The Journal of Laryngology & Otology (2011), 125, 1212–1217.

REVIEW ARTICLE
© JLO (1984) Limited, 2011
doi:10.1017/S0022215110002550

Management of malignant (necrotising)

otitis externa

S HOLLIS, K EVANS

ENT Department, Gloucestershire Royal Hospital, Gloucester, UK

Abstract
Although malignant (necrotising) otitis externa is not a common diagnosis, there have been a number of recently
reported cases with pathogens other than Pseudomonas aeruginosa as the causative organism. In addition, there are
many published reports of resistance to antibiotics in cases of malignant otitis externa caused by Pseudomonas
aeruginosa. This review aims to assess the cases reported and to clarify the current opinion on the diagnostic
criteria and management of such cases.

Key words: Otitis Externa; Diagnosis; Drug Resistance; Surgery; Management

Introduction diabetes6), including human immunodeficiency virus

Malignant (necrotising) otitis externa is a progressive (HIV) infection, acquired immunodeficiency syndrome
infection of the external auditory canal and adjacent (AIDS), neoplasia, leukaemia, lymphoma, splenect-
structures. It was first described as a clinical entity in omy and post-transplantation immunosuppression.
1968 by Chandler, who described the disease as a pseu- Malignant otitis externa is rarely seen in paediatric
domonal infection of the external ear causing cranial practice. However, when encountered it is commonly
base osteomyelitis in the elderly and diabetics.1 associated with immunocompromise (either malig-
As early as 1992,2 it was stated that there was no nancy or malnutrition). Diabetes is a less common
proven, agreed regime for treating malignant otitis comorbid factor in paediatric cases.7
externa. Many different therapeutic options have been
used to treat this condition, including hyperbaric
oxygen therapy,3 but there has been very little progress
in establishing a unified treatment protocol.
Pathophysiology
Malignant otitis externa is an invasive, granulomatous
Prior to the introduction of effective antibiotic
infection of the external auditory canal and skull
regimes, malignant otitis externa was fatal in nearly
base. It usually originates at the junction of the cartila-
50 per cent of cases, hence the renaming to include
ginous and bony portions of the external auditory
the word ‘malignant’.1 In early reviews, radical surgi-
canal. Pseudomonas aeruginosa is nearly always the
cal debridement was the mainstay of treatment. This
causative organism,8 although the use of topical anti-
has since been replaced by antibiotic treatment, with
biotics before collection of microbiology culture speci-
local debridement in some cases.
mens often prevents isolation of the pathogen. Fungal
This review aims to assess recent case reports and to
malignant otitis externa is also seen, although usually
summarise current knowledge regarding the manage-
in patients with HIV infection.
ment of patients with malignant otitis externa.
Malignant otitis externa has been associated with
irrigation of the external auditory canal with water as
Epidemiology treatment for cerumen impaction.9
Malignant otitis externa is predominantly seen in Both diabetes and age are associated with microvas-
elderly and/or diabetic patients. It is most commonly cular abnormalities. For this reason, diabetic patients
associated with diabetes mellitus; recent reviews have and the elderly are both predisposed to malignant
quoted the prevalence of diabetes in malignant otitis otitis externa,1 caused by pseudomonas (not a com-
externa cases as 90–100 per cent.4,5 Other immuno- mensal organism of the external auditory canal) invad-
compromised states also represent risk factors for ing blood vessels to cause a vasculitis with thrombosis
malignant otitis externa development (with or without and coagulation necrosis of surrounding tissue.

Accepted for publication 15 July 2010 First published online 3 October 2011
MANAGEMENT OF MALIGNANT OTITIS EXTERNA 1213

There has been speculation that the higher pH of TABLE I

cerumen found in the external auditory canal of dia- DIAGNOSTIC SIGNS OF MALIGNANT OTITIS EXTERNA14
betic patients,10 together with the increase in microbial
Obligatory (major) signs Occasional (minor)
growth seen following application of water to signs
cerumen,11 contributes to the development of invasive
pseudomonal infection. In addition, diabetic patients’ Pain Pseudomonas
Exudate Positive radiograph
polymorphonuclear cells have impaired immune func- Oedema Diabetes mellitus
tion, which could add to the relative ease with which Granulation Cranial nerve
infection occurs.12 Microabscess∗ involvement
Positive 99mTc scan or failure of local Debilitating
treatment after >1 wk condition
Diagnosis (Pseudomonas) Old age
Malignant otitis externa is diagnosed based on three ∗
Upon surgery.
parameters: clinical findings (e.g. polypoidal granula-
tion tissue arising from the external auditory canal);
raised serum inflammatory markers (notably the eryth-
The extent of disease influences the prognosis. For
rocyte sedimentation rate,8 although many laboratories
example, if nasopharyngeal involvement is seen at
now only routinely perform C-reactive protein
clinical examination or as a radiological finding, then
measurement); and radiographic evidence of soft
the patient is deemed to have true, type one malignant
tissue (with or without bone erosion) in the external
otitis externa.15 In Joshua and colleagues’ series,15 this
auditory canal and infratemporal fossa. If granulation
form had a fatal outcome in all patients within 40
tissue is not evident in the external auditory canal,
months of hospitalisation. However, facial nerve invol-
exposed bone on the canal floor at the bone–cartilage
vement at presentation is not deemed to be a poor prog-
junction may lead to suspicion of malignant otitis
nostic factor.16
externa.
Patients have often received multiple courses of treat-
ment within the primary care setting, which have failed Radiological investigation
to make any improvement to their severe otalgia. In Friedman and Cohen’s classification guidance, the
Children with malignant otitis externa often have an positive radiograph requirement alludes to the presence
acute illness and tend to develop facial nerve palsies of soft tissue in the external auditory canal. This is seen
earlier in the course of the infection,13 due to anatomical on computed tomography (CT) scans of the temporal
differences (i.e. the more medial location of the fissures bones and skull base, which are often undertaken
of Santorini, and the underdeveloped mastoid process). early in the patient’s admission. However, if the
The patient will typically complain of otorrhoea, patient has been treated over a prolonged period of
unremitting otalgia, aural fullness and hearing loss time in the community, then the disease process may
(which will be conductive in nature). Headache, tem- have been active for months by the time CT scanning
poromandibular joint pain and related trismus may is performed. Bone erosion is only demonstrated on
also be experienced, with a subsequent reduction in CT scans once bone demineralisation has occurred,
oral intake, which in the diabetic patient may hamper which can take several months and rarely reverses.
glycaemic control. Hence, CT scanning is a useful initial investigation
Fungal malignant otitis externa is seen to originate for assessing the anatomical extent of disease in
more often in the middle ear or mastoid, in contrast patients with malignant otitis externa.17
with the late middle-ear involvement observed in pseu- Unfortunately, there is no one single radiological
domonal malignant otitis externa. In patients with malig- investigation that provides sufficient anatomical and
nant otitis externa and HIV infection, there is often a physiological detail to diagnose malignant otitis
lack of typical granulation tissue. When granulation externa and subsequently to monitor treatment. Hence,
tissue from such patients is examined, the histopatholo- more complex imaging modalities are often utilised.
gist will typically report that the external auditory canal These include technetium scanning (using Tc 99m
shows epidermal inflammation, with acute and chronic methylene diphosphonate), which can be useful in
components of inflammation in the dermis. malignant otitis externa cases as the radiotracer
In 1987, Cohen and Friedman published diagnostic accumulates at the sites of osteoblastic activity.
criteria in an attempt to stratify the outcome of malig- However, such abnormal features are non-specific
nant otitis externa, and to differentiate between severe and can also occur in patients with simple otitis
otitis externa and malignant otitis externa;14 these are externa.18 Gallium scans (using gallium citrate Ga67)
given in Table I. viewed in conjunction with single photon emission
All of the obligatory signs must be present in order to CT scans have also been used in patients with malig-
diagnose true type one malignant otitis externa. The less nant otitis externa, as this gives more detailed infor-
severe type two form (or severe otitis externa) is diag- mation about specific areas of focally increased
nosed if one of the obligatory criteria is absent and the uptake (and active infection). However, such modal-
patient improves within a week of hospitalisation.15 ities are unavailable in most acute settings.
1214 S HOLLIS, K EVANS

The need to confirm and subsequently monitor bony that if P aeruginosa is not isolated from a patient sus-
involvement (i.e. osteomyelitis) requires radiological pected of having malignant otitis externa, then a bone
and radionuclide investigations. In practice, CT biopsy should be taken for culture. Biopsies are also
remains a useful initial imaging tool, with progression required to differentiate malignant otitis externa from
or resolution monitored using magnetic resonance temporal bone cancer and squamous cell carcinoma.
imaging (MRI). In 2005, Okpala et al.19 suggested
that CT scanning should be used to outline the anatom- Treatment
ical extent of disease, while MRI scanning was felt by Patients with malignant otitis externa may have been
Grandis et al.,20 to be useful in cases of skull base treated for a considerable period of time in the commu-
involvement to outline soft tissue changes (particularly nity before being seen in a hospital setting. Once
medullary bone space involvement and dural enhance- admitted to hospital, many patients may have no posi-
ment). Supported by case reports, these authors also tive results from ear swab cultures. If there is a high
proposed the use of technetium bone scanning as a level of clinical suspicion, empirical intravenous anti-
valuable additional investigation if the initial CT scan biotics are given. Once culture specimens have been
is negative despite a high clinical index of suspicion taken, a fluoroquinolone (usually ciprofloxacin) or an
of malignant otitis externa, and also during patient antipseudomonal cephalosporin (e.g. ceftazidime) are
follow up. prescribed.
There are many regional and international variations
Microbiology to this regime. The key management strategies are:
The commonest causative pathogen for malignant otitis close monitoring with regular aural toilet, systemic
externa, and indeed any otitis externa, is Pseudomonas antipseudomonal therapy, and tight glycaemic control
aeruginosa.21 Positive culture results have been in diabetic patients.
reported for as many as 75 per cent of patients,15 In those who are immunocompromised and unre-
although pseudomonas is often not isolated in patients sponsive to treatment, a microbiological diagnosis is
receiving community-prescribed antibiotics prior to even more important, and a careful search for an
culture specimen collection. In some cases, more viru- unusual pathogen (such as candida) should be com-
lent pseudomonal species have been isolated which menced.30 Oral fluoroquinolones remain the first line
contain a mucoid surface layer protecting the bacterium of treatment, together with careful monitoring of
from phagocytosis.22 Pseudomonal strains two, six and disease progression.
11 are associated with more aggressive otological Oral quinolones (such as ciprofloxacin) have been
infections in general,23 including malignant otitis shown to have excellent penetration into bone, together
externa. with a low toxicity profile.32 Peleg et al.33 have
It is important to consider malignant otitis externa as described a malignant otitis externa severity scoring
a diagnosis, even if pseudomonas cannot be isolated system: points ranging from one to four are allocated
from the culture, especially if the patient has received in order to guide treatment, with more than two
multiple antibiotics in the primary care setting. Other points indicating a categorisation of ‘severe’. Points
bacteria which have been isolated from (and hence are allocated as follows: one point for diagnosed type
implicated in) cases of malignant otitis externa one diabetes mellitus, and one point each for CT evi-
include klebsiella,24 Staphylococcus aureus25 and S dence of bony destruction of the temporal bone or the
epidermidis,26 although it is unclear if these bacterial skull base or the temporomandibular junction (see
species are true pathogens. Table II).
In the immunosuppressed, non-diabetic patient with A large, systematic review of topical antimicrobial
malignant otitis externa, fungi are relatively frequently treatment of acute otitis exterma34 reported a clinical
isolated, particularly in patients with HIV–AIDS. cure rate of 65–80 per cent within 10 days of commen-
However, fungal malignant otitis externa is extremely cing therapy. Malignant otitis externa was an exclusion
rare overall. The most commonly implicated fungi are criterion in many of the papers assessed by this review,
the aspergillus subtypes Aspergillus fumigatus,27 A by virtue of its chronicity. However, the review did
niger28 and A flavus.29 In a minority of cases, candidal
species have also been implicated.30 The wide variety
of implicated organisms has lead some clinicians to TABLE II
speculate that malignant otitis externa is polymicrobial; MALIGNANT OTITIS EXTERNA SEVERITY SCORING
SYSTEM
however, when more than one organism is isolated on
culture, the additional species are likely to represent Score Medical treatment Surgical treatment
normal skin flora. 0–2 Antibiotic Rx only Minimal EAC surgery in some
cases
Histopathology ≥3 Multiple Early surgery & debridement
antipseudomonal Rx of all affected areas∗
Pseudomonas is implicated in an overwhelmingly large
proportion of malignant otitis externa cases. It has Adapted with permission.33 ∗ Removal of bony sequestrum and
therefore been suggested by Rubin Grandis et al.31 necrosis. Rx = therapy; EAC = external auditory canal
MANAGEMENT OF MALIGNANT OTITIS EXTERNA 1215

show that quinolone drops increased bacteriological therapy; this is a significant change from the manage-
cure rates by 8 per cent, compared with non-quinolone ment described in early case reports.
drops. There is no dispute that the incidence of diabetes
Fluoroquinolones target bacterial topoisomerases, mellitus is increasing in developed countries world-
rendering the bacterial DNA physiochemically wide, and that more children are now presenting with
unstable. Specifically, quinolone antibiotics are strong type two diabetes mellitus. Hence, there will in future
inhibitors of type II enzymes (DNA gyrase and topoi- be a larger percentage of the population with the
somerase IV).35 Older fluoroquinolones such as cipro- most significant risk factor for development of malig-
floxacin have predominant activity against aerobic nant otitis externa. The increasing longevity of patients
Gram-negative bacilli, with ciprofloxacin having the with HIV infection, due to antiretroviral therapy, will
most activity of this group of drugs against P also potentially increase the incidence of malignant
aeruginosa.36 otitis externa.
Osteomyelitis due to Gram-negative bacilli has a cure When combined with the increasing life expectancy
rate of 70–80 per cent when treated with either ofloxacin and increasing cumulative antibiotic usage worldwide,
or ciprofloxacin.37 Where P aeruginosa is implicated in malignant otitis externa could become a real problem
osteomyelitis, an oral fluoroquinolone is the preferred when multi-resistant pathogen strains are encountered
treatment.35 Care must be taken in patients with renal as the causative organism.
impairment, and an adjusted dose used where the creati- Recent studies have shown that ciprofloxacin usage
nine clearance is less than 30 ml/min.38 does not have a significant impact on the speed with
Rubin et al.39 have suggested that the addition of which P aeruginosa acquires resistance to fluoroquino-
rifampicin complements ciprofloxacin treatment. lones.42 However, this is in contrast to other fluoro-
Despite the fact that all these authors’ patients’ infec- quinolones (e.g. levofloxacins), which if used may
tions involved organisms sensitive to ciprofloxacin predispose the patient to infection by resistant organ-
(given as an oral dose of 750 mg twice daily), there isms (especially in the setting of multiple commu-
was still only a minimal increase in inhibition and bac- nity-based antibiotic treatments prior to malignant
tericidal action when this drug was added to the treat- otitis externa diagnosis).
ment regime. Rifampicin (600 mg twice daily) was One review43 has also implicated purely topical
added to the therapy regime as it did not alter the phar- administration of fluoroquinolones as adding to the
macokinetics of ciprofloxacin when used concurrently, problem of resistant organisms. Consequently, it has
and could also be given as an oral preparation. been suggested that such treatment be limited to
Other groups have favoured urgent treatment conver- those patients who have had a full 10-day course of
sion to intravenous ceftazidime as an alternative to topical aminoglycoside drops in the first instance.15
ciprofloxacin,40 with the addition of an aminoglycoside There are of course issues relating to the theoretical
if no improvement is seen or if resistance is encoun- risk of ototoxicity in a potentially open middle ear,
tered.41 In such cases, there are the associated issues although a 2007 review suggested a maximum treat-
of administration route and prolonged hospitalisation. ment duration of two weeks’ topical aminoglycoside
The role of surgery, and of debridement in particular, usage in such cases.44
is controversial in the management of malignant otitis Fluoroquinolone resistance has been related to
externa. Surgical management is instigated in order to inadequate oral doses, short (and incomplete)
gain biopsy material and to remove areas of bony courses, use in upper respiratory tract infections, and
necrosis; however, only a few isolated reports have topical preparation use in simple otitis externa.
observed an improvement in symptoms following sur- Carfrae and Kesser’s review22 reported that, in the
gical debridement alone.15 out-patient setting, the incidence of P aeruginosa
ciprofloxacin resistance was 20 per cent in simple
Discussion otitis externa cases and 33 per cent in malignant otitis
At first presentation, malignant otitis externa is essen- externa cases. It is of concern that fluoroquinolone
tially a clinical diagnosis made in the presence of resistance has been documented for more than a
severe pain plus granulation tissue in the external audi- decade in malignant otitis externa cases.45
tory canal. In all cases, priority must be given to obtain- Should treatment with ciprofloxacin fail, the emer-
ing early microbiological culture specimens, in order to gence of drug-resistant strains may cause significant
guide treatment. In addition, regular culture specimens problems.4,43 When ciprofloxacin is given, it is impor-
should be obtained throughout the course of treatment tant that a full course of more than six weeks be com-
to ensure that antibiotic resistance has not developed. menced as early as possible, at full dose (i.e. 750 mg
Studies involving gallium citrate scanning have pro- orally twice daily). If resistance is encountered, debri-
posed that antipseudomonal treatment should continue dement and subsequent use of intravenous ceftazidime
for up to three months,2 as guided by the presence of is advocated.4
osteomyelitis. The role of surgery is generally limited Antimicrobial resistance has also been documented
to local debridement and biopsy collection, the latter in the fungal species seen in malignant otitis
both to exclude malignancy and to guide antimicrobial externa.46 However, it should be remembered that the
1216 S HOLLIS, K EVANS

small sub-set of patients with fungal malignant otitis 16 Soudry E, Joshua BZ, Sulkes J, Nageris BI. Characteristics and
prognosis of malignant external otitis with facial paralysis. Arch
externa will often have a multi-factorial cause for Otolaryngol Head Neck Surg 2007;133:1002–4
their condition, which may render their clinical 17 Sudhoff H, Rajagopal S, Mani N, Moumoulidis I, Axon PR,
course much more variable by comparison. Moffat D. Usefulness of CT scans in malignant external otitis:
effective tool for the diagnosis, but of limited value in predicting
Fluoroquinolones are used cautiously in children outcome. Eur Arch Otorhinolaryngol 2008;265:53–6
because of the problems (identified in animals) 18 Levin WJ, Shary JH, Nichols LT, Lucente FE. Bone scanning in
related to joint development;47 however, reviews high- severe external otitis. Laryngoscope 1986;96:1193–5
19 Okpala NCE, Siraj QH, Nilssen E, Pringle M. Radiological and
light ciprofloxacin as being safe in selected cases.48 radionuclide investigation of malignant otitis externa.
Successful treatment of children with ciprofloxacin J Laryngology Otol 2005;119:71–5
has been reported following failure of penicillin 20 Grandis JR, Curtin HD, Yu VL. Necrotising (malignant) exter-
nal otitis: prospective comparison of CT and MR imaging in
and aminoglycoside therapy.49 Paediatric cases are diagnosis and follow up. Radiology 1995;196:499–504
usually treated with intravenous cephalosporins.50 21 Ninkovic G, Dullo V, Saunders NC. Microbiology of otitis
externa in the secondary care in United Kingdom and antimicro-
bial sensitivity. Auris Nasus Larynx 2008;35:480–4
Conclusion 22 Carfrae MJ, Kesser BW. Malignant otitis externa. Otolaryngol
Malignant otitis externa is a rare condition, and may Clin North Am 2008;41:537–49
cause concern in patients who have had prolonged 23 Englender M, Harrell M, Guttman R, Segal S. Typing of
Psuedomonas aeruginosa ear infections related to outcome of
courses of treatment prior to diagnosis. The key man- treatment. J Laryngol Otol 1990;104:678–81
agement steps are to obtain a culture specimen, to 24 Garcia Rodriguez JA, Montes Martinez I, Gómez González JL,
undertake appropriate imaging, and to instigate suitable Ramos Macías A, López Alburquerque T. A case of malignant
external otitis involving Klebsiella oxytoca. Eur J Clin
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26 Barrow HN, Levenson MJ. Necrotising “malignant” external
reviewed. It is important that causative organisms otitis caused by Staphylococcal epidermidis. Arch Otolaryngol
(and their respective resistance to antibiotics) are Head Neck Surg 1992;118:94–6
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28 Bellini C, Antonini P, Ermanni S, Dolina M, Passega E,
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Clin Otolaryngol 2007;32:330–6 ENT Department,
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46 Hitchcock CA, Pye GW, Troke PF, Johnson EM, Warnock DW. Fax: +44 (0)8454 226432
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48 Forsythe CT, Ernst ME. Do fluoroquinolones commonly cause content of the paper
arthropathy in children? CJEM 2007;9:459–62 Competing interests: None declared