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10 2217/FMB 12 38 2012 Future Medicine Ltd ISSN 1746 0913Future Microbiol (2012) 7(6) 733 753

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icrobiology

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Otitis media represents a broad spectrum ofdisease: acute otitis media (AOM), otitis media

with effusion (OME), chronic OME (acute orchronic), mucoid otitis media and chronic sup-purative otitis media (CSOM). The manage-ment of AOM was addressed by the AmericanAcademy of Pediatrics (AAP) and AmericanAcademy of Family Physician (AAFP) in 2004,and OME was addressed by the AAP, the AAFPand the American Academy of Otolaryngology-Head and Neck Surgery in the same year [1,2].As immunization with the pneumococcal con-jugate vaccine has become more widespread, themicrobiological landscape of otitis media haschanged, which affects the treatment optionsfacing clinicians worldwide.

This review discusses the diagnosis andmedical management of acute and CSOM, thechanges noted over the past decade, and brieflyexpounds on the surgical management of theirsevere complications.

Acute otitis media

AOM has been defined as an infection of themiddle ear with acute onset, the presence of amiddle ear effusion, and signs and symptoms ofmiddle ear inflammation [1].

Epidemiology of AOM

AOM remains one of the most frequent diagno-ses in sick children in the USA [3,4], with highassociated healthcare costs and burden of disease[5]. In the USA it is the most common bacterialinfection in children treated with antibiotics[68]. At least 6080% of infants have their firstepisode by 1 year of age, with up to 8090%having their first episode by 23 years of age[8,9]. The incidence is the highest in the 624-month age group in the USA, with a subsequent

decline, prior to a small increase around the age

of school entry of 56 years old. AOM is less fre-quent in older school-age children, teenagers and

adults [8,9]. While the burden of AOM remainshigh, its epidemiology and microbiology havechanged within the past decade, likely due to thecombined effects of the pneumococcal conjugatevaccine and the widespread use of antibiotics [10].

Risk factors for AOM

Risk factors for AOM include: age [1124], day carewith four or more children [15], bottle propping[16], breast feeding for less than 3 months [17],exposure to tobacco smoke [19]and air pollution,pacifier use, race and ethnicity [21,24], lack of med-ical care access [22], family history [12], asthma [18],atopy [13]and genetics [21,24]. Risk factors for thepresence of amoxicillin-resistant bacteria includeday care attendance [14], antibiotic therapy withinthe previous 30 days [12]and age under 2 years[1,12,13]. Additionally, medical conditions suchas immunodeficiency, ciliary dysfunction, cleftpalate [16], craniofacial anomalies [12]and Downsyndrome play a role [11].

Pathogenesis of AOM

The middle ear is connected to the nasophar-ynx anteriorly by the Eustachian tube, with the

mastoid air cells located behind. Normally, themiddle ear experiences a slightly negative airpressure compared with the outside environ-ment. This negative pressure is relieved duringprocesses such as yawning or chewing. In manyinstances, impairment to Eustachian tube func-tion is the initial mechanism that triggers otitismedia [25].

A series of events, usually initiated by an upperrespiratory infection, leads to the pathogenesisof otitis media. An upper respiratory infectiontends to result in nasal congestion of the respi-

ratory mucosa of the nose, nasopharynx and

Otitis media

Michael Cunningham1, Elizabeth Guardiani2, Hung Jeffrey Kim2

& Itzhak Brook*1Walter Reed National Military Medical Center, Bethesda, MD, USA2Department of Otolaryngology Georgetown University School of Medicine, Washington, DC, USA*Author for correspondence: Department of Pediatrics Georgetown University School of Medicine,Washington, DC, USA nTel.: +1 202 744 8211 nFax: +1 202 244 6809 [email protected]

Otitis media represents a broad spectrum of disease, which include acute otitismedia and otitis media with effusion. As immunization with the pneumococcalconjugate vaccine has become more widespread, the microbiologicallandscape of otitis media has changed, which affects the treatment optionsfacing clinicians worldwide. This review discusses the diagnosis and medicalmanagement of acute and chronic suppurative otitis media, the changes notedover the past decade, and briefly expounds on the surgical management of thei rsevere complications.

Keywords

nacute otitis media

nantibiotic therapy

nHaemophilus influenzae

notitis media with effusion

npneumococcal conjuga

vaccination nStreptococc

pneumoniaentympanost

tubes

Re

view

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Eustachian tube. Congestion of the Eustachiantube mucosa obstructs the tube, preventingthe middle ear from relieving negative pres-sure. Negative pressure accumulates and is fol-lowed by increased secretions within the middleear, which cannot be drained via the clogged

Eustachian tube. Colonized upper respiratorytract viruses and bacteria reach the middle earvia aspiration, reflux or insufflation. Microbesthen grow in middle ear secretions and lead tothe clinical signs of AOM [2629].

Diagnosis of AOM

The accurate diagnosis of AOM is critical toensure proper patient care, appropriate antibi-otic use and reduce the development of resistantbacteria from antibiotic overuse [30,31].

AOM is not always a simple diagnosis in

infants and young children. A cooperative exam-ination can be challenging, and the tympanicmembranes (TMs) can easily be hidden behindthick cerumen. Additionally, AOM symptomscan overlap many other common upper respi-ratory tract illnesses [3234]. Parental concernsof ear rubbing, restless sleep, crying, irritability,and fever are not predictive of disease [35].

AOM diagnosis requires a history of acuteonset of signs and symptoms, the presence of amiddle ear effusion, and signs and symptoms ofmiddle ear inflammation. A middle ear effusioncan be diagnosed with a bulging TM, limited orabsent mobility of the TM, air-fluid level behindthe TM, or otorrhea in the setting of TM rup-ture or tympanostomy tubes (TTs). Middle earinflammation is described as distinct erythemaof the TM or distinct otalgia that alters normalactivity or sleep [1].

Pneumatic otoscopy is crucial to identify amiddle ear effusion. AOM will usually have abulging TM, while OME usually has a retractedor neutral TM. With AOM, the TM color canbe red, white or yellow, but in OME, it is morelikely to be amber or blue. OME will usually have

an air-fluid level or bubbles visualized behindthe TM. In AOM, pus can be visualized, bul-lae may be present or the TM maybe perforatedwith purulent otorrhea [36]. AOM represents aspectrum of disease, with variable positions ofthe TM depending on the stage of illness andtime of evaluation [37]. Given the requirement ofboth a middle ear effusion and acute symptomsfor diagnosis of AOM, it is imperative that aclinician is skilled with pneumatic otoscopy toaccurately make the diagnosis. A tympanometercan assist with determining the presence of a

middle ear effusion [25].

While the diagnosis of AOM can be straight-forward, it becomes complicated when AOMrecurs, it persists despite antibiotic therapy orsecondary extension of AOM creates furthercomplication. It is helpful in these circumstancesto obtain a culture of the middle ear fluid via

tympanocentesis, especially if there is concernfor a resistant bacterial organism. The antimi-crobial susceptibility against the pathogen willbe essential in selecting the best therapy for theresolution of symptoms.

Microbiology of AOM

Both bacterial and viral respiratory tract patho-gens can be responsible for AOM, and either oneor both will be isolated from the middle ear aspi-rates of children. Three species of bacteria areresponsible for the majority of AOM caused by

bacteria: Streptococcus pneumoniae, HaemophilusinfluenzaeandMoraxella catarrhalis[3842], witha change in incidence noted in various studiesafter the introduction of pneumococcal conju-gate vaccine 7 (PCV7) [43](TABLE1 & FIGURE1). Upto two-thirds of cases can involve both bacterialand viral etiologies in AOM [44]. The presenceof viruses can affect the bacterial response toantibiotic therapy, as viruses can increase middleear inflammation, decrease the function of neu-trophils and reduce antibiotic penetration intothe middle ear [4550].

Bilateral disease is more likely to have bacteriaisolated from middle ear aspirates, with H. influ-enzaebeing the bacterial pathogen identifiedmost commonly in bilateral disease. S. pneu-moniaeoccurred in equal frequencies in childrenwith bilateral and unilateral disease [51,52].

S. pneumoniae remains one of the most com-mon causes of AOM, accounting for 3545%of bacterial isolates. This pathogen frequentlycauses severe AOM with high fevers, severe otal-gia, significant TM erythema and bulging, andleukocyte and neutrophil counts in middle earfluid and peripheral blood [53]. The serotypes

responsible for infection have changed after theintroduction of the pneumococcal conjugate vac-cination. Prior to the introduction of the PCV7,the most common serotypes were: 19F, 23F, 14,6B, 6A, 19A and 9V. The serotypes includedin PCV7 accounted for up to 70% of bacteriaassociated with AOM in children [54]. Afterimmunization with PCV7 began in the USAin 2000, nonvaccine serotypes of S. pneumoniaehave become the most common species recoveredfrom the nasopharynx of asymptomatic children,as well as from middle ear aspirates of children

with AOM [40,5559].

Review Cunningham, Guardiani, Kim & Brook

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The use of PCV7 has led to increases ofthe nonvaccine serotypes 19A, 6C, 22F, 15and 33 [40,5772]. The change of serotypes maybe a result of the replacement phenomenon,with the nonvaccine serotypes becoming moreprevalent as PCV7 both directly and indirectly

prevents disease. It has been noted that sero-type 19A began to rise in prevalence in Spainand Korea prior to the introduction of PCV7.This suggests the overuse of antibiotics, spe-cifically cephalosporins and azithromycin,and not the replacement phenomenon, playa role in the shift of serotypes and the resis-tance pattern [73]. The nonvaccine serotype 19Ahas become a specific concern, as multidrug-resistant strains have been reported in resistantAOM, as well as mastoiditis [56,74,75]. Serotype19A incidence has increased since the intro-

duction of PCV7 in 2000, and has also beenassociated with an increase in multidrug resis-tance [56,57,62,65,68,69,76,77]. Capsular switching,expansion of existing clones and introductionof new clones appear to be responsible for theincreased invasive pneumococcal disease causedby serotype 19A. Given its role in more advanceddisease, serotype 19A has been included in thenew 13-valent pneumococcal conjugate vaccine(PCV13) licensed in 2010. Recent observationssupport the increased resistance of S. pneumoniaeas outlined in FIGURE2 . Ongoing surveillanceand subsequent adaptation for future immu-nizations will be paramount as PCV13 usebecomes more widespread and pneumococcicontinue to evolve.

H. influenzaeremains a common cause ofAOM and has become the most common bac-terial cause of AOM in the post-PCV7 world[72]. H. influenzae is most frequently associatedwith conjunctivitis, bilateral AOM, previousantibiotic treatment and recurrent disease [53].Most H. influenzae isolated from cultures ofthe middle ear are nontypeable [40], with up toa half of these strains producing b-lactamase[26,52]. In addition, strains of H. influenzaehavebeen shown to have ampicillin resistance in theabsence of b-lactamase [10,78]. Since over 90%of Haemophilus-caused AOM cases are causedby nontypeable strains, the conjugate Hibvaccine has not affected the rates of infection.With the decrease in S. pneumoniaeobservedafter the introduction of PCV7, the percentageof AOM caused by nontypeable H. influenzaehas risen from 40 to over 50% (TABLE 1)[39,43,79].

M. catarrhalis has been identified as thethird most common cause of AOM. It has

been associated with a significantly higher

proportion of mixed infections and first episodesof AOM. Fewer complications are associatedwithMoraxellaat the time of AOM diagnosis, as

there are lower rates of spontaneous perforationof the TM and no episodes of mastoiditis havebeen reported [53].Moraxella has been reportedto have up to 100% of strains producing b-lac-tamase [80], with its frequency rising over the pasttwo decades, ranging from 2 to 15% of AOM [81].

Group A Streptococcus(GAS) was the most fre-quently isolated pathogen in the first half of the20th century, especially in AOM associated withscarlet fever or measles [82]. Since the 1950s ithas been replaced by S. pneumoniae,nontypeable

Table 1. Antibiotic treatment versus observation in children with

acute otitis media.

Age Certain diagnosis Uncertain diagnosis

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H. influenzae andM. catarrhalis. It is now rankedfourth among AOM pathogens, and accounts forless than 10% of all cases [82]. GAS episodes havebeen characterized by patients with an older age,usually older than 5 years old, and higher locallyinvasive disease evidenced by higher rates of TMperforation and of mastoiditis [83]

Other bacterial causes of AOM are muchrarer. Neonates and young infants can beinfected with Group B Streptococcusand Gram-negative bacilli within the first 2 months of life[25,84,85]. Staphylococcus aureus is carried in thenares of up to 10% of children under the age of2 years. Approximately 3% of middle ear cul-tures in AOM with intact TMs grow S. aureus[25], with the rate as high as 18% of childrenwith spontaneously draining AOM [86].Nasalcarriage of S. aureusis inversely related to naso-

pharyngeal carriage of pneumococcal vaccineserotypes. As nasopharyngeal colonization withS. pneumoniaedecreases with vaccination, thereis the potential for increased incidence of AOMcaused by S. aureus [87,88]. In addition to higherrates of S. aureus with spontaneously drainingAOM, there have been higher rates of methi-cillin-resistant S. aureus(MRSA) [86]. This maybe explained by the increased use of high-doseamoxicillin, and increased prevalence of MRSAin the community, or the herd effect [86].

Viruses are frequently associated with AOM.

A review of data from 1982 to 1990 identified

respiratory viruses in middle ear fluid in up to16% of children with AOM, with respiratorysyncytial virus, rhinoviruses, influenza andadenoviruses the most frequent [89]. With newermicrobiological testing methods, such as reversetranscriptase PCR, virus detection has increased.A study of 92 children over a 1-year period dem-onstrated 49% of samples with a viral etiologyfor AOM [90]. Another series of 29 childrenwith AOM with new onset otorrhea and TTsdetected viruses in 70% of children [44]; how-ever, it appears that only 20% of cases are causedby viruses alone [91]. Additionally, viruses playan important role, as their colonization withinthe respiratory tract has both a synergistic andan antagonistic interaction leading to the naso-pharyngeal colonization with S. pneumoniae,nontypeable H. influenzaeandM. catarrhalis [92].

Colonization with nonpathogenic aerobicand anaerobic bacteria able to interfere with thegrowth of bacterial species pathogenic for otitismedia can play a role in protecting a patient frombacterial otitis media [93]. a-hemolytic strepto-cocci (mostly Streptococcus mitisand Streptococcussanguis) and the anaerobic Prevotella melanino-genicaand Peptostreptococcusanaerobius play arole in the prevention of upper respiratory infec-tions, including AOM [9395]. Children withincreased colonization of these species are notas prone to AOM as those with less colonization.

Children with decreased colonization by these

1998 1999 2000 2001 2002 2004 2006 2008 20092003 2005 2007

100

90

80

70

Susceptible(%)

Year

Amoxicillinclavulanate

High-dose penicillin

Ceftriaxone

Clindamycin

Levofloxacin

Figure 2. Streptococcus pneumoniaesusceptibility rates.Adapted with permission from [117].


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nonpathogenic bacteria have increased nontype-able H. influenzaeand S. pneumoniaecoloniza-tion, which is associated with higher frequencyof AOM [93]. It is theorized that the productionof bacteriocin and other inhibitory substances bythe nonpathogenic bacteria suppress the growth

of the common organisms associated with AOM,or that utilization of nutrients in the nasopha-ryngeal environment essential for the potentialAOM pathogens may explain this relationship[93,95,96]. The use of antibiotics can alter thenasopharyngeal flora, leading to decreased pro-tective species, and potentially place children athigher risk for AOM [9395], highlighting theimportance of proper use of antibiotic therapy.

Treatment of AOM

The AAP and AAFP Clinical Practice Guideline

on AOM outlined criteria for treatment of AOM(TABLE2). The AAP/AAFP provided the follow-ing criteria for observation versus antibacterialtherapy for patients with AOM [1]:

n Any child under the age of 6 months shouldreceive antibacterial therapy, regardless of thedegree of diagnostic certainty;

n Antibacterial therapy for children between theages of 6 months and 2 years is recommendedwhen the diagnosis of AOM is certain, or if itis uncertain and the illness is severe. Severe

illness is defined as moderate-to-severe otalgiaor temperature 39C in the previous 24 h.Observation for children in this age group isan option when the diagnosis is uncertain andthe illness is not severe;

n Antibacterial therapy for children older than2 years old is recommended when the diagno-sis of AOM is certain and the illness is severe.Observation is an option with certain diagno-sis and mild disease, as well as with diagnosticuncertainty;

n Observation is only considered an appropriateoption when follow-up can be ensured andantibacterial agents can be started if symptomspersist or worsen.

The publication of the 2004 AAP and AAFPguidelines for the diagnosis and managementof AOM has not resulted in a decrease in theprescription of antibiotics in the USA [97,98].While watchful waiting can be safely imple-mented and successful [99,100], some providershave been hesitant to implement this approachowing to a perceived parental reluctance to

accept this strategy [97]. Use of the guidelines

with watchful waiting has shown that childrenwho did not receive antibiotics for AOM weremore likely to have mild infections [97]. By reduc-

ing the unnecessary prescription of antibiotics,further increases in antibiotic resistance can beprevented [101].

With the increasing concerns for resistantpathogens resulting from the overuse of antibi-otics, ongoing education of providers as to theappropriate setting for antibiotic therapy forAOM is a necessity. Additionally, providers mustengage parents in a discussion regarding therisks and benefits of a watch and see approach,to reassure, as well as involve, them in the deci-sion making process [102], as up to 40% of par-ents are dissatisfied without receiving antibiotictherapy [99].

Antibiotic therapy

The selection of the appropriate antibiotic for thetreatment of AOM is vital to the eradication ofbacteria within the middle ear. Failure to suc-cessfully eradicate the bacterial infection is asso-ciated with treatment failure and persistent andrecurrent AOM [10,103,104]. Providers can falselypresume that bacterial eradication has occurredin the setting of improved clinical symptoms, asclinical improvement does not always correlate

with bacterial eradication [10,104]. When antibiot-ics are necessary for the treatment of AOM, itis imperative to select those that will both suc-cessfully treat AOM, and minimize the spread ofresistance. The 2004 AAP and AAFP guidelinesoutline a plan to do so, and have been reinforcedby recent assessments of bacterial resistance [10].

The 2004 AAP and A AFP guidelines recom-mend high-dose amoxicillin, 8090 mg/kg perday, for AOM in patients with mild illness. Thisdose is effective against all S. pneumoniae, exceptfor strains that are highly resistant to penicillin

[10,105]. Even with the increasing incidence of

Table 2. Observed ranges of culture-positive specimens pre- and

post-pneumococcal conjugate vaccine 7.

Bacteria Pre-PCV7 (%) Post-PCV7 (%)

Streptococcus pneumoniae 3354 2444

PCV7 serotypes 4276 3152

Non-PCV7 serotypes 1258 3270

Haemophilus influenzae 1843 2757

Moraxella catarrhalis 430 132

Streptococcus pyogenes 27 210

Staphylococcus aureus 817 1834

PCV7: Pneumococcal conjugate vaccine 7.Adapted with permission from [43].

Otitis media Revi

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H. influenzae, including higher rates of b-lac-tamase-producing strains, high dose remains theinitial therapy of choice, despite its decreasedefficacy against b-lactamase-positive H. influ-enzaestrains [10]. Amoxicillin should not be thefirst-line therapy in patients recently treated with

b-lactam antibiotics [12,13,106], children alreadyreceiving amoxicillin for chemoprophylaxis foreither recurrent AOM or urinary tract infections,or children with otitisconjunctivitis syndrome,as it is highly associated with H. influenzaeinfec-tion, which is more commonly a b-lactamaseproducer. Treatment failure with high-doseamoxicillin therapy is most commonly causedby b-lactamase-positive organisms (>50%) andpenicillin nonsusceptible S. pneumoniae(24%)with significantly altered penicil lin bindingproteins [10].

Amoxicill inclavulanate, also with a high-dose of the amoxicillin component, is recom-mended by the AAP/AAFP in cases of severeillness (moderate-to-severe otalgia or tempera-ture 39C in the preceding 24 h), after failedobservation in cases where the initial diagnosiswas uncertain and illness is severe, or after fail-ure to improve on amoxicillin after 4872 h oftherapy [1]. Given the increased prevalence ofresistant bacteria at day care centers, amoxicil-linclavulanate should be the first therapeuticchoice in the treatment of this patient population[91]. It has been shown to reduce the time to reso-lution of symptoms, reduce the overall symptomburden and reduce the rate of persistent signs ofacute infection on otoscopic examination, whencompared with placebo [107]. Amoxicillincla-vulanate is effective owing to its activity againstb-lactamase-producing H. influenzae andM. catarrhalis, but offers no additional cover-age against all strains of S. pneumoniaewhencompared with high-dose amoxicillin. Recentstudies reveal that amoxicillinclavulanate leadsto faster resolution of symptoms and signs ofacute infection on examination over placebo,

but can lead to more side effects, diarrhea beingthe most common [107,108]. A 10-day course ofhigh-dose amoxicillinclavulanate and a 3-daycourse of ceftriaxone are the only effective drugregimens that successfully eradicate resistantS. pneumoniaeand H. influenzae [10].

Macrolides such as azithromycin and clar-ithromycin are initial therapy options accord-ing to the 2004 treatment guidelines for patientswith mild illness and a history of type 1 allergyto penicillin [1]. They are not recommendedfor patients who are sensitive to penicillin or

who have suf fered a treatment failure with

amoxicillin, as macrolides have limited activityagainst nontypeable H. influenzae, and are onlyeffective against penicillin-susceptible strains ofS. pneumoniae [10]. Erythromycin is not an effec-tive option for AOM as pneumococcal resistanceis high [105,109].

The cephalosporins cefdinir, cefpodoxime andcefuroxime have been recommended as first-lineoral agents for patients with a non-type 1 peni-cillin allergy and mild illness [1]. They are effec-tive with penicillin-susceptible S. pneumoniae,have moderate effectiveness with penicillin-intermediate isolates and are ineffective withpenicillin-resistant isolates [10]. Unlike intra-venous or intramuscular ceftriaxone, they donot have adequate penetration to the middle earto eradicate penicillin-resistant S. pneumoniae,and their poor palatability can negatively affect

compliance [110]. With higher rates of antimi-crobial resistance, decreased effectiveness andpoor taste, oral cephalosporins should not beconsidered as a first-line agent for AOM unlessa patient has a mild illness with a history of anon-type 1 penicillin allergy. Resistance is likelyin patients who present with treatment failure ordisease recurrence, and therapy with these agentsin this setting is not recommended.

A single intramuscular dose of ceftriaxone,unlike the oral cephalosporins, provides highconcentrations in the middle ear for up to 48 h ata dose of 50 mg/kg. It is the choice of therapy forsevere illness in patients with a non-type 1 peni-cillin allergy, and in patients who have exhib-ited treatment failure with other antibiotics after4872 h [1]. The ideal dose duration of ceftriax-one is debatable. A single dose is approved by theUS FDA for treatment of AOM, but it has beensuggested that up to three doses 24 h apart isnecessary to eradicate disease [10,111]. Accordingto Leibovitz et al., 3 days of ceftriaxone is moreeffective for S. pneumoniae, while 1 day is effec-tive against H. influenzae [111].An alternativeto the three-dose regimen is to give the first

dose and observe for 48 h. If symptoms do notimprove and/or resolve, second and third dosescan be administered [112].

Trimethoprim-sulfamethoxazole (TMP-SMX) was used previously as second-line ther-apy for AOM, but high pneumococcal resistancecurrently exists against this agent [105,109]. If apatient fails therapy with high-dose amoxicil-lin, therapy with TMP-SMX should not be usedas resistant pneumococcal disease may exist. IfGAS infection is suspected, such as cases withTM perforation, TMP-SMX should not be

administered, as it is not effective against GAS.


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Although levofloxacin was not approved foruse in children, it was both safe and effective asan off-label therapy for children with high riskof recurrent or persistent AOM [113]. Althoughresistance is low (

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should be considered in select circumstances,(e.g., S. aureus) in patients with TTs [56,125]andGAS in cases with TM perforation. The clini-cian should recognize that a middle ear effusioncan persist for 3 months, and even up to 1 yearor longer in extreme cases [2]. A persistent middle

ear effusion after the resolution of acute symp-toms should not be considered a treatment fail-ure and should not be treated with antibiotics.

Recurrent AOM is defined as development ofthe signs and symptoms of AOM after the suc-cessful completion of antimicrobial therapy. Apatient must have acute signs and symptoms ofAOM, or it is likely that they only suf fer froma persistent sterile effusion. Recurrences withinthe first 2 weeks probably represent the samepathogen [103], while cases that recur within thesame month probably represent a new bacte-

rial organism [103,104]. Treatment for a recurrentinfection can follow the AAP/AAFP guidelinesfor a new infection if a new organism is sus-pected; however, for antibiotic coverage againstresistant organisms should be seriously consid-ered, and if possible, a culture of the middle eareffusion should be obtained.

A middle ear effusion, either associated withOME or AOM, can lead to either a persistentor temporary hearing loss. The hearing loss iscommonly conductive but can be sensorineu-ral in rare cases. The median loss of hearing isapproximately 25 dB, and it has been shownthat children with persistent effusions have lowertest scores for speech, language and cognitiveabilities [126].

TM perforation can occur with AOM. It is aresult of pressure from the middle ear effusionon the membrane leading to central ischemia,necrosis and subsequent perforation. S. pneu-moniae is the predominant organism identifiedfrom cultures of middle ear effusions in childrenwith spontaneous perforation [86,96], although itspredominance has slightly decreased since theintroduction of PCV7 [86]. Group A b-hemolytic

streptococci [83,86,96,127] and S. aureus [86] arealso commonly implicated in cases of sponta-neous perforation, with MRSA becoming thepredominant form of S. aureusidentified in thepost-PCV7 era [86]. These organisms should beconsidered when selecting antibacterial therapywhen AOM is complicated by perforation.

Extension of the middle ear infection of AOMinto nearby structures can lead to more seriouscomplications such as mastoiditis, labyrinthitisand petrositis. Intracranial complications such asmeningitis, epidural abscess, brain abscess, lateral

sinus thrombosis, cavernous sinus thrombosis,

subdural empyema and carotid artery thrombo-sis can occur [128,129]. These sequelae are rare indeveloped countries, but can been seen in popu-lations where access to care is limited.

Prevention of AOM

Prevention of AOM recurrence is important tolimit complications, healthcare costs and missedtime at work and school. Parental education, vac-cination, chemoprophylaxis and sometimes sur-gery can play a role in the prevention of AOMrecurrence [130133].

Clinicians are encouraged to educate parentsabout ways to reduce exposures in order to helpprevent AOM recurrence [1]. When applicable,the following risk factors can be discussed withparents [133]:

n Breastfeeding for at least 3 months canbe protective against AOM in the first yearof life;

n Day care use has a high correlation with recur-rent upper respiratory infections and recurrentAOM. While day care use is a necessity formany families, there may be selective instanceswhere day care use can be reduced to allow forfewer exposures;

n Children exposed to smoke are at risk forincreased AOM. Families should be remindedof the dangers of smoking and counseled

about preventing the exposure of theirchildren;

n Pacifier use after 6 months of age increases therisk of recurrence.

Immunization with the pneumococcal con-jugate vaccine and influenzae vaccine appearsto decrease the frequency of AOM, as well asthe need for TT placement. PCV7 has had areduction of up to 8% of infections in infants[134,135]. Culture confirmed cases of pneumococ-cal vaccine serotypes of AOM were decreased by

65%, physician visits for AOM decreased andthere was a small decrease in the number of TTsplaced by 3.5 years of age [134,136138]. Anotherstudy revealed an approximate 40% reduc-tion of TT placement by 45 years of age [139].Besides the protection from PCV7, which is nowreplaced by PCV13, children over 2 years of agewith recurrent AOM can receive an added ben-efit from the 23-valent pneumococcal conjugatevaccine.

The influenza vaccine offers a small ben-efit in decreasing the number of cases of cul-

ture-positive AOM with coexisting influenza


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infection [140]. Given the large number ofviral-mediated upper respiratory infectionspreceding AOM, it is not unexpected for theinfluenza vaccine to have a very small effecton the number of cases of AOM. Prevention ofAOM with existing and future vira l and bacte-

rial vaccines can help decrease disease burdenand consequences [101].

Chemoprophylaxis for AOM can be usefulin select circumstances. In the era of increasingantimicrobial resistance, prolonged chemopro-phylaxis can select for resistant bacteria withinthe nasopharynx [141,142]. Chemoprophylaxisreduces the occurrence of AOM and the totalnumber of AOM episodes [142], and can be ben-eficial for at risk populations [143]. The effects ofchemoprophylaxis do not persist after antibioticshave been discontinued, as children run the risk

of AOM recurrence [144]. There can be a smallbenefit of prophylaxis, but prolonged use shouldbe cautioned against to prevent the developmentof resistant organisms.

Myringotomy with TT placement aids withdraining middle ear fluid to allow for the heal-ing of middle ear mucosa. Although there areno exact criteria for the placement of TTs, itis agreed upon that patients should have hada minimum of three well-documented epi-sodes within 6 months or four episodes within12 months. TT placement has occurred withincreasing frequency as chemoprophylaxis hasfallen out of favor given concerns regarding thepromotion of resistant bacteria. TT placementhas a small decrease in AOM incidence [145], butis beneficial in allowing the drainage and healingof the middle ear cavity.

Other therapies with future considerationsfor prophylaxis against AOM have been stud-ied, including prophylaxis with xylitol gumand probiotics. Xylitol chewing gum and syruphave been shown to reduce the number of epi-sodes of AOM [11], with more recent reviewsreaffirming a possible role in AOM prophylaxis[146]. It appears that the pneumococcal capsulegene expression is altered in vitroby exposureto xylitol, possibly explaining the clinical effi-cacy in preventing AOM [147]. Probiotics havebeen shown to reduce the recurrence of AOM[148], but other studies have shown conflict-ing results, noting no change in recurrence oralteration in the nasopharyngeal carriage ofotitis pathogens in otitis-prone children [149].

Since a-hemolytic streptococci have beenshown to interfere with the growth of com-mon otopathogens within the nasopharynx, a

study was performed to determine if a sprayed

streptococcal solution would provide protec-tion over placebo in the prevention of AOMin otitis-prone patients [148]. This study of 108children showed promise for the preventionof AOM with the use of a streptococcal spray,as 42% of the children receiving the spray

remained healthy at their 3-month follow-up, compared with only 22% of children whoreceived placebo. However, the same group ofinvestigators showed no effect in treatment ofrecurrent otitis media and serous otitis media.This is a potential area for further investigationin the prevention of AOM.

Chronic suppurative otitis media

CSOM is typically defined as weeks to monthsof purulent otorrhea with the presence of perfo-ration. CSOM is almost always associated with

chronic mastoiditis. It is characterized by a pro-gression of otitis media to TM perforation andchronic suppuration. According to the WHO,it affects anywhere from 65 to 330 million indi-viduals worldwide, of which 60% have someresultant hearing loss [150]. Over 90% of casesare in the southeast Asia and western Pacificregions, Africa and the Pacific Rim. It is uncom-mon in the Americas, Europe, Austra lia and theMiddle East, but is still seen in select popula-tions, including indigenous and institutionalizedpopulations [150].

Predisposing factors

The etiology and risk factors for CSOM aremultifactorial and can vary based on the envi-ronment. Eustachian tube dysfunction underliesmost cases of CSOM in the developed world[151]. Other factors such as inadequate antimi-crobial therapy, frequent upper respiratory infec-tions, poor hygiene, poor nutrition and livingconditions, and decreased access to medicalcare can contribute to CSOM. TT placementcan also lead to CSOM and otorrhea is gener-ally accepted as the most common complication

of tube placement, occurring in approximately10% of cases [152]. The etiology of TT otorrheais thought to be from either chronic infectionfrom the indwelling tube or by allowing drain-age of a pre-existing chronic mucosal infection.The plastic tube allows bacteria to adhere to itssurface, as well as allowing the introductionof organisms from the external canal into themiddle ear.

Bacterial biofilms also have a recognized rolein CSOM. Biofilms occur on TTs, leading tochronic otorrhea, which resolves with removal

of the tube and antibiotic therapy. Biofilms may

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underlie CSOM even in the absence of TTs, asthey have been present in up to 60% of ears withCSOM and in up to 10% of noninfected ears[153]. Also, biofilm formation has been observedin patients undergoing middle ear/mastoid sur-gery for cholesteatoma [154]. They have been

observed on the adenoid pads of children withrecurrent otitis media and OME, suggestingthat biofilm formation on the adenoids may alsocontribute to chronic ear disease [155].

Microbiology of CSOM

The microbiology of chronic otitis media isoften characterized by polymicrobial infectionand involves a broader range of bacteria than inAOM. Pseudomonas aeruginosaand S. aureus arethe most common organisms; however, studiesthat employed methods for the recovery of anaero-

bic bacteria reported their recovery in only justover half of the infected ears. Because most studiesdo not evaluate for anaerobic bacteria, their rolein CSOM is under-reported. A review of 2254pediatric patients with CSOM in 20 studies thatutilized methods for recovery of anaerobic bacteriareported their isolation in 2971% of the patients.S. aureus and P. aeruginosawere the most prevalentaerobic isolates, and anaerobic Gram-positive cocciand anaerobic Gram-negative bacilli (includingpigmented Provotella and Porphyromonas spp.,Fusobacterium spp. and Bacteroides fragilis)werethe most common anaerobic organisms [156].

A study by Erkan et al.found aerobic bacteriain 89% of aspirates in CSOM with the most com-mon being P. aeruginosa, S. aureusand Klebsiellapneumoniaeand anaerobic bacteria, most com-monly Bacteroidesspecies [157]. Given these find-ings, it is important to obtain anaerobic cultures toadequately identify pathogenic bacteria in CSOM.

MRSA has an increasingly recognized role inCSOM. Park, et al., reported an increase in MRSAisolates in CSOM from 0.7% in 1998 to 11.4%in 2006, the majority of which was consideredto be community-acquired MRSA [158]. Yeo and

colleagues performed a multi-institutional studythroughout Korea looking at over 1000 patientswith CSOM and found P. aeruginosain 31.8% ofaspirates, MRSA in 24.2%,methicillin-sensitiveStaphylococcus aureusin 16.4% and coagulase-neg-ative Staphylococcusin 11.8% [159]. A more recentstudy by Lee et al.in 2008 looked at 1103 patientswith CSOM with and without cholesteatoma andfound P. aeruginosaand MRSA to be the mostcommonly isolated species each occurring in26% of patients, followed by methicillin-sensitiveStaphylococcus aureus(19.3%), coagulase-negative

Staphylococcus(13.0%) andProvidencia(2.2%).

They did not note any significant differencein bacterial isolation between CSOM with orwithout cholesteatoma [160].

The high incidence of P. aeruginosain CSOMmay be overestimated in studies where culturesare not taken directly from the middle ear.

Bacteria present in the external ear canal maynot be present in the middle ear and vice versa[96]. As P. aeruginosacommonly colonizes theear canal, cultures from otorrhea within the earcanal may reveal P. aeruginosa,even if it is notthe true pathogenic bacteria in the middle ear[161]. Therefore, direct middle ear space aspira-tion through a TM perforation is the preferredmethod of accurately sampling otorrhea.

The pathogens found in post-tympanos-tomy otorrhea can vary significantly, rangingfrom upper respiratory pathogens commonly

encountered in AOM such as S. pneumoniae,H. influenza andM. catarrhalis,to more chronicpathogens such as P. aeruginosaand S. aureusand anaerobes such as Peptostreptococcus sp.,Bacteroides sp. and Prevotellasp. [162165]. Upperrespiratory pathogens tend to be more commonin the otorrhea of younger children, with P. aeru-ginosaand S. aureusoccurring more commonlyin children age 6 years and over [165].

Fungi can also contribute to CSOM, occur-ring in less than 5% of cases [159]. Tuberculousotitis media is a rare cause of CSOM, accountingfor less than 1% of cases, but should be consid-ered in at-risk patients not responding to typicaltherapy [166].

Diagnosis of CSOM

A history of persistent otorrhea or recurrent otor-rhea accompanied by upper respiratory symp-toms is suggestive of CSOM. Patients typicallypresent with painless, mucoid and sometimesfoul-smelling otorrhea without fever, except inthe case of intracranial complication or concur-rent otitis externa. Otalgia is more often seenwith AOM or otitis externa and is less suggestive

of CSOM. As both AOM and otitis externa mayresult in otorrhea, the diagnosis of CSOM byotoscopy relies on the presence of a TM perfora-tion with associated drainage. This may requirecleaning of debris from the external ear canal tovisualize the entire TM, as well as the exposedmiddle ear mucosa. Examination will typicallyreveal thick mucoid fluid, a perforated TM andgranulation tissue. The presence of keratin debrisshould raise suspicion of a cholesteatoma. In thecase that cholesteatoma is suspected, a tempo-ral bone CT scan can help delineate any bony

erosion and the extent of the cholesteatoma.


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Treatment

Topical therapy

The mainstay of treatment in CSOM is topicaltherapy. It has been consistently shown that topi-cal therapy is superior to systemic therapy aloneand systemic therapy in combination with topi-

cal therapy may not be more effective than topi-cal therapy alone [150,167,168]. Fluoroquinolonedrops are preferentially used, given their activ-ity against the common pathogens in CSOMand lack of ototoxicity. A Cochrane review per-formed in 2000 found that topical quinoloneswere more effective than nonquinolone topicalagents [168]. It has been observed that just over50% of P. aeruginosaisolates were sensitive tociprofloxacin and approximately 44% weresensitive to levofloxacin [160]. This susceptibil-ity may be even greater in vivowhen the drops

are applied directly to the middle ear. Topicalcorticosteroids can also help reduce granula-tion and edema in the middle ear and are oftenused in conjunction with a fluoroquinolone.Approximately 80% of patients treated achieveda clinical cure at 14 days, and all patients achievea clinical cure at 21 days on ciprofloxacin plushydrocortisone [169]. Topical aminoglycosidepreparations such as gentamicin, tobramycinand neomycin may be effective in the treatmentof CSOM, but have ototoxic effects even whenapplied topically. The risks of potentially oto-toxic medications must be weighed against thebenefits, and when used, their duration shouldbe limited.

In order for topical therapy to be effectiveit must reach the middle ear; therefore, ceru-men and debris within in the ear canal must beremoved prior to instillation. Irrigation of the earwith half-strength acetic acid or betadine prior tothe initiation of topical antibiotic drops can helpthe antibiotic reach the middle ear, in additionto providing aural toilet [151]. Maneuvers such asstraightening the pinna and tragal pumping mayalso improve delivery [170]. Topical medications

in powder form, such as boric acid, chloram-phenical, amphotericin and sulfamethoxazole,may be introduced into the ear by insufflationand can create an environment that is resistantto bacterial and fungal growth [151,152].

Systemic therapy

Oral antibiotics are not first-line therapy forCSOM but may be considered as an adjunct to top-ical therapy when CSOM is refractory, when thereis evidence of systemic disease/infection or withimmunocompromised patients. Although culture-

driven antibiotic therapy is ideal, empiric treatment

is indicated when cultures are not available or notpossible. Fluoroquinolones are often used as first-line systemic therapy, given their antipseudomonalactivity. Treatments effective against anaerobicbacteria include clindamycin, metronidazole plus amacrolide and amoxicillinclavulanic acid. TMP-

SMX and clindamycin are an effective choicewhen community-acquired MRSA infection issuspected [158].

Parenteral antibiotics are reserved for cases ofCSOM without cholesteatoma that fail aggressivemedical therapy. Therapy for up to 68 weeksis indicated in these cases [152]. Culture-drivenantibiotic therapy is important for appropriate,effective treatment. When P. aeruginosais act-ing as a middle ear pathogen it can be treatedwith cefepime, ceftazidime, fluoroquinolones oraminoglycosides. Carbapenem and imipenem

will cover most organisms of CSOM, includinganaerobes. Vancomycin and linezolid are usefulin the parenteral treatment of MRSA CSOM.

Surgical therapy

Surgery for CSOM in the absence of choles-teatoma may be performed as an alternative toantibiotics when other therapy has failed. Whena cholesteatoma is present, it requires surgicalremoval, with both topical antibiotic and ste-roid therapy commonly used prior to surgery todecrease inflammation. When otorrhea is pres-ent in the setting of TTs, tube removal shouldbe considered if otorrhea persists longer than6 weeks with treatment. Often this will allevi-ate the problem, but if the otorrhea persists, thenfurther medical therapy must be pursued.

Complications

Complications of CSOM include both conduc-tive and sensorineural hearing loss, mastoiditis,cholesteatoma, facial nerve palsy and labyrinthinefistula. Intracranial complications are seen less fre-quently than in AOM, but do occur and includemeningitis, brain abscess, lateral sinus thrombosis,

otic hydrocephalus and cavernous sinus thrombo-sis [171]. Petrositis and Gradenigo syndrome, char-acterized by facial/retro-orbital pain, otitis mediaand ipsilateral abducens nerve palsy, can occurwhen infection tracts into the petrous apex [152].

Surgical treatment of otitis media

Otitis media resolves in most cases with con-servative management, supportive care or anti-bacterial therapy. Surgical treatment is typicallyreserved for the cases not responding to medicaltherapy and/or associated with their complica-

tions, such as acute mastoiditis, facial paralysis,

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epidural abscess, sigmoid sinus thrombosis,petrositis, suppurative labyrinthitis and otitichydrocephalus [172,173].

Myringotomy & tympanocentesis

A myringotomy, making a small incision in TM,

or tympanocentesis, drainage of middle ear effu-sion after making a small puncture of TM witha small-gauge needle, are indicated for cases ofAOM with a thickened bulging TM, severe pain,fever and mastoid tenderness. This is also indi-cated in persisting and recurring otitis media thatdoes not respond to antibacterial therapy. Otitismedia cases involving neonates and immuno-compromised individuals should undergo theseprocedures, as they are predisposed to atypi-cal microorganisms such as Listeria, Group BStreptococcus and fungi [174]. As the incidence of

penicillin resistant S. pneumoniaeand MRSAhas increased in otitis media, acquisition ofmiddle ear fluid for culture by a myringotomy isbecoming more important as a guide for propertreatment of recalcitrant otitis media [175177].

A myringotomy is performed to provide drain-age and obtain middle effusion for culture. It isperformed by making an incision in the inferiorpart of the TM, away from the important middleear structures such the stapes and jugular bulb.It usually well tolerated and a myringotomy sitecloses spontaneously in a few days.

There is no place for myringotomy withoutTT treatment when treating OME.

Insertion of tympanic tube placement

Insertion of a TT is the most common opera-tion performed in children. The TT ventilatesthe middle ear and equalizes the middle earpressure to atomospheric pressure. The indica-tions for TT placement depends on laterality(unilateral vs bilateral), duration of middle eareffusion, severity of associated symptoms, devel-opment risks for speech, language and learningproblems, and structural damage to the TM or

middle ear from chronic Eustachian tube dys-function [2]. Ultimately, the decision to performthe surgery must be individualized. CurrentlyTT placement is indicated in the cases of:

n Chronic OME unresponsive to antibiotictreatment, lasting for at least 3 months whenbilateral or 6 months when unilateral;

n Recurrent AOM with incidence of three ormore during the previous 6 months or four ormore attacks during the previous year;

n Presence of suppurative complications;

n Eustachian tube dysfunction with severeretraction pocket;

n Craniofacial anomalies predisposed to chronicEustachian tube dysfunction;

n Barotrauma associated with trauma or hyper-

baric oxygen therapy.

The major differences between the types ofear tubes that are available for placement are thelumens size, length and expected retention time.Currently, single-flanged tubes are commonlyused. They will stay in place longer comparedwith double-flanged grommets but shorter thanT-tubes.

In general, the short grommet tube extrudessooner than the longer T-shaped tubes. Thelarger the tubes bore, the longer it stays in place,

although it is more likely to result in a persistentperforation of the TM.The most common complication of TT is otor-

rhea. This can be due to bacterial contaminationof the middle ear by water-borne organisms, oracute or recurrent otitis media. In young childrenunder the age of 3 years, the organisms isolatedfrom the otorrhea are usually similar to thosecausing AOM; however, H. influenzaeis morecommonly isolated than S. pneumoniae[164]. Inolder children, Pseudomonasand Staphylococcusare more commonly recovered.

The treatment of otorrhea usually requirestopical antibiotic otic drops. In recalcitrantcases of otorrhea, the tube is removed. TMperforations are seen in 2% of children afterplacement of short-term (grommet-type) tubesand in up to 17% after long-term T-tubes [178].Approximately 2050% of children who hadTT will redevelop recurrent OME requiringanother set of TT placement [179]. If subsequentsurgery is necessary, adenoidectomy is typicallyalso recommended [180,181].

Adeneoidectomy and/or tonsillectomy

Adenoidectomy was once the primary surgicaltreatment of children with OME. However,since the 1960s, adenoidectomy has been per-formed far less often because of the successof TT [182]. Several prospective, randomizedclinical trials have shown that adenoidectomyis an effective treatment for OME and that itseffect is independent of the size of the adenoid[181,183]. Adenoidectomy is usually recommendedfor recurrent TT cases where the patient is overthe age of 4 years, but not at the time of theinitial placement of TT unless there are other

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adenoiditis, postnasal obstruction or chronicsinusitis. Currently, the efficacy of adenoidec-tomy for OME in children less than 4 years oldremains limited; however, the benefit of adenoid-ectomy can be found as early as 2 years old [180].

Adenoidectomy has a 0.2 0.5% incidence

of hemorrhage and 2% incidence of transientvelopharyngeal insufficiency [180,184]. The riskof other rare but debilitating risks of adenoid-ectomy, such as nasopharyngeal stenosis andpersistent velopharyngeal insufficiency, can beminimized with appropriate patient selectionand surgical technique.

Mastoidectomy

An acute suppurative otitis media that fails torespond to antibiotic therapy may proceed to amastoiditis. Several studies have reported the

rising incidence of suppurative complicationsof AOM, such as a mastoidits and subperiostealabscess, possibly due to increased prevalenceof antibiotic-resistant bacteria [129,177]. Othercomplications associated with acute suppurativeotitis media include facial paralysis, petrositis,epidural and intradural abscess, sigmoid sinusthrombosis, petrositis, suppurative labyrinthi-tis and otitic hydrocephalus. In the presenceof these complications, a cortical mastoidec-tomy is commonly performed in addition to amyrigotomy with TT placement.

Acute mastoiditi s is clas sif ied as eithernoncoalescent or coalescent, representing acontinuum of the disease process. Currently,noncoalescent mastoiditis is found more oftenthan coalescent, which led to the current lowfrequency of cortical mastoidectomy comparedwith the preantibiotic era. Coalescent mastoid-itis is manifested as destruction of mastoid aircell bony trabeculae or cortex and may notadequately respond to antibiotic therapy, lead-ing to other serious complications [172,173] . Acortical mastoidectomy is usually required fortreatment of coalescent mastoiditis. The bony

erosion of the mastoid in coalescent mastoid-itis can be demonstrated radiographically bycomputed tomography. For acute noncoalescentmastoiditis, a trial of antibiotics and myringot-omy without mastoidectomy is usually recom-mended unless there is no improvement within48 h of medical therapy.

When otitis media is severe and continues for sev-eral weeks, the middle ear mucosa and perisoteumbecome hypervascular and edematous and, subse-quently, obstruct the free drainage of mucopurulentsecretions from the mastoid cavity. The purulent

exudates under pressure in the mastoid combined

with severe inflammatory reaction result in resorp-tion of mastoid air cell bony trabeculae by demin-eralization and osteroclastic activity [173]. As a result,the mastoid air cells coalesce into the larger cavitiesfilled with purulent exudates and granulations. Acortical mastoidectomy involves removal of the lat-

eral cortex of the mastoid cavity using an otologicdrill. A mastoidectomy is performed to evacuatethe trapped infectious and granulation materials toreverse the demineralization process and osteoclas-tic activity. In addition, any obstructing granulationtissue and adhesions should be carefully removed tore-establish the normal drainage pathway, especiallyin the epitympanum and antrum.

The bony erosion from coalescent mastoiditisalso can progress into the thicker outer mastoidcortex and the bony plate over the sigmoid sinusand the posterior and middle fossa dura. This

destructive process can lead to serious complica-tions such as postauricular subperiosteal abscess,Bezolds abscess extending from the mastoid tipto neck, extradural and intradural abscess andsigmoid thrombophlebitis. In a case of postauric-ular subperiosteal abscess and Bezolds abscess,a surgical incision and drainage procedure anda cortical mastoidectomy are necessary. Theseprocedures can be performed as a single-stageprocedure, although some prefer an incision anddrainage first to allow the acutely infected ear tosubside, followed by a cortical mastoidectomy ata later date. When sigmoid sinus thrombophle-bitis is suspected, the bony sinus plate over thesigmoid sinus is removed to expose the granula-tion over the sinus until normal-appearing sinuswall and posterior fossa dura are reached.

Suppurative otitis media can also spread fromthe tympanic and mastoid mucosa to the jugularbulb, sigmoid sinus, dura, brain and facial nerveby propagating infectious thrombophlebitis ofvenules [172]. This process can result in complica-tions such as sinus thrombophlebitis, intraduraland intracerebral abscess and facial nerve palsy.Certain strains of streptococci and pneumococci

are more likely to cause complication by throm-bophlebitic extension than other types of organ-ism [185,186]. A cortical mastoidectomy with TTplacement is often required to obtain a culture,evacuate the infectious granulation tissue, andre-establish normal drainage and aeration of themastoid cavity.

Drainage of petrositis

Petrositis, a rare complication of otitis media,occurs when the inflammation process extendsto the pneumatized petrous apex air cells

[172,187]. The characteristic clinical presentation

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is retro-orbital pain. The classic symptoms ofGradenigos syndrome include retro-orbitalpain, abduscent cranial nerve palsy and ipsi-lateral otitis media. The treatment includesmyringotomy and TT placement for drainageof middle ear infection and obtaining middle

ear fluid for a culture. It can also require drain-age of the collection of purulent material fromthe petrous apex and aeration of the area. Thereare several available approaches for draining thepetrosus apex, which depend upon the pneu-matization patterns as determined by a high-resolution CT scan. The most commonly usedsurgical approaches to the petrous apex are theinfracochlear approach below the cochlear andthe infralabyrinthine approach below the pos-terior semicircular canal and above the jugularbulb. For recalcitrant cases, the circumferential

petrosectomy might be necessary to debridethe infected bone, in addition to long-termintravenous antibiotic therapy [187].

Surgery for cholesteatoma

Cholesteatoma is a cyst-like growth lined withkeratinizing squamous epithelium and filledwith desquamating debris, usually found in themiddle ear and mastoid. Cholesteatoma canbe classified as congenital and acquired [188].Acquired cholesteatoma is commonly associ-ated with a history of recurrent otologic infec-tions and Eustachian tube dysfunction. Themost commonly presenting symptoms includepainless otorrhea and hearing loss. Otalgia, ver-tigo and facial nerve palsy occur less frequently,but can be observed with an acute infectionor with serious complications similar to acutemastoiditis.

Surgical treatment is the standard of carefor cholesteatoma [188,189] . The goals of surgeryinclude complete removal of the cholesteatomaand its associated infection, reconstruction ofTM and ossicles to optimize hearing results, andprevention of recurrent disease. There are three

basic operations commonly used to managecholesteatoma [190,191]:

n Tympanoplasty;

n Canal wall-up (CWU) tympanomastoidectomy

n Canal wall-down (CWD) tympanomastoid-ectomy.

A choles teatoma ar ising from a TM per-foration will demonstrate growth of squa-mous epithelium medially to the perforation

into the middle ear space and possibly the

mastoid. When cholestatoma is limited to themiddle ear, a tympanoplasty is indicated toremove the cholesteatoma and repair the TMperforation.

For cholesteatoma arising from a retractionpocket of the epitympanum or mesotympa-

num, a tympanomastoidectomy, most com-monly via a postauricular approach, is typicallyrecommended to remove the cholesteatomaand reconstruct the ossicular chain, if indi-cated. A tympanomeatal flap is elevated, themiddle ear space is entered via the ear canaland the middle ear portion of the cholestatomais removed. Since acquired cholesteatoma com-monly extend to the epitympanum, antrumand mastoid cavity, a cortical mastoidectomy isperformed to remove the disease from the mas-toid side. In a CWU tympanomastoidectomy,

the bony ear canal is kept intact while thecholesteatoma is removed. In more extensivecholesteatoma cases in the presence of chronicEustachian tube dysfunction, a CWD tympa-nomastoid is recommended, and the posteriorand superior ear canal is removed to open up themastoid cavity to the ear cana l. CWU versusCWD tympanomastoidectomy remains a mat-ter of controversy, surgeon choice and extent ofdisease [188,190,191] . Cholesteatoma commonlyerodes the ossicular chain, especially theincudostapedial joint. Once eroded, optionsfor reconstructing the ossicular chain includeautologous (incus interposition) and manyalloplastic materials, including hydroxyapatite,Teflonand titanium.

Overall, residual or recurrent cholesteatoma isreported in approximately a third of cases [188].Frequently, CWU mastoidectomy operationsrequire a staged second exploration to elimi-nate any residual cholesteatoma, and ossicularchain reconstruction can be performed at thissecond stage. Patients undergoing CWU tym-panomastoidectomy must be followed regularlyto detect recurrences. Those with CWD tym-

panomastoidectomy must be followed regularlyfor mastoid bowl cleaning every 612 months inorder to prevent mastoid cavity otorrhea. Withthe mastoid cavity exteriorized, risk of recurrentdisease is lower than in CWU procedures.

Future perspective

The treatment of otitis media and its complica-tions remains challenging as the microbiologyof the infection continues to evolve. This is dueto the effects of vaccination against the majorAOM pathogens and the overuse of antimicro-

bials. The introduction of the new PCV13 and


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the planned introduction of a vaccine elicitingimmunity against nontypable H. influenzae [192]are expected to generate changes in nasopharyn-geal colonization and subsequent upper respira-tory infections, including otitis media. Thesechanges may also alter the rate of MRSA colo-

nization and infection. The use of these vaccinesworldwide would help reduce global morbidityin children.

Further studies for the prevention of earinfections should be continued. These includeexploring the role of xylitol gum in preventingAOM, as well as the use ofa-hemolytic strepto-cocci and other potential interfering bacteria toprevent the growth of otitis-causing organismswithin the nasopharynx.

The continuous change in the microbiol-ogy and antimicrobial susceptibility of the

pathogens causing ear infections requiresongoing monitoring and surveillance. Becauseof regional differences that are affected bynumerous factors, such as antimicrobial use,prevalence of day care center attendance, com-munity antibiotic use, weather and race, thesestudies should be performed in major citiesaround the world.

The effect of the introduction of the watch-ful waiting approach has to be further studiedand the guidelines of when and how to use itmay need further investigation and refinement.Although this approach was recommendedalmost a decade ago, it is still not universally

accepted by all clinicians.The inappropriate use of antimicrobials

must be reduced, with appropriate therapy tar-geted based on the accurate clinical diagnosisof infection. Given the requirement of botha middle ear effusion and acute symptoms todiagnosis AOM, it is imperative that a clinicianis skilled with an otoscope to accurately makethe diagnosis.

There is a need to continuously educate cli-nicians in the judicial use of antimicrobials toprevent treatment failure and development of

bacterial resistance.As antimicrobial resistance is on the increase,it is hopeful that newer agents effective againstpotential pathogens will be developed. Studyingavailable agents such as the fluoroquinolones inthe treatment of otitis media in children is alsowarranted. This is to ensure efficacy, as well assafety, in pediatric patients.

Executive summary

Bacterial strains isolated from the middle ear aspirates of cases of acute otitis media have changed after pneumococcal

conjugate vaccine 7

n There have been increases in Streptococcus pneumoniaeserotypes 19A, 6C, 22F, 15 and 33.

n Multidrug-resistant serotypes such as 19A have become a concern, and are included in the new pneumococcal conjugate vaccine 1

Acute otitis media caused by Haemophilus influenzaehas increased after pneumococcal conjugate vaccine 7 introductio

n Hib vaccination has not affected rates of Haemophilus influenzaeacute otitis media (AOM) as most are nontypeable strains.

n This is most often associated with conjunctivitis, bilateral AOM, previous antibiotic treatment and recurrent disease.

n Up to half of strains are b-lactamase producers.

Antibiotic selection is important for the eradication of bacteria within the middle ear

n Amoxicillinclavulanate and ceftriaxone are the most effective against penicillin-resistant pneumococcus and b-lactamase producin

organisms.

n Trimethoprim-sulfamethoxazole is ineffective against resistant pneumococcus and group A streptococcus.

n Macrolides are ineffective against resistant organisms.

n Clindamycin can be effective for pneumococcus, but provides no coverage against Gram-negative organisms.

Further studies for AOM prevention would be beneficial

n Exploring the role of xylitol gum in preventing AOM.

n Use of a-hemolytic streptococci to prevent the growth of otitis-causing organisms within the nasopharynx.

n Introduction of vaccination eliciting immunity against nontypeable H. influenzae.

Ongoing surveillance of the AOM-causing bacteria after pneumococcal conjugate vaccine 13 is required

n Chronic suppurative otitis media incorporates a broader scope of organisms than AOM.

n Pseudomonasand Staphylococcus aureusare the most common.

n Anaerobic Gram-positive and Gram-negative organisms are likely under-reported and underdiagnosed.

Surgical treatment is reserved for cases not responsive to medical therapy, or in cases of disease complication

n Complications such as mastoiditis, facial paralysis, epidural abscess, sigmoid sinus thrombosis, petrositis, suppurative labyrinthitis an

otitic hydrocephalus require surgical intervention.

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ReferencesPapers of special note have been highlighted as:nof interestnn of considerable interest

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Disclaimer

The views expressed in this article are those of

the authors and do not necessarily reflect the

official policy or position of the US Department

of the Navy, nor the US Government.

Financial & competing interests

disclosure

The authors have no relevant affiliations or

financial involvement with any organization or

entity with a financial interest in or financial

conflict with the subject matter or materials dis-

cussed in the manuscript. This includes employ-

ment, consultancies, honoraria, stock ownership

or options, expert testimony, grants or patents

received or pending, or royalties.

No writing assistance was utilized in the

production of this manuscript.


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