What is the aim of this review?
The aim of this Cochrane Review was to find out if topical antibiotics are effective in treating chronic suppurative otitis media and whether one type of topical antibiotic treatment is more effective than any other. We collected and analysed all relevant studies to answer this question.
There is a lot of uncertainty as to whether or not topical antibiotics improve the resolution of ear discharge in patients with chronic suppurative otitis media (CSOM). However, among this uncertainty there is some evidence to suggest that the use of topical antibiotics may be effective when compared to placebo, or when used in addition to a systemic antibiotic (oral or injected). There is also lots of uncertainty about which type of topical antibiotic is the most effective. Overall, the certainty of the evidence was very low.
What was studied in the review?
Chronic suppurative otitis media, sometimes referred to as chronic otitis media (COM), is a long-term (chronic) swelling and infection of the middle ear, with ear discharge (otorrhoea) through a perforated tympanic membrane (eardrum). The main symptoms of CSOM are ear discharge and hearing loss. Topical antibiotics (administered into the ear canal as ear drops, ointments, sprays or creams) are the most commonly used treatment for CSOM. Topical antibiotics kill or stop the growth of the micro-organisms that may be responsible for the infection. Topical antibiotics can be used on their own or added to other treatments for CSOM, such as antiseptics or ear cleaning (aural toileting) or systemic antibiotics (antibiotics taken either by mouth or by an injection into a muscle or vein). It was important in this review to examine whether there were any adverse effects from using topical antibiotics as they can cause irritation of the skin within the outer ear, which may cause discomfort, pain or itching. This review also examined whether different types of antibiotics were more effective at treating CSOM than others, as some antibiotics (such as aminoglycosides) may have the potential to be toxic to the inner ear (ototoxicity), with potential to cause irreparable hearing loss (sensorineural), dizziness or ringing in the ear (tinnitus).
What are the main results of the review?
We found 17 studies examining at least 2126 participants, but it was difficult to determine precisely how many participants were included as a number of studies did not clearly report the number. A number of different types of antibiotics and combinations of antibiotics were used.
Comparison of topical antibiotics to placebo or no treatment
One study compared topical antibiotics to a saline (salt water) ear wash. The topical antibiotics appeared to be more effective than the saline ear wash when assessed one to two weeks after treatment, but this study was too small to provide any certainty of the findings (very low-certainty evidence).
Comparison of topical antibiotics in addition to systemic (oral or injected) antibiotics
Four studies compared treatment with topical antibiotic (ciprofloxacin) drops in addition to a systemic (oral or injected) antibiotic. Treatment marginally favoured the combined topical and oral antibiotics compared to oral antibiotics only for resolution of discharge at one to two weeks and two to four weeks. These studies were too small to provide any certainty of the findings (low-certainty evidence).
Comparisons of different topical antibiotics
There were 12 studies that examined the effectiveness of different types of antibiotics. The certainty of the evidence for all outcomes in these comparisons is very low. Two studies did not report the number of included participants, or reported only the number of ears treated, so the total number of participants could not be calculated. Due to the low certainty of evidence it is not known which type of topical antibiotic is the most effective.
How up to date is this review?
The evidence is up to date to April 2019.
We are uncertain about the effectiveness of topical antibiotics in improving resolution of ear discharge in patients with CSOM because of the limited amount of low-quality evidence available. However, amongst this uncertainty there is some evidence to suggest that the use of topical antibiotics may be effective when compared to placebo, or when used in addition to a systemic antibiotic. There is also uncertainty about the relative effectiveness of different types of antibiotics; it is not possible to determine with any certainty whether or not quinolones are better or worse than aminoglycosides. These two groups of compounds have different adverse effect profiles, but there is insufficient evidence from the included studies to make any comment about these. In general, adverse effects were poorly reported.
Chronic suppurative otitis media (CSOM), sometimes referred to as chronic otitis media (COM), is a chronic inflammation and often polymicrobial infection (involving more than one micro-organism) of the middle ear and mastoid cavity, characterised by ear discharge (otorrhoea) through a perforated tympanic membrane. The predominant symptoms of CSOM are ear discharge and hearing loss. Topical antibiotics, the most common treatment for CSOM, act to kill or inhibit the growth of micro-organisms that may be responsible for the infection. Antibiotics can be used alone or in addition to other treatments for CSOM, such as antiseptics or ear cleaning (aural toileting).
To assess the effects of topical antibiotics (without steroids) for people with CSOM.
The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL via the Cochrane Register of Studies); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 1 April 2019.
We included randomised controlled trials (RCTs) with at least a one-week follow-up involving participants (adults and children) who had chronic ear discharge of unknown cause or CSOM, where the ear discharge had continued for more than two weeks.
The interventions were any single, or combination of, topical antibiotic agent(s) of any class, applied directly into the ear canal as ear drops, powders or irrigations, or as part of an aural toileting procedure.
The two main comparisons were topical antibiotic compared to a) placebo or no intervention and b) another topical antibiotic (e.g. topical antibiotic A versus topical antibiotic B).
Within each comparison we separated studies where both groups of participants had received topical antibiotic a) alone or with aural toileting and b) on top of background treatment (such as systemic antibiotics).
We used the standard Cochrane methodological procedures. We used GRADE to assess the certainty of the evidence for each outcome.
Our primary outcomes were: resolution of ear discharge or 'dry ear' (whether otoscopically confirmed or not), measured at between one week and up to two weeks, two weeks to up to four weeks and after four weeks; health-related quality of life using a validated instrument; ear pain (otalgia) or discomfort or local irritation. Secondary outcomes included hearing, serious complications and ototoxicity measured in several ways.
We included 17 studies with a total of 2198 participants. Twelve studies reported the sample size in terms of participants (not ears); these had a total of 1797 participants. The remaining five studies reported both the number of participants and ears, representing 401 participants, or 510 ears.
A: Topical antibiotics versus placebo or no treatment (with aural toilet in both arms and no other background treatment)
One small study compared a topical antibiotic (ciprofloxacin) with placebo (saline). All participants received aural toilet. Although ciprofloxacin was better than saline in terms of resolution of discharge at one to two weeks: 84% versus 12% (risk ratio (RR) 6.74, 95% confidence interval (CI) 1.82 to 24.99; 35 participants, very low-certainty evidence), the very low certainty of the evidence means that it is very uncertain whether or not one intervention is better or worse than the other. The study authors reported that "no medical side-effects and worsening of audiological measurements related to this topical medication were detected" (very low-certainty evidence).
B: Topical antibiotics versus placebo or no treatment (with use of oral antibiotics in both arms)
Four studies compared topical ciprofloxacin to no treatment (three studies; 190 participants) or topical ceftizoxime to no treatment (one study; 248 participants). In each study all participants received the same antibiotic systemically (oral ciprofloxacin, injected ceftizoxime). In at least one study all participants received aural toilet. Useable data were only available from the first three studies; ciprofloxacin was better than no treatment, resolution of discharge occurring in 88.2% versus 60% at one to two weeks (RR 1.47, 95% CI 1.20 to 1.80; 2 studies, 150 participants; low-certainty evidence). None of the studies reported ear pain or discomfort/local irritation.
C: Comparisons of different topical antibiotics
The certainty of evidence for all outcomes in these comparisons is very low.
Quinolones versus aminoglycosides
Seven studies compared an aminoglycoside (gentamicin, neomycin or tobramycin) with ciprofloxacin (734 participants) or ofloxacin (214 participants). Whilst resolution of discharge at one to two weeks was higher in the quinolones group the very low certainty of the evidence means that it is very uncertain whether or not one intervention is better or worse than the other (RR 1.95, 95% CI 0.88 to 4.29; 6 studies, 694 participants). One study measured ear pain and reported no difference between the groups.
Quinolones versus aminoglycosides/polymyxin B combination ± gramicidin
We identified three studies but data on our primary outcome were only available in one study. Comparing ciprofloxacin to a neomycin/polymyxin B/gramicidin combination, for an unknown treatment duration (likely four weeks), ciprofloxacin was better (RR 1.12, 95% CI 1.03 to 1.22, 186 participants). A "few" patients experienced local irritation upon the first instillation of topical treatment (numbers/groups not stated).
Other studies examined topical gentamicin versus a trimethoprim/sulphacetamide/polymixin B combination (91 participants) and rifampicin versus chloramphenicol (160 participants). Limited data were available and the findings were very uncertain.