ANL-1589; No. of Pages 6

Effect of nasal mometasone furoate on the nasal and nasopharyngeal flora

Fadlullah Aksoy a, Hasan Demirhan b, Gulum Ivgin Bayraktar b, Yavuz Selim Yıldırım c,*,Orhan Ozturan a, Nevriye Gonullu d, Burcu Sapmaz d

a Bezmialem Vakıf University, Medical Faculty, Department of Otorhinolaryngology and Head and Neck Surgery, Istanbul, Turkeyb Haseki Research and Training Hospital, Department of Otorhinolaryngology and Head and Neck Surgery, Istanbul, Turkey

c Elbistan State Hospital, Department of Otorhinolaryngology and Head and Neck Surgery, Kahramanmaras, Turkeyd Microbiology and Clinical Microbiology Department, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey

Received 3 February 2011; accepted 22 July 2011

Abstract

Objective: Mometasone furoate (MF) is one of the commonly used topical steroids, particularly for patients with allergic rhinitis. However,

its effect on the colonization of bacteria that may cause superinfections by suppressing the local immunity is not known. Thus, we investigated

the effect of MF use on the nasal and nasopharyngeal microbial flora.

Materials and methods: Swab samples were taken from 35 patients who required MF monotherapy, just before and after one month of the

treatment. Samples were maintained in Stuart’s medium. Each swab was transferred to 1 ml of a sterile saline solution, then into the standard

agar. After incubation under 5% carbon dioxide at 37 8C, colony number was detected per ml.

Results: Colony counts of nasal or nasopharyngeal microbial flora did not show any statistically significant alteration with one month use of

MF. However, an increase in potential pathogens as well as normal flora bacteria was determined in five of the patients and six patients

acquired new nasopharyngeal potential pathogens, mostly Moraxella catarrhalis, Pseudomonas aeruginosa and Staphylococcus aureus,

following the use of MF.

Conclusion: The use of MF for one month did not statistically significantly change the nasal and nasopharyngeal flora. This study indicates

that MF could be increase the colonization of the potential pathogens in some of the patients at the subclinical level particularly in the

nasopharyngeal area.

# 2011 Elsevier Ireland Ltd. All rights reserved.

Keywords: Allergic rhinitis; Microflora; Corticosteroid therapy; Bacterial colonization; Colony forming unit

www.elsevier.com/locate/anl

Auris Nasus Larynx xxx (2011) xxx–xxx

1. Introduction

Topical corticosteroid preparations are prescribed fre-

quently in otorhinolaryngology clinical practice. One of the

main aims of their use is the treatment of the inflammation in

nasal and paranasal sinus diseases; they are particularly very

effective in the treatment of allergic rhinitis [1]. They have

an important advantage of minimizing the adverse effects of

systemic steroid administration, including adrenal suppres-

Please cite this article in press as: Aksoy F, et al. Effect of nasal momet

Larynx (2011), doi:10.1016/j.anl.2011.05.008

* Corresponding author at: Elbistan Devlet Hastanesi Kulak Burun Bogaz

Klinigi, 46300, Karaelbistan, Kahramanmaras, Turkey.

Tel.: +90 344 4138001; fax: +90 344 4138005.

E-mail address: dryavuzselim@yahoo.com (Y.S. Yıldırım).

0385-8146/$ – see front matter # 2011 Elsevier Ireland Ltd. All rights reserved

doi:10.1016/j.anl.2011.05.008

sion [2,3]. Their topical administration to nasal mucosa

results quick anti-inflammatory response with only a few

adverse effects such as local nasal irritation and epistaxis

being the major ones [4,5]. Complaints related to nasal

irritation and reactive sneezing disappear in a few days.

Further, they can be used for long period of time, especially

by the patients with allergic rhinitis, according to the

duration of their complaints [6].

Mometasone furoate (MF) is one of the topical steroids

which has a widespread usage in dermatological disorders,

nasal polyposis and allergic rhinitis [7]. It is effective and

safe as monotherapy in patients with acute, uncomplicated

rhinosinusitis [8]. Smith et al. has reported that MF has a

high affinity for the glucocorticoid receptor and minimal

asone furoate on the nasal and nasopharyngeal flora. Auris Nasus

.

F. Aksoy et al. / Auris Nasus Larynx xxx (2011) xxx–xxx2

ANL-1589; No. of Pages 6

Table 1

Normal flora and potential pathogens isolated from nasal and nasopharyn-

geal mucosa of the patients before and after the treatment with MF. Data are

reported as number of patients (n) and the percentage (%) in total of 35

patients.

Number of culture positive patients Treatment

Before, n (%) After, n (%)

Nasal

Total 20 (57) 27 (77)

Micro flora 16 (46) 22 (63)

Potential pathogens 7 (20) 8 (23)

Microflora + potential pathogens 3 (9) 3 (9)

Nasopharyngeal

Total 34 (97) 32 (91)

Micro flora 33 (94) 27 (77)

Potential pathogens 15 (43) 14 (40)

Microflora + potential pathogens 14 (40) 9 (26)

systemic absorption therefore it can be considered as a

potent agent with the advantage of minimal side effects [9].

It has been determined that long term use of MF in patients

with perennial rhinitis does not adversely affect the nasal

mucosa as no atrophy or no change in epithelial thickness

was obtained in biopsy samples of the nasal mucosa [10].

Further, MF treatment reconstruct normal epithelial archi-

tecture and function in patients with perennial rhinitis by

reversing the changes in the epithelium due to inflammation

and glandular alteration [11].

Although well tolerated steroids have common adverse

effects such as epistaxis, headache and pharyngitis [12],

there is not any information in the literature about the effect

of nasal steroids on nasal or nasopharyngeal microbial flora

whether it could accelerate the colonization of bacteria and

cause superinfections by suppressing the local immunity or

modify the local defense systems. Hence, the aim of this

study was to determine the alteration in nasal and

nasopharyngeal microbial flora of the patients treated with

MF monotherapy comparing the culture results of nasal or

nasopharyngeal microbial flora of the patients just before

and after the administration of MF for one month.

2. Materials and methods

This prospective cross-sectional study investigates the

effects of MF on nasal and nasopharyngeal microbial flora in

patients with the complaints of persistent allergic rhinitis for

at last one year and nasal concha hypertrophy. The study was

carried out in Education and Research Hospital, 1st

Otorhinolaryngology Outpatient Clinic. Patients were

recruited during spring and summer seasons. Allergic

rhinitis was diagnosed with prick test. Patients with diabetes

mellitus or another chronic disease, using another agent,

systemic steroid, or immunosuppressant were excluded.

Patients with alcohol or smoking habits were also excluded.

Totally, 35 patients (20 female, 15 male) older than 18 year

old (18–35 year old) were included in the study. Study

protocol was reviewed by Haseki Education and Research

Hospital Ethics Committee. All of the patients were

informed about the study and approval forms were obtained.

Nasal and nasopharyngeal cultures of the patients were

taken just before and after one month of administration of

nasal MF (200 mg/day) twice daily. Swabs and samples

taken after the end of the treatment. Nasal and nasophar-

yngeal swabs taken from the patient with seat position.

Nasal swabs taken each nasal cavity and near the middle

meatus via nasal endoscope. Nasopharyngeal swabs taken

through orally route, under the uvula. The uvula pulled

forward and curved swab touched. Nasal and nasophar-

yngeal swabs were transferred and maintained in Stuart’s

medium and were sent to the Department of Microbiology

and Clinical Microbiology of Cerrahpasa Medical Faculty

within 30 min. After collection, each swab was transferred

to a tube containing 1 ml of a sterile saline solution. The

Please cite this article in press as: Aksoy F, et al. Effect of nasal momet

Larynx (2011), doi:10.1016/j.anl.2011.05.008

swab was discarded after the agitation of the tube on a vortex

mixer (500 rpm) for 1 min. A loop containing 0.01 ml

sample solution was transferred to a 5% sheep blood agar, a

chocolate agar and another 0.01 ml of the same solution was

transferred to a MacConkey agar plate. The inoculate was

spread homogeneously on the entire surface of the medium

and the plates were incubated under 5% carbon dioxide at

37 8C and examined at 24 and 48 h. The number of each type

of colony grown on the agar plates multiplied by 100

represented the total number of each bacteria found in

different nasal and nasopharyngeal regions [13,14] and

referred as colony forming unit (cfu).

Isolates were identified using conventional methods [15].

b-Lactamase production by Haemophilus influenzae was

assessed using the nitrocefin disk assay (Cefinase BBL,

Cockeysville, USA).

Impact of the use of MF on the nasal and nasopharyngeal

microbial flora was evaluated with Wilcoxon test. SPSS 16.0

program was used for the statistical analysis. Differences at

the level of P < 0.05 were accepted to be statistically

significant.

3. Results

In order to determine the possible alteration of the nasal

and nasopharyngeal microbial flora after the use of MF, 35

patients were included for evaluation. Alpha hemolytic

streptococci, Neisseria species, Gram positive rods, methi-

cilin-sensitive coagulase-negative staphylococci (MSCNS)

and methicilin-resistant coagulase-negative staphylococci

(MRCNS) were assessed as normal nasal and nasophar-

yngeal flora, whereas beta-hemolytic streptococci, Strepto-

coccus pneumoniae, Moraxella catarrhalis, H. influenzae,

methicilin-sensitive Staphylococcus aureus (MSSA), methi-

cillin-resistant S. aureus (MRSA), Pseudomonas and

Proteus species, Escherichia coli and lastly enterococci

were detected as potential pathogens (Tables 1 and 2).

asone furoate on the nasal and nasopharyngeal flora. Auris Nasus

F. Aksoy et al. / Auris Nasus Larynx xxx (2011) xxx–xxx 3

ANL-1589; No. of Pages 6

Table 2

Normal flora and potential pathogens isolated from nasal mucosa of the

patients before and after the treatment with MF. Data are reported as number

of patients (n) and the percentage (%) in total of 35 patients.

Normal flora Before treatment After treatment P value

n (%) n (%)

Alpha-hemolytic

streptoccoci

4 (11.4) 5 (14.2) 0.7179

Neisseria spp. 2 (5.7) 1 (2.8) 0.3594

Gram positive rods 3 (8.5) 8 (22.8) 0.625

MSCNS 6 (17.1) 7 (20) 0.3013

MRCNS 5 (14.2) 8 (22.8) 0.1514

Potential pathogens

Beta-hemolytic

streptococci

0 0 No growth

Streptococcus

pneumoniae

1 (2.8) 0 1

Moraxella

catarrhalis

1 (2.8) 3 (8.5) 0.375

Haemophilus

influenzae

0 1 (2.8) 1

MSSA 4 (11.4) 4 (11.4) 0.5781

MRSA 1 (2.8) 0 1

Pseudomonas spp. 0 0 No growth

Proteus spp. 0 0 No growth

Escherichia coli 0 0 No growth

Enterococci 0 0 No growth

Fig. 1. Scatter plot with mean showing colony forming units (CFU) of

microbial flora (normal microflora and potential pathogens) isolated from

nasal mucosa before and after MF treatment.

Statistical analysis of the data by Wilcoxon rank test did

not revealed any significant difference between the

colonization numbers of the each microorganism isolated

from nasal or nasopharyngeal mucosa before and after one

month MF treatment (Tables 1 and 2). However, cfu values

and types of normal or pathogenic bacterial flora, such as

MRSCN, Gram positive rods or some of the potential

pathogens, especially MRSA and M. catarrhalis, isolated

from several nasal and nasopharyngeal cultures showed

changes in individual patients.

3.1. Nasal cavity

Cultures from 20 patients produced at least one species of

bacterial growth before the MF treatment. Sixteen of these

patients had normal microflora, whereas 7 had potential

pathogen bacteria; 3 patients had both normal and pathogen

bacteria on their isolates. The average number of organisms

recovered per culture positive patient was 1.18 (Table 1).

After the treatment, the number of patients with at least

one species of bacterial growth increased to 27. Twenty-two

patients had normal flora, 8 had potential pathogen bacteria,

3 had both (Table 1).

Three patients did not show any type of bacterial growth

in any culture (before or after the treatment).

Before the treatment with MF, the most frequently

isolated bacteria of the normal nasal flora was MSCNS

(17.1%) whereas after the treatment it changed to Gram

positive rods and MRCNS, 22.8% for each (Table 1). Among

the pathogen bacteria both M. catarrhalis and MSSA were

Please cite this article in press as: Aksoy F, et al. Effect of nasal momet

Larynx (2011), doi:10.1016/j.anl.2011.05.008

found before and after the treatment. S. pneumoniae and

MRSA were isolated in two different patients before the

treatment and they were not isolated after one month MF

treatment. Haemophilus influenza was observed in one

patient after the treatment only. This patient showed also

new colonization of alpha-hemolytic streptococci after the

treatment. Pseudomonas species, E. coli, Proteus species,

enterococci and beta-hemolytic streptococci were not found

nor before neither after the treatment in the nasal cavity in

any patient (Table 2 and Fig. 1).

Overall, types of bacteria in the nasal cavity changed in

22 patients with the MF treatment.

3.2. Nasopharynx

Thirty-four patients had at least one species of bacterial

colonization in nasopharynx before the MF treatment. All

these patients except one had normal microflora bacteria.

Pathogen bacteria were isolated in the mucosal cultures of

15 patients. Fourteen patients had both types of micro-

organism. The average number of organisms recovered per

positive culture was 1.85 (Table 1).

Positive cultures for any type of bacteria were obtained in

32 patients after the treatment. The treatment decreased the

number of patients with normal flora to 27 whereas 14

patients had pathogenic bacterial growth in their cultures, 9

asone furoate on the nasal and nasopharyngeal flora. Auris Nasus

F. Aksoy et al. / Auris Nasus Larynx xxx (2011) xxx–xxx4

ANL-1589; No. of Pages 6

Fig. 2. Scatter plot with mean showing colony forming units (CFU) of

microbial flora (normal microflora and potential pathogens) isolated from

nasopharyngeal mucosa before and after MF treatment.

patients had both normal and pathogen bacterial growth

(Table 1).

Most of the patients had the colonization of alpha-

hemolytic streptococci in nasopharyngeal mucosa both

before and after the treatment (77.1% and 74.2%),

respectively (Table 3). The most frequently isolated

potential pathogen was M. catarrhalis; 17.1% of patients

before the treatment and 22.8% after the treatment had M.

catarrhalis in their cultures. The potential pathogens

MRSA, Pseudomonas or Proteus species were isolated in

the nasopharyngeal mucosa after the use of MF. However, no

colonization of H. influenza was observed before or after the

treatment (Table 3 and Fig. 2).

Overall, types of bacteria in the nasopharynx changed in

21 patients with the MF treatment.

4. Discussion

Nasal glucocorticoids are well defined common agents

used for localized anti-inflammatory responses when

administered topically to the nasal mucosa. MF is one of

the synthetic steroids which has been shown to be more potent

than beclomethasone dipropionate, betamethasone, dexa-

methasone, and hydrocortisone in inhibiting the synthesis and

release of proinflammatory mediators [16]. Because the

microbial flora activates the defensive mechanisms against

exogenous infectious pathogens, the interaction of the

external environment and mucosal surface area becomes to

be an important issue for initiation of the infections.

Please cite this article in press as: Aksoy F, et al. Effect of nasal momet

Larynx (2011), doi:10.1016/j.anl.2011.05.008

Table 3

Number and percentages of culture positive patients for normal flora and

potential pathogens isolated from nasopharyngeal mucosa. Data are

reported as number of patients (n) and the percentage (%) in total of 35

patients.

Normal flora Before treatment After treatment P value

n (%) n (%)

Alpha-hemolytic

streptoccoci

27 (77.1) 26 (74.2) 0.7221

Neisseria spp. 7 (20) 5 (14.2) 0.3346

Gram positive rods 2 (5.7) 3 (8.5) 0.5879

MSCNS 5 (14.2) 2 (5.7) 0.2809

MRCNS 6 (17.1) 1 (2.8) 0.0650

Potential pathogens

Beta-hemolytic

streptococci

3 (8.5) 0 0.2500

Streptococcus

pneumoniae

4 (11.4) 1 (2.8) 0.1975

Moraxella

catarrhalis

6 (17.1) 8 (22.8) 0.2152

Haemophilus

influenzae

0 0 No growth

MSSA 1 (2.8) 0 1.0000

MRSA 0 2 (5.7) 0.5000

Pseudomonas spp. 0 2 (5.7) 0.5000

Proteus spp. 0 1 (2.8) 1.0000

Escherichia coli 1 (2.8) 1 (2.8) 1.0000

Enterococci 1 (2.8) 1 (2.8) 1.0000

This is the first quantitative study examining the cfu/ml

from nasal and nasopharyngeal mucosa of patients with

allergic rhinitis treated with MF, a nasal corticosteroid. Here

we investigated bacterial flora on the basis of cfu/ml isolated

before and after the administration of MF for one month.

There was not any statistically significant difference

according to the overall bacteria colonization numbers

before and after the administration of MF in nasal and

nasopharyngeal cultures. However, the data from nasal or

nasopharyngeal mucosa of several patients showed note-

worthy increases in growth of some of the normal microbial

flora and potential pathogens.

Although we could not define any significant difference

in the alterations of microbial flora or potential pathogens

before and after use of MF, there was an increase in the

colonization of Gram positive rods, MSCNS, MRCNS, M.

catarrhalis and H. influenzae in the nasal cavity and

especially colonization of M. catarrhalis, Pseudomonas

species and MRSA in the nasopharynx. In addition to these,

after the treatment, potential pathogens such as Pseudomo-

nas and Proteus species or MRSA colonies were detected in

five of the patients with the colonizations of 5000–

10,000 cfu/ml in the nasopharynx although none of them

were positive before.

Recent studies indicated that bacterial infections or

colonization can influence the chronicity or severity of

chronic airway diseases such as asthma or perennial allergic

rhinitis. Gluck et al. has shown the high frequency of

potential pathogens in the nasopharyngeal mucosa of the

asone furoate on the nasal and nasopharyngeal flora. Auris Nasus

F. Aksoy et al. / Auris Nasus Larynx xxx (2011) xxx–xxx 5

ANL-1589; No. of Pages 6

patients with positive skin test to aeroallergens that could be

important for the pathogenesis of the allergic rhinitis [17].

Smith et al. showed that patients with perennial allergic

rhinitis have a significantly higher rate of nasal carriage of S.

aureus than nonallergic controls [9]. Furthermore, they also

found that the nasal symptom scores of the Staphlococcus

aureus-positive subjects were significantly higher than those

of non-carriers. In the present study 5.7% of the nasophar-

yngeal isolations were found to have MRSA whereas none of

the patients had MRSA colonization before the treatment.

Therefore, MF could raise the possibility of recurrence of the

disease by inducing the growth of some of the potential

pathogens in specific patients as indicated above. These

bacteria have clinical importance that they can cause life

threatening infectious diseases such as pneumoniae or

meningitis as well as some other infections like otitis,

sinusitis or pharyngitis [18]. It has been shown that 46 percent

of the patients with liver cirrhosis had positive nasal MSSA

[19]. S. aureus colonization that could cause osteomyelitis or

pnemoniae, has been shown to be present in the nasopharynx

of one third of adults [20].

Several patients showed an increase in the colonization of

alpha-hemolytic streptococci or Gram positive rods in the

nasal mucosa. The colonization number of alpha hemolytics

increased from 5000 to 10,000 and from 25,000 to

50,000 cfu/ml in two patients. Gram positive rods growth

was detected about 100,000 cfu/ml in some of the patients.

Besides, similar colonization numbers for Pseudomonas,

alpha hemolytics, Gram positive rods or M. catarrhalis were

found in the nasopharyngeal cultures of some patients.

Although these patients did not have any clinical outcome,

we cannot ignore this alteration effect of the MF.

Studies showed that MF at 200 mg dose twice daily,

improved symptoms of rhinosinusitis in uncomplicated

patients comparably to amoxicillin and placebo without

recurrence of the disease or bacterial infection [8]. Further, it

was shown that mometasone (0.5%) in buffer solution had in

vitro antibacterial activity against certain streptococci after

24 h incubation conditions but was found to be ineffective

against S. aureus, Pseudomonas aeruginosa and E. coli [21].

However, low concentrations caused an increase in CFUs of

Streptococcus milleri. Similarly, in the present study MF has

been found to reduce most of the pathogens such as S.

pneumoniae, MRSA in nasal cavity and beta-hemolytic

streptococci, S. pneumoniae, MSSA in the nasopharynx

while this effect was not found to be significant. Never-

theless, the clinical implications of these findings are not

clear since we have not correlated them with their clinical

outcome. The use of MF for one month did not statistically

significantly change the nasal and nasopharyngeal flora.

5. Conclusion

The use of intranasal corticosteroids in the treatment of

persistent allergic rhinitis and also rhinosinusitis has been

Please cite this article in press as: Aksoy F, et al. Effect of nasal momet

Larynx (2011), doi:10.1016/j.anl.2011.05.008

increasing in recent years. Studies show encouraging results

when the treatment groups are evaluated as a whole.

However, the results of the present study implicates that one

of the topical nasal corticosteroids, MF, could be increase

the colonization of the pathogens and potential pathogens in

some of the patients at the sub clinical level particularly in

the nasopharyngeal area.

The use of MF for one month did not statistically

significantly change the nasal and nasopharyngeal flora. A

longer follow-up period for this drug should be planned in

consideration of the alteration effect on the microbial flora

and potential pathogens in the future studies. Additionally if

the patients will use MF for a long duration, isolation of the

potent pathogens should be investigated periodically.

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