Management of Acute Otitis Media

426 Pages·2010·5.95 MB·English

Evidence Report/Technology Assessment
Number 198

Management of Acute Otitis Media: Update

Prepared for:
Agency for Healthcare Research and Quality
U.S. Department of Health and Human Services
540 Gaither Road
Rockville, MD 20850
www.ahrq.gov

Contract No. HHSA 290-2007-10056-I

Prepared by:
RAND Corporation, Santa Monica, CA 90407

Investigators
Paul G. Shekelle, M.D., Ph.D.
Glenn Takata, M.D., M.S.
Sydne J. Newberry, Ph.D.
Tumaini Coker, M.D.
Mary Ann Limbos, M.D., M.P.H.
Linda S. Chan, Ph.D.
Martha M. Timmer, M.S.
Marika J. Suttorp, M.S.
Jason Carter, B.A.
Aneesa Motala, B.A.
Di Valentine, J.D.
Breanne Johnsen, B.A.
Roberta Shanman, M.L.S.

AHRQ Publication No. 11-E004
November 2010
This report is based on research conducted by the RAND Evidence-based Practice Center
(EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville,
MD (Contract No. HHSA 290-2007-10056-I). The findings and conclusions in this document
are those of the author(s), who are responsible for its content, and do not necessarily represent
the views of AHRQ. 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.

The information in this report is intended to help clinicians, employers, policymakers, and
others make informed decisions about the provision of health care services. This report is
intended as a reference and not as a substitute for clinical judgment.

This report may be used, in whole or in part, as the basis for the development of clinical
practice guidelines and other quality enhancement tools, or as a basis for reimbursement and
coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of
such derivative products may not be stated or implied.
This document is in the public domain and may be used and reprinted without permission except
those copyrighted materials noted for which further reproduction is prohibited without the
specific permission of copyright holders.

Suggested Citation: Shekelle PG, Takata G, Newberry SJ, Coker T, Limbos M, Chan LS,
Timmer M, Suttorp M, Carter J, Motala A, Valentine D, Johnsen B, Shanman R. Management of
Acute Otitis Media: Update. Evidence Report/Technology Assessment No. 198. (Prepared by the
RAND Evidence-Based Practice Center under Contract No. 290 2007 10056 I). Rockville, MD:
Agency for Healthcare Research and Quality. November 2010.

No investigators have any affiliations or financial involvement (e.g., employment, consultancies,
honoraria, stock options, expert testimony, grants or patents received or pending, or royalties)
that conflict with material presented in this report.

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Preface
The Agency for Healthcare Research and Quality (AHRQ), through its Evidence-Based
Practice Centers (EPCs), sponsors the development of evidence reports and technology
assessments to assist public-and private-sector organizations in their efforts to improve the
quality of health care in the United States. This report was requested by the American Academy
of Pediatrics (AAP). The reports and assessments provide organizations with comprehensive,
science-based information on common, costly medical conditions and new health care
technologies. The EPCs systematically review the relevant scientific literature on topics assigned
to them by AHRQ and conduct additional analyses when appropriate prior to developing their
reports and assessments.
To bring the broadest range of experts into the development of evidence reports and health
technology assessments, AHRQ encourages the EPCs to form partnerships and enter into
collaborations with other medical and research organizations. The EPCs work with these partner
organizations to ensure that the evidence reports and technology assessments they produce will
become building blocks for health care quality improvement projects throughout the Nation. The
reports undergo peer review prior to their release.
AHRQ expects that the EPC evidence reports and technology assessments will inform
individual health plans, providers, and purchasers as well as the health care system as a whole by
providing important information to help improve health care quality.
We welcome comments on this evidence report. They may be sent by mail to the Task Order
Officer named below at: Agency for Healthcare Research and Quality, 540 Gaither Road,
Rockville, MD 20850, or by e-mail to [email protected].
Carolyn M. Clancy, M.D. Jean Slutsky, P.A., M.S.P.H.
Director Director, Center for Outcomes and Evidence
Agency for Healthcare Research and Quality Agency for Healthcare Research and Quality
Stephanie Chang, M.D., M.P.H. CAPT Ernestine Murray, R.N., B.S.N., M.A.S.
Director, EPC Program EPC Program Task Order Officer
Agency for Healthcare Research and Quality Agency for Healthcare Research and Quality
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Acknowledgments
We wish to acknowledge the invaluable guidance and expertise contributed to this project by the
Technical Expert Panel members who are listed in Appendix F. We also thank CAPT Ernestine
(Tina) Murray (AHRQ) for her patience, guidance, and input, and the Oregon Evidence-based
Practice Center, Rose Relevo, for assistance with research on drug safety, and the administrative
staff for assistance with preparation of the report.
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Structured Abstract
Context: Acute Otitis Media (AOM), a viral or bacterial infection of the ear, is the most
common childhood infection for which antibiotics are prescribed in the United States. In 2001,
the Southern California Evidence-based Practice Center conducted a systematic review of the
evidence comparing treatments of AOM.
Objectives: This review updates the 2001 review findings on diagnosis and treatment of
uncomplicated AOM, assesses the evidence for treatment of recurrent AOM, and assesses the
impact of the heptavalent pneumococcal conjugate (PCV7) vaccine on the microbiology of
AOM.
Data Sources and Study Selection: Searches of PubMed and the Cochrane databases were
conducted from January 1998 July 2010 using the same search strategies used for the 2001
report, with the addition of terms not considered in the 2001 review. The Web of Science was
also searched for citations of the 2001 report and its peer-reviewed publications.
Data Extraction: After review by two investigators against pre-determined inclusion/exclusion
criteria, we included existing systematic reviews and randomized controlled clinical trials for
assessment of treatment efficacy and safety. Pooled analysis was performed for comparisons
with three or more trials.
Results and Conclusions: Few studies were found that examined the accuracy and precision of
the diagnosis of AOM. Since PCV7’s introduction, AOM microbiology has shifted significantly,
with Streptococcus pneumoniae becoming less prevalent and Haemophilus influenzae (HF)
increasing in importance. For uncomplicated AOM, pooled analysis indicates that nine children
(95% CI: 6, 20) would need to be treated with ampicillin or amoxicillin rather than placebo to
note a difference in the rate of clinical success. However, in four studies of delayed treatment
approaches for uncomplicated AOM, two had higher rates of clinical success with immediate
antibiotic therapy while two did not, and in three studies, a marked decrease in antibiotic
utilization was noted. We are unable to draw definitive conclusions regarding the comparative
effectiveness of different antibiotics for AOM in children with recurrent otitis media (ROM). For
ROM, long-term antibiotic administration will decrease AOM episodes from 3 to 1.5 for every
12 months of treatment per otitis prone child during active treatment (95% CI: 1.2, 2.1);
however, potential consequences of long-term treatment need to be considered. Data were
insufficient to draw conclusions about comparative effectiveness of different treatment strategies
in subgroups of children with uncomplicated AOM. Adverse events were generally more
frequent for amoxicillin-clavulanate than for cefdinir, ceftriaxone, or azithromycin. Higher
quality studies and improved reporting of study characteristics related to quality are needed to
provide definitive conclusions for AOM and ROM treatment options.
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Contents
Executive Summary.........................................................................................................................1

Evidence Report.............................................................................................................................19

Chapter 1. Introduction ..................................................................................................................21

Diagnostic Accuracy..............................................................................................................21

Management...........................................................................................................................21

Pneumococcal Conjugate Vaccine.........................................................................................22

Chapter 2. Methods.......................................................................................................................23

Original Proposed Key Questions.............................................................................................23

Technical Expert Panel .............................................................................................................24

Definitions of Acute Otitis Media.............................................................................................24

Literature Search.......................................................................................................................25

Article Review ..........................................................................................................................26

Study Inclusion ..................................................................................................................... 26

Screening............................................................................................................................... 26

Data Abstraction & Synethesis of Results............................................................................... 27

Review and Assessment of Study Quality............................................................................ 27

Data Abstraction ................................................................................................................... 27

Supplemental Analysis for Key Question III........................................................................ 27

Supplemental Analysis for Key Question IV........................................................................ 29

Supplemental Analysis for Key Question V......................................................................... 29

Supplemental Analysis for Key Question VI........................................................................ 29

Use of Observational Studies to Assess Comparative Effectiveness.................................... 30

Rating the Overall Quality of Scientific Evidence ............................................................... 30

Peer Review .................................................................................................................................. 33

Chapter 3. Results ..........................................................................................................................35

Key Question I. Diagnosis of AOM: What are the Operating Characteristics (Sensitivity,

Specificity, and Likelihood Ratios) of Clinical Symptoms and Otoscopic Findings (Such As

Bulging Tympanic Membrane) to Diagnose Uncomplicated AOM and to Distinguish It from

OME? .............................................................................................................................................35

Description of the Studies..................................................................................................... 35

Findings for Key Question I ................................................................................................. 35

Key Question II. What Has Been the Impact of the Pneumococcal Heptavalent Immunization

(PCV7) on AOM Microbial Epidemiology (Including Acute Mastoiditis and Suppurative

Complications)?........................................................................................................................ 44

Description of the Studies..................................................................................................... 44

Findings for Key Question II ................................................................................................ 44

Findings According to Antibiotic History ............................................................................ 56

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Key Question III. What is the Comparative Effectiveness of Different Treatment Options for

Treating Uncomplicated Acute Otitis Media in Average Risk Children?................................ 56

Description of the Studies..................................................................................................... 56

Findings for Key Question III............................................................................................... 57

Ampicillin or Amoxicillin vs. Placebo ................................................................................. 79

Ampicillin or Amoxicillin vs. Ceftriaxone ........................................................................... 88

Amoxicillin-Clavulanate (7-10 days) vs. Ceftriaxone (single dose) .................................... 90

Amoxicillin-Clavulanate (7-10 days) vs. Azithromycin (≤5 days) ...................................... 93

Cefaclor vs. Azithromycin.................................................................................................... 99

Antibiotics vs. Wait-and-See/Prescription to Hold............................................................. 101

Other Meta-Analyses .......................................................................................................... 105

Summary............................................................................................................................. 105

Key Question IV. What Is the Comparative Effectiveness of Different Management

Options for Recurrent Otitis Media (Uncomplicated) and Persistent Otitis Media or Relapse

of Acute Otitis Media? ........................................................................................................... 108

Description of the Studies................................................................................................... 108

Findings on Treatment of Acute Otitis Media in Children with Recurrent Otitis Media ... 119

Findings on Prevention of Acute Otitis Media in Children with Recurrent Otitis Media .. 123

Summary............................................................................................................................. 128

Key Question V. Do Treatment Outcomes in Key Questions III and IV Differ by

Characteristics of the Condition (AOM), Patient, Environment, and/or Health Care

Delivery System?.................................................................................................................. 129

Age Factor in Uncomplicated Acute Otitis Media ............................................................. 130

Laterality Factor in Uncomplicated Acute Otitis Media..................................................... 151

Childcare Setting Factor in Uncomplicated Otitis Media................................................... 154

Other Factors Studied in Uncomplicated Otitis Media....................................................... 157

Effectiveness of Treatments in Recurrent Otitis Media, Stratified by Age, Laterality,

and Severity ........................................................................................................................ 160

Summary............................................................................................................................. 164

Key Question VI. What Adverse Effects Have Been Observed for the Treatments Whose

Outcomes Are Addressed in Key Questions 3 and 4? .......................................................... 165

Description of the Studies................................................................................................... 165

Adverse Effects Observed In Treatment of Uncomplicated Acute Otitis Media ............... 165

Adverse Effects in Studies of Treatment of Acute Otitis Media in Children with

Recurrent Otitis Media or Persistent Acute Otitis Media ................................................... 175

Adverse Events Associated with Prevention of Acute Otitis Media in Children with

Recurrent Otitis Media........................................................................................................ 183

Summary............................................................................................................................. 189

Chapter 4. Discussion ..................................................................................................................191

Limitations ..............................................................................................................................191

Publication Bias .................................................................................................................. 191

Study Quality ...................................................................................................................... 191

Conclusions........................................................................................................................... 191

Key Question I. Diagnosis of AOM ................................................................................... 191

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Key Question II. The impact of the Pneumococcal Heptavalent Immunization (PCV7)

on AOM Microbial Epidemiology...................................................................................... 192

Key Question III. Treatment of Uncomplicated AOM....................................................... 197

Key Question IV. Prevention or Treatment of Acute Otitis Media in Children with

Recurrent Otitis Media........................................................................................................ 193

Key Question V................................................................................................................... 194

Key Question VI ................................................................................................................. 194

Future Research Suggestions .................................................................................................194

Key Question I: Diagnostic Criteria for AOM ................................................................... 195

Key Question II: Effects of the PCV7 Vaccine .................................................................. 195

Key Questions III-VI: Treatment Efficacy and Adverse Effects........................................ 195

References....................................................................................................................................199

List of Acronyms/Abbreviations..................................................................................................207

Figures
Figure 1. Statistical Inference Using Confidence Interval (CI) and Minimal Clinically

Important Difference (MCID)........................................................................................................32

Figure 2. Shrinkage Plot for Ampicillin/Amoxicillin vs Placebo for Treatment Success .............80

Figure 3. Shrinkage Plot for Ampicillin/Amoxicillin vs. Placebo for Treatment Success

(Excluded Halsted 1967 Study) .....................................................................................................82

Figure 4. Shrinkage Plot for Ampicillin/Amoxicillin vs. Placebo for Treatment Success

(Included Studies with Quality Score 3, 4, or 5)............................................................................84

Figure 5. Shrinkage Plot for Ampicillin/Amoxicillin vs. Placebo for Treatment Success

(Included Studies with Quality Score 3, 4, or 5 (Excluded Halsted 1967 Study)..........................86

Figure 6. Shrinkage Plot for Ampicillin/Amoxicillin vs. Ceftriaxone for Treatment Success......90

Figure 7. Shrinkage Plot for Amoxicillin-clavulanate (7-10 days) vs. Ceftriaxone (single dose)

for Treatment Success....................................................................................................................93

Figure 8. Shrinkage Plot for Amoxicillin-Clavulanate (7-10 days) vs. Azithromycin (≤5 days)

for Treatment Success....................................................................................................................96

Figure 9. Shrinkage Plot for Amoxicillin-Clavulanate (7-10 days) vs, Azithromycin

(≤ 5 days) for Treatment Success (Excluded Pestalozza 1992 Study)...........................................97

Figure 10. Shrinkage Plot for Cefaclor vs. Azithromycin for Treatment Success ......................101

Figure 11. Shrinkage Plot for Ampicillin/Amoxicillin vs. Placebo for Treatment Success for

AGE ≤2 Years..............................................................................................................................146

Figure 12. Shrinkage Plot for Ampicillin/Amoxicillin vs. Placebo for Treatment Success for

AGE>2 Years...............................................................................................................................147

Figure 13. Shrinkage Plot for Amoxicillin-clavulanate (7-10 days) vs. Azithromycin

(<5 days) for Treatment Success for AGE ≤2 Years ...................................................................148

Figure 14. Shrinkage Plot for Amoxicillin-Clavulanate (7-10 days) vs. Azithromycin

(<5 days) for Treatment Success for AGE >2 Years ...................................................................149

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