Information about the natural history of acute infections commonly seen in primary care: a systematic review of clinical practice guidelines

DOI: https://doi.org/10.21203/rs.3.rs-1896415/v1

Abstract

Objectives

To examine the reporting of natural history information, and relevant antibiotic stewardship strategies, in clinical guidelines for acute infections commonly seen in primary care and sometimes managed with antibiotics.

Methods

A systematic review of national and international guidelines (2010 onwards), electronically available, for managing acute infections (respiratory, urinary, or skin and soft tissue). We searched MEDLINE, CINAHL, EMBASE, TRIP, and GIN databases and websites of 22 guideline-publishing organisations.

Results

We identified 82 guidelines, covering 114 eligible infections. Natural history information was reported in 49 (59.8%) of the guidelines and 66 (57.9%) of the conditions, most commonly for respiratory tract infections. Quantitative information about the expected infection duration was provided for 63.5% (n = 42) of the infections. Delayed prescribing was recommended for 34.2% (n = 39) of them and shared decision making for 21% (n = 24).

Conclusions

Just over half of the guidelines for acute infections that are commonly managed in primary care and often with antibiotics contained natural history information. As many of these infections spontaneously improve, this is a missed opportunity to disseminate this information to clinicians, promote antibiotic stewardship, and facilitate conversations with patients and informed decision-making.

Systematic review registration: CRD42021247048

1. Introduction

Antibiotic resistance is a major public health concern that threatens the effective treatment of bacterial infections [1]. Overuse and misuse of antibiotics are major drivers of antibiotic resistance [2]. Optimising the use of existing antibiotics has been identified as a major strategy in preventing resistance to antibiotics [3]. Primary care is responsible for more than 80% of antibiotic prescribing, some of which is for self-limiting acute infections and unnecessary [2, 4].

Acute infections are a common reason for patients to attend primary care [5], with many infections needing symptom management, but not necessarily antibiotics [6, 7]. The natural history of these conditions (defined as the course of a disease process over time, in the absence of treatment) [8] should be considered as part of clinical decision-making. Doing so may help to reduce antibiotic overuse.

Clinical practice guidelines are systematically developed statements to assist decision-making about appropriate healthcare for specific clinical circumstances [9]. They are tools to convey evidence-based information to clinicians with the goal of improving care quality and health outcomes [10]. Given the high rate of antibiotic prescribing in primary care, various antibiotic stewardship clinical strategies are recommended, including near-patient testing, delayed prescribing (or “wait and see”) and shared decision making [11–14]. Some of these strategies require natural history information and it is unknown if guidelines for common infections provide this information [15, 16].

The inclusion of natural history information in guidelines may help to facilitate conversations between clinicians and patients about the options for managing acute infections that are typically treated with antibiotics [17, 18]. Many patients and clinicians have unrealistic expectations about the effectiveness of antibiotics and are unaware that not using antibiotics is sometimes a legitimate management option [19–21]. Discussion about the options of using and not using antibiotics, along with the benefits and harms of each option, is vital for facilitating shared and informed decision-making about managing the infection [22, 23]. Providing clinicians with natural history information may also assist them to recognise subgroups of patients who may benefit from immediate antibiotic prescribing [7, 24]. The aims of this study were to examine the reporting of natural history information in guidelines about acute infections that are commonly seen in primary care and managed with antibiotics and whether references supporting the information were provided by research. We also assessed the reporting of relevant antibiotic stewardship clinical strategies that utilise natural history information (shared decision making, delayed prescribing).

2. Method

2.1. Design

This systematic review follows the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) reporting guideline [25] and the systematic review of clinical practice guidelines methodological guide by Johnston et al. 2019 [26]. We registered the protocol in PROSPERO- CRD42021247048 [27].

2.2. Data sources and searches

The search strategy was developed with the input of an experienced information specialist. Multiple databases were searched from 2010 till February 2021: MEDLINE (Ovid), CINAHL, and EMBASE (see Supplementary file A for the complete search strategy). We supplemented our databases search by manually searching the Turning Research into Practice (TRIP) medical database (which uses multiple strategies to locate guidelines) using a combination of MESH heading and free-text words, the Guideline International Network (GIN) and the websites of 22 guideline development organisations (see Supplementary file B).

2.3. Eligibility criteria

Guideline eligibility criteria were: published after 2010, electronically available with access to full text, produced by an international or national organisation involved in the publication of guidelines, and contained clinical recommendations on the management of acute infections that are commonly seen in primary care and may be managed with antibiotics (including acute respiratory infections (ARIs), lower urinary tract infections (UTIs), skin and soft tissue infections (SSTIs), conjunctivitis). If several versions of a guideline by the same authority were available, we included only the most recent version. Supplementary materials were considered as an extension of each guideline. No language limitations were imposed. For non-English language guidelines, we used Google Translate to determine their eligibility and extracted the relevant sections of the guideline after translating them to English.

We excluded consensus statements and expert group advice with no specific recommendations on managing the eligible conditions. Guidelines published in other forms such as books, booklets, government documents not issued as guidelines, workshop reports, and operational manuals, were excluded, as were those targeting settings other than primary care (e.g., hospitals) (see Supplementary file C).

2.4. Guideline selection process

Two reviewers (KP and MB) independently screened the titles and abstracts and then checked the full text of relevant guidelines to assess eligibility. Any disagreement was resolved by consensus or discussion with a third author (TH).

2.5. Data extraction process

We extracted the data from each guideline using a customised spreadsheet which was piloted by three authors (KB, NK, and MB) using a random sample of 10 eligible guidelines and minor modifications subsequently made. Each guideline was assigned a unique code to facilitate data extraction and analysis. A pair of authors (KP, and MB or NK) independently extracted the data outlined in Box 1. We extracted natural history information from the text, tables, and additional documents wherever mentioned in the guideline.

Box 1: Characteristics and outcomes for which data were extracted

2.6. Assessment of the quality of guidelines

A pair of authors (KP, and NK or MB) used the Appraisal of Guidelines for Research and Evaluation (AGREE II) assessment tool [28] to assess the methodological rigour, transparency, quality, and reporting of each guideline. Guidelines were evaluated using all 23 items, grouped into six domains: scope and purpose, stakeholder involvement, rigour of development, clarity of presentation, applicability, and editorial independence. Each item was scored on a Likert scale of seven points (where 1 = strongly disagree and 7 = strongly agree). To achieve rating consistency, assessors completed the training activity on the AGREE II website, independently assessed five eligible guidelines, and discussed their ratings.

2.7. Data synthesis and analysis

We calculated descriptive statistics using Microsoft® Excel® 365 (Microsoft, Redmond, WA, USA). We categorised natural history reporting into "extended” or “basic” [29], with reporting classified as “extended" if it included quantitative information about the likely duration of the infection or as “basic” if the guideline mentioned that the condition might spontaneously improve but provided no quantitative information. We grouped conjunctivitis with respiratory tract infections. As per the AGREE II recommendations, each domain score was calculated by summing up all the scores of the individual items in each domain and then standardising as follows: (score obtained – minimum possible score) / (maximum possible score – minimum possible score) to get a standardised score. We presented the individual score of each domain as a percentage

2.8. Modifications from the protocol

We clarified that the inclusion criteria were to include only guidelines published after 2010 to ensure currency in the sample of included guidelines, as most are updated within at least 10 years of publication. We also clarified the search database to include the GIN database. We did not describe in the protocol that verbatim information would be categorised as basic or extended.

3. Results

A total of 9132 records were identified from the biomedical and TRIP databases. After removal of duplicates and title and abstract screening, 302 full texts were checked, with 59 guidelines assessed as eligible. An additional search of the GIN database and websites of 22 guideline development or publishing organisations yielded 22 guidelines (see Fig. 1 for PRISMA flow diagram). Eighty-two guidelines (see list in Supplementary file D), covering 114 eligible acute conditions, were included.

3.1. Characteristics of included guidelines

Table 1 shows the characteristics of the included guidelines. Of the 82 guidelines, 5 were from multi-country organisations and professional societies, with the remainder from 19 countries. Half (50%, n = 41) were developed in Europe and 23.2% (n = 19) in the United States of America (USA), with 42.7% (n = 35) published between 2017 and 2019. More than half (61%, n = 50) focused on managing acute respiratory infections. Only 16% (n = 13) of guidelines scored ≥ 70% across all domains of the AGREE II. Most scored higher in the domains of scope and purpose, and clarity of presentation, with lower scores for applicability and editorial independence.

Table 1

Characteristics of included guidelines (n = 82)

Characteristic or classification

n (%)

Year of publication

  

2011–2013

15 (18.3)

2014–2016

21 (25.6)

2017–2019

35 (42.7)

2020-present

11 (13.4)

Continent of origin

  

Europe

41 (50.0)

North America

19 (23.2)

Asia

12 (14.6)

Australia

3 (3.7)

South America

2 (2.4)

Other*

5 (6.1)

Language of publication

  

English

57 (69.5)

Dutch

7 (8.5)

Finnish

5 (6.1)

German

4 (4.9)

Other**

9 (11.0)

Body system addressed by guideline

  

Respiratory***

50 (61.0)

Urinary

20 (24.4)

Skin and soft tissue (SSTI)

12 (14.6)

AGREE II domain scores across all guidelines

Domain score

% (SD)

Scope and purpose

85.2 (12.9)

Clarity of presentation

83.8 (11.3)

Rigour and development

73.5 (22.6)

Stakeholder involvement

71.4 (18.7)

Editorial independence

69.4 (23.5)

Applicability

64.5 (18.1)
* Multi-country organizations published guidelines.
** Other languages included French, Korean, Spanish, and Russian
***Including conjunctivitis

3.2. The inclusion of natural history information for acute infections in the guidelines

Of the 82 guidelines, 49 (59.8%) mentioned natural history information for at least one of the eligible infections. Of the 114 infections covered across the guidelines, natural history information was reported in 66 (57.9%), most commonly for respiratory tract infections (Table 2).

Table 2

Number and percentage of eligible conditions for which natural history information and references were provided.
 

Respiratory (n = 68)

Urinary

(n = 26)

SSTI

(n = 20)

Total

(n = 114)

Natural history information reported

Yes, n (%)

53 (78.0)

10 (38.5)

3 (15.0)

66 (57.9)

*Supporting reference for the information provided

Yes, n (%)

49 (92.5)

9 (90)

2 (66.7)

60 (91)
*For conditions with reported natural history information

Natural history information was provided in all guidelines that addressed acute bronchitis, acute sinusitis, tonsilitis, and conjunctivitis. For other infections, such as acute rhinitis, recurrent UTI, and cellulitis, it was not reported in any of the guidelines (see Fig. 2).

3.3. The reporting of natural history information

Table 3 contains verbatim examples of how guidelines reported natural history information. Of the pieces of natural history information in the guidelines, 63.6% (n = 42) were reported at an extended level. There was variation in the estimated duration of symptoms across guidelines addressing the same condition. For example, an Australian guideline (AUS 03) reported the duration for acute sinusitis to be 7–14 days, while a United Kingdom (UK) guideline (NICE 07) reported 14–21 days. Some guidelines provided a range for the expected infection duration, while others mentioned the estimated number of days those symptoms last. Figure 3 illustrates reporting of the quantitative duration of natural history for infections that are reported in two or more guidelines. Supplementary file F contains a list of duration for infections reported by only one guideline.

Table 3

Verbatim examples of natural history reporting for acute infections in guidelines, grouped by level of description and body system.

System

Extended level*

Basic level**

Respiratory

Examples

Acute Bronchitis
 

AUS 03: Acute bronchitis is a self-limiting lower respiratory tract infection. Explain that the cough lasts on average for 2 to 3 weeks and 90% of patients have cough resolution by four weeks. Occasionally, the cough may persist for up to 8 weeks.

DEN02: In uncomplicated acute bronchitis in otherwise healthy individuals, no marginal effect of antibiotic treatment measured on the duration or symptom reduction.
 

Acute sinusitis
 

NICE07: Acute sinusitis is usually caused by a virus, lasts for about 2 to 3 weeks, and most people get better without antibiotics. Acute sinusitis usually follows a common cold, and symptoms for around 10 days or less are more likely to be associated with a cold rather than viral or bacterial acute sinusitis. Therefore, the committee agreed that an antibiotic prescription should not be offered to people presenting with acute sinusitis symptoms for around 10 days or less.

FIN03: The majority of patients with sinusitis recover without antimicrobial therapy. Antimicrobial therapy should not be used to treat mild sinusitis because the disadvantages of treatment are more likely than its benefits.

Urinary

Urinary tract infection
 

SCT03: Lower UTI is a self-limiting disease. If untreated, increased daytime urinary frequency lasts on average 6.3 days, dysuria 5.2 days, urgency 4.7 days, and patients report feeling generally unwell for on average 5.3 days, with moderately bad or worse symptoms for 3.8 days.

NICE08: In most cases, managing lower UTIs will require antibiotic treatment. However, acute, uncomplicated lower UTI in non-pregnant women can be self-limiting and for some women delaying antibiotic treatment with a backup prescription to see if symptoms will resolve without antibiotic treatment may be an option.

SSTI

  
   

COL01: Impetigo is in principle self-resolving, in a case where the infection is mild and there are no comorbidities in the patients, it may not require specific treatment
*Extended reporting: provided natural history information that included the duration of infection.
**Basic reporting: provided minimal information, such as that the condition will typically spontaneously resolve.

3.4. Supporting references for natural history information reported in the guidelines

Of the 66 infections for which guidelines provided natural history information, supporting references were provided for most (91%, n = 60) (Table 2). Of the 125 references cited across the guidelines, 46.4% (n = 58) were from synthesised evidence (including 35 Cochrane systematic reviews, 16 systematic reviews of treatment effectiveness, 7 systematic reviews of cohort studies), 32.8% (n = 41) were primary studies (24 randomised controlled trials and 17 cohort studies) and 20.8% (n = 26) were references from other sources (such as other guidelines, editorials, position papers). There were variations in the cited references for the same conditions across different guidelines.

3.5. Reporting of relevant antibiotic stewardship clinical strategies

3.5.1. Delayed prescribing

A recommendation to use delayed prescribing was mentioned in 39% (n = 32) of the guidelines and for 34.2% (n = 39) of the eligible infections (Supplementary file G). It was most frequently recommended for respiratory tract infections (74.4%, n = 29), including in (92%, n = 11) of guidelines targeted at acute otitis media. For about half (51.3%, n = 20) of the infections, the recommendation for delayed prescribing included information about how long a patient should be advised to wait before deciding whether to fill the prescription. When timeframes were mentioned, there was variation across the guidelines. For example, for acute sinusitis the recommended waiting time ranged from 3 days (USA 04) to 7 days (NICE 07). Supplementary file H contains verbatim examples of the reporting of delayed prescribing and the suggested waiting periods.

3.5.2. Shared decision making and patient decision aids

In 22% (n = 18) of the guidelines and 21.1% (n = 24) of the infections, it was recommended that shared decision making occur between clinicians and patients when deciding about antibiotic use (see Supplementary file I for verbatim examples of recommendations). Using patient decision aids as a tool to support this conversation was mentioned in 18 of the 24 recommendations and an external link to an aid provided in all of these. Recommendations about shared decision making occurred most frequently for respiratory tract infections.

4. Discussion

4.1. Summary of the findings

In this systematic review of guidelines of acute infections commonly managed in primary care and with antibiotics, natural history information was reported for just over half of the eligible infections, most commonly for respiratory tract infections. For some infections (such as acute bronchitis, sinusitis, tonsilitis, conjunctivitis), natural history information was provided in all relevant guidelines, whereas for other infections (such as urinary tract infections and skin infections), it was rarely provided. In about two-thirds of the infections for which natural history was reported, quantitative information about the expected duration was provided. Delayed prescribing was recommended for about one-third of the assessed infections and shared decision making for about 21%.

4.2. Strengths and Limitations

To our knowledge, this is the first systematic review to investigate the reporting of natural history information in guidelines. The strength of this review lies in our comprehensive search strategy with no language restrictions. A limitation is that we may have missed guidelines that were not indexed in the databases searched or those that are not electronically accessible. Despite our supplementary search across well-known international guideline publishing organisations, we did not identify any eligible guidelines from Africa and only two from South America. Also, we did not assess the quality and appropriateness of the references used by the guidelines as support for the natural history information provided.

4.3. Comparison with existing research

While guideline methodological quality has been assessed [30], there appears to be no other research that has explored the reporting of the natural history of acute infections. The methodological quality of guidelines in our sample is similar to findings of other reviews of acute infection guidelines [31, 32]. However, an assessment of methodological quality does not consider the thoroughness of the content included in the guidelines and natural history is a specific type of information that is not required for all conditions.

Some findings in our study can be compared to systematic reviews of guidelines that targeted specific acute infections. For example, a systematic review of European guidelines for the management of acute otitis media in children found 88% of the guidelines recommended a delayed prescribing approach [31]. In our review, 92% of otitis media guidelines recommended delayed prescribing.

Despite international calls for antibiotic stewardship in primary care [7, 33, 34], across all the guidelines in our review, a minority recommended delayed prescribing and shared decision making. This is similar to the findings of a systematic review of upper respiratory tract infections guidelines, where delayed prescribing for otitis media was recommended in only 3 of the 13 guidelines [32]. This is despite evidence of the usefulness of delayed prescribing in reducing antibiotic prescribing and use [35]. While awareness of shared decision making is increasing [36, 37], along with the evidence of its effectiveness at facilitating antibiotic stewardship for acute respiratory infections [38], shared decision making is a reasonably new strategy and some guideline developers may not have been aware of it when guidelines were developed. Also, some guidelines are not primary care specific but are condition-specific, which may have contributed to low awareness of such strategies by guideline developers. Furthermore, historically antibiotic stewardship strategies that have been promoted for primary care have included clinician education, diagnostic testing, audit and feedback, with less focus on delayed prescribing and shared decision making [39].

4.4. Implications for practice

Many clinicians use guidelines from their country or professional organisation to stay up-to-date and the omission of natural history information in synthesised evidence resources such as guidelines is a missed opportunity to disseminate this information, which can inform clinician-patient conversations and decision-making. Natural history information is crucial for initiatives such as Choosing Wisely [40] campaigns in which patients and clinicians are encouraged to discuss “what happens if I don’t do anything?”. It is challenging to answer that question if research-informed natural history information is not readily available. Clinicians and patients can only know the difference a treatment, such as antibiotics, might make if they know what happens without that treatment. Knowing this may be an underutilised way of facilitating a conversation between clinicians and patients, managing patient expectations and misconceptions about the effectiveness of antibiotics, and reducing patient re-consultation for self-limiting acute infections [38, 41]. This may also contribute to reducing unnecessary prescribing and use of antibiotics in primary care.

4.5. Implications for research

Across the guidelines, we found differences in the estimated duration of symptoms for many of the infections. This is most likely due to the differences in the design and quality of the studies chosen to provide the natural history information. For example, while the Australian Therapeutic Guidelines cite a Cochrane review [42] to support the natural history information about acute bronchitis, the Danish and Dutch guidelines cite different prospective cohort studies [43, 44] with different natural history duration for the same condition. The inclusion of natural history content is not a focus of guidelines and no guidance on how to search for, select, and report this information exists. Including natural history information in guidelines would be aided if more studies (primary and systematic reviews) with the primary aim of establishing the natural history of acute infections were conducted.

5. Conclusion

Our review found an important gap in the inclusion and reporting of natural history information in guidelines, with just over half containing this information. Given the potential usefulness of natural history information in facilitating antibiotic stewardship strategies and the influence of guidelines on what treatment options clinicians present to patients, this is a missed opportunity to disseminate natural history information to clinicians and encourage its use in discussions with patients and informed decision-making.

Abbreviations

PRISMA

Preferred Reporting Items for Systematic Reviews and Meta-analysis

TRIP

Turning Research into Practice

GIN

Guideline International Network

ARI

Acute Respiratory Infections

SSTI

Skin and Soft Tissue Infection

UTI

Urinary Tract Infection

AGREE

Appraisal of Guidelines for Research and Evaluation

Declarations

Acknowledgments: We gratefully acknowledge the early and valuable discussions about this research project with the late Professor Chris Del Mar. We want to thank Justin Clark for his consultation and valuable advice in developing the search strategy.

Funding: No specific funding was received for this systematic review. The first author (KBP) is supported with a PhD scholarship, which is funded by the Centre for Research Excellence in Minimising Antibiotic Resistance in the Community (CRE-MARC), supported by the Australia National Health and Medical Research Council (NHMRC) grant (Reference Number: 1153299). MB and NK are postdoctoral research fellows on this grant. TH is a chief investigator of CRE-MARC.

Availability of data and materials: All data generated and analysed during this study are included in this published article [and its supplementary information files].

Ethics approval and consent: Not Applicable

Competing interest: The authors declare they have no competing interests.

Consent for publication: Not applicable. 

Authors’ contributions: Kwame Peprah Boaitey (KPB), Mina Bakhit (MB) and Tammy Hoffmann (TH) conceived the study. KPB developed the search strategy with information specialist Justin Clark with consultations from MB, and TH. KPB, MB, and NK assessed the eligibility and the quality of the included guidelines with consultation from TH. KPB analysed the data and created the figures with consultation from MB, and TH. KPB is responsible for data management and storage. KPB drafted the manuscript, and all authors reviewed the manuscript and approved the final version for submission.

Authors’ information: Kwame Peprah Boaitey, Mina Bakhit, Natalia Krzyzaniak, and Tammy Hoffmann

Faculty of Health Sciences and Medicine, Institute for Evidence-Based Healthcare, Bond University. Faculty of Health Sciences and Medicine, Institute for Evidence-Based Healthcare, Bond University, 14 University Dr, Robina, QLD 4229, Australia

Corresponding Author

Correspondence to Kwame Peprah Boaitey

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