language or cultural difficulties (Johnson 2007) may also need to be extended to low socio-economic populations.

A parallel RCT of patients with acute infective conjunctivitis similarly reported shortest symptom duration with immediate, followed by delayed and then no antibiotics (the last resulting in least antibiotic use). There was no difference between the groups for patient satisfaction (Everitt 2006).

A recent randomised controlled trial published in 2010 (Worrall 2010) comparing delayed prescriptions dated either the day of the office visit or two days later, but not comparing with either immediate or no antibiotics, demonstrated no significant difference between the two groups in terms of antibiotic use.

RCTs comparing delayed with no antibiotics (concluding that they were both equally acceptable alternatives to immediate antibiotics as a means of reducing antibiotic prescriptions) (Little 2001; Little 2005a) led to recommending delayed instead of no antibiotics to address concerns about risks of complications (Little 2005b). Doctors worried about the risk of serious infective complications consequent to adopting a no antibiotic rather than delayed strategy might take comfort from a UK observational study showing that reduced prescribing resulted in no increase in admissions to hospital for peri-tonsillar abscess or rheumatic fever (Sharland 2005), although mastoiditis might be a risk at the rate of 2500 children needing to be treated with antibiotics to prevent one case (Van Zuijlen 2001). Thirty-five per cent of parents in the AOM trials (Chao 2008; Little 2001; Spiro 2006) used their delayed script suggesting that the number of delayed scripts required to prevent one case of mastoiditis would be significantly higher than 2500. Doctors often find it difficult to identify patients at risk of serious complications from respiratory infections (Kumar 2003). Patients probably perform even less well, despite their self confidence in making this decision if given a delayed antibiotic prescription. This concern is supported by empirical data: respiratory disease severity does not correlate with patients' immediate preference for an antibiotic prescription (Macfarlane 1997). This review did not find any significant difference for complication rates between prescribing strategies.

There is little controversy within published guidelines that immediate antibiotics are recommended for patients who appear to be seriously unwell, fit multiple criteria indicating bacterial tonsillitis, are under six months of age with AOM, have bilateral AOM or have AOM with otorrhoea (Tan 2008). American guidelines also recommend immediate antibiotics for children under two with definite AOM (OMTG 2004). It seems then that for the majority of respiratory infections that do not meet these criteria, clinicians have the option of delayed or no antibiotics. It seems clear that no antibiotics will result in least antibiotic use and therefore less antibiotic resistance. Concerns about patient and doctor satisfaction with no antibiotics appear to be driving the use of a delayed strategy. Some doctors use the delay strategy to reduce antibiotic use, empower patients and save the patient time and money without jeopardising the doctor-patient relationship (Arroll 2002b). A qualitative study conducted in 2002 (Arroll 2002b) found that while some patients appreciated the option of controlling the decision as to whether and when to take antibiotics, others expected "the physician to decide". Concern was expressed by one physician that patients might view delayed prescribing as physician incompetence, substantiated by comments from some patients. Shared decision-making (Butler 2001; Legare 2007) and education campaigns for doctors (Sung 2006) have been proposed as ways of helping doctors and patients avoid unnecessary antibiotic use. One suggestion is that delayed antibiotics may in time become redundant as doctors and their patients gain more reassurance in the safety of not using antibiotics (Arroll 2003b).

 

Authors' conclusions

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms

 

Implications for practice

A strategy of immediate antibiotics is more likely to confer the modest benefits of antibiotics on clinical outcomes such as symptoms for acute otitis media and sore throat than delayed antibiotics. There were no differences in complication rates between immediate and delayed antibiotics nor between delayed and no antibiotics. Immediate antibiotics had slightly higher levels of patient satisfaction than delayed antibiotics, which reached statistical significance but is of marginal clinical significance (92% versus 87%). Patient satisfaction was similarly high in the delayed and no antibiotic groups with a trend towards delayed antibiotics that was neither statistically nor clinically significant (87% versus 83%). Delayed antibiotic prescribing strategies achieved lower rates of antibiotic use compared to immediate antibiotics (32% versus 93%). No antibiotics achieved lower rates of antibiotic use compared to delayed antibiotics (13% versus 32%).

Delayed antibiotics for respiratory infections is a strategy which reduces antibiotic use compared to immediate antibiotics but has not been shown by this review to be different to no antibiotics in terms of symptom control and disease complications. In patients with respiratory infections where clinicians feel it is safe not to prescribe antibiotics immediately, 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 delayed antibiotics.

 
Implications for research

Further research into antibiotic prescribing strategies for respiratory infections may best be focused on identifying patient groups at high risk of disease complications, enhancing doctors' communication with patients to maintain satisfaction and ways of reducing doctors' anxieties about not prescribing antibiotics for respiratory infections. Future randomised controlled trials of delaying antibiotics as an intervention should fully report symptoms, patient satisfaction, doctor satisfaction and disease complications as well as changes in prescription rates. They should also include a no antibiotic arm.

 

Acknowledgements

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms

The review authors wish to thank the following people for commenting on the 2010 updated review: Alison Thomas, Bill Hueston, Max Bulsara and Tom Fahey. We also thank the following people for commenting on this 2013 updated review: Amanda Roberts, Sandra Arnold, Bill Hueston, Sree Nair and Tom Fahey.

 

Data and analyses

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms
Download statistical data

 
Comparison 1. Sore throat - pain; delayed versus immediate antibiotics

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Pain on day 31Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Pain severity on day 31Mean Difference (IV, Fixed, 95% CI)Totals not selected

 
Comparison 2. Sore throat - malaise; delayed versus immediate antibiotics

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Malaise on day 31Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Malaise severity1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 
Comparison 3. Sore throat - fever; delayed versus immediate antibiotics

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Fever severity on day 32343Std. Mean Difference (IV, Fixed, 95% CI)0.53 [0.31, 0.74]

 2 Fever severity on day 12343Std. Mean Difference (IV, Fixed, 95% CI)-0.07 [-0.29, 0.14]

 
Comparison 4. AOM - pain; delayed versus immediate antibiotics

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Pain on day 31Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Pain on days 4 to 61Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Pain on day 71Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 4 Pain severity on day 31Mean Difference (IV, Fixed, 95% CI)Totals not selected

 5 Pain severity on day 71Mean Difference (IV, Fixed, 95% CI)Totals not selected

 
Comparison 5. AOM - malaise; delayed versus immediate antibiotics

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Malaise on day 31Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Malaise severity on day 31Mean Difference (IV, Fixed, 95% CI)Totals not selected

 3 Malaise severity on day 71Mean Difference (IV, Fixed, 95% CI)Totals not selected

 
Comparison 6. Supplementary medicine consumption; delayed versus immediate antibiotics

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Spoons of paracetamol/day1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 2 Use of paracetamol and ibuprofen1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 7. AOM - fever; delayed versus immediate antibiotics

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Fever Days 4 to 61Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 8. AOM - pain; delayed versus no antibiotics

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Otitis media pain on Day 3 delayed versus none1Odds Ratio (M-H, Random, 95% CI)Totals not selected

 
Comparison 9. AOM - fever; delayed versus no antibiotics

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Otitis media number of patients with fever on day 3 delayed versus none1Odds Ratio (M-H, Random, 95% CI)Totals not selected

 
Comparison 10. Common cold - pain; delayed versus immediate antibiotics

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Pain on day 31Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Pain on day 71Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 11. Common cold - fever; delayed versus immediate antibiotics

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Fever on day 31Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Fever on day 71Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Fever severity on day 11Mean Difference (IV, Fixed, 95% CI)Totals not selected

 4 Fever severity on day 31Mean Difference (IV, Fixed, 95% CI)Totals not selected

 5 Fever severity on day 71Mean Difference (IV, Fixed, 95% CI)Totals not selected

 
Comparison 12. Common cold - cough; delayed versus immediate antibiotics

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Cough on day 31Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Cough on day 71Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 13. Antibiotic use: delayed versus immediate antibiotics

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Antibiotic use: delayed versus immediate antibiotics6Odds Ratio (M-H, Random, 95% CI)Totals not selected

    1.1 Antibiotic use: delayed (prescription at time of visit) versus immediate antibiotics
2Odds Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    1.2 Antibiotic use: delayed (return for prescription) versus immediate antibiotics
4Odds Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 
Comparison 14. Antibiotic use: delayed versus no antibiotics

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Antibiotic use: delayed versus no antibiotics3Odds Ratio (M-H, Random, 95% CI)Totals not selected

    1.1 Antibiotic use: delayed (prescription at time of visit) versus no antibiotics
1Odds Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    1.2 Antibiotic use: delayed (return for prescription) versus no antibiotics
2Odds Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 
Comparison 15. Patient satisfaction: delayed versus immediate antibiotics

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Patient satisfaction: delayed versus immediate antibiotics51334Odds Ratio (M-H, Random, 95% CI)0.52 [0.35, 0.76]

    1.1 Patient satisfaction: delayed (prescription at time of consult) versus immediate antibiotics
1129Odds Ratio (M-H, Random, 95% CI)1.47 [0.32, 6.85]

    1.2 Patient satisfaction: delayed (return for prescription) versus immediate antibiotics
41205Odds Ratio (M-H, Random, 95% CI)0.48 [0.33, 0.71]

 
Comparison 16. Patient satisfaction: delayed versus no antibiotics

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Patient satisfaction: delayed versus no antibiotics3938Odds Ratio (M-H, Random, 95% CI)1.44 [0.99, 2.10]

    1.1 Patient satisfaction: delayed (prescription provided at visit) versus no antibiotics
1206Odds Ratio (M-H, Random, 95% CI)2.00 [0.65, 6.18]

    1.2 Patient satisfaction: delayed (return for prescription) versus no antibiotics
2732Odds Ratio (M-H, Random, 95% CI)1.38 [0.93, 2.06]

 
Comparison 17. Adverse events: delayed versus immediate antibiotics

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Vomiting3Odds Ratio (M-H, Random, 95% CI)Totals not selected

 2 Diarrhoea4Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Rash2Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 4 Stomach ache1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 18. Adverse events: delayed versus no antibiotics

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Vomiting1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Diarrhoea2Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Rash1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 4 Stomach ache1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 19. Re-consultation rate; delayed versus immediate antibiotics

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Re-consultation rate2379Odds Ratio (M-H, Fixed, 95% CI)1.04 [0.55, 1.98]

 
Comparison 20. Subsequent consultation rates in the 12 months following the index consultation (excluding first month following consultation); delayed versus immediate antibiotics

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Re-consultation in the 12 months following the index consultation (excluding the first month following the index consultation)1Rate Ratio (Fixed, 95% CI)Totals not selected

 

Appendices

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms
 

Appendix 1. Ovid EMBASE search strategy

1     exp Respiratory Tract Infection/ (172448)
2     exp Upper Respiratory Tract Infection/ (22007)
3     (upper respiratory tract infection$ or urti).mp. (14226)
4     exp Otitis Media/ (15047)
5     otitis media.mp. (16846)
6     exp Pharyngitis/ (13679)
7     pharyngitis.mp. (9017)
8     exp Tonsillitis/ (5085)
9     tonsillitis.mp. (4596)
10     exp Common Cold/ (4421)
11     common cold.mp. (5401)
12     exp Bronchitis/ (24102)
13     bronchitis.mp. (17391)
14     exp Sinusitis/ (19381)
15     sinusitis.mp. (18397)
16     sore throat$.mp. (8421)
17     or/1-16 (234854)
18     exp Antibiotic Agent/ (544500)
19     antibiotic$.mp. (328859)
20     or/18-19 (628363)
21     (delay$ adj15 prescri$).mp. (841)
22     17 and 20 and 21 (102)

 

Appendix 2. CENTRAL search strategy

#1        MeSH descriptor: [Respiratory Tract Infections] explode all trees       9072
#2        (upper next respiratory next tract infection*) or URTI             1061
#3        MeSH descriptor: [Otitis Media] explode all trees        1009
#4        otitis next media          1926
#5        MeSH descriptor: [Pharyngitis] explode all trees          841
#6        pharyngitis       1237
#7        MeSH descriptor: [Tonsillitis] explode all trees            322
#8        tonsillitis          651
#9        MeSH descriptor: [Common Cold] explode all trees    375
#10      common next cold*     729
#11      MeSH descriptor: [Bronchitis] explode all trees           1416
#12      bronchitis         2754
#13      MeSH descriptor: [Sinusitis] explode all trees  626
#14      sinusitis            1362
#15      sore next throat*          826
#16      #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13 or #14 or #15           14213
#17      MeSH descriptor: [Anti-Bacterial Agents] explode all trees     8199
#18      antibiotic*        15634
#19      #17 or #18       19843
#20      delay* near/15 prescri*           87
#21      #16 and #19 and #20   28

 

Appendix 3. EBSCO CINAHL search strategy

S15 S10 and S13 and S14
S14 TI delay* N15 prescri* or AB delay* N15 prescri*
S13 S11 or S12
S12 TI antibiotic* or AB antibiotic*
S11 (MH "Antibiotics+")
S10 S1 or S2 or S3 or S4 or S5 or S6 or S7 or S8 or S9
S9 TI ( otitis media or pharyngitis or tonsillitis or common cold* or bronchitis or sinusitis or sore throat* ) or AB ( otitis media or pharyngitis or tonsillitis or common cold* or bronchitis or sinusitis or sore throat* )
S8 (MH "Sinusitis+")
S7 (MH "Bronchitis+")
S6 (MH "Common Cold")
S5 (MH "Tonsillitis+")
S4 (MH "Pharyngitis")
S3 (MH "Otitis Media+")
S2 TI ( upper respiratory tract infection* or urti ) or AB ( upper respiratory tract infection* or urti )
S1 (MH "Respiratory Tract Infections+")

 

Appendix 4. ISI Current Contents Connect search strategy

#14 #13 AND #12 AND #9
#13 TS=antibiotic*
#12 #11 OR #10
#11 TS=immediate*
#10 TS=delay*
#9 #8 OR #7 OR #6 OR #5 OR #4 OR #3 OR #2 OR #1
#8 TS=sore throat
#7 TS=sinusitis
#6 TS=bronchitis
#5 TS=common cold*
#4 TS=tonsillitis
#3 TS=pharyngitis
#2 TS=otitis media
#1 TS=respiratory tract infection*

 

Feedback

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms
 

Feedback: Analysis 15.01 Comparison 15 may have some errors, 9 June 2008

 

Summary

Feedback: Analysis 15.01 Comparison 15 Patient satisfaction immediate versus delayed antibiotics, Outcome 01 Patient satisfaction: immediate versus delayed antibiotics may have some errors.

We think that the extracted data has been entered under the wrong headings, i.e. for Little 1997, it reports that 165/177 were satisfied with delayed antibiotics but the RevMan forest plot has 165/177 under the immediate antibiotics.

Data extracted from one article (Dowell 2001) may have been entered incorrectly, i.e. the percentage has been entered into RevMan directly rather than as the actual number. In other words, for Dowell 2001, the paper reports 100% (73% very satisfied and 27% moderately satisfied), whereas the forest plot has reported the 73% as 73/75. This is a double query ? see below for issue of inconsistent grouping of satisfaction scores.

Suggest that the data extracted for Dowell 2001 should be consistent with the logic used for Arroll 2002 in their results for the same outcome.
We think that possibly the forest plot analysis should be conducted with the figures below. We have looked at all the original papers.

Arroll 2002a   
 64/67* Delayed Antibiotics
 58/62* Immediate Antibiotics
Dowell 2001
 71/73# Delayed Antibiotics
 75/75# Immediate Antibiotics
Little 1997    
 165/177 Delayed Antibiotics   
 202/211 Immediate Antibiotics
Little 2001
 115/150 Delayed Antibiotics
 123/135 Immediate Antibiotics
Little 2005a   
 147/190 Delayed Antibiotics
 166/194 Immediate Antibiotics

Arroll et al noted that  for these results, groups responding 1 and 2 have been combined and groups 3 and 4 have been combined where: 1= very satisfied; 2= moderately satisfied; 3 = slightly satisfied; 4 = not at all satisfied.

Using similar logic as Arroll et al, results for groups responding ?very satisfied? and ?moderately satisfied? have been combined, as have ?not very satisfied? and ?not at all satisfied? to get the figures in the table above for Dowell 2001. (Note: in the review table, the figures were extracted directly from the ?very satisfied? column only, where they were presented as a percentage without then recalculating them as a whole figure).

We don't think these possible errors effect the overall conclusions made by the authors in the review.

Submitter agrees with default conflict of interest statement:
I certify that I have no affiliations with or involvement in any organisation or entity with a financial interest in the subject matter of my feedback.

 

Reply

We thank those who have given feedback on this review. We greatly appreciate the work you have done to uncover these errors and the opportunity you have given us to correct them. We agree with all the feedback you have submitted and have made corrections to analysis 15 comparison 15.1, analysis 16 comparison 16.1, analysis 13 comparison 13.1 (antibiotic use delayed versus immediate), analysis 14 comparison 14.1 (antibiotic use delayed versus none) and analysis 3 comparison 3.1 (fever severity on day 3). We have also added an analysis 17: adverse events delayed versus no antibiotics.

Theses changes have not fundamentally changed the results of the review. However the text and outcome tables have been amended to reflect changes made.

Geoff Spurling, Chris Del Mar, Liz Dooley
Feedback reply added 25 June 2008

 

Contributors

Dianne Lowe, Rebecca Ryan
Feedback comment added 16 June 2008

 

It would be interesting to explore the comparative evidence base for the most effective method of delayed prescription, 18 March 2009

 

Summary

Feedback: It would be interesting to explore the comparative evidence base for the most effective method of "delayed prescription" e.g.:
1. Script dated today given to patient
2. Script dated 2-3 days from now - given to patient
3. Script held at practice

Submitter agrees with default conflict of interest statement:
I certify that I have no affiliations with or involvement in any organization or entity with a financial interest in the subject matter of my feedback.

 

Reply

We thank you for your feedback on this review. We agree that it would be interesting to explore the comparative evidence base for the most effective method of delayed prescription. Subgroups highlighting the method of delayed prescribing have been added for the outcomes antibiotic use and patient satisfaction. Unfortunately, there was great heterogeneity in the methods of delayed prescribing that makes combining studies difficult. Methods of delayed prescribing ranged from issuing a prescription at the time of the initial consults with instruction to delay, to holding the delayed prescription at reception to be picked up if symptoms hadn't improved after a specified period of time. The recommended periods of delay ranged from three to fourteen days.

The three studies included in this systematic review published prior to 1992 examined the concern that immediate antibiotics for streptococcal pharyngitis might impair the body's immune response and predispose the patient to a relapse of pharyngitis. Six of the included studies published after 1992 were conducted to evaluate the role of delayed antibiotics as a way of reducing antibiotic use for respiratory infections compared to immediate antibiotics. While all six studies found that antibiotic use was significantly reduced in the delayed antibiotic group compared to the immediate antibiotic group. There were significant differences in the way antibiotics were delayed which may have contributed to the marked heterogeneity of this result. Of the seven studies published after 1991, four had the delayed script kept at reception to be picked up (Dowell 2001; Little 1997; Little 2001; Little 2005a) and in three, the script was issued to patients with instructions to delay (Arroll 2002a; Chao 2008; Spiro 2006). For the delayed arms of the four studies where the script was left at reception, antibiotics were used in 28% of cases (173/618) compared with antibiotics being used in 40% of cases (122/305) where antibiotics were issued to patients with instructions to delay.

None of the included studies specifically addressed whether or not prescriptions had been post-dated. However, a recent randomised controlled trial published in 2010, (Worrall 2010) comparing delayed prescriptions dated either the day of the office visit or 2 days later, but not comparing with either immediate or no antibiotics, demonstrated no significant difference between the two groups in terms of antibiotic use.

Geoff Spurling, Chris Del Mar, Liz Dooley, Rebecca Farley
Feedback reply added 25 March 2012

 

Contributors

Jas Janjuha, Occupation Pharmacist

 

What's new

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms

Last assessed as up-to-date: 28 February 2013.


DateEventDescription

28 February 2013New search has been performedThe searches have been updated. Two new papers (Little 2006; Moore 2009) were included. They reported longer-term outcomes of two previously included studies (Little 2001; Little 2005a) including impact of delayed antibiotic prescribing on earache recurrence and subsequent consultation rates in the 12 months following the initial consultation. Three new trials were excluded (Fischer 2009; Newson 2009; Vouloumanou 2009). Our conclusions remain unchanged.

28 February 2013New citation required but conclusions have not changedA new author joined the team to update the review.



 

History

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms

Protocol first published: Issue 4, 2003
Review first published: Issue 4, 2004


DateEventDescription

5 August 2010AmendedContact details updated.

27 March 2009New search has been performedSearches conducted. This 2009 update contains one new study (Chao 2008) and Feedback on a comment submitted via The Cochrane Library.

16 June 2008Feedback has been incorporatedFeedback comment added.

16 June 2008AmendedConverted to new review format.

21 January 2007New search has been performedSearches conducted.

9 January 2004New search has been performedSearches conducted.



 

Contributions of authors

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms

Chris Del Mar (CDM) conceived the review.
Geoff Spurling (GS) and CDM designed the review.
Ruth Foxlee (RF) and GS performed the literature searches.
RF, Liz Dooley (LD) and CDM appraised articles and extracted data from these articles.
GS and Rebecca Farley (RFa) entered data into RevMan with contributions from LD, RF and CDM.
GS secured funding for the review with the assistance of CDM.

 

Declarations of interest

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms

No known conflict of interest.

 

Sources of support

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms
 

Internal sources

  • Bond University, Gold Coast, Australia.
  • The Discipline of General Practice at the University of Queensland, Australia.
    For providing the infrastructure which allowed the first publication of this review to be conducted.

 

External sources

  • General Practice Education and Training, Australia.

* Indicates the major publication for the study

References

References to studies included in this review

  1. Top of page
  2. AbstractRésumé
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. Feedback
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. Additional references
  22. References to other published versions of this review
Arroll 2002a {published and unpublished data}
  • Arroll B, Kenealy T, Kerse N. Do delayed prescriptions reduce the use of antibiotics for the common cold? A single-blind controlled trial. Journal of Family Practice 2002;51(4):324-8.
Chao 2008 {published data only (unpublished sought but not used)}
  • Chao J, Kunkov S, Reyes L, Lichten S, Crain E. Comparison of two approaches to observation therapy for acute otitis media in the emergency department. Pediatrics 2008;121(5):1352-6.
Dowell 2001 {published data only}
  • Dowell J, Pitkethy M, Bain J, Martin S. A randomised controlled trial of delayed antibiotic prescribing as a strategy for managing uncomplicated respiratory tract infection in primary care. British Journal of General Practice 2001;51(464):200-5.
El-Daher 1991 {published data only}
  • El-Daher N, Rawashedeh N, Al-Khalil I, Abu-ektaish F. Immediate versus delayed treatment of group A beta-haemolytic streptococcal pharyngitis with penicillin V. Pediatric Infectious Disease Journal 1991;10(2):126-30.
Gerber 1990 {published data only}
Little 1997 {published data only}
  • Little P, Williamson I, Warner G, Gould C, Gantley M, Kinmonth AL. Open randomised trial of prescribing strategies in managing sore throat. BMJ 1997;314(7082):722-7.
Little 2001 {published and unpublished data}
  • Little P, Gould C, Williamson I, Moore M, Warner G, Dunleavey J. Pragmatic randomised controlled trial of two prescribing strategies for childhood acute otitis media. BMJ 2001;322(7282):336-42.
  • Little P, Moore M, Warner G, Dunleavy J, Williamson I. Longer term outcomes from a randomised trial of prescribing strategies in otitis media. British Journal of General Practice 2006;56(524):176-82.
Little 2005a {published data only}
  • Little P, Rumsby K, Kelly J, Watson L, Moore M, Warner G, et al. Information leaflet and antibiotic prescribing strategies for acute lower respiratory infection. JAMA 2005;293(24):3029-35.
  • Moore M, Little P, Rumsby K, Kelly J, Watson L, Warner G, et al. Effect of antibiotic prescribing strategies and an information leaflet on longer-term reconsultation for acute lower respiratory tract infection. British Journal of General Practice 2009;59(567):728-34.
Pichichero 1987 {published data only}
  • Pichichero M, Disney F, Talpey W, Green J, Francis A, Roghmann K, et al. Adverse and beneficial effects of immediate treatment of group A beta-haemolytic streptococcal pharyngitis with penicillin. Pediatric Infectious Disease Journal 1987;6(7):635-43.
Spiro 2006 {published data only}

References to studies excluded from this review

  1. Top of page
  2. AbstractRésumé
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. Feedback
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. Additional references
  22. References to other published versions of this review
Cates 1999 {published data only}
  • Cates C. An evidence based approach to reducing antibiotics use in children with acute otitis media: controlled before and after study. BMJ 1999;318:715-6.
Fischer 2009 {published data only}
  • Fischer T, Singer A, Chale S. Observation option for acute otitis media in the emergency department. Paediatric Emergency Care 2009;25(9):575-8.
Newson 2009 {published data only}
  • Newson L. Delayed prescribing. Practice Nurse 2009;37(2):21.
Siegel 2003 {published data only}
  • Siegel R, Kiely M, Bien JP, Joseph EC, Davis JB, Mendel SG, et al. Treatment of otitis media with observation and a safety-net antibiotic prescription. Pediatrics 2003;112(3):527-31.
Vouloumanou 2009 {published data only}
  • Vouloumanou E, Karageorgopoulos D, Kazanti M, Kapaskelis A, Falagas M. Antibiotics versus placebo or watchful waiting for acute otitis media: a meta-analysis of randomized controlled trials. Journal of Antimicrobial Chemotherapy 2009;64(1):16-24.

Additional references

  1. Top of page
  2. AbstractRésumé
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. Feedback
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. Additional references
  22. References to other published versions of this review
Arason 1996
  • Arason A, Kristinsson KG, Sigurdson JA, Stefansdottir G, Molstad S, Gudmundsson S. Do antimicrobials increase the carriage rate of penicillin resistant pneumoccci in children? Cross sectional prevalence study. BMJ 1996;313:387-91.
Arroll 2002b
  • Arroll B, Goodyear-Smith F, Thomas D, Kerse N. Delayed antibiotic prescriptions: what are the experiences and attitudes of physicians and patients?. Journal of Family Practice 2002;51(11):954-9.
Arroll 2003a
  • Arroll B, Kenealy T, Kerse N. Do delayed prescriptions reduce antibiotic use in respiratory tract infections? A systematic review. British Journal of General Practice 2003;53:871-7.
Arroll 2003b
Arroll 2010
  • Arroll B, Kenealy T. Antibiotics for the common cold and acute purulent rhinitis. Cochrane Database of Systematic Reviews 2010, Issue 2. [DOI: 10.1002/14651858.CD000247.pub2]
Berman 1997
  • Berman S, Byrns PJ, Bondy J, Smith PJ, Lezotte D. Otitis media-related antibiotic prescribing patterns, outcomes, and expenditures in a pediatric medicaid population. Pediatrics 1997;100(4):585-92.
Brook 1998
Butler 2001
Datta 2008
  • Datta M. Review: delayed or immediate prescriptions of antibiotics have similar clinical outcomes in respiratory infections. Evidence Based Medicine 2008;13(2):42.
Dickersin 1994
  • Dickersin K, Scherer R, Lefebvre C. Identifying relevant studies for systematic reviews. BMJ 1994;309(6964):1286-91.
Everitt 2006
French 1950
  • French JRP. Field experiments: changing group productivity. In: Miller JG editor(s). Experiments in Social Process: A Symposium on Social Psychology. McGraw-Hill, 1950:82.
Higgins 2011
  • Higgins JPT. Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S editor(s). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0. The Cochrane Collaboration [updated March 2011]. Chichester, UK: Wiley-Blackwell, 2011.
Johnson 2007
Kumar 2003
Legare 2007
  • Legare F, Labrecque M, Leblanc A, Thivierge R, Godin G, Laurier C, et al. Does training family physicians in shared decision making promote optimal use of antibiotics for acute respiratory infections? Study protocol of a pilot clustered randomised controlled trial. BMC Family Practice 2007;8:65.
Levitt 2011
  • Levitt SD, List JA. Was there really a Hawthorne Effect at the Hawthorne Plant? An analysis of the original illumination experiments. American Economic Journal: Applied Economics 2011;3(1):224-38.
Little 2005b
Little 2006
  • Little P, Moore M, Warner G, Dunleavy J, Williamson I. Longer term outcomes from a randomised trial of prescribing strategies in otitis media. British Journal of General Practice 2006;56(524):176-82.
Macfarlane 1997
  • Macfarlane J, Holmes W, Macfarlane R, Britten N. Influence of patient's expectations on antibiotic management of acute lower respiratory tract illness in general practice: questionnaire study. BMJ 1997;315:1211-4.
Moore 2009
  • Moore M, Little P, Rumsby K, Kelly J, Watson L, Warner G, et al. Effect of antibiotic prescribing strategies and an information leaflet on longer-term reconsultation for acute lower respiratory tract infection. British Journal of General Practice 2009;59(567):728-34.
Niemela 1999
  • Niemela M, Uhari M, Mottonen M, Pokka T. Costs arising from otitis media. Acta Paediatrica 1999;88(5):553-6.
OMTG 2004
  • Otitis Media Treatment Guidelines. Diagnosis and management of acute otitis media. Pediatrics 2004;113(5):1451-65.
RevMan 5.2
  • The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). 5.2. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012.
Sharland 2005
  • Sharland M, Kendall H, Yeates D, Randall A, Hughes G, Glasziou P, et al. Antibiotic prescribing in general practice and hospital admissions for peritonsillar abscess, mastoiditis and rheumatic fever in children: time trend analysis. BMJ 2005;331(7512):328-9.
Smith 2011
  • Smith SM, Fahey T, Smucny J, Becker LA. Antibiotics for acute bronchitis. Cochrane Database of Systematic Reviews 2011, Issue 11. [DOI: 10.1002/14651858.CD000245.pub2]
Spinks 2011
  • Spinks A, Glasziou PP, Del Mar C. Antibiotics for sore throat. Cochrane Database of Systematic Reviews 2011, Issue 9. [DOI: 10.1002/14651858.CD000023.pub3]
Sung 2006
  • Sung L, Arroll J, Arroll B, Goodyear-Smith F, Kerse N, Norris P. Antibiotic use for upper respiratory tract infections before and after a education campaign as reported by general practitioners in New Zealand. New Zealand Medical Journal 2006;119(1233):U1956.
Tan 2008
Van Zuijlen 2001
  • Van Zuijlen DA, Schilder AG, Van Balen FA, Hoes AQ. National differences in incidences of acute mastoiditis: relationship to prescribing patterns for acute otitis media. Pediatric Infectious Disease 2001;20:140-4.
Venekamp 2013
  • Venekamp RP, Sanders S, Glasziou PP, Del Mar CB, Rovers MM. Antibiotics for acute otitis media in children. Cochrane Database of Systematic Reviews 2013, Issue 1. [DOI: 10.1002/14651858.CD000219.pub3]
Verkatesum 1995
Worrall 2010
  • Worrall G, Kettle A, Graham W, Hutchinson J. Postdated versus usual delayed antibiotic prescriptions in primary care. Canadian Family Physician 2010;56:1032-6.

References to other published versions of this review

  1. Top of page
  2. AbstractRésumé
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. Feedback
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. Additional references
  22. References to other published versions of this review
Spurling 2007
Spurling 2010
  • Spurling GKP, Del Mar CB, Dooley L, Foxlee R. Delayed antibiotics for respiratory infections. Cochrane Database of Systematic Reviews 2010, Issue 1. [DOI: 10.1002/14651858.CD004417.pub2]