Objectives: To assess the efficacy of topical (group 1) vs. oral (group 2) antibiotics  in paediatric chronic rhinosinusitis.
Methods: Retrospective controlled study. Patients were divided, after 4-week  treatment, into 3 categories (0, 1 or 2 or more symptoms). Outcome measured through  decrease in frequency of symptoms (chi-square test) and reduction in total symptoms  score (two sample t-test). 
Results: We included 99 patients (mean age 5.5y). The results showed no  significant difference in age (p=0.11), gender (p=0.98), or pre-treatment total  symptoms score (p=0.45). We found significant decrease in frequency of symptoms  post-treatment (p <0.05) and the symptom control was similar in both groups; 69.74%  symptom-free in group 1 vs. 47.83% in group 2 (p=0.06). The total symptom score  decreased more significantly in group 1 (p=0.01). We found no positive impact of  adjuvant therapy on the results.
Conclusion: Topical intranasal antibiotics might be as effective as oral antibiotics  in treating children with uncomplicated chronic rhinosinusitis. 

• Sinus

• Rhinosinusitis

• Antibiotics

• Topical

• Pediatrics

Barazi R, Bawab I, Dunia G, Bitar MA (2016) The Use of Topical Intranasal Antibiotics in Pediatric Chronic Rhinosinusitis. Ann Otolaryngol Rhinol 3(12): 1150.

Chronic Inflammation of the nasal cavities and the paranasal sinuses is not an uncommon finding in the paediatric population [1]. Children are known to have an immature immune response [1]. They are also exposed to a significant and variable viral load in their daily activities herd community. The result is a higher incidence of viral upper respiratory tract infections [1]. The concomitant nasal mucosal inflammation, edema and dysfunction of the muco-ciliary clearance system set the stage for superimposed bacterial rhinosinusitis; not to mention the active role of the adenoids in sinonasal infections [2].

The frequency and severity of such episodes are aggravated by any background of atopy, exposure to environmental toxins, immunodeficiency and/or anatomical abnormality [3]. Iatrogenic aggravators of chronic rhinosinusitis (CRS) include the unwise and untimely use of antibiotics which have led to a rise in resistant bacterial strains [4]. A mainstay of treatment of CRS is nasal topical steroids, nasal saline wash in addition to systemic antibacterial agents [5,6]. However, given certain age groups, compliance has been a huge obstacle. With recalcitrant cases, conflicting evidence has suggested a role for (1) broader spectrum penicillin (2) prolonged low-dose erythromycin therapy (3) prolonged IV antibiotics and (4) topical antibiotic delivery [7]

Given the efficacy of systemic antibiotics and their therapeutic concentration in nasal mucosa, one would argue against any benefit from topical antimicrobial treatment. However, the latter would deliver high concentrations of active drug with the advantage of less systemic exposure; hence causing less alterations in endogenous flora and development of resistance. Not to mention the proposed role for local antimicrobials against biofilm infections [8]. The pharmacologic rational behind aerosolized antibiotics lies in the need for lower systemic concentrations to achieve mucosal therapeutic levels. This is evident in the indispensable role for intranasal topical antimicrobials in the management of recurrent infections and colonization with P. Aeruginosa in cystic fibrosis [9]. In addition, recent studies have accumulated evidence towards the use of topical antibiotics in the intensive care unit setting for the treatment of ventilator associated pneumonia and in patients with acute or chronic sinus infection with previous endoscopic sinus surgery [10-14].

We have reviewed our experience in treating children with CRS with topical intranasal antibiotics to assess its efficacy compared to oral antibiotics in a case control study.

After IRB approval, the medical records of all paediatric patients with CRS who presented to the senior author’s clinic between January 2003 and December 2012 were reviewed. The inclusion criteria included: age between 1 and 18 year old, symptoms of rhinosinusitis lasting for or more than three months, and endoscopic or radiologic signs of CRS according to the criteria mentioned in the European position paper on CRS [15]. The exclusion criteria included: immunosuppressed patients, cystic fibrosis patients, symptoms of rhinosinusitis of less than three months, patients older than 18 year old, patient who underwent adenoidectomy and/or functional endoscopic surgery in the past, patients with moderate to severe septal deviation and patients who were lost to follow up. Diagnosis made clinically, and included nasal endoscopy.

All the included patients met the criteria of CRS and received the following treatment which consists of nasal saline spray application and either oral antibiotic or topical intranasal antibiotic via a spray for 4 weeks. The oral antibiotic used was amoxicillin-clavulanic acid for three weeks and if penicillin allergy existed then clarithromycin was used. The topical intranasal antibiotic consisted of ciprofloxacin in nasal saline used as 2 puffs in each nostril twice daily for 4 weeks. The solution was prepared as follow: a ready-made 30 ml saline spray solution was used where 5 ml of saline was removed and 10 ml of ciprofloxacin (at a concentration of 0.3%) ear drop was added giving a final ciprofloxacin concentration of 0.085%. Our use of ciprofloxacin for topical intranasal application is off-label, but the concentration used is much more diluted than the one approved for ear application (0.085% vs. 0.2-0.3%) and the amount used is small (the application is in the form of a spray and not a nasal wash with a bulb).

The patients received either type of treatment depending on the parents’ decision. The parents were given the option to choose either the conventional treatment (oral antibiotics) or the suggested topical option. The parents were instructed to follow strictly our instructions and to call us if there is any concern regarding the treatment.

On follow-up visit after 4 weeks, care was taken to ensure that the prescribed treatment was accurately followed. Those found to be non-compliant, were not included in this study. We gathered the patients who received intranasal antibiotics into group 1 and those who received the oral antibiotics into group 2.

Data collected included age; gender; medication received; presenting and post-treatment symptoms including nasal congestion, mucopurulent rhinorrhea, purulent crust, headache, halitosis, night-time cough and postnasal drip. Any use of concomitant adjuvant therapy, like antihistamine, nasal steroid, was reviewed.

The demographic data was compared between both groups using the wicoxon rank sum test. All reviewed patients had at least 2 symptoms of CRS at presentation. We classified the patients after treatment into 3 categories: category 1 included patients with no symptoms, category 2 had patients with 1 remaining symptom and category 3 included patients with persistent 2 or more symptoms (i.e. indicating no improvement).

The various reviewed variables were compared between both groups using the chi-square test (e.g. pre-treatment symptoms, adjuvant therapy, post-treatment symptoms). The clinical improvement was measured by the degree of reduction in total symptoms; and the change in number of symptoms from pre- to post-treatment was compared between both groups using the two-sample t-test.

We retrospectively reviewed the prospectively collected data that was documented during treatment. We included a total of 99 patients who met the inclusion criteria and were found to be compliant to the prescribed treatment. Their age ranged between 1 and 13.5 years (mean 5.3y), with 60 M and 39 F. Seventy-six patients were included in group 1, and 23 patients in group 2. The mean age of patients in group 1 is 5.1y compared to 5.9y in group 2, with no significant difference (p=0.110) (Figure 1).

Figure 1: Age distribution of patients belonging to groups 1 and 2.

Group 1 included 46 males and 30 females while group 2 included 14 males and 9 females. The gender difference was not statistically significant (p=0.976).

The symptoms that were reported in each group prior and post treatment included nasal congestion, mucopurulent rhinorrhea, purulent crust, headache, halitosis, night-time  cough and postnasal drip. The frequency of various symptoms prior to treatment in both groups was similar with no statistical significant difference except for nasal obstruction (Table 1).

Table 1: The incidence of various CRS symptoms in both groups prior to treatment.

The presence of nasal obstruction prior to treatment was associated with more improvement in symptoms, regardless of kind of treatment (p?0.001). The distribution of total number of pre-treatment symptoms (Table 2)

Table 2: Distribution of pre-treatment symptoms.

did not show statistically significant difference between both groups (p=0.447).

Adjuvant therapy, including antihistamine (desloratadine), montelukast, nasal steroid (mometasone furoate) and topical decongestant (xylometazoline), was used differently among the patients of both groups but the difference between the 2 groups was not statistically significant except for antihistamine and decongestant’s use (Table 3).

Table 3: The use of adjuvant therapy in both groups.

Regardless of the type of treatment (oral or topical antibiotics), the use of topical intranasal decongestants was associated with less favourable outcome, p=0.003 (i.e. negative effect on the decrease in number of symptoms), while the use of antihistamine had no impact on the degree of change in symptoms (p=0.688).

At the end of treatment, the patients’ symptoms were checked and compared to those present prior to treatment. Regardless of the treatment’s type, all symptoms improved at the end of the treatment course (Table 4).

Table 4: The prevalence of CRS symptoms in all enrolled patients prior to and after treatment.

When we looked at the change in symptoms in each group, both groups had significantly less symptoms compared to prior to treatment and the difference between the 2 groups was not statistically significant (Table 5).

Table 5: The prevalence of CRS symptoms post treatment, in each group.

Looking at the total number of remaining symptoms after treatment, there was again no statistically significant difference between both groups, though group 1 showed a trend towards better symptom control compared to group 2 (69.7% of patients in group 1 have no symptoms compared to 47.8% in group 2, p= 0.06) (Table 6).

Table 6: Total number of symptoms post-treatment.

We then looked at the magnitude of decrease in the total number of symptoms (Table 7).

Table 7: The mean reduction in the total number of symptoms post treatment

It was interesting to find that there was more statistically significant decrease in the total number of symptoms in the topical treatment group compared to the oral antibiotic group (p=0.009) (Figure 2).

Figure 2: Comparison of the magnitude of reduction in CRS symptoms among patients belonging to both groups.

Chronic rhinosinusitis in children has not been well studied compared to adults. A lot of the data on paediatric CRS is extrapolated from adult studies. Paediatric CRS is considered a multifactorial inflammatory disease, which treatment is more challenging due to the presence of adenoid pathology (infection or hypertrophy) and frequent upper respiratory tract infection [3].

So far, and according to the European position paper on rhinosinusitis and nasal polyps 2012, there is no evidence based treatment for children with CRS [15]. The available data favours long-term over short-term oral antibiotics, intranasal topical corticosteroid, and nasal saline washes [15]. More recently, a Clinical Consensus Statement on CRS seconded these three treatment options, with endorsement of the 20 days’ course of oral antibiotics [6].

Though they are still the mainstay of treatment of CRS, oral antibiotics may not be very effective in the presence of bacterial biofilms, which have been demonstrated in the nasal cavities and the adenoids of children with CRS [2]. In a recent study by Doht et al., lower effects of IV-antibiotic treatment was found on sinonasal than on pulmonary inflammatory markers, highlighting the limited effect of systemic antibiotics in controlling sinus infection [16]. Topical antibiotics may be seen as a potential alternative to systemic antibiotics in treating CRS as they have the ability to reach directly and safely to the affected site in a high concentration which cannot be attained systemically without antibiotic toxicity [5]. In fact, the usage of topical intranasal antibiotics has been practiced in the treatment of cystic fibrosis patients to eradicate early infection, as prophylaxis to prevent infections or as a chronic suppressive treatment [8].

Although no randomized controlled trials exist, many studies done in the adult population showed benefit of nebulized antibiotics as a treatment of acute and/or chronic sinusitis in patients post endoscopic sinus surgery [11-14]. A study by Scheinberg et al., even showed that nebulized antibiotic is safe and effective in patients with acute exacerbation of chronic rhinosinusitis, post endoscopic sinus surgery, who failed systemic antibiotics.14 A systemic review done by Lim et al showed that topical antibiotics appear to be effective in the management of chronic rhinosinusitis [11]. Another study by Wahl et al showed that intranasal nebulized antibiotics should be used in patients with chronic rhinosinusitis who failed PO systemic antibiotics before proceeding to intravenous antibiotics and/or endoscopic sinus surgery [17].

Topical intranasal antibiotic therapy is an appealing modality that may increase compliance of the parents in treating their children. We have tried in this study to see if it can substitute the conventional oral antibiotic treatment, by providing at least an equivalent efficacy in relieving the symptoms of CRS. According to our findings, intranasal topical antibiotic treatment might have the same efficacy of oral antibiotics in resolving the symptoms of patients with CRS. In fact, intranasal antibiotic treatment reduced more significantly the symptoms of CRS compared to oral antibiotic regimen. In addition, we noticed a trend, though not statistically significant, towards better improvement in the group receiving the intranasal antibiotic.

A number of variables is considered when designing a topical intranasal antibiotic; activity against the probable pathogens, the minimum inhibitory concentration and the delivery method (drops, spray, washes or nebulized) [8]. These factors are affected by the site being treated (nose, sinus, lungs), the availability of a budget, and the ability to prepare the requested solution in the desired delivery system. The availability of such preparation to the outpatients is limited and not present in all countries. Though our treatment was not culture guided, we chose ciprofloxacin as the treatment agent in our study because it has good coverage for staphylococcus species, pseudomonas, and streptococcus pneumonia. Ciprofloxacin is readily available for topical use as an otic or ophthalmic solution. We chose the cheapest and easiest way to deliver the topical intranasal antibiotic treatment.

Despite the for-mentioned advantages, one should not overlook the possible drawback of this treatment modality. These may include an allergic reaction to one of the ingredients, the unknown typical concentration to be used and the difficulty in reaching the sinus mucosa. The treatment may need to be repeated as the presumed biofilms are still residing in the adenoids. Though removing the adenoids does not ensure a complete cure of CRS, their presence poses a high risk factor for recurrence of the disease, and thus the need to repeat the topical treatment [2,4,7]. On the other hand, our patients did not have sinus surgery prior to treatment and as such did not have open sinus cavities that make delivery of the medication more convenient. Therefore, one can assume that the used antibiotic could only target pathogens present in the nasal cavities, middle meatus and or nasophayrnx. This may be enough in the paediatric patients in whom the adenoids play an important role in the pathogenesis of rhinosinusitis. In addition, cultures from the middle meatus are known to correlate well with those of the adenoids in children with CRS [2]. Whether the antibiotic is targeting the pathogens in the middle meatus and or adenoids, the observed improvement in the symptoms that might be comparable to that of oral antibiotics seems to be supportive of this assumption.

Although topical antibiotic therapy for management of CRS is not part of the recommended treatment, [6,15] our preliminary results with may encourage other colleagues to perform further similar studies taking into consideration the followings:

- To take a culture from the middle meatus pre and post treatment (if feasible)

- To compare different delivery methods (spray, washes, nebulized)

- To conduct single or double blinded controlled trial where in addition to the oral and topical antibiotic groups, a third control group is added to receive a topical saline solution.

- To have a long follow-up on these patients to study the need for repeated courses of such treatment. Our study has a few limitations :

1. It is a retrospective study

2. Parents decided on the treatment option (topical versus systemic)

3. We completely relied on the chart when reporting symptoms in the data sheet. Severity of symptoms was not captured.

4. We do not have a long follow up period.

Topical intranasal antibiotics might be as effective as oral antibiotics in treating children with uncomplicated CRS. The significant ability of the topical intranasal antibiotics to cause symptoms reduction is encouraging and would invite further studies in the future, preferably prospective controlled, to confirm these findings. This treatment may have a temporary relieving effect and may need to be repeated. Longer follow-up periods would clarify that.

We would like to thank Ms Liz Barnes from the National Health & Medical Research Council (NHMRC), Clinical Trials Centre, University of Sydney, for helping in the statistical analysis.

This study was presented on the podium of the annual meeting of the Australian Society of Otolaryngology Head & Neck Surgery, Sydney, Australia (8 Mar 2015).

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