Fungal Causes of Otitis Externa and Tympanostomy Tube Otorrhea

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International Journal of Pediatric Otorhinolaryngology (2005) 69, 15031508

www.elsevier.com/locate/ijporl

Fungal causes of otitis externa and


tympanostomy tube otorrhea
Timothy J. Martin, Joseph E. Kerschner, Valerie A. Flanary *

Department of Otolaryngology and Communication Sciences, Division of Pediatric Otolaryngology,


Medical College of Wisconsin, 9000 West Wisconsin Avenue, Milwaukee, WI 53226, USA

Received 6 November 2004; received in revised form 25 March 2005; accepted 6 April 2005

KEYWORDS Summary
Otorrhea;
Fungus; Objective: To describe the occurrence of fungal organisms in the setting of otitis
Tympanostomy tube externa and tympanostomy tube otorrhea, review the treatment course, timing of
otorrhea; diagnosis, organism identified and time to resolution with fungal infections.
Otitis media; Design: Retrospective review.
Otitis externa Setting: Pediatric otolaryngology clinic within a tertiary care hospital.
Patients: One hundred and sixty-six patients (ages 16 days to 18 years) with fungal
organisms on ear culture.
Outcome measures: Number of prior therapies, number of office visits, time to
resolution and anti-fungal therapy.
Results: Ear cultures positive for fungal organisms were found in 166 patients seen
between 1 January 1996 and 30 September 2003 from a total of 1242 patients
undergoing ear culture. Comparing the 3-year period (19961998) prior to the
availability of fluoroquinolone ototopical drops to the 3-year period after (1999
2001), there is a statistically significant increase in the incidence of positive fungal
culture ( p < 0.001). Otitis media was diagnosed in 72% of these children, with otitis
externa comprising 25%. Approximately 3% carried a diagnosis of both otitis externa
and otitis media. Candida albicans was identified in 43% of fungal organism-positive
cultures. Candida parapsilosis was found in 24% of and Aspergillus fumigatus in 13%.
The remainder of the cultures yielded three other Candida and three other Aspergillus
species, each at less than 5%. Time to resolution ranged from 1 week to 9 months, with
a median of 3.8 weeks for symptom resolution. Patients were treated with an average
of 1.7 oral antibiotics and 1.1 ototopical agent before a culture was taken.
Conclusions: Otorrhea due to fungal organisms occurs in the setting of refractory
infection and is often discovered after multiple oral and ototopical antibacterial
medications. Due to the extended treatment period required to clear fungal organ-
ism, timely diagnosis with culture for bacteria and fungus is required in patients with

* Corresponding author. Tel.: +1 414 266 6472; fax: +1 414 266 6989.
E-mail address: [email protected] (V.A. Flanary).

0165-5876/$ see front matter # 2005 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.ijporl.2005.04.012
1504 T.J. Martin et al.

persistent otorrhea. An increase in incidence of fungal infections of the ear was found
in the period after widespread use of ofloxacin began.
# 2005 Elsevier Ireland Ltd. All rights reserved.

1. Introduction Microbiology at Childrens Hospital of Wisconsin


was searched for all ear cultures performed with
Otitis externa and tympanostomy tube otorrhea are no alteration in culture technique between 1996 and
common occurrences in the pediatric patient popu- 2003. From a total number of 1242 patients who
lation. Tympanostomy tube otorrhea alone can be underwent ear culture, 166 patients were identified
found in and estimated 1030% of the nearly 2 with positive fungal cultures. The patient popula-
million patients per year who receive them [1]. tion identified by these cultures was investigated for
These diagnoses account for a large number of both the details listed in Table 1.
office visits and phone calls to both pediatricians For the purposes of this study, otitis media was
and otolaryngologists [2,3]. defined as infections involving the middle ear space.
Infectious causes of otorrhea can be recalcitrant Otitis externa is defined as infection of the external
and difficult to control. There are numerous forms of auditory canal that does not extend to the middle ear.
treatments including topical preparations, systemic Care was taken in review of the physical findings to
therapies and office-based debridement [1,4]. differentiate otorrhea from tympanostomy tubes or
Though several options exist for the treatment otitis tympanic membrane perforations and otorrhea asso-
externa, the use of ototopical agents in the setting ciated with infection of the canal skin. Patient co-
of open middle ear space created by tympanostomy morbidities were identified as diagnoses carried by
tube insertion or tympanic membrane perforation the patient chart in history and physical information.
continues to be debated [412]. However, the use of Therapies prior to culture were identified as antimi-
ototopicals in the fluoroquinolone class is now more crobial therapies, including ototopical preparations,
widely accepted. instituted in conjunction with an office visit for
Beyond the debate over the use of anti-bacterial otorrhea before culture was taken. This included
agents, discussion also continues with regard to the antibiotics prescribed at the office visit or over the
timing, validity and technique used in culturing the phone. Anti-fungal therapy used included both topi-
draining ear [1315]. Central to this debate is cal agents and systemic therapy prescribed both prior
whether simple external ear canal culture provides to culture and after culture data became available.
useful information in comparison to fluid sampled Number of office visits before culture was defined
directly from the middle ear or medial ear canal as office visits to the otolaryngologist during which
after microscopic ear canal debridement. Most otorrhea was a chief complaint or physical findings.
sources agree that ear canal debridement promotes Recording of visits prior to culture began with the
more rapid resolution of otitis, however, frequent first visit during which otorrhea was identified and
debridement comes at the cost of increased office ended when culture was taken. Number of office
visits and patient discomfort [3]. visits after culture began with the office visit after
It has been suggested that the incidence of fungal culture was taken and included all visits at which
otitis has increased recently, perhaps related to otorrhea or otitis externa was present. The final visit
increased use of topical fluoroquinolone antibiotics counted was the first visit after culture during which
[1619]. To further characterize the population of the cultured ear demonstrated no further physical
patients with fungal infection of the external audi-
tory canal and the middle ear, a retrospective Table 1 Data collected on patients with cultures posi-
review of culture data was undertaken. The goals tive for fungus
of this study were to identify both patient and
Data collected
organism factors that exist and to characterize
the treatments for these patients. Organism cultured
Otitis media or externa
Patient co-morbidities
Therapies prior to culture
2. Methods Anti-fungal agent used
Presence of tympanostomy tubes
A retrospective chart review of all patients seen at Time to resolution
Childrens Hospital of Wisconsin between 1996 and Number of office visits before culture
2003 with fungal organism found on ear culture was Number of office visits after culture
performed. The database of the Department of
Fungal causes of otitis externa and tympanostomy tube otorrhea 1505

Table 2 Yearly incidence of cultures positive for fun- frequently identified organisms. The remainder of
gal organisms the organisms identified included two Candida spe-
Year Number of OM OE Both cies, two Aspergillus species, a Trichosporon species
cultures and a Scedosporium species.
1996 7 6 1 0 Statistical analysis was undertaken using Chi-
1997 3 3 0 0 square testing comparing the number of fungus
1998 5 3 2 0 positive cultures and fungus negative cultures for
1999 16 13 3 0 a given year. As an example, comparing 1996 to
2000 30 17 11 2 1997, fungus positive cultures for each year were
2001 37 27 6 4 seven and three, respectively. Fungus negative cul-
2002 32 25 7 0 tures were 64 and 130. This yielded a p-value of
2003 36 25 11 0 0.017. This was done to analyze rates rather than
Total 166 119 41 6 actual numbers to account for the increase in total
cultures over the time period studied. Table 4 dis-
plays the remainder of the consective year statis-
findings of infection. Time to resolution is defined as tical analysis. Comparing the 3-year period (1996
the time period between initial presentation and 1998) prior to the availability of fluoroquinolone
the visit at which no physical findings of infection ototopical drops to the 3-year period after (1999
were identified. 2001) with the same Chi-square analysis, there is a
statistically significant increase in the incidence of
positive fungal culture ( p < 0.001).
3. Results Number of office visits prior to culture ranged
from one to eight visits with a mean of 2.8 visits. The
A total of 166 patients were identified with fungal mean number of visits after culture for this popula-
organism growth on ear culture. Ages ranged from tion was 2.6 visits. Time to resolution for the entire
16 days to 18 years with a mean age of 4 years, 1 population ranged from 1 week to 9 months with a
month. The gender distribution was 57% (94) male mean of 3.8 weeks. Time to resolution for otitis
patients and 43% (72) female patients. Otitis media media was 3.1 weeks, while time to resolution for
was identified in 71.7% (119) patients. Otitis externa otitis externa was 4.4 weeks. All patients had reso-
was identified in 24.7% (41) patients. Six patients lution of infection with treatment.
displayed evidence of infection of both the middle Combining medications received prior to visits
ear and external auditory canal. with our physicians and those received from our
The occurrence of fungal organism-positive cul- physicians, patients received an average of 1.7 oral
ture by year and the yearly occurrence of otitis antibiotics and 1.1 ototopical agents before culture
media and otitis externa can be found in Table 2. was taken. Due to the inconsistent reporting of
Table 3 displays the organisms identified in cul- medications received prior to being seen in our
ture. Candida albicans represented the most fre- clinic, no trends in the use of oral antibiotics were
quently cultured bacteria with 43.4% (72). Candida identified. Reliable information on the occurrence
parapsilosis (23.5%, 39 patients) and Aspergillus of office-based debridement could not be obtained
fumigatus (21%, 21 patients) were the next most from patient records.

Table 3 Fungal organisms identified on culture


Organism Total 1996 1997 1998 1999 2000 2001 2002 2003
C. albicans 72 3 1 3 8 12 13 15 17
C. parapsilosis 39 1 2 0 5 5 10 7 9
A. fumigatus 21 0 0 1 1 4 6 5 4
A. niger 10 2 0 0 0 3 1 1 3
C. tropicalis 6 0 0 0 1 2 1 1 1
C. lusitaniae 3 0 0 1 0 1 0 1 0
A. flavus 3 0 0 0 0 1 1 1 0
T. beigelii 1 1 0 0 0 0 0 0 0
S. prolificans 1 0 0 0 0 0 1 0 0
Multiple fungi 10 0 0 0 1 2 4 1 2
Total 166 7 3 5 16 30 37 32 36
1506 T.J. Martin et al.

Table 4 Statistical analysis and p-values generated by Table 5 Treatment used and time to resolution for
Chi-square testing each treatment
Anti-fungal used Number of Average time
patients to resolution
receiving (weeks)
Clotrimazole topical 27 2.5
Tolnaftate topical 27 4.1
Fluconazole 25 3.2
Acetic acid alone 14 4.6
Topical with fluconazole 10 3.25
Topical, fluconazole, 6 5.5
acetic acid
Vioform powder 5 2.8
Amphotericin B oral 2 3.1
Nystatin topical 1 5.2
Treatment unspecified 50 N/A

Table 6 Most frequent patient co-morbidities identi-


fied during review of records
Patient co-morbidity Incidence in
population
Cleft palate 18
Sensorineural hearing loss 6
PierreRobin 5
Charge 2
Cholesteatoma 2
Other (single occurrence) 23
Multiple condition 14

As the incidence of fungal organisms found on ear


culture began to increase within our practice in
1999, questions regarding the most appropriate
therapy were investigated. The appropriate timing
of ear culture has, essentially, been a matter of
individual clinical judgment. Patient factors such as
immuno-competence, structural oro-nasal abnorm-
Anti-fungal therapies used for the patients in this ality and degree of systemic illness must be con-
study were quite variable and can be found in Table 5. sidered in the setting of a draining ear. No consensus
Specific details of the therapy were unclear in a on the indication, timing or technique of ear culture
number of the chart reviews. The treatment unspe- could be found within our clinical practice or in the
cified includes these patients and patients that current literature.
were lost to follow-up. Data on patient co-morbid- This study demonstrates that the use of ear
ities were gathered and is presented in Table 6. culture varied from the first visit to eighth visit.
While numerous studies within the literature debate
the validity of ear culture and the appropriate
4. Discussion location of culture sampling, no reported guidelines
for the use of ear culture in the management of
The office-based management of a child with a otorrhea could be found [1315]. The establishment
draining ear can be both a challenging and labor of guidelines for the appropriate timing of ear cul-
intensive process, with multiple return visits and ture is difficult due to significant variability in the
repetitive ear debridement. Issues of antibiotic characteristics of patient that present with otor-
resistance and increasing occurrences of fungal rhea. What is clear from the relative rarity of the
organisms serve only to increase the difficulty of persistently draining ear as a complaint is that the
this management [1619]. vast majority of patients with otorrhea will have
Fungal causes of otitis externa and tympanostomy tube otorrhea 1507

symptom resolution with the use of empiric therapy found in this population, all occurring much more
directed at common bacterial pathogens. However, frequently in this small population of 166 patients
the possibility of a fungal organism contributing to than would be seen in the general population. Due
recalcitrant disease should be appreciated and cul- to the complexity of these patients management,
ture diagnosis is needed to appropriately treat these early culture and aggressive anti-fungal treatment
patients. may be necessary.
The higher likelihood of finding a Candida species While topical preparations to treat fungal organ-
can be correlated with physical findings commonly isms are available, the use of oral fluconazole as
associated with fungal infection. Candida species treatment bears some examination. In contrast to
are commonly associated with thick, white fluid. In topical preparations, which require frequent appli-
contrast, black hyphae visible in Aspergillus infec- cation and may require in-office debridement to
tions provide obvious clues to fungal infection. The reach the site of efficacy, fluconazole is adminis-
appearance of these physical findings, in the setting tered orally. This simplification may make compli-
of a draining ear that has not resolved with standard ance with therapy more likely. Additionally,
treatment would benefit from both ear culture and fluconazole is known to be effective against Candida
treatment directed at fungal organisms. species while maintaining a favorable side effect
Many reports have questioned whether fungal profile. There have been no studies specifically
organisms identified on culture represent coloniza- looking at the efficacy of oral fluconazole or the
tion or infectious agents. Recently, Vennewald et al. optimal treatment time for this therapy in treating
investigated the occurrence of fungal organisms in fungal otitis. This would be an important area of
the middle ear in association with inflammatory future investigation as a treatment alternative.
changes [17]. Their finding of diminished inflamma- Despite the finding of increased fungal infections,
tion with the use of topical anti-mycotic therapies the relatively new quinolone ototopicals have sig-
supports the idea that fungal organisms found on nificantly improved the management of otitis in
culture of infectious material within the ear may children. These medications provide excellent cov-
represent infectious cause rather than contamina- erage of pathogens, both for otitis media and
tion. In the setting of otorrhea that persists despite externa, and they have significantly improved the
multiple systemic and topical antibacterial and potential side-effect profile of the topical medica-
topical agents, appropriate investigation into fun- tions available for treating these diseases by elim-
gal, as well as anatomic causes, including CT scan, is inating the potential for ototoxicity.
necessary. Although this study demonstrates an increase in
The use of ototopical anti-bacterial agents has the rate of ear cultures positive for fungus after the
been debated in the literature for many years. introduction of fluroquinolone ototopical drops,
Issues of efficacy and toxicity continue to be a these findings are limited, primarily due to the
matter of debate [412]. Schrader and Isaacson retrospective collection of this data. Given that
have postulated that the aggressive use of anti- patients had wide variety of treatments prior to
bacterial agents within the ear may be a factor in culture, the increasing incidence serves to highlight
the occurrence of fungal infections of the ear [19]. that fungal otorrhea is on the rise, that clinical
Our finding of 1.7 oral and 1.1 ototopical anti-bac- suspicion in the setting of the persistently draining
terial agents used prior to culture demonstrating ear must be heightened and that further study is
fungal organisms would support this concept. It has warranted to determine the potential causality of
been well-documented that fungal overgrowth this finding to the increasing use of fluroquinolone
occurs with the use of broad-spectrum antibiotics ototopical agents.
in other areas of the body [20,21], and similar Given the limited nature of this review, several
findings in the treatment of otitis are not surprising. topics of further study can be identified. To aid the
The data collected for this study represents clinician in further characterizing the likelihood
patients seen at an exclusively pediatric otolaryn- that otorrhea is due to fungal organisms, its occur-
gology clinic within a tertiary care setting. There- rence relative to otorrhea of all causes must be
fore, these patients include both the uncomplicated clarified. The method of patient selection used in
children with recurrent otitis media and otitis this study made this data unobtainable. Clarification
externa and patients with challenging medical con- of the role of oral fluconazole in the treatment of
ditions. In these challenging patients, who are more fungal otorrhea, specifically the efficacy, timing and
frequently hospitalized and more frequently trea- appropriate dose, must be investigated. A more
ted with broad-spectrum antibiotics, special atten- comparative review that limits the confounding
tion must be given when otorrhea arises. Table 5 factors, such as concurrently changing patterns of
highlights the wide spectrum of medical conditions oral antibiotic therapy for otitis, would be required
1508 T.J. Martin et al.

to demonstrate a causative relationship between [8] J.E. Dohar, Topical quinolones in the treatment of chronic
the use of antibacterial topical agents and the suppurative otitis media and recurrent otorrhea, Ear Nose
Throat J. 81 (2002) 20.
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[10] E.L. Goldblatt, J. Dohar, R.J. Nozza, R.W. Nielsen, T. Gold-
5. Conclusions berg, J.D. Sidman, M. Seidlin, Topical ofloxacin versus sys-
temic amoxicillin/clavulanate in purulent otorrhea in
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setting of refractory infection and is often discov- Pediatr. Otorhinolaryngol. 46 (1998) 91101.
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