Introduction
Tympanostomy tube (TT) insertion is one of the most commonly performed operations
in children (1). TTs are most often inserted for the correction of hearing loss in
persistent otitis media with effusion (OME) or for recurrent acute otitis media (rAOM).
One in every two patients undergoing TT insertion will experience at least one episode
of ear discharge (otorrhoea) (2), which has adverse effects on quality of life (3)
and is a common indication for antimicrobial prescriptions (4,5).
Risk factors
Patient risk factors for developing TT otorrhoea (TTO) include young age, a history
of recurrent upper respiratory tract infections, and having older siblings (2). Patients
having TTs inserted for rAOM are also at greater risk of developing TTO than those
with OME (2). The risks associated with water and tobacco exposure remain more contentious.
Previous trials have shown little to no benefit from water precaution measures (6),
resulting in current United States of America (USA) guidelines advising against routine
prophylactic water precautions for children with TTs (4). Exposure to second hand
tobacco smoke is a cause of upper respiratory tract inflammation and OME; however,
two large retrospective studies have reported conflicting results regarding its association
with TTO (2,7).
In addition to patient-specific factors, TTs themselves determine the risk of TTO.
A 2018 randomised controlled trial of 378 children comparing four types of TT found
that silicone tubes had a significantly longer otorrhoea-free interval after insertion
than fluoroplastic tubes, although there was no difference in overall infection rate
(8). In this trial, tube shape (short versus long) did not affect number or timing
of infections. Ex vivo studies of TTs have shown biofilms—adherent bacterial communities
encapsulated in an extracellular polymer matrix—favour particular sites in several
common TT designs (9). In particular, perpendicular junctions of tubes seem particularly
vulnerable to biofilm formation, suggesting that geometric modifications to TT designs
could be beneficial. Other avenues of active research include TT material modifications
and antimicrobial coverings to inhibit biofilm formation (9).
Microbiology of TTO
The microbiology of TTO tends to reflect the organisms found in middle ear infections,
which are predominantly bacterial in nature. Common bacteria can be thought of as
either typically nasopharyngeal (for example Streptococcus pneumoniae, Haemophilus
influenzae, and Moraxella catarrhalis) or external ear canal in origin (for example
Pseudomonas aeruginosa and Staphylococcus aureus). The former is typically associated
with younger children and the latter with older children (10,11).
Viral co-infection is also common. In one small study viral co-infection was present
in two thirds of children with TTO; picornavirus was the most prevalent (41%), followed
by rhinovirus (20%) and enterovirus (10%) (12). Fungal causes of TTO are typically
preceded by antibiotic therapy; common organisms include candida albicans, candida
parapsilosis, and aspergillus fumigatus (13).
Prophylactic antimicrobials
In order to reduce TTO some clinicians historically advocated the routine prescription
of a course of topical antimicrobial therapy following TT insertion. A cochrane review
of 15 randomised studies identified that whilst a post operative course of topical
antimicrobial therapy does reduce the incidence of otorrhoea, the effect is not greater
than saline rinses combined with a single intra-operative dose of a topical antimicrobial
agent, and the former involves greater financial cost and confers an increased risk
of antimicrobial resistance (14). Therefore, current USA guidance advises against
the routine prescribing of a course of topical antimicrobial therapy following TT
insertion. However, a single intra-operative dose immediately following TT placement
may be used at the surgeon’s discretion (4).
Treatment of TTO
Whilst prolonged courses of topical antimicrobial therapies are of limited value for
the prophylaxis of TTO, they have a key role in treating episodes of TTO when it occurs.
A large trial of children with TTO published in 2014 found evidence strongly in support
of topical antimicrobial treatment over other approaches to treatment: only 5% of
patients had persistent otorrhoea after topical therapy versus 44% with oral antimicrobials
and 55% with active observation alone (15). This study and others were included in
a large network meta-analysis in 2017 by Steele et al., which further confirmed the
greater efficacy of topical over oral antimicrobial therapy (odds ratio of 5.3; 95%
confidence interval: 1.2–27) (16). This is reflected in the recently updated 2022
American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF) guidelines,
which recommend the use of topical rather than oral antimicrobial therapy for episodes
of TTO (4). The Steele et al. meta-analysis also demonstrated that topical antimicrobial-glucocorticoid
combinations are more effective than topical antimicrobial monotherapy alone.
Although topical delivery is the favoured route of treatment for TTO, ear drops typically
require several applications per day, which many individuals find difficult, leading
to poor compliance. One study based on topical treatments for otitis externa in adults
found that alarmingly only 40% of patients successfully applied ear drops with an
error rate of less than 25% after 3 days, and this dropped to only 32% at 11 days
(17). Similar studies of the adherence to topical ear drops amongst children do not
exist, but factors such as potentially poor understanding of reasons for treatment
and dependence on caregivers to administer the medication would suggest that compliance
is possibly lower in this group (18).
Novel agents for TTO
Otic gels
One method to overcome the challenge of poor compliance is to reduce the frequency
required for topical therapy application, but without compromising efficacy. Ciprofloxacin
otic gel (COG) is a single-application agent, which slowly releases ciprofloxacin
over time. COG has been trialed as a prophylactic agent against TTO in a study that
directly compared COG to TT insertion alone (without any topical antimicrobial agent)
and demonstrated a lower rate of otorrhoea in the COG group (19). This study did not
look at the use of COG in treating TTO, which would be a valuable area for further
research. It is noteworthy that the COG formulation presented above is solely an antimicrobial
agent without glucocorticoid. However, it is understood from the Steele et al. meta-analysis
that the addition of glucocorticoid to antimicrobial agents might result in greater
efficacy for the treatment of TTO (16). Ku et al. recently published a pre-clinical
study of a ciprofloxacin-dexamethasone combination hydrogel, which has demonstrated
safety in vivo in an animal model, but confirmation of efficacy in human clinical
trials is awaited (20).
Targeted biofilm disruption
Biofilms are known to form on TTs, helping protect bacteria from both antimicrobial
treatments and the host immune system, in turn contributing to TTO (21). In addition
to TT design modifications to prevent biofilm formation, targeted treatments to degrade
biofilms are under development. One example is the use of modified release antimicrobial
pellets, which have shown promise in biofilm eradication in vitro (22). More recent
efforts have used monoclonal antibodies against DNABII proteins, which are integral
to the structure of the extracellular matrix, and this strategy has been shown to
be effective in a chinchilla model (23). Other approaches include using photo-dynamic
therapy (PDT), in which excitation of a light sensitive drug releases cyotoxic singlet
oxygen molecules (24). This has shown efficacy in otopathogen-specific biofilms, but
as with the other anti-biofilm treatment approaches described, is yet to enter routine
clinical practice.
Future research into treatment options for TTO
Future research must continue to examine the dynamically changing microbiology of
TTO as this can be changed by the introduction or modification of national vaccination
programmes, amongst other factors, and will likely lead to changes in disease aetiology
and optimal treatment strategies (25).
It is also important to remain cognisant that certain patient groups are at higher
risk of TTO. Many trials to date consider TTO as a discrete entity, but it is important
that future research on the role of ototopical therapies, including otic gels and
agents for the disruption of biofilms, specifically consider efficacy in these at-risk
patient groups; in order to evaluate whether particular agents are more or less effective
in these selected circumstances, such as stratifying by patient age or operative indication.
Such differences could enable a personalised approach to treatment for the most at-risk
patients of TTO and offer a welcome addition to the presently constrained range of
treatment options.
Supplementary
The article’s supplementary files as
10.21037/tp-22-387