Otitis media medical therapy: Difference between revisions
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{{CMG}} | {{CMG}} {{AE}} {{Maliha}}; {{SC}}; {{MM}}; {{LRO}} | ||
==Overview== | |||
The mainstay of therapy for acute otitis media (AOM) is antimicrobial therapy. High-dose [[Amoxicillin]] is the drug of choice for initial antibiotic therapy; high-dose [[Amoxicillin-Clavulanate]] or [[intramuscular]] [[Ceftriaxone]] should be reserved for patients who fail to respond to first-line treatment within 48 to 72 hours. Antimicrobial agents covering common bacterial pathogens (e.g., ''[[Streptococcus pneumoniae]]'', ''[[Moraxella catarrhalis]]'', and non-typeable ''[[Haemophilus influenzae]]'') have been used with success in selected patients to accelerate the recovery and lower the risk of [[tympanic membrane perforation]]s and contralateral AOM episodes.<ref>{{Cite journal| doi = 10.1002/14651858.CD000219.pub3| issn = 1469-493X| volume = 1| pages = –000219| last1 = Venekamp| first1 = Roderick P.| last2 = Sanders| first2 = Sharon| last3 = Glasziou| first3 = Paul P.| last4 = Del Mar| first4 = Chris B.| last5 = Rovers| first5 = Maroeska M.| title = Antibiotics for acute otitis media in children| journal = The Cochrane Database of Systematic Reviews| date = 2013| pmid = 23440776}}</ref> The optimal duration of antibiotics remains uncertain: a 10-day course of antibiotic therapy is recommended for children younger than 2 years and children with severe symptoms. In the absence of severe symptoms, a 7- or 5-day course is advisable for children 2 to 5 years of age or children 6 years and older, respectively. Current guidelines recommend observation for children age 6 to 24 months with unilateral AOM without [[otorrhea]] or children older than 2 years with unilateral or bilateral AOM without [[otorrhea]].<ref>{{Cite journal| doi = 10.1136/archdischild-2013-305550| issn = 1743-0593| last1 = Siddiq| first1 = Somiah| last2 = Grainger| first2 = Joe| last3 = Prentice| first3 = Philippa| title = The diagnosis and management of acute otitis media: American Academy of Pediatrics Guidelines 2013| journal = Archives of Disease in Childhood. Education and Practice Edition| date = 2014-11-12| pmid = 25395494}}</ref> [[Otalgia]] is generally managed with [[Acetaminophen]], [[Ibuprofen]], or [[narcotic]] [[analgesic]]s with [[Codeine]].<ref>{{Cite journal| doi = 10.1136/archdischild-2013-305550| issn = 1743-0593| last1 = Siddiq| first1 = Somiah| last2 = Grainger| first2 = Joe| last3 = Prentice| first3 = Philippa| title = The diagnosis and management of acute otitis media: American Academy of Pediatrics Guidelines 2013| journal = Archives of Disease in Childhood. Education and Practice Edition| date = 2014-11-12| pmid = 25395494}}</ref> | |||
==Medical Therapy== | ==Medical Therapy== | ||
===Acute Otitis Media | ===Initial Management of Uncomplicated Acute Otitis Media with High Certainty of Diagnosis=== | ||
{| style=" | {| style="font-size: 85%;" | ||
|+ '''Clinical Practice Guideline from the American Academy of Pediatrics'''<ref>{{Cite journal| doi = 10.1136/archdischild-2013-305550| issn = 1743-0593| last1 = Siddiq| first1 = Somiah| last2 = Grainger| first2 = Joe| last3 = Prentice| first3 = Philippa| title = The diagnosis and management of acute otitis media: American Academy of Pediatrics Guidelines 2013| journal = Archives of Disease in Childhood. Education and Practice Edition| date = 2014-11-12| pmid = 25395494}}</ref> | |||
| style="padding: 2px 10px; background: #4479BA; color: #FFFFFF;" | Age | |||
| style="padding: 2px 10px; background: #4479BA; color: #FFFFFF;" | AOM With Otorrhea | |||
| | | style="padding: 2px 10px; background: #4479BA; color: #FFFFFF;" | AOM With Severe Symptoms<sup>†</sup> | ||
| style="padding: 2px 10px; background: #4479BA; color: #FFFFFF;" | Bilateral AOM Without Otorrhea | |||
|- | | style="padding: 2px 10px; background: #4479BA; color: #FFFFFF;" | Unilateral AOM Without Otorrhea | ||
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| style="padding: | | style="padding: 2px 10px; background: #DCDCDC;" | 6 months to 2 years old | ||
| | | style="padding: 2px 10px; background: #F5F5F5;" | Antibiotic therapy | ||
| style=" | | style="padding: 2px 10px; background: #F5F5F5;" | Antibiotic therapy | ||
| | | style="padding: 2px 10px; background: #F5F5F5;" | Antibiotic therapy | ||
| style="padding: | | style="padding: 2px 10px; background: #F5F5F5;" | Antibiotic therapy or additional observation | ||
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|- | |- | ||
| style="padding: 2px 10px; background: #DCDCDC;" | ≥ 2 years old | |||
| style="padding: 2px 10px; background: #F5F5F5;" | Antibiotic therapy | |||
| style="padding: 2px 10px; background: #F5F5F5;" | Antibiotic therapy | |||
| style="padding: 2px 10px; background: #F5F5F5;" | Antibiotic therapy or additional observation | |||
| style="padding: 2px 10px; background: #F5F5F5;" | Antibiotic therapy or additional observation | |||
|} | |} | ||
|} | <SMALL><sup>†</sup> A toxic-appearing child, persistent otalgia more than 48 h, temperature ≥39°C (102.2°F) in the past 48 h, or if there is uncertain access to follow-up after the visit.</SMALL> | ||
===Rationale for Antibiotic Therapy Choice=== | |||
The rationale for antibiotic therapy in children with AOM is based on a high prevalence of bacteria from [[tympanocentesis]] cultures. A significant benefit of immediate antibiotic therapy is most evident in bilateral AOM, AOM with severe symptotms, AOM with [[otorrhea]], or ''[[Streptococcus pneumoniae]]'' infection.<ref>{{Cite journal| doi = 10.1016/S0140-6736(06)69606-2| issn = 1474-547X| volume = 368| issue = 9545| pages = 1429–1435| last1 = Rovers| first1 = Maroeska M.| last2 = Glasziou| first2 = Paul| last3 = Appelman| first3 = Cees L.| last4 = Burke| first4 = Peter| last5 = McCormick| first5 = David P.| last6 = Damoiseaux| first6 = Roger A.| last7 = Gaboury| first7 = Isabelle| last8 = Little| first8 = Paul| last9 = Hoes| first9 = Arno W.| title = Antibiotics for acute otitis media: a meta-analysis with individual patient data| journal = Lancet| date = 2006-10-21| pmid = 17055944}}</ref> Antibiotic therapy is recommended in the following settings: | |||
* AOM (bilateral or unilateral) in children 6 months and older with '''severe signs or symptoms''' (i.e., moderate or severe otalgia or otalgia for at least 48 hours, or temperature 39°C [102.2°F] or higher) | |||
* '''Bilateral''' AOM in children younger than 24 months without severe signs or symptoms | |||
When a decision to treat with antibiotics has been made, high-dose [[amoxicillin]] is recommended if all of the following criteria are fulfilled:<ref>{{Cite journal| doi = 10.1542/peds.2012-3488| issn = 1098-4275| volume = 131| issue = 3| pages = –964-999| last1 = Lieberthal| first1 = Allan S.| last2 = Carroll| first2 = Aaron E.| last3 = Chonmaitree| first3 = Tasnee| last4 = Ganiats| first4 = Theodore G.| last5 = Hoberman| first5 = Alejandro| last6 = Jackson| first6 = Mary Anne| last7 = Joffe| first7 = Mark D.| last8 = Miller| first8 = Donald T.| last9 = Rosenfeld| first9 = Richard M.| last10 = Sevilla| first10 = Xavier D.| last11 = Schwartz| first11 = Richard H.| last12 = Thomas| first12 = Pauline A.| last13 = Tunkel| first13 = David E.| title = The diagnosis and management of acute otitis media| journal = Pediatrics| date = 2013-03| pmid = 23439909}}</ref> | |||
*The patient has not received [[amoxicillin]] in the past 30 days. | |||
*The patient does not have concurrent purulent [[conjunctivitis]]. | |||
*The patient is not allergic to [[penicillin]]. | |||
Additional [[Beta-lactamase|β-lactamase]] coverage should be considered if any of the following criteria is fulfilled:<ref>{{Cite journal| doi = 10.1542/peds.2012-3488| issn = 1098-4275| volume = 131| issue = 3| pages = –964-999| last1 = Lieberthal| first1 = Allan S.| last2 = Carroll| first2 = Aaron E.| last3 = Chonmaitree| first3 = Tasnee| last4 = Ganiats| first4 = Theodore G.| last5 = Hoberman| first5 = Alejandro| last6 = Jackson| first6 = Mary Anne| last7 = Joffe| first7 = Mark D.| last8 = Miller| first8 = Donald T.| last9 = Rosenfeld| first9 = Richard M.| last10 = Sevilla| first10 = Xavier D.| last11 = Schwartz| first11 = Richard H.| last12 = Thomas| first12 = Pauline A.| last13 = Tunkel| first13 = David E.| title = The diagnosis and management of acute otitis media| journal = Pediatrics| date = 2013-03| pmid = 23439909}}</ref> | |||
*The patient has received [[amoxicillin]] in the past 30 days. | |||
*The patient has concurrent [[purulent]] [[conjunctivitis]]. | |||
*The patient has a history of recurrent AOM unresponsive to [[amoxicillin]]. | |||
===Duration of Therapy=== | |||
*Standard 10-day course of antibiotic therapy is recommended for children younger than 2 years and children with severe symptoms. | |||
*In the absence of severe symptoms, a 7- or 5-day course is advisable for children 2 to 5 years of age or children 6 years and older, respectively. | |||
===Antibiotic Regimens=== | |||
====Initial (Immediate or Delayed) Antibiotic Treatment==== | |||
*Preferred Regimen | |||
**[[Amoxicillin]] 80–90 mg/kg/d bid {{or}} [[Amoxicillin]] 90 mg/kg/d with [[Clavulanate]] 6.4 mg/kg/d | |||
*Alternative Regimen (if allergic to [[penicillin]]) | |||
**[[Cefdinir]] 14 mg/kg/d qd or bid {{or}} [[Cefuroxime]] 30 mg/kg/d bid {{or}} [[Cefpodoxime]] 10 mg/kg/d bid {{or}} [[Ceftriaxone]] 50 mg/kg IM/IV qd | |||
====After Failure of Initial Antibiotic Treatment==== | |||
*Preferred Regimen | |||
**[[Amoxicillin]] 90 mg/kg/d with [[Clavulanate]] 6.4 mg/kg/d {{or}} [[Ceftriaxone]] 50 mg/kg IM/IV qd | |||
*Alternative Regimen | |||
**[[Clindamycin]] 30–40 mg/kg/d tid ± 3° [[Cephalosporin]] ± [[Tympanocentesis]] | |||
===Pain Management=== | |||
Episodes of AOM are commonly associated with [[otalgia]], managed by the following: | |||
*[[Acetaminophen]] | |||
*[[Ibuprofen]] | |||
|- | *[[Codeine]] | ||
| | **Should be used with caution in the treatment of severe [[otalgia]] due to the risk of [[respiratory depression]], [[altered mental status]], [[abdominal pain|gastrointestinal upset]], and [[constipation]]. <ref>{{Cite journal| doi = 10.1542/peds.2012-3488| issn = 1098-4275| volume = 131| issue = 3| pages = –964-999| last1 = Lieberthal| first1 = Allan S.| last2 = Carroll| first2 = Aaron E.| last3 = Chonmaitree| first3 = Tasnee| last4 = Ganiats| first4 = Theodore G.| last5 = Hoberman| first5 = Alejandro| last6 = Jackson| first6 = Mary Anne| last7 = Joffe| first7 = Mark D.| last8 = Miller| first8 = Donald T.| last9 = Rosenfeld| first9 = Richard M.| last10 = Sevilla| first10 = Xavier D.| last11 = Schwartz| first11 = Richard H.| last12 = Thomas| first12 = Pauline A.| last13 = Tunkel| first13 = David E.| title = The diagnosis and management of acute otitis media| journal = Pediatrics| date = 2013-03| pmid = 23439909}}</ref> | ||
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=== | ===Antimicrobial regimens=== | ||
*'''Acute otitis media''' <ref name="pmid23439909">{{cite journal| author=Lieberthal AS, Carroll AE, Chonmaitree T, Ganiats TG, Hoberman A, Jackson MA et al.| title=The diagnosis and management of acute otitis media. | journal=Pediatrics | year= 2013 | volume= 131 | issue= 3 | pages= e964-99 | pmid=23439909 | doi=10.1542/peds.2012-3488 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23439909 }} </ref> | |||
:*'''1. Causative pathogens''' | |||
::*Streptococcus pneumoniae | |||
::*Hemophilus influenzae | |||
::*Moraxella catarrhalis | |||
::*Polymicrobial | |||
::*Viral | |||
:*'''2. Empiric antimicrobial therapy''' | |||
::*Preferred regimen: [[Amoxicillin]] 40–90 mg/kg/day PO q12h {{or}} [[Amoxicillin-Clavulanate]] 90/6.4 mg/kg/day PO q12h | |||
::*Alternative regimen: [[Cefdinir]] 14 mg/kg/day PO q12 or q24h {{or}} [[Cefuroxime]] 30 mg/kg/day PO q12h {{or}} [[Cefpodoxime]] 10 mg/kg/day PO q12h {{or}} [[Ceftriaxone]] 50 mg/kg/day IM or IV q24h | |||
::*Note: [[Amoxicillin-Clavulanate]] may be considered in patients with recent [[Amoxicillin]] intake or concomitant conjunctivitis. Alternative regimens should be considered in patients with [[Penicillin]] allergies. Re-evaluate after 2-3 days for treatment response. | |||
:*'''3. Special considerations''' | |||
::*'''3.1 Acute otitis media post-treatment failure (48-72 hours)''' | |||
:::*Preferred regimen: [[Amoxicillin-Clavulanate]] 90/6.4 mg/kg/day PO q12h {{or}} [[Ceftriaxone]] 50 mg/kg/day IM or IV q24h | |||
:::*Alternative regimen: [[Clindamycin]] 30–40 mg/kg/day PO q8h '''±''' ([[Cefdinir]] 14 mg/kg/day PO q12 or q24h {{or}} [[Cefuroxime]] 30 mg/kg/day PO q12h {{or}} [[Cefpodoxime]] 10 mg/kg/day PO q12h {{or}} [[Ceftriaxone]] 50 mg/kg/day IM or IV q24h) | |||
::*'''3.2 Acute otitis media post-intubation'''<ref>{{cite book | last = Gilbert | first = David | title = The Sanford guide to antimicrobial therapy | publisher = Antimicrobial Therapy | location = Sperryville, Va | year = 2015 | isbn = 978-1930808843 }}</ref> | |||
:::*Preferred regimen: [[Ceftazidime]] 2 g IV q8h {{or}} [[Cefepime]] 2 g IV q12h {{or}} [[Imipenem]] 0.5 g IV q6h {{or}} [[Meropenem]] 500 mg IV q8h {{or}} [[Piperacillin-Tazobactam]] 4–6 g IV q4–6h {{or}} [[Ticarcillin-Clavulanate]] 3 g IV q4h {{or}} [[Ciprofloxacin]] 400 mg IV q12h {{or}} [[Ciprofloxacin]] 750 mg PO q12h | |||
==References== | ==References== | ||
{{reflist|2}} | {{reflist|2}} | ||
[[Category:Disease]] | [[Category:Disease]] | ||
[[Category:Inflammations]] | [[Category:Inflammations]] | ||
[[Category:Otolaryngology]] | [[Category:Otolaryngology]] | ||
[[Category:Otology]] | [[Category:Otology]] | ||
[[Category:Pediatrics]] | [[Category:Pediatrics]] | ||
[[Category:Infectious Disease Project]] | |||
Latest revision as of 23:30, 29 July 2020
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maliha Shakil, M.D. [2]; Shanshan Cen, M.D. [3]; Mohamed Moubarak, M.D. [4]; Luke Rusowicz-Orazem, B.S.
Overview
The mainstay of therapy for acute otitis media (AOM) is antimicrobial therapy. High-dose Amoxicillin is the drug of choice for initial antibiotic therapy; high-dose Amoxicillin-Clavulanate or intramuscular Ceftriaxone should be reserved for patients who fail to respond to first-line treatment within 48 to 72 hours. Antimicrobial agents covering common bacterial pathogens (e.g., Streptococcus pneumoniae, Moraxella catarrhalis, and non-typeable Haemophilus influenzae) have been used with success in selected patients to accelerate the recovery and lower the risk of tympanic membrane perforations and contralateral AOM episodes.[1] The optimal duration of antibiotics remains uncertain: a 10-day course of antibiotic therapy is recommended for children younger than 2 years and children with severe symptoms. In the absence of severe symptoms, a 7- or 5-day course is advisable for children 2 to 5 years of age or children 6 years and older, respectively. Current guidelines recommend observation for children age 6 to 24 months with unilateral AOM without otorrhea or children older than 2 years with unilateral or bilateral AOM without otorrhea.[2] Otalgia is generally managed with Acetaminophen, Ibuprofen, or narcotic analgesics with Codeine.[3]
Medical Therapy
Initial Management of Uncomplicated Acute Otitis Media with High Certainty of Diagnosis
Age | AOM With Otorrhea | AOM With Severe Symptoms† | Bilateral AOM Without Otorrhea | Unilateral AOM Without Otorrhea |
6 months to 2 years old | Antibiotic therapy | Antibiotic therapy | Antibiotic therapy | Antibiotic therapy or additional observation |
≥ 2 years old | Antibiotic therapy | Antibiotic therapy | Antibiotic therapy or additional observation | Antibiotic therapy or additional observation |
† A toxic-appearing child, persistent otalgia more than 48 h, temperature ≥39°C (102.2°F) in the past 48 h, or if there is uncertain access to follow-up after the visit.
Rationale for Antibiotic Therapy Choice
The rationale for antibiotic therapy in children with AOM is based on a high prevalence of bacteria from tympanocentesis cultures. A significant benefit of immediate antibiotic therapy is most evident in bilateral AOM, AOM with severe symptotms, AOM with otorrhea, or Streptococcus pneumoniae infection.[5] Antibiotic therapy is recommended in the following settings:
- AOM (bilateral or unilateral) in children 6 months and older with severe signs or symptoms (i.e., moderate or severe otalgia or otalgia for at least 48 hours, or temperature 39°C [102.2°F] or higher)
- Bilateral AOM in children younger than 24 months without severe signs or symptoms
When a decision to treat with antibiotics has been made, high-dose amoxicillin is recommended if all of the following criteria are fulfilled:[6]
- The patient has not received amoxicillin in the past 30 days.
- The patient does not have concurrent purulent conjunctivitis.
- The patient is not allergic to penicillin.
Additional β-lactamase coverage should be considered if any of the following criteria is fulfilled:[7]
- The patient has received amoxicillin in the past 30 days.
- The patient has concurrent purulent conjunctivitis.
- The patient has a history of recurrent AOM unresponsive to amoxicillin.
Duration of Therapy
- Standard 10-day course of antibiotic therapy is recommended for children younger than 2 years and children with severe symptoms.
- In the absence of severe symptoms, a 7- or 5-day course is advisable for children 2 to 5 years of age or children 6 years and older, respectively.
Antibiotic Regimens
Initial (Immediate or Delayed) Antibiotic Treatment
- Preferred Regimen
- Amoxicillin 80–90 mg/kg/d bid OR Amoxicillin 90 mg/kg/d with Clavulanate 6.4 mg/kg/d
- Alternative Regimen (if allergic to penicillin)
- Cefdinir 14 mg/kg/d qd or bid OR Cefuroxime 30 mg/kg/d bid OR Cefpodoxime 10 mg/kg/d bid OR Ceftriaxone 50 mg/kg IM/IV qd
After Failure of Initial Antibiotic Treatment
- Preferred Regimen
- Amoxicillin 90 mg/kg/d with Clavulanate 6.4 mg/kg/d OR Ceftriaxone 50 mg/kg IM/IV qd
- Alternative Regimen
- Clindamycin 30–40 mg/kg/d tid ± 3° Cephalosporin ± Tympanocentesis
Pain Management
Episodes of AOM are commonly associated with otalgia, managed by the following:
- Acetaminophen
- Ibuprofen
- Codeine
- Should be used with caution in the treatment of severe otalgia due to the risk of respiratory depression, altered mental status, gastrointestinal upset, and constipation. [8]
Antimicrobial regimens
- Acute otitis media [9]
- 1. Causative pathogens
- Streptococcus pneumoniae
- Hemophilus influenzae
- Moraxella catarrhalis
- Polymicrobial
- Viral
- 2. Empiric antimicrobial therapy
- Preferred regimen: Amoxicillin 40–90 mg/kg/day PO q12h OR Amoxicillin-Clavulanate 90/6.4 mg/kg/day PO q12h
- Alternative regimen: Cefdinir 14 mg/kg/day PO q12 or q24h OR Cefuroxime 30 mg/kg/day PO q12h OR Cefpodoxime 10 mg/kg/day PO q12h OR Ceftriaxone 50 mg/kg/day IM or IV q24h
- Note: Amoxicillin-Clavulanate may be considered in patients with recent Amoxicillin intake or concomitant conjunctivitis. Alternative regimens should be considered in patients with Penicillin allergies. Re-evaluate after 2-3 days for treatment response.
- 3. Special considerations
- 3.1 Acute otitis media post-treatment failure (48-72 hours)
- Preferred regimen: Amoxicillin-Clavulanate 90/6.4 mg/kg/day PO q12h OR Ceftriaxone 50 mg/kg/day IM or IV q24h
- Alternative regimen: Clindamycin 30–40 mg/kg/day PO q8h ± (Cefdinir 14 mg/kg/day PO q12 or q24h OR Cefuroxime 30 mg/kg/day PO q12h OR Cefpodoxime 10 mg/kg/day PO q12h OR Ceftriaxone 50 mg/kg/day IM or IV q24h)
- 3.2 Acute otitis media post-intubation[10]
- Preferred regimen: Ceftazidime 2 g IV q8h OR Cefepime 2 g IV q12h OR Imipenem 0.5 g IV q6h OR Meropenem 500 mg IV q8h OR Piperacillin-Tazobactam 4–6 g IV q4–6h OR Ticarcillin-Clavulanate 3 g IV q4h OR Ciprofloxacin 400 mg IV q12h OR Ciprofloxacin 750 mg PO q12h
References
- ↑ Venekamp, Roderick P.; Sanders, Sharon; Glasziou, Paul P.; Del Mar, Chris B.; Rovers, Maroeska M. (2013). "Antibiotics for acute otitis media in children". The Cochrane Database of Systematic Reviews. 1: –000219. doi:10.1002/14651858.CD000219.pub3. ISSN 1469-493X. PMID 23440776.
- ↑ Siddiq, Somiah; Grainger, Joe; Prentice, Philippa (2014-11-12). "The diagnosis and management of acute otitis media: American Academy of Pediatrics Guidelines 2013". Archives of Disease in Childhood. Education and Practice Edition. doi:10.1136/archdischild-2013-305550. ISSN 1743-0593. PMID 25395494.
- ↑ Siddiq, Somiah; Grainger, Joe; Prentice, Philippa (2014-11-12). "The diagnosis and management of acute otitis media: American Academy of Pediatrics Guidelines 2013". Archives of Disease in Childhood. Education and Practice Edition. doi:10.1136/archdischild-2013-305550. ISSN 1743-0593. PMID 25395494.
- ↑ Siddiq, Somiah; Grainger, Joe; Prentice, Philippa (2014-11-12). "The diagnosis and management of acute otitis media: American Academy of Pediatrics Guidelines 2013". Archives of Disease in Childhood. Education and Practice Edition. doi:10.1136/archdischild-2013-305550. ISSN 1743-0593. PMID 25395494.
- ↑ Rovers, Maroeska M.; Glasziou, Paul; Appelman, Cees L.; Burke, Peter; McCormick, David P.; Damoiseaux, Roger A.; Gaboury, Isabelle; Little, Paul; Hoes, Arno W. (2006-10-21). "Antibiotics for acute otitis media: a meta-analysis with individual patient data". Lancet. 368 (9545): 1429–1435. doi:10.1016/S0140-6736(06)69606-2. ISSN 1474-547X. PMID 17055944.
- ↑ Lieberthal, Allan S.; Carroll, Aaron E.; Chonmaitree, Tasnee; Ganiats, Theodore G.; Hoberman, Alejandro; Jackson, Mary Anne; Joffe, Mark D.; Miller, Donald T.; Rosenfeld, Richard M.; Sevilla, Xavier D.; Schwartz, Richard H.; Thomas, Pauline A.; Tunkel, David E. (2013-03). "The diagnosis and management of acute otitis media". Pediatrics. 131 (3): –964-999. doi:10.1542/peds.2012-3488. ISSN 1098-4275. PMID 23439909. Check date values in:
|date=
(help) - ↑ Lieberthal, Allan S.; Carroll, Aaron E.; Chonmaitree, Tasnee; Ganiats, Theodore G.; Hoberman, Alejandro; Jackson, Mary Anne; Joffe, Mark D.; Miller, Donald T.; Rosenfeld, Richard M.; Sevilla, Xavier D.; Schwartz, Richard H.; Thomas, Pauline A.; Tunkel, David E. (2013-03). "The diagnosis and management of acute otitis media". Pediatrics. 131 (3): –964-999. doi:10.1542/peds.2012-3488. ISSN 1098-4275. PMID 23439909. Check date values in:
|date=
(help) - ↑ Lieberthal, Allan S.; Carroll, Aaron E.; Chonmaitree, Tasnee; Ganiats, Theodore G.; Hoberman, Alejandro; Jackson, Mary Anne; Joffe, Mark D.; Miller, Donald T.; Rosenfeld, Richard M.; Sevilla, Xavier D.; Schwartz, Richard H.; Thomas, Pauline A.; Tunkel, David E. (2013-03). "The diagnosis and management of acute otitis media". Pediatrics. 131 (3): –964-999. doi:10.1542/peds.2012-3488. ISSN 1098-4275. PMID 23439909. Check date values in:
|date=
(help) - ↑ Lieberthal AS, Carroll AE, Chonmaitree T, Ganiats TG, Hoberman A, Jackson MA; et al. (2013). "The diagnosis and management of acute otitis media". Pediatrics. 131 (3): e964–99. doi:10.1542/peds.2012-3488. PMID 23439909.
- ↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.