Improving Antibiotic Prescribing for Uncomplicated Acute Respiratory Tract Infections

692 Pages·2016·4.36 MB·English

Comparative Effectiveness Review
Number 163
Improving Antibiotic
Prescribing for
Uncomplicated
Acute Respiratory
Tract Infections
Comparative Effectiveness Review
Number 163

Improving Antibiotic Prescribing for Uncomplicated
Acute Respiratory Tract Infections

Prepared for:
Agency for Healthcare Research and Quality
U.S. Department of Health and Human Services
5600 Fishers Lane
Rockville, MD 20857
www.ahrq.gov

Contract No. 290-2012-00014-I

Prepared by:
Pacific Northwest Evidence-based Practice Center
Portland, OR

Investigators:
Marian McDonagh, Pharm.D.
Kim Peterson, M.S.
Kevin Winthrop, M.D., M.P.H.
Amy Cantor, M.D., M.P.H.
Brittany Holzhammer, M.P.H.
David I. Buckley, M.D., M.P.H.

AHRQ Publication No. 15(16)-EHC033-EF
January 2016
This report is based on research conducted by the Pacific Northwest Evidence-based Practice
Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ),
Rockville, MD (Contract No. 290-2012-00014-I). The findings and conclusions in this document
are those of the authors, who are responsible for its contents; the findings and conclusions do not
necessarily represent the views of AHRQ. Therefore, no statement in this report should be
construed as an official position of AHRQ or of the U.S. Department of Health and Human
Services.

None of the investigators have any affiliations or financial involvement that conflicts with
the material presented in this report.

The information in this report is intended to help health care decisionmakers—patients and
clinicians, health system leaders, and policymakers, among others—make well-informed
decisions and thereby improve the quality of health care services. This report is not intended to
be a substitute for the application of clinical judgment. Anyone who makes decisions concerning
the provision of clinical care should consider this report in the same way as any medical
reference and in conjunction with all other pertinent information, i.e., in the context of available
resources and circumstances presented by individual patients.

This report is made available to the public under the terms of a licensing agreement between the
author and the Agency for Healthcare Research and Quality. This report may be used and
reprinted without permission except those copyrighted materials that are clearly noted in the
report. Further reproduction of those copyrighted materials is prohibited without the express
permission of copyright holders.

AHRQ or U.S. Department of Health and Human Services endorsement of any derivative
products that may be developed from this report, such as clinical practice guidelines, other
quality enhancement tools, or reimbursement or coverage policies, may not be stated or implied.

This report may periodically be assessed for the currency of conclusions. If an assessment is
done, the resulting surveillance report describing the methodology and findings will be found on
the Effective Health Care Program Web site at www.effectivehealthcare.ahrq.gov. Search on the
title of the report.

Persons using assistive technology may not be able to fully access information in this report. For
assistance contact [email protected].

Suggested citation: McDonagh M, Peterson K, Winthrop K, Cantor A, Holzhammer B, Buckley
DI. Improving Antibiotic Prescribing for Uncomplicated Acute Respiratory Tract Infections.
Comparative Effectiveness Review No. 163. (Prepared by the Pacific Northwest Evidence-based
Practice Center under Contract No. 290-2012-00014-I.) AHRQ Publication No. 15(16)-EHC033-
EF. Rockville, MD: Agency for Healthcare Research and Quality; January 2016.
www.effectivehealthcare.ahrq.gov/reports/final.cfm.
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Preface
The Agency for Healthcare Research and Quality (AHRQ), through its Evidence-based
Practice Centers (EPCs), sponsors the development of systematic reviews to assist public- and
private-sector organizations in their efforts to improve the quality of health care in the United
States. These reviews provide comprehensive, science-based information on common, costly
medical conditions, and new health care technologies and strategies.
Systematic reviews are the building blocks underlying evidence-based practice; they focus
attention on the strength and limits of evidence from research studies about the effectiveness and
safety of a clinical intervention. In the context of developing recommendations for practice,
systematic reviews can help clarify whether assertions about the value of the intervention are
based on strong evidence from clinical studies. For more information about AHRQ EPC
systematic reviews, see www.effectivehealthcare.ahrq.gov/reference/purpose.cfm.
AHRQ expects that these systematic reviews will be helpful to health plans, providers,
purchasers, government programs, and the health care system as a whole. Transparency and
stakeholder input are essential to the Effective Health Care Program. Please visit the Web site
(www.effectivehealthcare.ahrq.gov) to see draft research questions and reports or to join an
email list to learn about new program products and opportunities for input.
If you have comments on this systematic review, they may be sent by mail to the Task Order
Officer named below at: Agency for Healthcare Research and Quality, 5600 Fishers Lane,
Rockville, MD 20857, or by email to [email protected].

Richard G. Kronick, Ph.D. Arlene S. Bierman, M.D., M.S.
Director Director
Agency for Healthcare Research and Quality Center for Evidence and Practice Improvement
Agency for Healthcare Research and Quality

Stephanie Chang, M.D., M.P.H. Elisabeth U. Kato, M.D., M.R.P.
Director Task Order Officer
Evidence-based Practice Center Program Center for Evidence and Practice Improvement
Center for Evidence and Practice Improvement Agency for Healthcare Research and Quality
Agency for Healthcare Research and Quality

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Acknowledgments
The authors gratefully acknowledge the following individuals for their contributions to this
project: Leah Williams, B.S., for editorial support; Elaine Graham, M.L.S., for assistance with
project management; Jessica Griffin, M.S., and Sujata Thakurta, M.P.A.:H.A., for work on the
refinement phase of this project; Rebecca Holmes, M.D., M.S., for assistance with quality
assessment of observational studies; and Ryan Stoner, M.A., and Laura LaLonde for data
extraction and bibliographic assistance. We would also like to thank our AHRQ Task Order
Officer, Elisabeth Kato, M.D., M.R.P., for her support and guidance in developing this report
and our Associate Editor, Eric Bass, M.D., for his review of this report.
Key Informants
In designing the study questions, the EPC consulted several Key Informants who represent
the end-users of research. The EPC sought the Key Informant input on the priority areas for
research and synthesis. Key Informants are not involved in the analysis of the evidence or the
writing of the report. Therefore, in the end, study questions, design, methodological approaches,
and/or conclusions do not necessarily represent the views of individual Key Informants.
Key Informants must disclose any financial conflicts of interest greater than $10,000 and any
other relevant business or professional conflicts of interest. Because of their role as end-users,
individuals with potential conflicts may be retained. The TOO and the EPC work to balance,
manage, or mitigate any conflicts of interest.
The list of Key Informants who participated in developing this report follows:

Beth Bolick, D.N.P., P.P.C.N.P.-B.C., Thomas File, M.D., M.Sc., M.A.C.P.,
CPNP-AC, CCRN FIDSA, FCCP*
Professor Chair, Division of Infectious Disease
Director, Acute Care Pediatric Nurse Summa Health System
Practitioner Program Professor of Internal Medicine, Master
Department of Women, Children, and Teacher, and Chair
Family Nursing Infectious Diseases Section
Rush University College of Nursing Northeast Ohio Medical University
Chicago, IL Rootstown, OH

Carrie Byington, M.D.* Bernard Guglielmo, Pharm.D.
Associate Vice President for Academic Professor of Clinical Pharmacy
Affairs and Faculty University of California, San Francisco
HA and Edna Benning Professor of School of Pharmacy
Pediatrics San Francisco, CA
University of Utah Health Sciences Center
Salt Lake City, UT John Hickner, M.D., M.Sc.
Department Head
Anna Marie Chang, M.D., M.S.C.E. Professor of Clinical Family Medicine
Assistant Professor University of Illinois at Chicago
Department of Emergency Medicine Chicago, IL
Oregon Health & Science University
Portland, OR
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Lauri Hicks, D.O.* Janet Patin, M.D.
Medical Epidemiologist Family Medicine
Respiratory Diseases Branch Dune Family Health Care Clinic
Centers for Disease Control and Prevention Reedsport, OR
Atlanta, GA
Madalyn Schaefgen, M.D., FAAFP*
David Jacoby, M.D. Cetronia Primary Care
Professor of Medicine, Allentown, PA
Physiology/Pharmacology, and
Anesthesiology and Peri-Operative Micah Thorp, D.O., M.P.H., FACP, FASN
Medicine Associate Medical Director
Chief, Pulmonary and Critical Care Chief, Department of Nephrology
Medicine Kaiser Permanente Northwest
Edwards Professor of Pulmonary Medicine Portland, OR
Vice-Chair for Research, Department of
Medicine Michael Wilkes, M.D., Ph.D.
Director, MD/PhD Training Program Professor of Internal Medicine
Associate Director for Education and University of California, Davis
Mentorship, Oregon Clinical and Davis, CA
Translational Research Institute
Oregon Health & Science University
Portland, OR

* Denotes Key Informants who also provided peer review of the draft report.

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Technical Expert Panel
In designing the study questions and methodology at the outset of this report, the EPC
consulted several technical and content experts. Broad expertise and perspectives were sought.
Divergent and conflicted opinions are common and perceived as healthy scientific discourse that
results in a thoughtful, relevant systematic review. Therefore, in the end, study questions, design,
methodologic approaches, and/or conclusions do not necessarily represent the views of
individual technical and content experts.
Technical Experts must disclose any financial conflicts of interest greater than $10,000 and
any other relevant business or professional conflicts of interest. Because of their unique clinical
or content expertise, individuals with potential conflicts may be retained. The TOO and the EPC
work to balance, manage, or mitigate any potential conflicts of interest identified.
The list of Technical Experts who participated in developing this report follows:

Alan Barker, M.D.* Lauri Hicks, D.O.*
Professor of Medicine Medical Epidemiologist
Pulmonary and Critical Care Respiratory Diseases Branch
Oregon Health & Science University Centers for Disease Control and Prevention
Portland, OR Atlanta, GA

Carrie Byington, M.D.* Paul Little, M.B.B.S., M.D., DLSHTM,
Associate Vice President for Academic MRCP, FRCGP, FMedSci*
Affairs and Faculty Professor of Primary Care Research
HA and Edna Benning Professor of University of Southampton
Pediatrics Southhampton, United Kingdom
University of Utah Health Sciences Center
Salt Lake City, UT Conan McDougall, Pharm.D., M.A.S.,
BCPS*
Dimitri Drekonja, M.D., M.S.* Associate Professor of Clinical Pharmacy
Assistant Professor of Medicine University of California, San Francisco
University of Minnesota School of Pharmacy
Member of the Infectious Disease Section San Francisco, CA
Minneapolis VA Health Care System
Minneapolis, MN Matthew Thompson, M.B.Ch.B.,
D.T.M.&H., M.P.H., D.Phil., MRCGP*
Thomas File,* M.D., M.Sc., MACP, Professor and Vice Chair for Research
FIDSA, FCCP Department of Family Medicine
Chair, Division of Infectious Disease University of Washington
Summa Health System Seattle, WA
Professor of Internal Medicine, Master
Teacher, and Chair
Infectious Diseases Section
Northeast Ohio Medical University
Rootstown, OH

* Denotes Technical Expert Panel members who also provided peer review of the draft report.
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Peer Reviewers
Prior to publication of the final evidence report, EPCs sought input from independent Peer
Reviewers without financial conflicts of interest. However, the conclusions and synthesis of the
scientific literature presented in this report do not necessarily represent the views of individual
reviewers.
Peer Reviewers must disclose any financial conflicts of interest greater than $10,000 and any
other relevant business or professional conflicts of interest. Because of their unique clinical or
content expertise, individuals with potential nonfinancial conflicts may be retained. The TOO
and the EPC work to balance, manage, or mitigate any potential nonfinancial conflicts of interest
identified.
The list of Peer Reviewers follows:

Chris Butler, M.D. Amanda McCullough, Ph.D., PGCHET
University of Oxford Research Fellow
Oxford, United Kingdom Bond University
Queensland, Australia
Chris Del Mar, FAFPHM, M.B.B.Chir.,
M.A., M.D., FRACGP Guillermo Sanchez, M.P.H., PA-C
Bond University Centers for Disease Control and Prevention
Queensland, Australia Atlanta, GA

Peter Glassman, M.B.B.S., M.Sc., FACP Jan Verbakel, M.D., Ph.D.
VA Greater Los Angeles Healthcare System Department of Public Health and Primary
Los Angeles, CA Care
KU Leuven (University of Leuven),
Malene Hansen, M.D., Ph.D. Belgium
Research Fellow Department of Primary Care Health
Bond University Sciences
Queensland, Australia University of Oxford
Oxford, United Kingdom
Stephen Kahn, Ph.D., DABCC, FACB
Loyola University Chicago - Health
Sciences Division
Maywood, IL

Jeffrey A. Linder, M.D., M.P.H., FACP
Associate Professor of Medicine
Division of General Medicine and Primary
Care
Brigham and Women’s Hospital
Harvard Medical School
Boston, MA

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Interventions To Improve Antibiotic Prescribing for
Uncomplicated Acute Respiratory Tract Infections
Structured Abstract

Objectives. To assess the comparative effectiveness of interventions for improving antibiotic use
for acute respiratory tract infections (RTIs) in adults and children.

Data sources. Electronic databases (MEDLINE® from 1990 and the Cochrane Library databases
from 2005 to February 2015), reference lists of included systematic reviews, and Scientific
Information Packets from point-of-care test manufacturers and experts.

Review methods. Using predefined criteria, we selected studies of any intervention designed to
improve antibiotic use for acute RTIs for which antibiotics are not indicated. Interventions were
organized into education, communication, clinical, system-level, and multifaceted categories. We
identified interventions that had evidence of reducing resistance to antibiotics, improving
appropriate prescribing (i.e., concordant with guidelines), or decreasing overall prescribing of
antibiotics for acute RTIs and not causing adverse consequences such as medical complications
or patient dissatisfaction. The quality of included studies was rated and the strength of the
evidence was assessed. Clinical and methodological heterogeneity limited quantitative analysis.

Results. Although reduction in antibiotic resistance is a major goal of these interventions, there
were too few studies to assess this outcome. The few studies that attempted to assess appropriate
prescribing had important limitations and lack of consistency in outcome definition and
ascertainment methods across studies. Therefore, reduction in overall prescribing was the only
commonly reported benefit across interventions. Actual use of antibiotics was also reported in
too few studies to assess separately from prescribing. No intervention had high-strength evidence
for any outcome. The best evidence, from an evidence base of 133 studies, including 88
randomized controlled trials, was for four interventions with moderate-strength evidence of
improved or reduced antibiotic prescribing compared with usual care that also had low-strength
evidence of not causing adverse consequences. These were clinic-based parent education (21%
overall prescribing reduction; similar return visits); public patient education campaigns
combined with clinician education (improved appropriate prescribing; 7% reduction in overall
prescribing; similar complications and satisfaction); procalcitonin for adults (12% to 72% overall
prescribing reduction; similar continuing symptoms, limited activity, missing work, adverse
events or lack of efficacy, treatment failure, hospitalizations, and mortality); and electronic
decision support systems (improved appropriate prescribing and 5% to 9% reduction in overall
prescribing; similar complications and health care use). Additionally, public parent education
campaigns had low-strength evidence of reducing overall prescribing, not increasing diagnosis of
complications, and decreasing subsequent visits. Other interventions had evidence of improved
or reduced prescribing, but evidence on adverse consequences was lacking (streptococcal antigen
testing, rapid multiviral testing in adults), insufficient (clinician and patient education plus audit
and feedback plus academic detailing), or mixed (delayed prescribing, C-reactive protein [CRP]
testing, clinician communication training, communication training plus CRP testing).
Interventions with evidence of no impact on antibiotic prescribing were clinic-based education
for parents of children 24 months or younger with acute otitis media, point-of-care testing for
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influenza or tympanometry in children, and clinician education combined with audit and
feedback. Furthermore, limited evidence suggested that using adult procalcitonin algorithms in
children is not effective and results in increased antibiotic prescribing.

Conclusions. The best evidence supports the use of specific education interventions for
patients/parents and clinicians, procalcitonin in adults, and electronic decision support to reduce
overall antibiotic prescribing (and in some cases improve appropriate prescribing) for acute RTIs
without causing adverse consequences, although the reduction in prescribing varied widely.
Other interventions also reduced prescribing, but evidence on adverse consequences was lacking,
insufficient, or mixed. Future studies should use a complex intervention framework and better
evaluate measures of appropriate prescribing, adverse consequences such as hospitalization,
sustainability, resource use, and the impact of potential effect modifiers.

PROSPERO number: CRD42014010094.

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