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Interventions to Influence Consulting and Antibiotic Use for Acute Respiratory Tract Infections in Children: A Systematic Review and Meta-Analysis

  • Talley Andrews,

    Affiliation Department of Family Medicine, Oregon Health and Science University, Portland, Oregon, United States of America

  • Matthew Thompson ,

    matthew.thompson@phc.ox.ac.uk

    Affiliation Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom

  • David I. Buckley,

    Affiliation Department of Family Medicine, Oregon Health and Science University, Portland, Oregon, United States of America

  • Carl Heneghan,

    Affiliation Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom

  • Rick Deyo,

    Affiliation Department of Family Medicine, Oregon Health and Science University, Portland, Oregon, United States of America

  • Niamh Redmond,

    Affiliation Academic Unit of Primary Health Care, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom

  • Patricia J. Lucas,

    Affiliation School for Policy Studies, University of Bristol, Bristol, United Kingdom

  • Peter S. Blair,

    Affiliation School of Social and Community Medicine, St Michael's Hospital, University of Bristol, Bristol, United Kingdom

  • Alastair D. Hay

    Affiliation Academic Unit of Primary Health Care, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom

Interventions to Influence Consulting and Antibiotic Use for Acute Respiratory Tract Infections in Children: A Systematic Review and Meta-Analysis

  • Talley Andrews, 
  • Matthew Thompson, 
  • David I. Buckley, 
  • Carl Heneghan, 
  • Rick Deyo, 
  • Niamh Redmond, 
  • Patricia J. Lucas, 
  • Peter S. Blair, 
  • Alastair D. Hay
PLOS
x

Abstract

Background

Respiratory tract infections (RTIs) are common in children and generally self-limiting, yet often result in consultations to primary care. Frequent consultations divert resources from care for potentially more serious conditions and increase the opportunity for antibiotic overuse. Overuse of antibiotics is associated with adverse effects and antimicrobial resistance, and has been shown to influence how patients seek care in ensuing illness episodes.

Methodology/Principal Findings

We conducted a systematic review and meta-analysis to assess the effectiveness of interventions directed towards parents or caregivers which were designed to influence consulting and antibiotic use for respiratory tract infections (RTIs) in children in primary care. Main outcomes were parental consulting rate, parental knowledge, and proportion of children subsequently consuming antibiotics. Of 5,714 references, 23 studies (representing 20 interventions) met inclusion criteria. Materials designed to engage children in addition to parents were effective in modifying parental knowledge and behaviour, resulting in reductions in consulting rates ranging from 13 to 40%. Providing parents with delayed prescriptions significantly decreased reported antibiotic use (Risk Ratio (RR) 0.46 (0.40, 0.54); moreover, a delayed or no prescribing approach did not diminish parental satisfaction.

Conclusions

In order to be most effective, interventions to influence parental consulting and antibiotic use should: engage children, occur prior to an illness episode, employ delayed prescribing, and provide guidance on specific symptoms. These results support the wider implementation of interventions to reduce inappropriate antibiotic use in children.

Introduction

Respiratory tract infections (RTIs) are common in children and drive the majority of antibiotic prescribing for this population [1]. On average, a third of all children in the United Kingdom and United States are seen in primary care for RTIs or related symptoms each year [2], [3]. When parental time off work is added to the costs of health care, RTIs pose a major financial burden [1], [2], [3], [4]. Clinical uncertainty regarding the diagnosis and management of RTIs is illustrated by wide variations in antibiotic use in primary care between individual clinicians, general practitioner (GP) practices, and countries [5], [6], [7], [8]. Antibiotics can cause side effects in children, such as rash or diarrhoea, and rarely allergic reactions [9]. Overuse of antibiotics in primary care contributes to resistance [10], thus reducing the benefits of antibiotics, and can lead to subsequent “medicalisation of illness” where patients believe they need to consult when similar symptoms recur [11] – thereby creating a ‘vicious cycle’. Combined with a slowing in the development of new antibiotics, resistance constitutes a major threat to public health [12]. Although public education campaigns are ongoing in many countries [13], targeted efforts are also needed at the practice and patient level to reduce population-wide risk of antibiotic resistance.

In the UK, the Department of Health Standing Medical Advisory Committee's ‘Path of Least Resistance’ report (1998) outlined the pivotal role primary care must play to avert the public health disaster of ineffective antibiotics for serious infections [14]. Recent guidelines highlight the need for patients and primary care professionals to stop seeing a role for antibiotics in the symptomatic relief of RTIs, and to adopt “no or delayed antibiotic” prescribing for the majority of patients [15]. To apply these recommendations, knowledge translation strategies are needed at the parental level to influence consulting behaviour and use of antibiotics, and at the primary care interface to influence consultation skills and prescribing behaviour.

Our goal was to systematically review the evidence for the effectiveness of interventions directed towards parents and/or caregivers to promote more appropriate consulting and antibiotic use for children with RTIs. We originally intended to also include interventions targeted to clinicians designed to change antibiotic prescribing, but decided to focus on interventions targeted to parents and caregivers based on feedback during peer review as research in this area had not been synthesised previously. The systematic review was based on a conceptual model (Figure S1) developed by the research team (consisting of qualitative and quantitative researchers, primary care clinicians, and parents) that incorporates knowledge, beliefs, and attitudes regarding decisions to consult and to use antibiotics for RTIs. These factors are often informed by past experience; for example, receiving antibiotics for a previous cough or cold may reinforce the belief that antibiotics are indicated and the decision to consult [16]. As such, repeated consultation and antibiotic prescribing experiences can contribute to ‘vicious’ or ‘virtuous’ cycles.

Our rationale for adopting a comprehensive approach to interventions rather than focussing more narrowly on individual components (e.g. delayed prescribing) takes account of the relatedness of the interventions and their effects at multiple points within the parent-doctor interaction. We therefore identified interventions that are applicable to multiple components of the parent-doctor interaction surrounding consultations, including parental knowledge of when to consult, and antibiotic use (measured by parental report of filling prescriptions or giving antibiotics to their child), including parental knowledge and attitudes related to use of antibiotics.

Methods

Search

We searched MEDLINE/PubMed [1966–November 2011], EMBASE [1974–March 2011], CINAHL [1981–March 2011], PsycINFO, and the Cochrane Library using a combination of terms on respiratory tract infection, children and parents, education, antibiotic prescription, and consultation (Table S1). No limits were applied for language. One author (TA) independently screened titles and abstracts based on the inclusion criteria to identify potentially relevant studies. Following the initial search, TA reviewed reference lists of selected studies and searched related citations to identify additional references. Two authors (TA and MT) reviewed the full-text of all potentially relevant studies to determine final inclusion. Disagreements were settled through discussions with a third author (CH or DB). Review protocol is available by request.

Selection

We included studies that used randomised, cluster randomised, or non-randomised controlled designs, or one group pre/post-test designs, to assess the effect of educational or behavioural interventions directed at caregivers to influence consulting or antibiotic use for acute RTIs in children (birth to 18 years), in developed countries (based on OECD member classification [17]). Comparisons included no-treatment or alternate treatment controls. We excluded studies that did not report outcomes for children with RTIs; study designs without a control group; evaluations of national treatment guidelines, public health interventions targeting multiple stakeholders at the population level, or diagnostic tests; studies of hospitalised children or those with serious comorbidities (e.g. cystic fibrosis, cancer, or other causes of immunocompromise); or studies from less developed countries (as the generalizability of the data from ‘less developed’ countries where the risk of severe complications from infection is higher will be limited).

Study characteristics

We sought data on three primary outcomes related to RTIs in children: 1) parental knowledge related to consultations or parental consultation rate, 2) parental knowledge or attitudes related to antibiotic use, and 3) antibiotic use. Secondary outcomes included adverse effects, health outcomes, and costs of interventions.

Data abstraction

Two reviewers (TA, MT) independently extracted data from included studies, using a predetermined extraction form, for study design, setting, patient population, definitions of included illnesses, intervention and comparison, theoretical framework, outcome(s) assessed, and method of assessment. Disagreements were resolved by discussion with a third author (DB or CH). When necessary we contacted study authors for additional information. Reviewers were not blinded to any aspect of the studies.

Validity assessment

Two review authors (TA and MT) independently assessed study quality using a framework adapted from the Cochrane Handbook risk of bias tool [18]. Our framework included a set of criteria selected to assess educational and behavioural interventions. For randomized or cluster randomized trials we assessed risk of bias based on the following criteria: randomization (description of method, differences between experimental groups), blinding, description of intervention (content and mode of delivery), exposure to intervention (and consistency in delivery), and generalisability (to primary care practice). Non-randomized controlled trials were assessed on the basis of comparability of groups, intervention description, exposure to intervention, and generalisability. One-group designs were assessed on the basis of intervention description, exposure to intervention, and generalisability. A judgment of “low”, “high”, or “unclear” was made regarding the risk of bias for each criterion; based on this, each study was then given an overall judgement of “minimum”, “likely”, or “high” risk of bias (Table S2). The overall quality assessments were used to interpret the main findings.

Quantitative data synthesis

For interventions which measured changes in mean or median numbers we calculated mean differences with 95% confidence intervals (CI), and for changes in rates we calculated odds ratios (OR) with 95% CI, using Yates's correction and Fisher's exact test where an expected cell was below five, for each of the study outcomes (EpiInfo version 3.4.3). Where raw data were unavailable, we presented proportional or mean differences. When possible we pooled outcomes and calculated risk ratio using a random effects model; we then calculated heterogeneity using I2 and where it was greater than 50% looked for clinical and statistical explanations. Considerable statistical and clinical heterogeneity prevented pooling of most outcomes; therefore results of each study are presented individually and interpreted using narrative analysis.

Results

Flow of included studies

From 5,714 initial studies, 137 met the criteria for full-text review, of which 114 were excluded (Figure S2). A total of 23 studies (representing 20 interventions) were included in the review; 12 interventions were from the US, six from the UK, and two from Israel. (Characteristics of included studies are reported in Table S3).

1. Interventions to influence parental consulting

We identified nine studies of eight interventions which aimed to change the number or rate of parental consultations for paediatric RTIs, involving a total of 1488 parents, 1580 families, and 558 children [19], [20], [21], [22], [23], [24], [25], [26], [27]. Interventions were delivered at home in four studies [22], [24], [26], [27], and at GP surgeries or emergency departments in the remainder. All interventions involved written material (e.g. book, pamphlet), complemented by brief verbal education in five studies [19], [20], [21], [24], [25]. In three of these studies, intervention materials included cartoons and/or illustrations [22], [25], [27]. The studies measured change in rate or number of consultations or re-consultations for RTIs [19], [21], [22], [25], [26], [27], or change in knowledge about reasons to consult [19], [20], [21], [23], [24], Follow-up periods ranged from 3 days to 17 months. Results are shown in Table 1 and 2.

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Table 1. Effectiveness of interventions to influence parent knowledge related to consulting for respiratory tract infections in children.

https://doi.org/10.1371/journal.pone.0030334.t001

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Table 2. Effectiveness of interventions to change parent consulting rate for respiratory tract infections in children.

https://doi.org/10.1371/journal.pone.0030334.t002

Knowledge related to consulting.

Outcomes were mixed in the five studies that assessed change in parent knowledge in relation to consulting [19], [20], [21], [23], [24] (Table 1). Interventions significantly improved parents' knowledge about RTIs compared to controls in two studies [21], [23], but did not measure effects on actual consultations. Similarly, the three studies which measured future consultation intentions also found significantly increased knowledge about appropriate reasons to consult, but again their impact on actual consultations was not measured [19], [20], [24].

Consultation rate.

Six studies assessed the effects of interventions designed to reduce the number of consultations for RTIs [19], [21], [22], [25], [26], [27] (Table 2). Three studies found that providing parents with informative, illustrated booklets prior to their child becoming ill resulted in lower rates of consulting for sore throat, cough, respiratory tract infection and otitis media [22], [25], [27]. Usherwood et al found that consultations per household decreased nearly 16% for sore throat (p = 0.0002) and 13% for cough (p = 0.013) [27]. In the study by Roberts, there was a relative reduction of 40% in the number of consultations per person/year for acute otitis media and other RTIs [25]. In one study, parents received books with information on multiple symptoms of respiratory infection (for example, cough, sore throat, and runny nose), yet consulting decreased significantly among all age groups only for sore throat (p<0.05) [22]. The method of randomization was not reported in two of these studies, and generalisability may be limited given they were published 20–30 years ago [22], [27]. Thomson et al provided mothers of infants in the intervention group with a guide for assessing severity of illness, and found similar numbers of infants subsequently had RTIs recorded by a clinician (52% vs. 50%, p = 0.718), however infants in the intervention group were more likely to receive prescriptions for oral antibiotics (OR 1.43 [95%CI 1.07–1.91]) [26]. Two studies assessed interventions delivered at point of consulting and designed to reduce re-consultations within a given illness episode; neither found significant differences in proportions re-consulting between intervention and control groups [19], [21]. Adverse events (hospital admission ≤2 nights) were reported in one trial and were similar among intervention and control [19]. Adverse effects were generally not assessed, however Roberts et al noted a non-significant reduction in “necessary” consultations (those for more severe symptoms of respiratory infection, defined by the authors as “symptom clusters suggesting that diagnostic testing or drug therapy might be cost-effective”) among African American and Medicaid patients receiving the intervention [25].

2. Interventions to influence parents' decision towards use of antibiotics

We identified 10 studies of nine interventions designed to influence antibiotic use for RTIs in children (Table 3, 4, and 5) [28], [29], [30], [31], [32], [33], [34], [35], [36], [37]. Studies involved 2,916 participants with follow-up periods ranging from 1 day to 36 weeks. The majority of interventions took place during the consultation, with only two [29], [30] designed to influence parental attitudes or knowledge before their children became ill.

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Table 3. Effectiveness of interventions to improve parent knowledge of appropriate antibiotic use for respiratory tract infections in children.

https://doi.org/10.1371/journal.pone.0030334.t003

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Table 4. Effectiveness of interventions to improve parental attitudes toward appropriate antibiotic use for respiratory tract infections in children.

https://doi.org/10.1371/journal.pone.0030334.t004

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Table 5. Change in parental satisfaction with a ‘no prescribing’ intervention.

https://doi.org/10.1371/journal.pone.0030334.t005

Knowledge of appropriate antibiotic use.

Five of the studies were set in primary care [28], [31], [33], [34], [37] and two in emergency departments [32], [36]; the remaining interventions took place at home or in day care centres (Table 3). Interventions most often used video or written materials (pamphlets or handouts). Four [31], [32], [33], [34] of the five studies which measured the effects of interventions on parental knowledge of appropriate antibiotic use (using a variety of different scores) found significant increases compared to the control groups, though in one study improvement only occurred among parents with college education [30], and two studies [31], [33] had higher risk of bias due to weak study design (pre/post test) and low rates of exposure to the intervention. Three of these studies used interventions designed to engage children as well as their parents, such as cartoon-animation videos and colouring books [30], [31], [32]. Schnellinger et al found that parental knowledge increased immediately and was maintained at one month (p<0.001) following a three minute cartoon-animated video, compared to parents only given pamphlets in whom knowledge improved immediately, but significantly waned at one month (p = 0.002) [32]. One study, however, found no improvement when parents were given a video and brochure (prior to an illness episode) and instructed to view it at home as often as they preferred [29]. It is unclear if the lack of effect was due to the home setting, or to specific attributes of the video (e.g. length of video was 20 minutes).

Attitudes towards antibiotic use.

Two studies measured effects on parental attitudes towards antibiotic use (Table 4). Taylor et al found that a ‘personalised’ video intervention (featuring a paediatrician from the local clinic) was more effective in changing attitudes about when not to use antibiotics for specific illnesses (e.g. nasal discharge) and less effective in changing general perspectives about antibiotics (e.g. threat of antibiotic resistance) [34]. A video intervention studied by Wheeler et al [33] demonstrated moderate success in increasing the proportion of parents with appropriate attitudes towards antibiotic use (i.e. fewer parents wanting antibiotics, OR 0.20 [0.10–0.39]); however less than 60% of surveyed parents reported exposure to the intervention at any time. Despite significant improvements in parental attitudes toward judicious use of antibiotics, neither study found changes in antibiotic prescribing rates over follow-up periods of 6 to 12 months (data not shown).

Satisfaction with a ‘no prescribing’ approach.

Two studies [36], [37] assessed parent satisfaction with a ‘watchful waiting,’ or no prescribing approach, neither of which found significant differences in parent satisfaction between intervention and control groups (Table 5). In addition, McCormick et al [37] found no difference in persistence of acute otitis media symptoms at 30 days, and that more children in the control group reported adverse events (side effects of antibiotics). Treatment costs for children in the intervention group (watchful waiting) averaged $11.43 per child compared to $47.41 per child in the immediate antibiotic group. Chao et al reported no adverse events or increase in consultations related to intervention [36].

3. Interventions to influence antibiotic use in children with RTIs

We found six studies of five interventions that reported the effects of interventions to influence antibiotic use in children with RTIs [19], [36], [38], [39], [40], [41]; all but one assessed the effect of delayed prescribing or watchful waiting therapy for AOM, the other study [19] involved a book for parents of children with RTIs.

Use of antibiotic prescriptions.

Each of the five interventions designed to influence antibiotic use was effective compared to control, with a combined RR 0.39 (0.29, 0.53) (not shown in table). Combining a delayed or no prescribing strategy with brief education significantly decreased antibiotic use in four studies [36], [38], [40], [41], and an interactive book [19] resulted in 19% fewer children taking antibiotics during the two weeks following consultation compared to controls (p<0.001) (Table 6). In pooled analyses we found significant heterogeneity (p = 0.002, I2 = 77%) due to one study [38] in which nearly 100% of parents in the control group reported antibiotic use. After removal of this study, parents in the intervention groups were still significantly less likely to report antibiotic use, combined RR 0.46 (0.40, 0.54) (p = 0.51, I2 = 0%) (Figure S3). Although the duration of acute otitis media symptoms was slightly shorter among children prescribed immediate antibiotics [38], [41], follow-up did not show significant differences in increased risk of relapse at either three months or one year [39]. More adverse outcomes related to antibiotic use (diarrhoea) were reported in one study among children in the control group than those receiving the intervention [41].

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Table 6. Effectiveness of interventions to influence filling antibiotic prescription for children with respiratory tract infections.

https://doi.org/10.1371/journal.pone.0030334.t006

Discussion

We systematically reviewed and synthesised the evidence for the effectiveness of interventions targeted at parents to modify consulting behaviour and antibiotic use for children with RTIs. To the best of our knowledge, this is the first systematic review of interventions to increase appropriate care-seeking behaviour in parents of children with acute respiratory tract infections. Providing educational materials to parents reduced rates of consulting by up to 40% in three studies; however all were published nearly 20 years ago and therefore may not translate to contemporary primary care [22], [25], [27]. Interventions may be more successful when delivered prior to the child's illness rather than during consultations [19], [22], [25], [27], and when focussed on specific symptoms rather than generic messages about antibiotic overuse and resistance [34]. Effects were more consistent for certain symptoms (e.g. sore throat) than others (e.g. cough), which may reflect features specific to certain RTIs (particularly duration of illness which is short for sore throat and longer for cough), or merely the studies we identified [22], [27]. Delayed or no prescribing interventions reduced rates of antibiotic use by up to half. Finally, educational materials that include cartoons and illustrations and which engage the child as well as their parents may be more successful than text-only materials; this approach was successful in several studies from different settings [22], [25], [27], [30], [31], [32].

Previous reviews [42], [43], [44], [45] have approached the problem of antibiotic overuse by assessing effectiveness of interventions to reduce clinician antibiotic prescribing. Our review, in contrast, has focussed on interventions targeted to parents or caregivers. In practice, change is needed by clinicians and parents and/or patients to reduce antibiotic use and control resistance. Our finding that framing education around specific presenting symptoms may be more meaningful to parents than less focussed approaches echoes a review by Glascoe [46] of general health education interventions directed toward parents. As with reviews by Arroll [47] and Spurling [48] which assessed the effect of delayed prescriptions in patients of all ages, we also found this strategy reduces antibiotic use in children as reported by their parents; importantly, our review demonstrates that parents accept this approach.

Our review adds to the literature by integrating the research on parental consulting and antibiotic use; we feel it is crucial to consider these elements together as they influence one another, often as part of a ‘vicious cycle’ of consulting and antibiotic-seeking. Decisions to consult or use antibiotics are not isolated events. Rather, they involve interactions between several stakeholders (e.g. parents, clinicians), in multiple situations (e.g. home, GP surgery), and at multiple moments in time (RTIs occur repeatedly). Although it increased the complexity of the review, the main strength of our approach is that it allowed us to identify overarching intervention components that appear effective.

Limitations

Our literature search was limited to studies reported in peer-reviewed journals, and therefore we may have missed relevant, unpublished research. To counter publication bias we searched multiple databases and did not limit by language. This review was focussed on studies from OECD countries (and mostly the US), which may limit generalisability to other countries or clinical settings. We included studies which used a range of study designs and follow-up periods, which limited our ability to synthesise results quantitatively. Several of the studies which showed reductions in consultation were published over 20 years ago [22], [25], [27], when prescribing for RTIs was higher generally, and thus may not apply to contemporary practice where antibiotic use has declined. Of the 20 interventions included in the review, 13 studies reported receipt of funding or support. The majority of funding organizations were governmental (only three studies [32], [33], [34] reported sole funding from private organizations). Included studies generally lacked explicit diagnostic criteria and excluded children with severe cases of infection or those at higher risk of complication. Thus, our findings may be less generalisable to these populations. Finally, few studies reported harms of interventions (e.g. missed treatment of serious infection).

Conclusions

The key finding of our review for clinicians is that interventions (such as written materials with focussed information for parents) can reduce the number of consultations for RTIs by 10 to 40%, and that use of antibiotics can be reduced by up to half through delayed prescribing. Importantly, reductions in antibiotic use do not seem to occur at the expense of parent satisfaction. Given the high frequency of paediatric consultations in primary care, a change in parental consulting behaviour for RTIs could potentially create a ‘virtuous cycle’ of reductions in workload and antibiotic use. We found moderate evidence that interventions are more effective when delivered to parents and children. Moreover, our findings have important implications for the content, format, and timing of delivery of patient information materials (see Table 7). Written information with focussed content (to a specific symptom) appears to be more effective than generic messages about avoiding antibiotics or antibiotic resistance. Furthermore, altering consultations for certain RTIs (e.g. sore throat) seems to be more achievable than for others (e.g. cough). It is unclear whether this simply reflects the studies included in this review, or whether effectiveness differs for different RTIs because of parent (and clinician) perceptions about severity or risk of complications of different RTIs. Clinicians might want to look carefully at the format of the information they hand to parents; those with cartoons or illustrations seemed to be more effective than bland text. The few studies which examined video interventions showed mixed results, and none explored online technologies.

Reducing unnecessary antibiotic use in primary care with the explicit goal of avoiding further spread of antibiotic resistance is a policy priority in many countries. To some extent it has been successful – prescribing of antibiotics fell by 24% in the UK during the 1990 s [1]. Although some clinicians worry that reductions in prescribing have gone “too far” leading to increased incidence of complications of RTIs [49], [50], there is broad agreement that prescribing rates remain inappropriately high for many RTIs. Our findings provide policy makers with evidence they need to implement or commission effective interventions in community settings to reduce consultations and antibiotic use. Moreover, interventions to reduce antibiotic use do not seem to occur at the expense of parent satisfaction, although evidence for conditions other than acute otitis media was limited. GPs implementing any of the strategies identified in this review should be mindful of the possibility of unintended adverse effects, such as reducing consultations for illness episodes that ought to be managed by a GP, as seen in the Roberts study [25]. Paradoxically, reducing the overall numbers of consultations for RTIs may filter a higher proportion of children with more severe illness presenting to primary care, highlighting the need for effective strategies to identify children at highest risk of complications and who are most likely to benefit from antibiotics; our group is currently conducting such research (see http://www.targetstudy.org.uk/).

Recommendations for future research

We have several suggestions to improve the primary research in this area. Firstly, reporting should include detailed descriptions of the intervention, the extent of exposure to the intervention, and whether the trial was conducted in communities where public media campaigns related to antibiotics were occurring (see study [29]). Secondly, follow-up periods need to be long enough to measure the longevity of interventions given that RTIs recur frequently. Further, potential outcomes should include number of symptomatic days, hospitalisations, and time off work or school [42], [51]; most importantly, adverse outcomes should be assessed and reported. Finally, we urge the use of “head-to-head trials” [42] that compare the effectiveness of several delivery formats [32] (including online resources) for communicating information to parents. Going forward, interventions should be developed to influence consulting and antibiotic use for RTIs in children, rather than address these outcomes in isolation.

RTIs in children are a common cause for consultation and antibiotic use. We found several intervention strategies effective at improving parent knowledge about RTIs and when to consult, decreasing actual number of consultations, and reducing antibiotic use. Implementing one or a combination of the approaches identified in this review may reduce unnecessary consulting and use of antibiotics for children with RTIs in primary care.

Supporting Information

Figure S1.

Conceptual framework for consulting and prescribing antibiotics for children with respiratory tract infections: ‘virtuous’ cycle.

https://doi.org/10.1371/journal.pone.0030334.s001

(TIF)

Figure S3.

Effects of interventions to influence filling antibiotic prescription for children with respiratory tract infection.

https://doi.org/10.1371/journal.pone.0030334.s003

(TIF)

Table S2.

Quality assessment of included studies.

https://doi.org/10.1371/journal.pone.0030334.s005

(DOC)

Table S3.

Characteristics of included studies.

https://doi.org/10.1371/journal.pone.0030334.s006

(DOC)

Acknowledgments

We would like to acknowledge the support of all other members of the TARGET Programme Management Committee, who include: Peter Brindle, Christie Cabral, Hannah Christensen, Brendan Delaney, Margaret Fletcher, Sandra Hollinghurst, Jenny Ingram, Jeremy Horwood, John Leeming, Paul Little, Andrew Lovering, Peter Muir, Sue Mulvenna, Tim Peters, and Hannah Thornton. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health.

Author Contributions

Conceived and designed the experiments: ADH MT TA CH DIB RD. Performed the experiments: TA MT CH. Analyzed the data: TA MT CH PSB DIB. Wrote the paper: TA MT CH DIB RD PJL NR PSB ADH.

References

  1. 1. Thompson PL, Spyridis N, Sharland M, Gilbert RE, Saxena S, et al. (2009) Changes in clinical indications for community antibiotic prescribing for children in the UK from 1996 to 2006: will the new NICE prescribing guidance on upper respiratory tract infections just be ignored? Arch Dis Child 94: 337–340.PL ThompsonN. SpyridisM. SharlandRE GilbertS. Saxena2009Changes in clinical indications for community antibiotic prescribing for children in the UK from 1996 to 2006: will the new NICE prescribing guidance on upper respiratory tract infections just be ignored?Arch Dis Child94337340
  2. 2. Hay AD, Heron J, Ness A (2005) The prevalence of symptoms and consultations in pre-school children in the Avon Longitudinal Study of Parents and Children (ALSPAC): a prospective cohort study. Fam Pract 22: 367–374.AD HayJ. HeronA. Ness2005The prevalence of symptoms and consultations in pre-school children in the Avon Longitudinal Study of Parents and Children (ALSPAC): a prospective cohort study.Fam Pract22367374
  3. 3. Fendrick AM, Monto AS, Nightengale B, Sarnes M (2003) The economic burden of non-influenza-related viral respiratory tract infection in the United States. Arch Intern Med 163: 487–494.AM FendrickAS MontoB. NightengaleM. Sarnes2003The economic burden of non-influenza-related viral respiratory tract infection in the United States.Arch Intern Med163487494
  4. 4. Hollinghurst S, Gorst C, Fahey T, Hay AD (2008) Measuring the financial burden of acute cough in pre-school children: a cost of illness study. BMC Fam Pract 9: 10.S. HollinghurstC. GorstT. FaheyAD Hay2008Measuring the financial burden of acute cough in pre-school children: a cost of illness study.BMC Fam Pract910
  5. 5. Stanton N, Francis NA, Butler CC (2010) Reducing uncertainty in managing respiratory tract infections in primary care. Br J Gen Pract 60: e466–475.N. StantonNA FrancisCC Butler2010Reducing uncertainty in managing respiratory tract infections in primary care.Br J Gen Pract60e466475
  6. 6. Ferech M, Coenen S, Malhotra-Kumar S, Dvorakova K, Hendrickx E, et al. (2006) European Surveillance of Antimicrobial Consumption (ESAC): outpatient antibiotic use in Europe. J Antimicrob Chemother 58: 401–407.M. FerechS. CoenenS. Malhotra-KumarK. DvorakovaE. Hendrickx2006European Surveillance of Antimicrobial Consumption (ESAC): outpatient antibiotic use in Europe.J Antimicrob Chemother58401407
  7. 7. Ashworth M, Charlton J, Ballard K, Latinovic R, Gulliford M (2005) Variations in antibiotic prescribing and consultation rates for acute respiratory infection in UK general practices 1995–2000. Br J Gen Pract 55: 603–608.M. AshworthJ. CharltonK. BallardR. LatinovicM. Gulliford2005Variations in antibiotic prescribing and consultation rates for acute respiratory infection in UK general practices 1995–2000.Br J Gen Pract55603608
  8. 8. Howie JG (1976) Clinical judgement and antibiotic use in general practice. Br Med J 2: 1061–1064.JG Howie1976Clinical judgement and antibiotic use in general practice.Br Med J210611064
  9. 9. Clavenna A, Bonati M (2009) Adverse drug reactions in childhood: a review of prospective studies and safety alerts. Arch Dis Child 94: 724–728.A. ClavennaM. Bonati2009Adverse drug reactions in childhood: a review of prospective studies and safety alerts.Arch Dis Child94724728
  10. 10. Costelloe C, Metcalfe C, Lovering A, Mant D, Hay AD (2010) Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis. BMJ 340: c2096.C. CostelloeC. MetcalfeA. LoveringD. MantAD Hay2010Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis.BMJ340c2096
  11. 11. Little P, Gould C, Williamson I, Warner G, Gantley M, et al. (1997) Reattendance and complications in a randomised trial of prescribing strategies for sore throat: the medicalising effect of prescribing antibiotics. BMJ 315: 350–352.P. LittleC. GouldI. WilliamsonG. WarnerM. Gantley1997Reattendance and complications in a randomised trial of prescribing strategies for sore throat: the medicalising effect of prescribing antibiotics.BMJ315350352
  12. 12. Hughes JM (2011) Preserving the lifesaving power of antimicrobial agents. JAMA 305: 1027–1028.JM Hughes2011Preserving the lifesaving power of antimicrobial agents.JAMA30510271028
  13. 13. Huttner B, Goossens H, Verheij T, Harbarth S (2010) Characteristics and outcomes of public campaigns aimed at improving the use of antibiotics in outpatients in high-income countries. Lancet Infect Dis 10: 17–31.B. HuttnerH. GoossensT. VerheijS. Harbarth2010Characteristics and outcomes of public campaigns aimed at improving the use of antibiotics in outpatients in high-income countries.Lancet Infect Dis101731
  14. 14. Standing Medical Advisory Committee, Sub-Group on Antimicrobial Resistance (1998) The path of least resistance. London: UK Department of Health. Standing Medical Advisory Committee, Sub-Group on Antimicrobial Resistance1998The path of least resistanceLondonUK Department of Health
  15. 15. NICE Short Clinical Guidelines Technical Team (2008) Respiratory tract infections – antibiotic prescribing. Prescribing of antibiotics for self-limiting respiratory tract infections in adults and children in primary care. NICE Short Clinical Guidelines Technical Team2008Respiratory tract infections – antibiotic prescribing.Prescribing of antibiotics for self-limiting respiratory tract infections in adults and children in primary careLondon: National Institute for Health and Clinical Excellence. London: National Institute for Health and Clinical Excellence.
  16. 16. Watson RL, Dowell SF, Jayaraman M, Keyserling H, Kolczak M, et al. (1999) Antimicrobial use for pediatric upper respiratory infections: reported practice, actual practice, and parent beliefs. Pediatrics 104: 1251–1257.RL WatsonSF DowellM. JayaramanH. KeyserlingM. Kolczak1999Antimicrobial use for pediatric upper respiratory infections: reported practice, actual practice, and parent beliefs.Pediatrics10412511257
  17. 17. The World Bank (2011) Country and Lending Groups: High-income OECD members. The World Bank2011Country and Lending Groups: High-income OECD members
  18. 18. Higgins JP, Green S, editors. (2009) Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2: The Cochrane Collaboration. JP HigginsS. Green2009Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2: The Cochrane Collaboration
  19. 19. Francis NA, Butler CC, Hood K, Simpson S, Wood F, et al. (2009) Effect of using an interactive booklet about childhood respiratory tract infections in primary care consultations on reconsulting and antibiotic prescribing: a cluster randomised controlled trial. BMJ 339: b2885.NA FrancisCC ButlerK. HoodS. SimpsonF. Wood2009Effect of using an interactive booklet about childhood respiratory tract infections in primary care consultations on reconsulting and antibiotic prescribing: a cluster randomised controlled trial.BMJ339b2885
  20. 20. Herman A, Young KD, Espitia D, Fu N, Farshidi A (2009) Impact of a health literacy intervention on pediatric emergency department use. Pediatr Emerg Care 25: 434–438.A. HermanKD YoungD. EspitiaN. FuA. Farshidi2009Impact of a health literacy intervention on pediatric emergency department use.Pediatr Emerg Care25434438
  21. 21. Isaacman DJ, Purvis K, Gyuro J, Anderson Y, Smith D (1992) Standardized instructions: do they improve communication of discharge information from the emergency department? Pediatrics 89: 1204–1208.DJ IsaacmanK. PurvisJ. GyuroY. AndersonD. Smith1992Standardized instructions: do they improve communication of discharge information from the emergency department?Pediatrics8912041208
  22. 22. Morrell DC, Avery AJ, Watkins CJ (1980) Management of minor illness. Br Med J 280: 769–771.DC MorrellAJ AveryCJ Watkins1980Management of minor illness.Br Med J280769771
  23. 23. Anderson JE, Morrell DC, Avery AJ, Watkins CJ (1980) Evaluation of a patient education manual. Br Med J 281: 924–926.JE AndersonDC MorrellAJ AveryCJ Watkins1980Evaluation of a patient education manual.Br Med J281924926
  24. 24. Robbins H, Hundley V, Osman LM (2003) Minor illness education for parents of young children. J Adv Nurs 44: 238–247.H. RobbinsV. HundleyLM Osman2003Minor illness education for parents of young children.J Adv Nurs44238247
  25. 25. Roberts CR, Imrey PB, Turner JD, Hosokawa MC, Alster JM (1983) Reducing physician visits for colds through consumer education. JAMA 250: 1986–1989.CR RobertsPB ImreyJD TurnerMC HosokawaJM Alster1983Reducing physician visits for colds through consumer education.JAMA25019861989
  26. 26. Thomson H, Ross S, Wilson P, McConnachie A, Watson R (1999) Randomised controlled trial of effect of Baby Check on use of health services in first 6 months of life. BMJ 318: 1740–1744.H. ThomsonS. RossP. WilsonA. McConnachieR. Watson1999Randomised controlled trial of effect of Baby Check on use of health services in first 6 months of life.BMJ31817401744
  27. 27. Usherwood TP (1991) Development and randomized controlled trial of a booklet of advice for parents. Br J Gen Pract 41: 58–62.TP Usherwood1991Development and randomized controlled trial of a booklet of advice for parents.Br J Gen Pract415862
  28. 28. Alder SC, Trunnell EP, White GL Jr, Lyon JL, Reading JP, et al. (2005) Reducing parental demand for antibiotics by promoting communication skills. AM J Health Educ 36: 132–139.SC AlderEP TrunnellGL White JrJL LyonJP Reading2005Reducing parental demand for antibiotics by promoting communication skills.AM J Health Educ36132139
  29. 29. Bauchner H, Osganian S, Smith K, Triant R (2001) Improving parent knowledge about antibiotics: a video intervention. Pediatrics 108: 845–850.H. BauchnerS. OsganianK. SmithR. Triant2001Improving parent knowledge about antibiotics: a video intervention.Pediatrics108845850
  30. 30. Croft DR, Knobloch MJ, Chyou P–H, Ellen DV, Janette C, et al. (2007) Impact of a child care educational intervention on parent knowledge about appropriate antibiotic use. WMJ 106: 78–84.DR CroftMJ KnoblochP–H ChyouDV EllenC. Janette2007Impact of a child care educational intervention on parent knowledge about appropriate antibiotic use.WMJ1067884
  31. 31. Maor Y, Raz M, Rubinstein E, Derazne E, Ringel S, et al. (2011) Changing parents' opinions regarding antibiotic use in primary care. Eur J Pediatr 170: 359–364.Y. MaorM. RazE. RubinsteinE. DerazneS. Ringel2011Changing parents' opinions regarding antibiotic use in primary care.Eur J Pediatr170359364
  32. 32. Schnellinger M, Finkelstein M, Thygeson MV, Vander Velden H, Karpas A, et al. (2010) Animated video vs pamphlet: comparing the success of educating parents about proper antibiotic use. Pediatrics 125: 990–996.M. SchnellingerM. FinkelsteinMV ThygesonH. Vander VeldenA. Karpas2010Animated video vs pamphlet: comparing the success of educating parents about proper antibiotic use.Pediatrics125990996
  33. 33. Wheeler JG, Fair M, Simpson PM, Rowlands LA, Aitken ME, et al. (2001) Impact of a waiting room videotape message on parent attitudes toward pediatric antibiotic use. Pediatrics 108: 591–596.JG WheelerM. FairPM SimpsonLA RowlandsME Aitken2001Impact of a waiting room videotape message on parent attitudes toward pediatric antibiotic use.Pediatrics108591596
  34. 34. Taylor JA, Kwan-Gett TSC, McMahon EM Jr (2003) Effectiveness of an educational intervention in modifying parental attitudes about antibiotic usage in children. Pediatrics 111: e548–554.JA TaylorTSC Kwan-GettEM McMahon Jr2003Effectiveness of an educational intervention in modifying parental attitudes about antibiotic usage in children.Pediatrics111e548554
  35. 35. Taylor JA, Kwan-Gett TSC, McMahon EM Jr (2005) Effectiveness of a parental educational intervention in reducing antibiotic use in children: a randomized controlled trial. Pediatric Infectious Disease Journal 24: 489–493.JA TaylorTSC Kwan-GettEM McMahon Jr2005Effectiveness of a parental educational intervention in reducing antibiotic use in children: a randomized controlled trial.Pediatric Infectious Disease Journal24489493
  36. 36. Chao JH, Kunkov S, Reyes LB, Lichten S, Crain EF (2008) Comparison of two approaches to observation therapy for acute otitis media in the emergency department. Pediatrics 121: e1352–1356.JH ChaoS. KunkovLB ReyesS. LichtenEF Crain2008Comparison of two approaches to observation therapy for acute otitis media in the emergency department.Pediatrics121e13521356
  37. 37. McCormick DP, Chonmaitree T, Pittman C, Saeed K, Friedman NR, et al. (2005) Nonsevere acute otitis media: a clinical trial comparing outcomes of watchful waiting versus immediate antibiotic treatment. Pediatrics 115: 1455–1465.DP McCormickT. ChonmaitreeC. PittmanK. SaeedNR Friedman2005Nonsevere acute otitis media: a clinical trial comparing outcomes of watchful waiting versus immediate antibiotic treatment.Pediatrics11514551465
  38. 38. Little P, Gould C, Williamson I, Moore M, Warner G, et al. (2001) Pragmatic randomised controlled trial of two prescribing strategies for childhood acute otitis media. BMJ 322: 336–342.P. LittleC. GouldI. WilliamsonM. MooreG. Warner2001Pragmatic randomised controlled trial of two prescribing strategies for childhood acute otitis media.BMJ322336342
  39. 39. Little P, Moore M, Warner G, Dunleavy J, Williamson I (2006) Longer term outcomes from a randomised trial of prescribing strategies in otitis media. Br J Gen Pract 56: 176–182.P. LittleM. MooreG. WarnerJ. DunleavyI. Williamson2006Longer term outcomes from a randomised trial of prescribing strategies in otitis media.Br J Gen Pract56176182
  40. 40. Pshetizky Y, Naimer S, Shvartzman P, Pshetizky Y, Naimer S, et al. (2003) Acute otitis media–a brief explanation to parents and antibiotic use. Fam Pract 20: 417–419.Y. PshetizkyS. NaimerP. ShvartzmanY. PshetizkyS. Naimer2003Acute otitis media–a brief explanation to parents and antibiotic use.Fam Pract20417419
  41. 41. Spiro DM, Tay KY, Arnold DH, Dziura JD, Baker MD, et al. (2006) Wait-and-see prescription for the treatment of acute otitis media: a randomized controlled trial. JAMA 296: 1235–1241.DM SpiroKY TayDH ArnoldJD DziuraMD Baker2006Wait-and-see prescription for the treatment of acute otitis media: a randomized controlled trial.JAMA29612351241
  42. 42. Ranji SR, Steinman MA, Shojania KG, Gonzales R (2008) Interventions to reduce unnecessary antibiotic prescribing: a systematic review and quantitative analysis. Med Care 46: 847–862.SR RanjiMA SteinmanKG ShojaniaR. Gonzales2008Interventions to reduce unnecessary antibiotic prescribing: a systematic review and quantitative analysis.Med Care46847862
  43. 43. Patel SJ, Larson EL, Kubin CJ, Saiman L (2007) A review of antimicrobial control strategies in hospitalized and ambulatory pediatric populations. Pediatr Infect Dis J 26: 531–537.SJ PatelEL LarsonCJ KubinL. Saiman2007A review of antimicrobial control strategies in hospitalized and ambulatory pediatric populations.Pediatr Infect Dis J26531537
  44. 44. Arnold SR, Straus SE (2005) Interventions to improve antibiotic prescribing practices in ambulatory care. Cochrane Database Syst Rev CD003539.SR ArnoldSE Straus2005Interventions to improve antibiotic prescribing practices in ambulatory care.Cochrane Database Syst RevCD003539
  45. 45. Boonacker CW, Hoes AW, Dikhoff MJ, Schilder AG, Rovers MM (2010) Interventions in health care professionals to improve treatment in children with upper respiratory tract infections. Int J Pediatr Otorhinolaryngol 74: 1113–1121.CW BoonackerAW HoesMJ DikhoffAG SchilderMM Rovers2010Interventions in health care professionals to improve treatment in children with upper respiratory tract infections.Int J Pediatr Otorhinolaryngol7411131121
  46. 46. Glascoe FP, Oberklaid F, Dworkin PH, Trimm F (1998) Brief approaches to educating patients and parents in primary care. Pediatrics 101: E10.FP GlascoeF. OberklaidPH DworkinF. Trimm1998Brief approaches to educating patients and parents in primary care.Pediatrics101E10
  47. 47. Arroll B, Kenealy T, Kerse N (2003) Do delayed prescriptions reduce antibiotic use in respiratory tract infections? A systematic review. Br J Gen Pract 53: 871–877.B. ArrollT. KenealyN. Kerse2003Do delayed prescriptions reduce antibiotic use in respiratory tract infections? A systematic review.Br J Gen Pract53871877
  48. 48. Spurling GK, Del Mar CB, Dooley L, Foxlee R (2007) Delayed antibiotics for respiratory infections. Cochrane Database Syst Rev CD004417.GK SpurlingCB Del MarL. DooleyR. Foxlee2007Delayed antibiotics for respiratory infections.Cochrane Database Syst RevCD004417
  49. 49. Sharland M, Kendall H, Yeates D, Randall A, Hughes G, et al. (2005) Antibiotic prescribing in general practice and hospital admissions for peritonsillar abscess, mastoiditis, and rheumatic fever in children: time trend analysis. BMJ 331: 328–329.M. SharlandH. KendallD. YeatesA. RandallG. Hughes2005Antibiotic prescribing in general practice and hospital admissions for peritonsillar abscess, mastoiditis, and rheumatic fever in children: time trend analysis.BMJ331328329
  50. 50. Thompson PL, Gilbert RE, Long PF, Saxena S, Sharland M, et al. (2009) Effect of antibiotics for otitis media on mastoiditis in children: a retrospective cohort study using the United kingdom general practice research database. Pediatrics 123: 424–430.PL ThompsonRE GilbertPF LongS. SaxenaM. Sharland2009Effect of antibiotics for otitis media on mastoiditis in children: a retrospective cohort study using the United kingdom general practice research database.Pediatrics123424430
  51. 51. Finch RG, Metlay JP, Davey PG, Baker LJ (2004) Educational interventions to improve antibiotic use in the community: report from the International Forum on Antibiotic Resistance (IFAR) colloquium, 2002. Lancet Infect Dis 4: 44–53.RG FinchJP MetlayPG DaveyLJ Baker2004Educational interventions to improve antibiotic use in the community: report from the International Forum on Antibiotic Resistance (IFAR) colloquium, 2002.Lancet Infect Dis44453