Review question
We reviewed the evidence for the benefits and harms of systemic (given by mouth) or topical (given by nose) antibiotics for people with chronic rhinosinusitis.
Background
Chronic rhinosinusitis is a common condition that is defined as inflammation of the nose and paranasal sinuses (a group of air-filled spaces behind the nose, eyes and cheeks). Patients experience at least two or more of the following symptoms for at least 12 weeks: blocked nose, discharge from their nose or runny nose, pain or pressure in their face and/or a reduced sense of smell (hyposmia). Some people will also have nasal polyps, which are grape-like swellings of the normal nasal lining inside the nasal passage and sinuses.
Study characteristics
We included five randomised controlled trials (RCTs) with a total of 293 participants. The studies were small (43 to 79 participants). Four recruited adults and the fifth children. Three studies only included people with chronic rhinosinusitis without nasal polyps, one a mix of people with and without polyps and the remaining study only people with polyps. All used different types of oral antibiotics; none looked at topical antibiotics. The antibiotics were given to patients as either antimicrobial or anti-inflammatory agents and for different lengths of time, although in all cases we were able to look at the outcomes after three months. Antibiotics were compared with placebo, with intranasal (in the nose) steroids or with oral steroids. One study used antibiotics as an additional treatment, on top of nasal saline irrigation and most people also took intranasal steroids in this study.
Key results and quality of the evidence
When compared to a placebo (three studies), there was moderate quality evidence in one study that there may be an improvement in disease-specific health-related quality of life (HRQL) with oral antibiotics in people with chronic rhinosinusitis (without polyps) at the end of treatment (three months), but it is unclear if HRQL was still improved three months later. There may have been an increase in gastrointestinal disturbances and suspected allergic reaction (rash or skin irritation) with antibiotics but we are very uncertain and the quality of the evidence is very low.
Antibiotics were used alongside nasal saline irrigation and intranasal steroids (compared to placebo plus the same) in one study. It is not clear if there was an important difference in disease-specific HRQL after treatment (three months) or at three months after treatment was completed (low quality evidence). There may have been more people in the antibiotics group who felt they had 'improved' at the end of treatment, but there were also people who had worse symptoms in both groups (very low quality evidence). It is very uncertain if there was a difference in gastrointestinal disturbances between groups.
When compared with intranasal steroids in people with chronic rhinosinusitis (without polyps), it was very uncertain if there was a difference in disease severity (using a combined score for four different symptoms) between the antibiotics and intranasal steroids groups in one study (low quality evidence). No information was given about adverse events.
The one study that compared antibiotics with oral steroids (in people with chronic rhinosinusitis with polyps) did not present any effectiveness results that we could use. It was uncertain if there was any difference in gastrointestinal disturbances or skin irritation in the antibiotics group (very low quality evidence).
There were no reports of any serious adverse effects in any of the studies.
Conclusions
We found very little evidence that oral antibiotics are effective in patients with chronic rhinosinusitis. We did find moderate quality evidence of a modest improvement in disease-specific quality of life in adults with chronic rhinosinusitis without polyps receiving three months of a macrolide antibiotic. The size of the improvement was moderate (0.5 points on a five-point scale) and only seen at the end of the three-month treatment; by three months later no difference was found.
Despite a general understanding that antibiotics can be associated with adverse effects, including gastrointestinal disturbances, the results in this review were very uncertain because the studies were small and few events were reported.
More research in this area, particularly evaluating longer-term outcomes and adverse effects, is required.
We found very little evidence that systemic antibiotics are effective in patients with chronic rhinosinusitis. We did find moderate quality evidence of a modest improvement in disease-specific quality of life in adults with chronic rhinosinusitis without polyps receiving three months of a macrolide antibiotic. The size of improvement was moderate (0.5 points on a five-point scale) and only seen at the end of the three-month treatment; by three months later no difference was found.
Despite a general understanding that antibiotics can be associated with adverse effects, including gastrointestinal disturbances, the results in this review were very uncertain because the studies were small and few events were reported.
No RCTs of topical antibiotics met the inclusion criteria.
More research in this area, particularly evaluating longer-term outcomes and adverse effects, is required.
This review is one of six looking at the primary medical management options for patients with chronic rhinosinusitis.
Chronic rhinosinusitis is common and is characterised by inflammation of the lining of the nose and paranasal sinuses leading to nasal blockage, nasal discharge, facial pressure/pain and loss of sense of smell. The condition can occur with or without nasal polyps. Systemic and topical antibiotics are used with the aim of eliminating infection in the short term (and some to reduce inflammation in the long term), in order to normalise nasal mucus and improve symptoms.
To assess the effects of systemic and topical antibiotics in people with chronic rhinosinusitis.
The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; CENTRAL (2015, Issue 8); MEDLINE; EMBASE; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 29 September 2015.
Randomised controlled trials (RCTs) with a follow-up period of at least three months comparing systemic or topical antibiotic treatment to (a) placebo or (b) no treatment or (c) other pharmacological interventions.
We used the standard methodological procedures expected by Cochrane. Our primary outcomes were disease-specific health-related quality of life (HRQL), patient-reported disease severity and the commonest adverse event - gastrointestinal disturbance. Secondary outcomes included general HRQL, endoscopic nasal polyp score, computerised tomography (CT) scan score and the adverse events of suspected allergic reaction (rash or skin irritation) and anaphylaxis or other very serious reactions. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.
We included five RCTs (293 participants), all of which compared systemic antibiotics with placebo or another pharmacological intervention.
The varying study characteristics made comparison difficult. Four studies recruited only adults and one only children. Three used macrolide, one tetracycline and one a cephalosporin-type antibiotic. Three recruited only patients with chronic rhinosinusitis without nasal polyps, one recruited patients with chronic rhinosinusitis with nasal polyps and one had a mixed population. Three followed up patients for 10 to 12 weeks after treatment had finished.
Systemic antibiotics versus placebo
Three studies compared antibiotics with placebo (176 participants).
One study (64 participants, without polyps) reported disease-specific HRQL using the SNOT-20 (0 to 5, 0 = best quality of life). At the end of treatment (three months) the SNOT-20 score was lower in the group receiving macrolide antibiotics than the placebo group (mean difference (MD) -0.54 points, 95% confidence interval (CI) -0.98 to -0.10), corresponding to a moderate effect size favouring antibiotics (moderate quality evidence). Three months after treatment, it is uncertain if there was a difference between groups.
One study (33 participants, with polyps) provided information on gastrointestinal disturbances and suspected allergic reaction (rash or skin irritation) after a short course of tetracycline antibiotic compared with placebo. We are very uncertain if antibiotics were associated with an increase in gastrointestinal disturbances (risk ratio (RR) 1.36, 95% CI 0.22 to 8.50) or skin irritation (RR 6.67, 95% CI 0.34 to 128.86) (very low quality evidence).
Systemic antibiotics plus saline irrigation and intranasal corticosteroids versus placebo plus saline irrigation and intranasal corticosteroids
One study (60 participants, some with and some without polyps) compared a three-month course of macrolide antibiotic with placebo; all participants also used saline irrigation and 70% used intranasal corticosteroids. Disease-specific HRQL was reported using SNOT-22 (0 to 110, 0 = best quality of life). Data were difficult to interpret (highly skewed and baseline imbalances) and it is unclear if there was an important difference at any time point (low quality evidence). To assess patient-reported disease severity participants rated the effect of treatment on a five-point scale (-2 for "desperately worse" to 2 for "cured") at the end of treatment (three months). For improvement in symptoms there was no difference between the antibiotics and placebo groups; the RR was 1.50 (95% CI 0.81 to 2.79; very low quality evidence), although there were also slightly more people who felt worse after treatment in the antibiotics group. There was no demonstrable difference in the rate of gastrointestinal disturbances between the groups (RR 1.07, 95% CI 0.16 to 7.10). General HRQL was measured using the SF-36. The authors stated that there was no difference between groups at the end of treatment (12 weeks) or two weeks later.
Systemic antibiotics versus intranasal corticosteroids
One study (43 participants, without polyps) compared a three-month course of macrolide antibiotic with intranasal corticosteroids. Patient-reported disease severity was assessed using a composite symptom score (0 to 40; 0 = no symptoms). It is very uncertain if there was a difference as patient-reported disease severity was similar between groups (MD -0.32, 95% CI -2.11 to 1.47; low quality evidence).
Systemic antibiotics versus oral corticosteroids
One study (28 participants, with polyps) compared a short course of tetracycline antibiotic (unclear duration, ~20 days) with a 20-day course of oral corticosteroids. We were unable to extract data on any of the primary efficacy outcomes. It is uncertain if there was a difference in gastrointestinal disturbances (RR 1.00, 95% CI 0.16 to 6.14) or skin irritation (RR 2.00, 95% CI 0.20 to 19.62) as the results for these outcomes were similar between groups (very low quality evidence).