Topical antibiotics for chronic suppurative otitis media.

Background: Chronic suppurative otitis media (CSOM), sometimes referred to as chronic otitis media, 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 are ear discharge and hearing loss. Topical antibiotics, the most common treatment for CSOM, aim to kill or inhibit the growth of micro-organisms that may be responsible for the infection. Antibiotics can be used alone or with other treatments for CSOM, such as antiseptics or ear cleaning (aural toileting). This is an update of a Cochrane review first published in 2020 and one of a suite of seven reviews evaluating the effects of non-surgical interventions for CSOM.

Objectives: To evaluate the benefits and harms of topical antibiotics (without steroids) for people with chronic suppurative otitis media (CSOM).

Search methods: We searched the Cochrane ENT Register, CENTRAL, Ovid MEDLINE, Ovid Embase, and five other databases. We searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. The latest search date was 15 June 2022.

Selection criteria: We included randomised controlled trials with at least a one week of follow-up involving adults and children with 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(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 placebo or no intervention, and compared to another topical antibiotic (e.g. topical antibiotic A versus topical antibiotic B).

Data collection and analysis: We used standard Cochrane methodology. 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 and up to four weeks, and after four weeks; health-related quality of life using a validated instrument; and ear pain (otalgia) or discomfort or local irritation. Secondary outcomes were hearing, serious complications, and ototoxicity. We used GRADE to assess the certainty of the evidence for each outcome.

Main results: This update found one new study (100 participants). Overall, we included 18 studies with 1783 participants (in 16 studies), plus 108 ears that could not be accounted for in participant numbers (in two studies). 1. Topical antibiotics versus placebo or no treatment (with aural toilet in both arms and no other background treatment) One study (50 participants, data unavailable for 15 participants) compared a topical antibiotic (ciprofloxacin) with placebo (saline). All participants received aural toilet. Topical ciprofloxacin may increase resolution of discharge at one to up to two weeks compared with placebo (84% with antibiotic versus 12% with placebo; risk ratio (RR) 6.74, 95% confidence interval (CI) 1.82 to 24.99; 35 participants; very low-certainty evidence). The study authors reported "no medical side-effects and worsening of audiological measurements related to this topical medication were detected." 2. Topical antibiotics versus placebo or no treatment (with use of oral antibiotics in both arms) Four studies (438 participants) compared topical antibiotics versus no treatment, with oral antibiotics in both arms. These compared topical ciprofloxacin to no treatment (3 studies, 190 participants) or topical ceftizoxime to no treatment (1 study, 248 participants). In each study, all participants received the same antibiotic systemically (oral ciprofloxacin or injected ceftizoxime). In at least one study, all participants received aural toilet. There were no useable data comparing topical ceftizoxime to no treatment. Topical antibiotics in addition to systemic antibiotics may increase resolution of ear discharge at one to up to two weeks compared with systemic antibiotics alone (resolution of discharge occurring in 88% with topical antibiotics versus 60% without topical antibiotics; RR 1.47, 95% CI 1.14 to 1.88; 1 study, 100 participants; low-certainty evidence). One study (40 participants) stated "no side effect was recorded in any patient" (low-certainty evidence). 3. Comparisons of different topical antibiotics Eight studies (794 participants, plus 40 ears) compared aminoglycosides (gentamicin, neomycin, or tobramycin) with quinolones (ciprofloxacin or ofloxacin). Resolution of discharge at one to up to two weeks may be higher in the quinolones group, but the evidence is very uncertain (RR 1.92, 95% CI 1.00 to 3.67; 7 studies, 794 participants; very low-certainty evidence). There was considerable heterogeneity (I² = 97%). One study (308 participants) stated there were no differences between the different groups for resolution of ear discharge after four weeks (low-certainty evidence). The evidence is very uncertain about the effects of topical antibiotics on ear pain (1 study reported no differences between groups). The evidence is very uncertain about the effects of topical antibiotics on hearing loss (2 studies reported no differences between groups). 4. Other comparisons We assessed five studies (501 participants, plus 68 ears) over the following three additional comparisons: quinolones versus aminoglycosides/polymyxin B with/without gramicidin, aminoglycosides versus trimethoprim-sulphacetamide-polymixin B, and rifampicin versus chloramphenicol. However, these results have not been included in the abstract.

Authors' conclusions: We are very uncertain about the effectiveness of topical antibiotics in improving resolution of ear discharge in people with CSOM because of the limited amount of low- or very low-certainty evidence available. This was mostly due to risk of bias and imprecision. 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 whether 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, harmful effects were poorly reported. Limitations of the review include lack of recency in data, and limited information on certain population groups or interventions.