European Review for Medical and Pharmacological Sciences
Fluticasone nasal spray as an adjunct to
Amoxicillin for acute sinusitis in children:
a randomized controlled trial
M.B. RAHMATI, S. MOHEBI1, S. SHAHMOHAMMADI2, M.S. REZAI3
Department of Pediatrics, 1Department of ENT, Hormozgan University of Medical Sciences,
Bandarabas, Iran
2
Journal of Pediatrics Review, Mazandaran University of Medical Sciences, Sari, Iran
3
Department of Pediatrics, Antimicrobial Resistant Nosocomial Infection Research Center
Mazandaran University of Medical Sciences, Sari, Iran
Abstract. BACKGROUND: Approximately
0.5-2% of upper respiratory tract infections in
adults and 6-13% of viral upper respiratory tract
infections in children are complicated by acute
sinusitis. This study was aimed to evaluate the
coadministration effect of fluticasone nasal
spray (FNS) with amoxicillin for AS in children.
PATIENTS AND METHODS: One hundred chil-
dren 2 to 14 years of age with acute sinusitis re-
ferred to Shahid Mohammadi Pediatric Hospital
in Bandar Abbas were randomly allocated into
two equal intervention and control groups to re-
ceive amoxicillin with fluticasone nasal spray
one puff twice daily for 14 days and amoxicillin
80 to 100 mg/kg/ day for 14 days respectively.
RESULTS: Twenty one (42%) of children in in-
tervention group were cured completely and 2
(4%) children in control group had complete re-
covery (p < 0.001). Symptom severity score was
22.98 2.95 before treatment that reduced to
13.26 3.20 after treatment (p < 0.001).
CONCLUSIONS: Use of fluticasone can reduce
the severity of symptoms of sinusitis in children.
Key Words:
Fluticasone nasal spray, Amoxicillin, Acute sinusitis
pediatrics, Randomized controlled trial.
Introduction
Acute sinusitis (AS) is an infection of the
paranasal sinuses with inflammation of the nose.
Association of viral upper respiratory-tract infec-
tion with common colds is the most common
cause of acute sinusitis known as acute rhinosi-
nusitis1. Approximately, 6-13% of viral upper
respiratory tract infections in children are com-
plicated by the development of acute bacterial si-
nusitis (ABS)2-4. The most pathogens involved in
AS are Streptococcus pneumoniae, Haemophilus
influenzae and Moraxella catarrhalis5.
3068 Corresponding Author: Mohammad Sadegh Rezai, MD; e-mail: drmsrezaii@yahoo.com
2013; 17: 3068-3072
Paranasal sinuses are usually sterile. Although,
the membranes that cover the sinuses are similar
to nasal membranes, they may become contami-
nated with bacteria colonized in the nose and na-
sopharynx. Contaminated with bacteria are usu-
ally removed by mucociliary clearance. When
this defense mechanism is impaired, secondarily
infection by inoculated bacteria in sinuses cavi-
ties may develop to AS. Viral upper respiratory
tract infections are the most important risk factor
for the development of ABS6.
Kindergarten children are at higher risk of in-
fection. Also, allergic rhinitis is another impor-
tant risk factor7. Upper respiratory tract infection
can lead to swelling and possibly immune re-
sponse deficiency through topical and systemic
pathway8.
Clinical symptoms, radiographic findings,
clinical course, persistence and severity of symp-
toms of AS in children are similar to the upper
respiratory tract infection. Then this situation is
reversed and purulent discharge becomes clear
again that can be seen in the upper airway viral
infection without antimicrobial therapy. Children
with untreated AS are at higher risk of severe
complications, which may causes patients refer
with complications of the disease. Complications
may occur as a result of intraocular and intracra-
nial involvements. Findings that indicate the in-
tracranial development of the disease are includ-
ed swollen eyes with a combination of persistent
headache and vomiting, which may require hos-
pitalization, especially in older children. Other
neurologic complications are change in level of
consciousness, local neurological defects or
meningeal irritability signs9,10. Gold standard for
the diagnosis of AS is the performance of a sinus
aspirate that produces bacteria in high density
104 colony forming units (CFU) per mL4.
 Fluticasone nasal spray as an adjunct to Amoxicillin for acute sinusitis in children
The main point in the differential diagnosis of
AS is differentiating the disease from upper airway
viral infection, allergic rhinosinusitis and secondary
bacterial infections of paranasal sinuses. Clinical
course and severity of disease is important in differ-
entiating the two diseases. Non-complicated rhinos-
inusitis usually improve within 7 to 10 days without
treatment. Although AS may be improved without
treatment, antibiotic therapy can accelerate recovery
and reduce the risks of orbital and intracranial com-
plications. Differentiate between acute viral rhinosi-
nusitis and AS is extremely important because an-
tibiotic treatment is ineffective in acute viral rhinos-
inusitis and should be applied logically. Using an-
tibiotics in the treatment of AS is controversial.
Some have no believe to use of antibiotics because
of difficulty in distinguishing between viral rhinosi-
nusitis and AS that cure spontaneous11, while others
have known antibiotics as a cornerstone of treat-
ment of bacterial sinusitis. Also, the antibiotics have
to create cover against Streptococcus pneumoniae,
Haemophilus influenzae and Moraxella catarrhalis.
Other factors that should be considered are severity
of the symptoms of disease and previous use of an-
tibiotics12.
Inhaled corticosteroids reduce mucous mem-
branes inflammation that causes obstruction of
sinuses opening theorically. We found only one
study has shown the beneficial effects of inhaled
corticosteroids in addition to antibiotics in the
treatment of AS among children13 and the results
of other studies were different. So that further
studies are need in this field. This study aimed to
evaluate the effect of fluticasone nasal spray
(FNS) combined with amoxicillin for AS in chil-
dren 2 to 14 years of age.
Patients and Methods
This single-blind clinical trial was performed
on 100 children 2 to 14 years of age with acute
bacterial sinusitis referred to infectious and Oto-
laryngology Departments of Shahid Mohammadi
Pediatric Hospital in Bandar Abbas Port City.
The Ethic Committee of Research vice chancel-
lor of Hormozgan University of Medical Sci-
ences was approved the study and informed con-
sent from was obtained from the parents of chil-
dren asked to join the study.
The eligible patients with AS were randomly
allocated into two equal intervention and control
groups. The intervention group was assigned to
receive amoxicillin with FNS one puffs twice
daily for 14 days and the control group assigned
to receive only amoxicillin 80 to 100 mg/kg/ day
for 14 days.
Inclusion criteria were children 2 to 14 years
of age, development of AS based on criteria of
Americas Children Association include: com-
mon colds persistent more than 10 to 14 days
with nasal or postnasal discharge with any quali-
ty or common cold less than 10 days with puru-
lent nasal discharge, and 3 to 4 days rectal
recorded fever over 39C.
Patients that had ABS over 4 weeks, allergic
rhinitis, nasal obstruction due to deviated nasal
septum, nasal polyps, lack of parental coopera-
tion, contraindications to use of the studied medi-
cine and wound or lesion in the nasal mucosa
were excluded.
Physical examination was the diagnostic tech-
nique, because the graphy is not recommended
for diagnosis of AS. The patients were assigned a
severity score on basis of their presenting clinical
signs and symptoms. Each variable was scored as
0 for not affected, 1 for very little problem, 2 for
mild problem, 3 for moderately bad,4 for bad and
5 scored for severe.
The Specialists co-workers who assessed the
therapeutic effects and treatment complications
were blinded to the random allocation.
In addition to the therapeutic effect of fluticas-
one in acute bacterial sinusitis, its effectiveness
in improving associated symptoms such as
cough, headache, hoarseness, malaise, facial pain
and irritability were studied too.
Demographic characteristics including age,
sex, clinical symptoms such as fever, lethargy,
headaches, facial pain, toothache, purulent dis-
charge and nasal congestion have been recorded
in a self- structured form prepared by the re-
searchers. Complete recovery of symptoms was
recorded as a recovery day.
Clinical data were recorded in several stages;
before intervention, on day 4 by phone or visit of
the subject at the clinic and then on days 10 to 14
by follow-up.
Whenever, no improvement was seen in fever,
nasal congestion or cough or exacerbation of the
disease, patients were assessed again and the an-
tibiotics were changed if necessary at any time.
Patient was excluded if no improvement was ob-
served after the fourth day of therapeutic period.
Statistical Analysis
Collected data were analyzed by SPSS 17 sta-
tistical software (SPSS Inc., Chicago, IL, USA)
3069
 M.B. Rahmati, S. Mohebi, S. Shahmohammadi, M.S. Rezai

using statistical tests t-test and kappa coefficient.
p value of < 0.05 was used to indicate statistical
significance.
Results
In total, 100 patients were enrolled. Forthy-
eight (48%) of the patients were female and 52
(52%) were male. The mean age in intervention
and control group was 6.38 3.07 years and 7.28
2.54 years respectively.
Demographic and clinical characteristics of
patients in the two groups have demonstrated in
Table I. As shown in the table, clinical features
were almost similar at baseline of the study in the
both studied groups and the differences between
them are negligible.
Severity score of symptoms before treatment
was 22.46 2.61 in intervention group and 23.50
3.19 in control group and there was little differ-
ence between the two groups.
At the end of the treatment, symptom severity
score in intervention and control group was
11.68 2.66 and 14.84 2.92 respectively.
Symptom severity score in intervention group
was significantly lower than in the control group
at the end of the therapeutic period (p < 0.001).
Of the 50 children in intervention group, 21
(42%) were cured completely and 29 (58%) were
improved relatively. Whereas, 2 (4%) children in
control group had complete recovery and 48 (96%)
experienced relative improvement and the differ-
ence was statistically significant (p < 0.001).
As a whole, symptom severity score was 22.98
2.95 before treatment that reduced to 13.26
3.20 after treatment (p < 0.001).
Discussion
Although, in theory, inhaled corticosteroids can
be effective to reduce symptoms of acute sinusitis
and inflammation of the mucus membranes, few
clinical trials have shown the beneficial effect of
topical intranasal steroids in children14,15.
The results of this study demonstrated the ben-
eficial effect of co-administration of the amoxi-
cillin with fluticasone nasal spray (FNS) one puff
twice daily for 14 days compared with control

Table I. Comparison of clinical characteristics in the both groups after intervention.

Intervention group Control group

Characteristics Score No. (%) No. (%) p value

Congestion score 2 32 (64%) 10 (20%) < 0.001

3 16 (32%) 32 (64%)
4 2 (4%) 8 (16%)
Anterior discharge score 2 38 (76%) 3 (6%) < 0.001
3 11 (22%) 35 (70%)
4 1 (2%) 2 (4%)
Posterior discharge 2 42 (84%) 20 (40%) < 0.001
3 8 (16%) 28 (56%)
4 0 (0%) 2 (4%)
Fullness 1 44 (88%) 29 (58%) 0.001
2 5 (10%) 21 (42%)
Headache 1 46 (92%) 30 (60%) < 0.001
2 4 (8%) 20 (40%)
Toothache 1 46 (92%) 44 (88%) 0.370
2 4 (8%) 6 (12%)
Cough 1 32 (64%) 16 (32%) 0.005
2 16 (32%) 32 (64%)
3 2 (4%) 2 (4%)
Malodorous 1 45 (90%) 34 (68%) 0.006
2 5 (10%) 16 (32%)
Exhaustion 1 47 (92%) 47 (92%) 0.661
2 3 (6%) 3 (6%)
Fever 1 49 (98%) 49 (98%) 0.753
2 1 (2%) 1 (2%)
Recovery Complete 21 (42%) 2 (4%) < 0.001
Relative 29 (58%) 48 (96%)

3070
 Fluticasone nasal spray as an adjunct to Amoxicillin for acute sinusitis in children
group. We found that concurrent administration
of FNS and antibiotic therapy in management of
AS in children was associated with full recovery
in a greater percentage of the patients. The sever-
ity of symptoms after treatment was less in inter-
vention group compared with controls. Overall,
our findings indicate, the beneficial effects of flu-
ticasone in the treatment of sinusitis in children.
This beneficial effect of intranasal corticosteroid
is also seen in several similar studies with slight
different on patients with a history of chronic
rhinitis or recurrent sinusitis15.
Our study has also demonstrated that coad-
ministration of intranasal corticosteroids with an-
tibiotics significantly alleviate congestion, anteri-
or and posterior discharge, fullness, headache,
cough and malodorous breathing. This finding
has been supported by previous controlled trials
that have shown the benefit of intranasal corti-
costeroids with their known anti-inflammatory
properties, with or without antibiotics in acute
rhinosinusiteis (ARS)16.
Also, Fluticasone positive effect on nasal ob-
struction, rhinorrhea, and postnasal discharge has
been shown in an investigation by Aukema et
al17. In a study reported by Hansen et al18, use of
Fluticasone has been associated with reduction of
mucosal edema in sinusitis. Our work showed no
positive effects of fluticasone on tooth pain, fa-
tigue and fever. Similar results have also reported
by Dijkstra et al19. However, the difference be-
tween the former study with ours was they found
no positive therapeutic effect by fluticasone pro-
pionate aqueous nasal spray (FPANS) compared
with placebo. Although we observed no thera-
peutic effect of fluticasone expect for the three
mentioned above symptoms, it was preferred for
the treatment of other symptoms.
In Parikh20 and Dolor et al15, other positive as-
pects of Fluticasone implications that was not
consider by our investigation has reported, like as
rapid improvement of the symptoms of the dis-
ease. They have both concluded that the use of
fluticasone in patients with sinusitis can acceler-
ate recovery.
Conclusions
This study showed that use of fluticasone
nasal spray can reduce the severity of symptoms
of sinusitis in children. It is suggested that this
treatment should be considered in children with
acute sinusitis.
Conflict of Interest
The Authors declare that they have no conflict of interests.
References
1) CHERRY JD, SHAPIRO NL. Sinusitis. In: Feigin RD,
Cherry JD, Demmler-Harrison GJ, Kaplan SL
(Eds). Textbook of Pediatric Infectious Diseases,
6th ed. Saunders, Philadelphia 2009; p. 201.
2) WALD ER, N ASH D, E ICKHOFF J. Effectiveness of
amoxicillin/clavulanate potassium in the treatment
of acute bacterial sinusitis in children. Pediatrics
2009; 124: 9-15.
3) FENDRICK AM, SAINT S, BROOK I, JACOBS MR, PELTON S,
SETHI S. Diagnosis and treatment of upper respira-
tory tract infections in the primary care setting.
Clin Ther 2001; 23: 1683-1706.
4) WALD ER, GUERRA N, BYERS C. Upper respiratory
tract infections in young children: duration of and
frequency of complications. Pediatrics 1991; 87:
129-133.
5) WALD ER. Microbiology of acute and chronic si-
nusitis in children and adults. Am J Med Sci 1998;
316: 13-20.
6) REVAI K, DOBBS LA, NAIR S, PATEL JA, GRADY JJ, CHON-
MAITREE T. Incidence of acute otitis media and si-
nusitis complicating upper respiratory tract infec-
tion: the effect of age. Pediatrics 2007; 119:
e1408-1412.
7) WALD ER, DASHEFSKY B, BYERS C, GUERRA N, TAYLOR F.
Frequency and severity of infections in day care. J
Pediatr 1988; 112: 540-546.
8) CARSON JL, COLLIER AM, HU SS. Acquired ciliary de-
fects in nasal epithelium of children with acute vi-
ral upper respiratory infections. N Engl J Med
1985; 312: 463-468.
9) GOYTIA VK, GIANNONI CM, EDWARDS MS. Intraorbital
andintracranial extension of sinusitis: comparative
morbidity. J Pediatr 2011; 158: 486-491.
10) HICKS CW, WEBER JG, REID JR, MOODLEY M. Identify-
ing and managing intracranial complications of si-
nusitis in children: a retrospective series. Pediatr
Infect Dis J 2011; 30: 222-226.
11) GARBUTT JM, GOLDSTEIN M, GELLMAN E, SHANNON W,
LITTENBERG B. A randomized, placebo-controlled tri-
al of antimicrobial treatment for children with clini-
cally diagnosed acute sinusitis. Pediatrics 2001;
107: 619-625.
12) SLAVIN RG, SPECTOR SL, BERNSTEIN IL, KALINER MA,
KENNEDY DW, VIRANT FS, WALD ER, KHAN DA, BLESS-
ING-MOORE J, LANG DM, NICKLAS RA, OPPENHEIMER JJ,
P ORTNOY JM, S CHULLER DE, T ILLES SA, B ORISH L,
NATHAN RA, SMART BA, VANDEWALKER ML; AMERICAN
ACADEMY OF ALLERGY, ASTHMA AND IMMUNOLOGY; AMERI-
CAN COLLEGE OF ALLERGY, ASTHMA AND IMMUNOLOGY;
JOINT COUNCIL OF ALLERGY, ASTHMA AND IMMUNOLOGY.
The diagnosis and management of sinusitis: a
practice parameter update. J Allergy Clin Immunol
2005; 116(6 Suppl): S13-S47.
3071
 M.B. Rahmati, S. Mohebi, S. Shahmohammadi, M.S. Rezai
13) B ARLAN IB, E RKAN E, B AKIR M, B ERRAK S, B A ARAN
MM. Intranasal budesonide spray as an adjunct
to oral antibiotic therapy for acute sinusitis in
children. Ann Allergy Asthma Immunol 1997; 78:
598-601.
14) MELTZER EO, ORGEL HA, BACKHAUS JW, BUSSE WW,
DRUCE HM, METZGER WJ, MITCHELL DQ, SEINER SC,
SHAPIRO GG, VAN BAYEL GH. Intranasal flunisolide
spray as an adjunct to oral antibiotic therapy for
sinusitis. J Allergy Clin Immunol 1993; 92: 812-
823.
15) DOLOR RJ, WITSELL DL, HELLKAMP AS, WILLIAMS JW
JR, CALIFF RM, SIMEL DL. Comparison of cefurox-
ime with or without intranasal fluticasone for the
treatment of rhinosinusitis: the CAFFS Trial: a
randomized controlled trial. JAMA 2001; 286:
3097-3105.
16) ZALMANOVICI A, YAPHE J. Steroids for acute sinusi-
ti s. C ochrane D atabas e Sy s t R ev 2007;
CD005149.
3072
17) AUKEMA AA, MULDER PG, FOKKENS WJ. Treatment of
nasal polyposis and chronic rhinosinusitis with flu-
ticasone propionate nasal drops reduces need for
sinus surgery. J Allergy Clin Immunol 2005; 115:
1017-1023.
18) HANSEN FS, DJUPESLAND PG, FOKKENS WJ. Prelimi-
nary efficacy of fluticasone delivered by a novel
device in recalcitrant chronic rhinosinusitis. Rhi-
nology 2010; 48: 292-299.
19) DIJKSTRA MD, EBBENS FA, POUBLON RM, FOKKENS WJ.
Fluticasone propionate aqueous nasal spray does
not influence the recurrence rate of chronic rhi-
nosinusitis and nasal polyps 1 year after function-
al endoscopic sinus surgery. Clin Exper Allergy
2004; 34: 1395-1400.
20) PARIKH A, SCADDING GK, DARBY Y, BAKER RC. Topical
corticosteroids in chronic rhinosinusitis: a ran-
domized, double-blind, placebo-controlled trial us-
ing fluticasone propionate aqueous nasal spray.
Rhinology 2001; 39: 75-79.