International Journal of Pediatric Otorhinolaryngology 116 (2019) 173–176

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International Journal of Pediatric Otorhinolaryngology

journal homepage: www.elsevier.com/locate/ijporl

Characteristics of children with refractory acute otitis media treated at the T

pediatric emergency department
Jacob Pitaro∗, Sofia Waissbluth, Marie-Claude Quintal, Anthony Abela, Annie Lapointe
Department of Pediatric Otolaryngology - Head and Neck Surgery, Université de Montréal, Centre Hospitalier Universitaire Sainte-Justine, 3175 Côte Sainte-Catherine,
Montréal, Québec, H3T 1C5, Canada

ARTICLE INFO ABSTRACT

Keywords: Introduction: Refractory acute otitis media (rAOM) is defined as the persistence of signs and symptoms of AOM
Refractory acute otitis media for more than 48 to 72 hours after the initiation of antibiotic treatment. These patients are often referred to the
pediatric emergency department (PED). We sought to study rAOM cases referred to our PED, and to evaluate
their clinical characteristics and response to our local management guidelines.
Methods: A retrospective chart review of all children treated for rAOM between 1/2012-3/2014 was performed.
Data recorded included demographics, clinical presentation, antibiotic treatments, need for surgery, and culture
results.
Results: A total of 255 patients were included with a mean age of 19 months. Prior to admission, all the children
had received at least one course of antibiotics. Amoxicillin was the most common first-line antibiotic prescribed
while amoxicillin-clavulanic acid was the most common second and third-line antibiotic given. Intravenous
ceftriaxone was the treatment administered at the PED. Myringotomy and pressure equalizing tube (PET) in-
sertion were required in 60% of cases. Middle ear cultures (55 ears) were positive for Streptococcus pneumoniae in
two, and Moraxella catarrhalis in only one culture. There were no differences between the mean age of children
who had PET insertion and those who did not with regards to fever, rhinorrhea, and preschool or school at-
tendance. Children presenting with otorrhea were less likely to undergo surgery (P = 0.013).
Conclusions: This is the first study evaluating the established local practice guideline with regards to clinical
characteristics and need for surgical management. We showed that myringotomy and PET insertion due to
antibiotic failure is commonly performed for cases of rAOM. The majority of the middle ear cultures were sterile.

1. Introduction
Acute otitis media (AOM) is a common cause of office and emer-
gency department visits, antibiotics prescription, and surgical proce-
dures in children [1]. By one year of age, approximately 60% of chil-
dren will experience at least one episode of AOM, and by the age of
three, about 80% [2,3]. The peak incidence for AOM occurs between 6
and 12 months of age, and a second (but lower) peak occurs between
the ages of 4 and 5 years [2]. The most common causative organisms for
AOM are bacteria: Streptococcus pneumoniae (SP), non-typeable Hae-
mophilus influenza (HI), and Moraxella catarrhalis (MC) [4–6]. Viruses as
the sole pathogen account for approximately 20% of AOM episodes [7].
Current clinical guidelines for the treatment of AOM recommend anti-
biotic therapy, however, considering the age of the patient and clinical
findings, the possibility of watchful waiting and close follow-up can be
considered in certain situations [8]. The guidelines also recommend
treatment with amoxicillin or amoxicillin-clavulanate as the first-line of
treatment and amoxicillin-clavulanate or ceftriaxone as the second-line
treatment. When various courses of antibiotics have been prescribed
and there is no clinical improvement, a tympanocentesis should be
considered and middle-ear fluid (MEF) sent for bacterial culture and
antibiotic sensitivity [8].
Refractory acute otitis media (rAOM) is defined as persistence of
signs and symptoms of AOM for more than 48–72 h following an initial
antibiotic treatment, or clinical relapse within one month of being
treated for AOM with antibiotics. Reasons for treatment failure include
treatment noncompliance, concurrent viral infections and bacterial re-
sistance. Many countries have already implemented the use of the

Abbreviations: AOM, acute otitis media; rAOM, refractory acute otitis media; PED, pediatric emergency department; MEF, middle-ear fluid; SP, Streptococcus
pneumoniae; HI, Haemophilus influenza; MC, Moraxella catarrhalis; PCV, pneumococcal conjugated vaccine; TM, tympanic membrane
∗
Corresponding author.
E-mail addresses: pitarojacob@gmail.com, pitaroj@asaf.health.gov.il (J. Pitaro).

https://doi.org/10.1016/j.ijporl.2018.10.045
Received 29 May 2018; Received in revised form 31 July 2018; Accepted 28 October 2018
Available online 31 October 2018
0165-5876/ © 2018 Elsevier B.V. All rights reserved.
J. Pitaro et al. International Journal of Pediatric Otorhinolaryngology 116 (2019) 173–176

pneumococcal conjugated vaccines (PCVs) for children, and various Table 1

studies have described a shift in pathogens and SP strains causing AOM Demographics for patients with rAOM consulting at the pe-
[9]. In Quebec, Canada, PCV has been part of the province im- diatric emergency department.
munization program since 2004, and currently the PCV-13 is being Patients No. (%)
administered to all children [10].
Since 2004, our institution has implemented a clinical practice Total 255
Age (months)
guideline for the treatment of children with rAOM consulting to the
Range 3–77
pediatric emergency department (PED), which was developed by a Mean ± SD 19 ± 11.2
multidisciplinary team [11]. The objective of the present study was to Median 15
review cases of rAOM treated at our PED according to the local pro- Gender
Male 151 (59)
tocol, and to study their clinical characteristics, culture results, and
Female 104 (41)
response to treatment. Immunization up to datea 237 (93)
Attends preschool/school 219 (86)
2. Materials and methods Myringotomy and PET 152 (60)
No surgery 99 (39)
Refractory AOM on PETs 4 (1)
2.1. Patients
a
Having received all of the vaccines included in the child-
Following approval by the local institutional review board, we hood immunization program of Quebec, according to age.
performed a retrospective chart review of all children treated for rAOM
at Centre Hospitalier Universitaire Sainte-Justine, a 350-bed tertiary Tukey's honest significant difference post hoc testing. P value < 0.05
care pediatric centre in Montreal, Canada, between January 2012 and was considered statistically significant. The student T-test was used to
March 2014. The local practice guideline was initiated in 2003, how- evaluate age differences between the group of children requiring sur-
ever, the pneumococcal vaccine is part of the immunization program in gery and the group that did not. Statistical analysis was performed
Quebec since 2004 (PCV-7), and the vaccines administered have using the GraphPad Prism software (GraphPad Prism statistics for
changed with time, with the PHiD-CV vaccine being administered in Windows, version 7.03).
2009 and then the PCV-13 in 2011 [10]. It was therefore decided to
begin the study one year following the latest vaccine at that time. Only 3. Results
children who were referred to the PED due to failure to previous anti-
biotic treatments were included. Children who were referred to the PED A total of 255 patients with a mean age of 19 months (range: 3–77)
due to other reasons and were primarily diagnosed with AOM were were included. There was a slight male predominance (n = 151, 59%).
excluded. Data recorded and analyzed included age, gender, clinical Patient demographics are summarized in Table 1 and age distribution
presentation, previous antibiotic treatments, need for surgery and MEF in Fig. 1. Clinically, patients presented with fever (96.9%), rhinorrhea
culture results. (80.4%), otalgia (55.7%), and otorrhea (37.3%). Ninety-eight children
(37%) had a history of recurrent AOM (mean = 4 episodes). Other as-
2.2. Local practice guidelines sociated medical conditions are summarized in Fig. 2. Concurrent in-
fections include bronchiolitis (8%), pneumonia (2%), and pyelone-
Clinical presentation for rAOM was defined as: (1) otoscopic find- phritis (2%).
ings compatible with AOM; and (2) (a) persistence of symptoms of AOM Prior to admission to the PED, all the children had received at least
for more than 48–72 h after initiation of antibiotics, or (b) clinical re- one course of antibiotics. Amoxicillin was the most common first-line
lapse within the month after an episode of AOM treated with anti- antibiotic prescribed in 70% of the children, amoxicillin-clavulanic acid
biotics. For patients who had already received high dose amoxicillin- was the most common second-line and third-line (in this case, amox-
clavulanate treatment, intravenous (IV) or intramuscular (IM) cef- icillin-clavulanic acid was repeated) antibiotic given in 44% and 49%,
triaxone (50 mg/kg/day for 3 days; maximum: 2g/day) was re- respectively. Patients received on average 8.4 days of amoxicillin
commended [11]. If no response was observed following 3 days of (range 1–14 days), and 8.7 days of amoxicillin-clavulanic acid (range
ceftriaxone treatment, myringotomy with pressure equalizing tube 4–10 days). Fifty two percent of the children had received two courses
(PET) insertion and obtaining MEF for culture was offered to the par- of antibiotics before consulting, while 32% had received three courses
ents. The local guideline was developed by the departments of otorhi- of antibiotics.
nolaryngology, infectious diseases and pediatrics at our institution, and There was no significant difference between the mean age of
are in line with the American Academy of Pediatrics guidelines on the
diagnosis and management of acute otitis media [8].

2.3. Sample collection

When surgical intervention was required, the parents’ consent was

obtained, and myringotomy and PET insertion were performed under
general anesthesia. Myringotomy was performed in the anterior inferior
quadrant, and MEF was collected using either a designated sterile
cotton swab or a suction-assisted collecting tube. In patients with
otorrhea, fluid was obtained directly from the external auditory canal
or through an existing tympanic membrane perforation under micro-
scopic visualization. All samples were delivered to the microbiology
laboratory for processing within 24–48 h.

2.4. Statistical analysis Fig. 1. Age distribution for patients presenting with rAOM at the pediatric
emergency department.
Analyses were performed with analysis of variance followed by * statistically significant difference.

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J. Pitaro et al. International Journal of Pediatric Otorhinolaryngology 116 (2019) 173–176

Fig. 2. Associated medical conditions for children presenting with rAOM.

Table 2 Fig. 3. Middle-ear fluid aerobic bacterial culture results.

Comparison by age between children requiring surgery and children that did
not require surgery. guidelines (amoxicillin with or without clavulanate) was prescribed to
M & PET (Mean No surgery (Mean P-value the majority of the children before consulting at the PED. Amoxicillin
age ± SD) age ± SD) was the most common first-line antibiotic, and amoxicillin-clavulanate
the most common second-line antibiotic; in accordance with the pub-
Fever 17.1 ± 8.5 19.5 ± 12.6 0.076
Rhinorrhea 17.2 ± 10.1 18.5 ± 10.3 0.395 lished clinical guidelines [8]. A recently published study showed that
Otorrhea 16.0 ± 8.5 29.6 ± 24.7 0.013 the susceptibility of SP strains to penicillin has significantly increased in
Attends preschool/ 17.8 ± 9.5 20.5 ± 13.1 0.092 the post-PCV era as compared to the pre-vaccine era, a fact that sup-
school ports the use of amoxicillin as the first-line treatment in AOM [12].
Failure of antibiotic treatment in AOM has been attributed to different
M: myringotomy; PET: pressure equalizing tubes; SD: standard deviation.
factors including inappropriate antibiotic use or dosage, bacterial re-
sistance, concomitant viral infections, and the formation of biofilms
children who underwent surgical intervention and those who did not
[13].
with regards to fever, rhinorrhea, and preschool or school attendance
Ruohola et al. examined the MEF cultures obtained from 79 children
(Table 2). Children presenting with otorrhea were less likely to undergo
presenting with otorrhea through PETs. They observed that in 66% of
surgery (P = 0.013) (Table 2). Ceftriaxone IV was given as the first-line
the cultures, both bacteria and viruses were found; only 4% presented
treatment as described in the local practice guideline (mean dura-
with a sole viral pathogen. Picornaviruses were the most common
tion = 2.5 days). In 60% of the children, the 3 doses of ceftriaxone were
viruses isolated, and contrary to the present study, bacteria were found
administered. However, in 31% of children, two doses were given, and
in 92% of the cases. They also observed that 70% of the MEF obtained
in 9% one dose was given before requiring the myringotomy and PET
were positive for respiratory viruses [14]. In our series, four of the
insertion. These patients did not complete the three-day treatment de-
children presented with rAOM with PETs already in place. Bacterial
scribed in the local practice guideline as they remained symptomatic,
cultures were obtained from one ear which demonstrated normal ex-
and surgery was required ahead of time.
ternal auditory canal flora.
Surgery was required in 60% of the patients, most of them between
It has been shown that in children unresponsive to antibiotic
the ages of 13 and 24 months (57.3%). The differences in age between
treatment, viruses are more commonly detected in their MEF, as com-
the group that underwent surgery and the group that did not require
pared to children with newly diagnosed AOM [15]. In some children,
surgery was statistically significant (P = 0.0456); the children requiring
viruses may be the cause of the infection [16]. Viruses may affect an-
surgery were younger (mean age: 17.2 months vs 18.3 months).
tibiotic penetration into the middle ear. Canafax et al. showed that
Cultures were obtained from 45 patients (55 ears). All anaerobic cul-
amoxicillin concentrations were lowest in the MEF obtained from virus-
tures were negative while aerobic cultures were positive in 58% (32/
infected children, and greatest in children with bacterial infections
55). Cultures were positive for SP in 2 ears (3.6%), and for MC in 1 ear
[16]. They concluded that amoxicillin dosage should be modified to
(1.8%). The rest of the aerobic cultures grew non-typical otopathogens
eradicate SP in AOM. Viruses may produce poor outcomes due to in-
(Fig. 3).
creasing middle ear inflammation, decreasing neutrophil function, and
Interestingly, four of the children that presented with rAOM at the
decreasing antibiotic penetration into the middle ear [16–19].
PED already had PETs in place (patent and functional). A bacterial
Pumarola et al. have shown a shift in bacterial otopathogens fol-
culture was obtained from one ear which was described as normal ex-
lowing the post-PCV era [20]. They found that in AOM treatment
ternal auditory canal flora.
failures and in recurrent AOM cases, the most common bacteria de-
tected was non-typeable HI. Kaur et al. also observed a shift in AOM
4. Discussion pathogens, as they reported a surge in HI prevalence [9].
Bacterial resistance may be another cause for treatment failure.
The present study demonstrated that a large share of children seen Resistance of SP isolated from MEF in AOM has been reported in up to
in our PED clinic with rAOM did not improve with IV or IM ceftriaxone 65% of isolates and multidrug-resistance in about 67% of isolates.
requiring a myringotomy and PET insertion for the resolution of their These results were obtained from pediatric patients that were admitted
symptoms. In our population, 60% needed PET insertion, the majority for rAOM at a children's hospital in Poland, and the children were not
being between the ages of 13–24 months. immunized with the 7-valent PCV [5]. Also, bacterial resistance can
The majority of MEF evaluated with bacterial cultures were sterile. vary according to geographical location due to different use of anti-
The first-line antibiotic that is recommended by the published biotics [21].

175
J. Pitaro et al.
In the present study, the majority of the children had fever and
rhinorrhea when consulting at the PED suggesting that rAOM coincides
with an upper respiratory tract infection.
Strengths of the present study include that it is a large re-
presentative cohort that may be generalized to children with rAOM
treated at a pediatric emergency department in Quebec. Limitations
include the fact that it is a retrospective study and that we cannot
specify the dosage of antibiotics given prior to the PED. In addition, 55
cultures were available although 152 children were operated since
different treating physicians performed the surgeries and the decision to
obtain cultures was at the physicians’ own discretion and based on their
experience. We also did not have data regarding viral cultures and
bacterial serotyping.
5. Conclusion
The majority of our patients needed PET insertion and a large
number of rAOM cases can have sterile bacterial cultures. Therefore,
treatment failures may be due to causes other than antibiotic resistance
such as concomitant viral infections. Further research is needed in order
to determine which children will most probably fail antibiotic treat-
ment in the post-vaccination era as well as determine the role of viruses
in cases of rAOM.
Conflicts of interest
None.
Funding
No external funding was available for this study.
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