Benefits and risks of antibiotics taken orally or given as an injection to treat chronic suppurative otitis media (persistent or recurring ear infection with discharge)

Why is this question important?

Chronic suppurative otitis media (CSOM), also known as chronic otitis media (COM), is an inflammation and infection of the middle ear that lasts for two weeks or more. People with CSOM usually experience recurrent or persistent discharge – fluid that leaks out from a hole or tear in the eardrum – and hearing loss.

CSOM can be treated with antibiotics (medicines that fight bacterial infections) taken orally or given as an injection (i.e. systemic treatment in which the whole body is treated). Systemic antibiotics can be used:

- alone;
- in combination with antibiotics in the form of drops, sprays, ointments or creams (topical, i.e. localised surface treatment); or
- in combination with other treatments such as steroids (anti-inflammation medicines) or antiseptics (substances that stop or slow down the growth of micro-organisms).

To find out how effective systemic antibiotics are for treating CSOM, and whether they lead to side effects, we reviewed the evidence from research studies.

How did we identify and evaluate the evidence?

First, we searched the medical literature for studies that followed people with CSOM for at least one week and compared:

- a systemic antibiotic used alone against a placebo (dummy) treatment, no treatment or another systemic antibiotic;
- a systemic antibiotic combined with another treatment, against that treatment alone.

We then compared the results, and summarised the evidence from all the studies. Finally, we rated our confidence in the evidence, based on factors such as study methods and sizes, and the consistency of findings across studies.

What did we find?

We found 18 studies that involved a total of 2135 people with CSOM. People were treated for between five days and 12 weeks, and were followed for up to one year. Four studies provided information about how they were funded or who supplied the medicines: two were publicly funded, and medicines were provided by pharmaceutical companies in the other two studies.

Studies compared:

- systemic antibiotics against no treatment (one study);
- systemic antibiotics plus topical antibiotics against topical antibiotics alone (six studies);
- systemic antibiotics plus other treatments (other than topical antibiotics alone), against these same treatments without systemic antibiotics (four studies);
- different systemic antibiotics against one another (eight studies).

Systemic antibiotics alone against no treatment

We cannot determine from the only study we found whether systemic antibiotics alone are better or worse than no treatment. This is mainly because the study:

- was small;
- was conducted in ways that could have introduced error in the results; and
- reported limited information.

Systemic antibiotics plus topical antibiotics against topical antibiotics alone

Systemic antibiotics plus topical antibiotics may have little to no effect on whether discharge stops after one to two weeks, compared against topical antibiotics alone (five studies). We do not know if systemic antibiotics added to topical antibiotics have any other positive or negative effects, because:

- there are too few studies;
- available studies were small and may have been conducted in ways that introduce error in their results.

Systemic antibiotics plus other treatments (other than topical antibiotics alone), against these same treatments without systemic antibiotics

We cannot determine from the evidence available whether systemic antibiotics are effective or lead to adverse events when added to treatments other than topical antibiotics only. This is mainly because the few studies available reported limited information.

Comparisons between different systemic antibiotics

We do not know whether some systemic antibiotics are better than others. This is mainly because the way studies were conducted is likely to have introduced error in their results.

What does this mean?

There is insufficient robust evidence to determine whether systemic antibiotics are effective treatments for CSOM, and whether they lead to side effects. Evidence about side effects is particularly limited. When added to topical antibiotics, systemic antibiotics may make little to no difference to whether discharge resolves after one to two weeks. We do not know if some systemic antibiotics are better than others.

How-up-to date is this review?

The evidence in this Cochrane Review is current to March 2020.

Authors' conclusions: 

There was a limited amount of evidence available to examine whether systemic antibiotics are effective in achieving resolution of ear discharge for people with CSOM. When used alone (with or without aural toileting), we are very uncertain if systemic antibiotics are more effective than placebo or no treatment. When added to an effective intervention such as topical antibiotics, there seems to be little or no difference in resolution of ear discharge (low-certainty evidence). Data were only available for certain classes of antibiotics and it is very uncertain whether one class of systemic antibiotic may be more effective than another. Adverse effects of systemic antibiotics were poorly reported in the studies included. As we found very sparse evidence for their efficacy, the possibility of adverse events may detract from their use for CSOM.

Read the full abstract...
Background: 

Chronic suppurative otitis media (CSOM) is a chronic inflammation and infection 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.

Systemic antibiotics are a commonly used treatment option for CSOM, which 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.

Objectives: 

To assess the effects of systemic antibiotics for people with CSOM.

Search strategy: 

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 16 March 2020.

Selection criteria: 

We included randomised controlled trials comparing systemic antibiotics (oral, injection) against placebo/no treatment or other systemic antibiotics with at least a one-week follow-up period, involving patients with chronic (at least two weeks) ear discharge of unknown cause or due to CSOM. Other treatments were allowed if both treatment and control arms also received it.

Data collection and analysis: 

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.

Main results: 

We included 18 studies (2135 participants) with unclear or high risk of bias.

1. Systemic antibiotics versus no treatment/placebo

It is very uncertain if there is a difference between systemic (intravenous) antibiotics and placebo in the resolution of ear discharge at between one and two weeks (risk ratio (RR) 8.47, 95% confidence interval (CI) 1.88 to 38.21; 33 participants; 1 study; very low-certainty evidence). The study did not report results for resolution of ear discharge after two weeks. Health-related quality of life was not reported. The evidence is very uncertain for hearing and serious (intracranial) complications. Ear pain and suspected ototoxicity were not reported.

2. Systemic antibiotics versus no treatment/placebo (both study arms received topical antibiotics)

Six studies were included of which five presented useable data. There may be little or no difference in the resolution of ear discharge at between one to two weeks for oral ciprofloxacin compared to placebo or no treatment when ciprofloxacin ear drops were used in both intervention arms (RR 1.02, 95% CI 0.93 to 1.12; 390 participants; low-certainty evidence). No results after two weeks were reported. Health-related quality of life was not reported. The evidence is very uncertain for ear pain, serious complications and suspected ototoxicity.

3. Systemic antibiotics versus no treatment/placebo (both study arms received other background treatments)

Two studies used topical antibiotics plus steroids as background treatment in both arms. It is very uncertain if there is a difference in resolution of ear discharge between metronidazole and placebo at four weeks (RR 0.91, 95% CI 0.51 to 1.65; 40 participants; 1 study; very low-certainty evidence). This study did not report other outcomes. It is also very uncertain if resolution of ear discharge at six weeks was improved with co-trimoxazole compared to placebo (RR 1.54, 95% CI 1.09 to 2.16; 98 participants; 1 study; very low-certainty evidence). Resolution of ear discharge was not reported at other time points. From the narrative report there was no evidence of a difference between groups for health-related quality of life, hearing or serious complications (very low-certainty evidence).

One study (136 participants) used topical antiseptics as background treatment in both arms and found similar resolution of ear discharge between the amoxicillin and no treatment groups at three to four months (RR 1.03, 95% CI 0.75 to 1.41; 136 participants; 1 study; very low-certainty evidence). The narrative report indicated no evidence of differences in hearing or suspected ototoxicity (both very low-certainty evidence). No other outcomes were reported.

4. Different types of systemic antibiotics

This is a summary of four comparisons, where different antibiotics were compared to each other. Eight studies compared different types of systemic antibiotics against each other: quinolones against beta-lactams (four studies), lincosamides against nitroimidazoles (one study) and comparisons of different types of beta-lactams (three studies). It was not possible to conclude if there was one class or type of systemic antibiotic that was better in terms of resolution of ear discharge. The studies did not report adverse events well.