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Medwave 2015;15(Suppl 2):e6295 doi: 10.5867/medwave.2015.6295
Antibióticos para la otitis media aguda en niños
Antibiotics for acute otitis media in children
María Pía Nitsche, Monica Carreño
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Abstract

Acute otitis media is one of the most common infectious diseases diagnosed in children. Antibiotic treatment use remains controversial. This summary aims to evaluate the effectiveness and safety of antibiotics in children with acute otitis media. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified six systematic reviews including 18 randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded antibiotics reduce pain at 48-72 hours and reduce the risk of tympanic perforations in children with acute otitis media, but they do not reduce late recurrences and increase the risk of side effects (rash, vomiting and diarrhea).


 
Problem

Acute otitis media is defined as the presence of tympanic effusion (demonstrated by pneumatic otoscopy, fluid level or impedanciometry) associated with signs and symptoms of acute inflammation of the middle ear. Acute otitis media occurs more frequently in children at an early age and the most serious complications are mastoiditis, meningitis and tympanic perforation.

The use of antibiotics for the treatment of acute otitis media varies considerably among countries because its real efficacy and safety have not been determined. On one side, the expected benefits of antibiotics include reducing the number of complications, the duration of symptomatic stage and the risk of recurrences. On the other side, the inappropriate use of antibiotics can cause adverse effects and increases antibiotic resistance.

Methods

We used Epistemonikos database, which is maintained by screening more than 30 databases, to identify systematic reviews and their included primary studies. With this information, we generated a structured summary using a pre-established format, which includes key messages, a summary of the body of evidence (presented as an evidence matrix in Epistemonikos), meta-analysis of the total of studies, a summary of findings table following the GRADE approach and a table of other considerations for decision-making.

Key messages

  • Antibiotics reduce pain at 48-72 hours and reduce the risk of tympanic perforation in children with acute otitis media. However, they do not reduce late recurrences and increase the risk of side effects (rash, vomiting and diarrhea).
  • Even though the certainty of the evidence is high, the decision on the use of this intervention depends on other individual and population factors. 
About the body of evidence for this question

What is the evidence.
See evidence matrix  in Epistemonikos later

 We found six systematic reviews [1],[2],[3],[4],[5],[6] including 18 randomized controlled trials reported
in 24 references  [7],[8], [9],[10],[11],[12],[13],[14],[15],[16],
[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30].

What types of patients were included

The eighteen studies included patients between 2 months and 15 years. Only one study [13] included patients under 6 months, five studies [10], [17],[23],[28],[30] included only patients older than 2 years and 13 studies included patients under 2 years [7],[9],[13],[14],[15],[16],[18],[19],[21],[22],[25],[26],[27].

What types of interventions were included

Thirteen studies evaluated the use of antibiotics versus placebo 
[7],[9],[10][13],[14],[15],[16],[18],[22],[26],[27],[28],[30]. Five studies evaluated the use of antibiotics versus expectant management [17],[21],[22],[23],[25]. Within the antibiotics, eight studies used amoxicillin [10],[16],[18],[19],[21],[22],[23],[30], four used amoxicillin with clavulanate [7],[14],[26],[27], two used ampicillin [13],[15], two used penicillin [17],[22] and six studies used non-standardized antibiotic regimen or other antibiotic [13],[15],[22],[23],[25],[28].

What types of outcomes
were measured

The main outcomes reported were:

  • Pain
  • Tympanic perforation
  • Late recurrences
  • Antibiotic side effects
Summary of findings

The information about the effects of antibiotic treatment for acute otitis media is based on 18 randomized studies that included 4,550 patients. Thirteen studies compared antibiotics versus placebo [7],[9],[10],[13],[14],[15],[16],[18],[22],[26],[27],[28],[30]. Seven studies reported pain [7],[13],[16],[18],[22],[26],[28], five reported tympanic perforation [10],[14],[22],[26],[27], eight reported antibiotics side effects [1],[10],[14],[18],[22],[26],[27],[28], and six studies reported the late recurrence of acute otitis media [14],[16],[18],[22],[28],[30].

  • Antibiotics reduce pain at 48-72 hours in children with acute otitis media. The certainty of the evidence is high.
  • Antibiotics do not reduce late recurrences of acute otitis media. The certainty of the evidence is high.
  • Antibiotics reduce the risk of tympanic perforation. The certainty of the evidence is high.
  • Antibiotics increase the number of side effects (rash, vomiting and diarrhea). The certainty of the evidence is high.


Other considerations for decision-making

To whom this evidence does and does not apply
  • This evidence can be applied to pediatric population between 2 months and 15 years old with the diagnostic of acute otitis media. The diagnosis can be based on clinical manifestations, on otoscopy findings or pneumo-otoscopy findings. This evidence can be used either in primary or secondary care. 
About the outcomes included in this summary
  • The critical outcomes for decision-making were selected based on the opinion of the authors of this summary. 
Balance between benefits and risks, and certainty of the evidence
  • This is an intervention for which we have high certainty evidence that shows both benefits and risks. On one hand, it can be argued the use of antibiotics is beneficial and relatively safe, but on the other hand, the natural progression is positive even without antibiotics in many cases, and overuse of antibiotics can lead to increased bacterial resistance at population level  [31].
  • It may be possible that in high risk groups, as children under two years, the decision can be different. Also it will vary depending on the values and preferences of individual patients and epidemiological context.
What would patients and their doctors think about this intervention
  • Pediatric practice requires the consideration of parental apprehensions. Physicians should not exclude parents from decision-making. In those patients that receive expectant management it is reasonable to consider an early follow-up.
Resource considerations
  • Antibiotics for the treatment of acute otitis media have low cost and are highly available.
  • Expectant management requires a health system that allows follow-up at 48 hours and availability for early control if needed.

Differences between this summary and other sources
  • Our summary is consistent with the systematic reviews that were analized.
  • The clinical practice guidelines of the American Academy of Pediatrics were reviewed [31] and they are consistent with the conclusions of our summary.
Could this evidence change in the future?
  • The likelihood that future evidence can change the key findings of this summary is very low due to the high certainty of this evidence.
  • We are not aware of ongoing studies that could provide new information. 
How we conducted this summary

Using automated and collaborative means, we compiled all the relevant evidence for the question of interest and we present it as a matrix of evidence.

Follow the link to access the interactive version: Antibiotics for acute otitis media in children

Notes

The upper portion of the matrix of evidence will display a warning of “new evidence” if new systematic reviews are published after the publication of this summary. Even though the project considers the periodical update of these summaries, users are invited to comment in Medwave or to contact the authors through email if they find new evidence and the summary should be updated earlier. After creating an account in Epistemonikos, users will be able to save the matrixes and to receive automated notifications any time new evidence potentially relevant for the question appears.

The details about the methods used to produce these summaries are described here http://dx.doi.org/10.5867/medwave.2014.06.5997.

Epistemonikos foundation is a non-for-profit organization aiming to bring information closer to health decision-makers with technology. Its main development is Epistemonikos database (www.epistemonikos.org).

These summaries follow a rigorous process of internal peer review.

Conflicts of interest
The authors do not have relevant interests to declare.

Licencia Creative Commons Esta obra de Medwave está bajo una licencia Creative Commons Atribución-NoComercial 3.0 Unported. Esta licencia permite el uso, distribución y reproducción del artículo en cualquier medio, siempre y cuando se otorgue el crédito correspondiente al autor del artículo y al medio en que se publica, en este caso, Medwave.

 

Acute otitis media is one of the most common infectious diseases diagnosed in children. Antibiotic treatment use remains controversial. This summary aims to evaluate the effectiveness and safety of antibiotics in children with acute otitis media. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified six systematic reviews including 18 randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded antibiotics reduce pain at 48-72 hours and reduce the risk of tympanic perforations in children with acute otitis media, but they do not reduce late recurrences and increase the risk of side effects (rash, vomiting and diarrhea).

Autores: María Pía Nitsche[1,2], Monica Carreño[2,3]

Filiación:
[1] Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
[2] Proyecto Epistemonikos, Santiago, Chile
[3] Departamento de Pediatría, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile

E-mail: carreno.monica@gmail.com

Correspondencia a:
[1] Facultad de Medicina, Pontificia Universidad Católica de Chile
Lira 63
Santiago Centro
Chile

Citación: Nitsche MP, Carreño M. Antibiotics for acute otitis media in children. Medwave 2015;15(Suppl 2):e6295 doi: 10.5867/medwave.2015.6295

Fecha de publicación: 29/10/2015

Ficha PubMed

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  1. Damoiseaux RA, van Balen FA, Hoes AW, de Melker RA. Antibiotic treatment of acute otitis media in children under two years of age: evidence based? Br J Gen Pract. 1998 Dec;48(437):1861-4. | PubMed |
  2. Del Mar C, Glasziou P, Hayem M. Are antibiotics indicated as initial treatment for children with acute otitis media? A meta-analysis. BMJ. 1997 May 24;314(7093):1526-9. | PubMed |
  3. Gisselsson-Solen M. The importance of being specific--a meta-analysis evaluating the effect of antibiotics in acute otitis media. Int J Pediatr Otorhinolaryngol. 2014 Aug;78(8):1221-7. | CrossRef | PubMed |
  4. Venekamp RP, Sanders SL, Glasziou PP, Del Mar CB, Rovers MM. Antibiotics for acute otitis media in children. Cochrane Database Syst Rev. 2015 Jun 23;6:CD000219. | CrossRef | PubMed |
  5. Rovers MM, Glasziou P, Appelman CL, Burke P, McCormick DP, Damoiseaux RA, et al. Antibiotics for acute otitis media: a meta-analysis with individual patient data. Lancet. 2006 Oct 21;368(9545):1429-35. | PubMed |
  6. Vouloumanou EK, Karageorgopoulos DE, Kazantzi MS, Kapaskelis AM, Falagas ME. Antibiotics versus placebo or watchful waiting for acute otitis media: a meta-analysis of randomized controlled trials. J Antimicrob Chemother. 2009 Jul;64(1):16-24. | CrossRef | PubMed |
  7. Appelman CL, Claessen JQ, Touw-Otten FW, Hordijk GJ, de Melker RA. Co-amoxiclav in recurrent acute otitis media: placebo controlled study. BMJ. 1991 Dec 7;303(6815):1450-2. | PubMed |
  8. Appelman CL, Claessen JQ, Touw-Otten FW, Hordijk GJ, de Melker RA. Severity of inflammation of tympanic membrane as predictor of clinical course of recurrent acute otitis media. BMJ. 1993 Apr 3;306(6882):895. | PubMed |
  9. Bezáková N, Damoiseaux RA, Hoes AW, Schilder AG, Rovers MM. Recurrence up to 3.5 years after antibiotic treatment of acute otitis media in very young Dutch children: survey of trial participants. BMJ. 2009 Jun 30;338:b2525. | CrossRef | PubMed |
  10. Burke P, Bain J, Robinson D, Dunleavey J. Acute red ear in children: controlled trial of non-antibiotic treatment in general practice. BMJ. 1991 Sep 7;303 (6802):558-62. | PubMed |
  11. Claessen JQ, Appelman CL, Touw-Otten FW, de Melker RA, Hordijk GJ. Persistence of middle ear dysfunction after recurrent acute otitis media. Clin Otolaryngol Allied Sci. 1994 Feb;19(1):35-40. | PubMed |
  12. Damoiseaux RA, van Balen FA, Hoes AW, Verheij TJ, de Melker RA. Primary care based randomised, double blind trial of amoxicillin versus placebo for acute otitis media in children aged under 2 years. BMJ. 2000 Feb 5;320(7231):350-4. | PubMed |
  13. Halsted C, Lepow ML, Balassanian N, Emmerich J, Wolinsky E. Otitis media. Clinical observations, microbiology, and evaluation of therapy. Am J Dis Child. 1968 May;115(5):542-51. | PubMed |
  14. Hoberman A, Paradise JL, Rockette HE, Shaikh N, Wald ER, Kearney DH, et al. Treatment of acute otitis media in children under 2 years of age. N Engl J Med. 2011 Jan 13;364(2):105-15. | CrossRef | PubMed |
  15. Howie VM, Ploussard JH. Efficacy of fixed combination antibiotics versus separate components in otitis media. Effectiveness of erythromycin estrolate, triple sulfonamide, ampicillin, erythromycin estolate- triple sulfonamide, and placebo in 280 patients with acute otitis media under two and one-half years of age. Clin Pediatr (Phila). 1972 Apr;11(4):205-14. | PubMed |
  16. Kaleida PH, Casselbrant ML, Rockette HE, Paradise JL, Bluestone CD, Blatter MM, Reisinger KS, Wald ER, Supance JS. Amoxicillin or myringotomy or both for acute otitis media: results of a randomized clinical trial. Pediatrics. 1991 Apr;87(4):466-74. | PubMed |
  17. Laxdal OE, Merida J, Jones RH. Treatment of acute otitis media: a controlled study of 142 children. Can Med Assoc J. 1970 Feb 14;102(3):263-8. | PubMed |
  18. Le Saux N, Gaboury I, Baird M, Klassen TP, MacCormick J, Blanchard C, et al. A randomized, double-blind, placebo-controlled noninferiority trial of amoxicillin for clinically diagnosed acute otitis media in children 6 months to 5 years of age. CMAJ. 2005 Feb 1;172(3):335-41. | PubMed |
  19. Little P, Gould C, Williamson I, Moore M, Warner G, Dunleavey J. Pragmatic randomised controlled trial of two prescribing strategies for childhood acute otitis media. BMJ. 2001 Feb 10;322(7282):336-42. | PubMed |
  20. Little P, Moore M, Warner G, Dunleavy J, Williamson I. Longer term outcomes from a randomised trial of prescribing strategies in otitis media. Br J Gen Pract. 2006 Mar;56(524):176-82. | PubMed |
  21. McCormick DP, Chonmaitree T, Pittman C, Saeed K, Friedman NR, Uchida T, et al. Nonsevere acute otitis media: a clinical trial comparing outcomes of watchful waiting versus immediate antibiotic treatment. Pediatrics. 2005 Jun;115(6):1455-65. | PubMed |
  22. Mygind N, Meistrup-Larsen KI, Thomsen J, Thomsen VF, Josefsson K, Sørensen H. Penicillin in acute otitis media: a double-blind placebo-controlled trial. Clin Otolaryngol Allied Sci. 1981 Feb;6(1):5-13. | PubMed |
  23. Neumark T, Mölstad S, Rosén C, Persson LG, Törngren A, Brudin L, Eliasson I. Evaluation of phenoxymethylpenicillin treatment of acute otitis media in children aged 2-16. Scand J Prim Health Care. 2007 Sep;25(3):166-71. | PubMed |
  24. Paradise JL, Hoberman A, Rockette HE, Shaikh N. Treating acute otitis media in young children: what constitutes success? Pediatr Infect Dis J. 2013 Jul;32(7):745-7. | CrossRef | PubMed |
  25. Spiro DM, Tay KY, Arnold DH, Dziura JD, Baker MD, Shapiro ED. Wait-and-see prescription for the treatment of acute otitis media: a randomized controlled trial. JAMA. 2006 Sep 13;296(10):1235-41. | PubMed |
  26. Tähtinen PA, Laine MK, Huovinen P, Jalava J, Ruuskanen O, Ruohola A. A placebo-controlled trial of antimicrobial treatment for acute otitis media. N Engl J Med. 2011 Jan 13;364(2):116-26. | CrossRef | PubMed |
  27. Tapiainen T, Kujala T, Renko M, Koivunen P, Kontiokari T, Kristo A, et al. Effect of antimicrobial treatment of acute otitis media on the daily disappearance of middle ear effusion: a placebo-controlled trial. JAMA Pediatr. 2014 Jul;168(7):635-41. | CrossRef | PubMed |
  28. Thalin A, Densert O, Larsson A, Lyden E, Torvald R. Is penicillin necessary in the treatment of acute otitis media? International conference on acute and secretory otitis media. International conference on acute and secretory otitis media; 1985: 4416. | Link |
  29. Thomsen J, Meistrup-Larsen KI, Sørensen H, Larsen PK, Mygind N. Penicillin and acute otitis: short and long-term results. Ann Otol Rhinol Laryngol Suppl.1980 May-Jun;89(3 Pt 2):271-4. | PubMed |
  30. van Buchem FL, Dunk JH, van't Hof MA. Therapy of acute otitis media: myringotomy, antibiotics, or neither? A double-blind study in children. Lancet. 1981 Oct 24;2(8252):883-7. | PubMed |
  31. Lieberthal AS, Carroll AE, Chonmaitree T, Ganiats TG, Hoberman A, Jackson MA, et al. The diagnosis and management of acute otitis media. Pediatrics. 2013 Mar;131(3):e964-99. | CrossRef | PubMed |
Damoiseaux RA, van Balen FA, Hoes AW, de Melker RA. Antibiotic treatment of acute otitis media in children under two years of age: evidence based? Br J Gen Pract. 1998 Dec;48(437):1861-4. | PubMed |

Del Mar C, Glasziou P, Hayem M. Are antibiotics indicated as initial treatment for children with acute otitis media? A meta-analysis. BMJ. 1997 May 24;314(7093):1526-9. | PubMed |

Gisselsson-Solen M. The importance of being specific--a meta-analysis evaluating the effect of antibiotics in acute otitis media. Int J Pediatr Otorhinolaryngol. 2014 Aug;78(8):1221-7. | CrossRef | PubMed |

Venekamp RP, Sanders SL, Glasziou PP, Del Mar CB, Rovers MM. Antibiotics for acute otitis media in children. Cochrane Database Syst Rev. 2015 Jun 23;6:CD000219. | CrossRef | PubMed |

Rovers MM, Glasziou P, Appelman CL, Burke P, McCormick DP, Damoiseaux RA, et al. Antibiotics for acute otitis media: a meta-analysis with individual patient data. Lancet. 2006 Oct 21;368(9545):1429-35. | PubMed |

Vouloumanou EK, Karageorgopoulos DE, Kazantzi MS, Kapaskelis AM, Falagas ME. Antibiotics versus placebo or watchful waiting for acute otitis media: a meta-analysis of randomized controlled trials. J Antimicrob Chemother. 2009 Jul;64(1):16-24. | CrossRef | PubMed |

Appelman CL, Claessen JQ, Touw-Otten FW, Hordijk GJ, de Melker RA. Co-amoxiclav in recurrent acute otitis media: placebo controlled study. BMJ. 1991 Dec 7;303(6815):1450-2. | PubMed |

Appelman CL, Claessen JQ, Touw-Otten FW, Hordijk GJ, de Melker RA. Severity of inflammation of tympanic membrane as predictor of clinical course of recurrent acute otitis media. BMJ. 1993 Apr 3;306(6882):895. | PubMed |

Bezáková N, Damoiseaux RA, Hoes AW, Schilder AG, Rovers MM. Recurrence up to 3.5 years after antibiotic treatment of acute otitis media in very young Dutch children: survey of trial participants. BMJ. 2009 Jun 30;338:b2525. | CrossRef | PubMed |

Burke P, Bain J, Robinson D, Dunleavey J. Acute red ear in children: controlled trial of non-antibiotic treatment in general practice. BMJ. 1991 Sep 7;303 (6802):558-62. | PubMed |

Claessen JQ, Appelman CL, Touw-Otten FW, de Melker RA, Hordijk GJ. Persistence of middle ear dysfunction after recurrent acute otitis media. Clin Otolaryngol Allied Sci. 1994 Feb;19(1):35-40. | PubMed |

Damoiseaux RA, van Balen FA, Hoes AW, Verheij TJ, de Melker RA. Primary care based randomised, double blind trial of amoxicillin versus placebo for acute otitis media in children aged under 2 years. BMJ. 2000 Feb 5;320(7231):350-4. | PubMed |

Halsted C, Lepow ML, Balassanian N, Emmerich J, Wolinsky E. Otitis media. Clinical observations, microbiology, and evaluation of therapy. Am J Dis Child. 1968 May;115(5):542-51. | PubMed |

Hoberman A, Paradise JL, Rockette HE, Shaikh N, Wald ER, Kearney DH, et al. Treatment of acute otitis media in children under 2 years of age. N Engl J Med. 2011 Jan 13;364(2):105-15. | CrossRef | PubMed |

Howie VM, Ploussard JH. Efficacy of fixed combination antibiotics versus separate components in otitis media. Effectiveness of erythromycin estrolate, triple sulfonamide, ampicillin, erythromycin estolate- triple sulfonamide, and placebo in 280 patients with acute otitis media under two and one-half years of age. Clin Pediatr (Phila). 1972 Apr;11(4):205-14. | PubMed |

Kaleida PH, Casselbrant ML, Rockette HE, Paradise JL, Bluestone CD, Blatter MM, Reisinger KS, Wald ER, Supance JS. Amoxicillin or myringotomy or both for acute otitis media: results of a randomized clinical trial. Pediatrics. 1991 Apr;87(4):466-74. | PubMed |

Laxdal OE, Merida J, Jones RH. Treatment of acute otitis media: a controlled study of 142 children. Can Med Assoc J. 1970 Feb 14;102(3):263-8. | PubMed |

Le Saux N, Gaboury I, Baird M, Klassen TP, MacCormick J, Blanchard C, et al. A randomized, double-blind, placebo-controlled noninferiority trial of amoxicillin for clinically diagnosed acute otitis media in children 6 months to 5 years of age. CMAJ. 2005 Feb 1;172(3):335-41. | PubMed |

Little P, Gould C, Williamson I, Moore M, Warner G, Dunleavey J. Pragmatic randomised controlled trial of two prescribing strategies for childhood acute otitis media. BMJ. 2001 Feb 10;322(7282):336-42. | PubMed |

Little P, Moore M, Warner G, Dunleavy J, Williamson I. Longer term outcomes from a randomised trial of prescribing strategies in otitis media. Br J Gen Pract. 2006 Mar;56(524):176-82. | PubMed |

McCormick DP, Chonmaitree T, Pittman C, Saeed K, Friedman NR, Uchida T, et al. Nonsevere acute otitis media: a clinical trial comparing outcomes of watchful waiting versus immediate antibiotic treatment. Pediatrics. 2005 Jun;115(6):1455-65. | PubMed |

Mygind N, Meistrup-Larsen KI, Thomsen J, Thomsen VF, Josefsson K, Sørensen H. Penicillin in acute otitis media: a double-blind placebo-controlled trial. Clin Otolaryngol Allied Sci. 1981 Feb;6(1):5-13. | PubMed |

Neumark T, Mölstad S, Rosén C, Persson LG, Törngren A, Brudin L, Eliasson I. Evaluation of phenoxymethylpenicillin treatment of acute otitis media in children aged 2-16. Scand J Prim Health Care. 2007 Sep;25(3):166-71. | PubMed |

Paradise JL, Hoberman A, Rockette HE, Shaikh N. Treating acute otitis media in young children: what constitutes success? Pediatr Infect Dis J. 2013 Jul;32(7):745-7. | CrossRef | PubMed |

Spiro DM, Tay KY, Arnold DH, Dziura JD, Baker MD, Shapiro ED. Wait-and-see prescription for the treatment of acute otitis media: a randomized controlled trial. JAMA. 2006 Sep 13;296(10):1235-41. | PubMed |

Tähtinen PA, Laine MK, Huovinen P, Jalava J, Ruuskanen O, Ruohola A. A placebo-controlled trial of antimicrobial treatment for acute otitis media. N Engl J Med. 2011 Jan 13;364(2):116-26. | CrossRef | PubMed |

Tapiainen T, Kujala T, Renko M, Koivunen P, Kontiokari T, Kristo A, et al. Effect of antimicrobial treatment of acute otitis media on the daily disappearance of middle ear effusion: a placebo-controlled trial. JAMA Pediatr. 2014 Jul;168(7):635-41. | CrossRef | PubMed |

Thalin A, Densert O, Larsson A, Lyden E, Torvald R. Is penicillin necessary in the treatment of acute otitis media? International conference on acute and secretory otitis media. International conference on acute and secretory otitis media; 1985: 4416. | Link |

Thomsen J, Meistrup-Larsen KI, Sørensen H, Larsen PK, Mygind N. Penicillin and acute otitis: short and long-term results. Ann Otol Rhinol Laryngol Suppl.1980 May-Jun;89(3 Pt 2):271-4. | PubMed |

van Buchem FL, Dunk JH, van't Hof MA. Therapy of acute otitis media: myringotomy, antibiotics, or neither? A double-blind study in children. Lancet. 1981 Oct 24;2(8252):883-7. | PubMed |

Lieberthal AS, Carroll AE, Chonmaitree T, Ganiats TG, Hoberman A, Jackson MA, et al. The diagnosis and management of acute otitis media. Pediatrics. 2013 Mar;131(3):e964-99. | CrossRef | PubMed |

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