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PhiliPPine Journal of otolaryngology-head and neck Surgery Vol. 25 no. 1 January – June 2010 In vitro Antibacterial Activity of Mometasone
Furoate, Fluticasone Propionate and
Department of Otolaryngology Head and Neck Surgery Fluticasone Furoate Nasal Preparations
Against Streptococcus pneumoniae,
Hemophilus influenzae, Streptococcus
viridans, Staphylococcus aureus,
Pseudomonas aeruginosa,
and Escherichia coli
ABSTRACT
Objective: To test the antibacterial properties of three commercially available nasal corticosteroid
preparations containing Mometasone Furoate (MF), Fluticasone Propionate (FP) and Fluticasone
Furoate (FF) against S. pneumoniae, S. viridans, S. aureus, H. influenza, P. aeruginosa and E. coli.
Methods:
Study Design: Experimental in vitro study using the disc diffusion method.
Clinical isolates of Streptococcus pneumoniae, Hemophilus influenzae, Streptococcus viridans, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli were inoculated on separate plates. 0.15 ml of nasal corticosteroid preparations containing MF, FP and FF were applied to blank paper discs, then placed on the plates, including an empty disc. Following 24 and 48 hours of incubation, the inhibition zones were measured to the nearest mm from the point of abrupt inhibition of growth.
Results: After 24 and 48 hours of incubation, S. pneumoniae, S. viridans, and S. aureus showed
inhibition zones to all three preparations. S. aureus and S. viridans show the largest zones of
inhibition at 24 and 48 hours respectively. H. influenza, P. aeruginosa and E. coli were negative.
Department of Otorhinolaryngology Head and Neck Surgery The inhibition zones of each bacteria were shown to be statistically different. The preparation containing FP had the largest zone of inhibition at 24 and 48 hours, although post hoc tests showed their difference was not significant.
Reprints will not be available from the author.
Conclusion: The present study demonstrates possible antimicrobial properties of commercially-
No funding support was received for this study. The authors available nasal corticosteroid preparations. However, it is unclear whether these can be attributed signed a disclosure that they have no proprietary or financial interests with any organization that may have direct interest to the steroids, their excipients, or both. Further studies testing each component may offer better in the subject matter of this manuscript, or in any product insights into their therapeutic use.
Presented at the Analytical Research Contest (1st Place), Philippine Society of Otolaryngology Head and Neck Surgery, Keywords: Mometasone Furoate, Fluticasone Propionate, Fluticasone Furoate, antibacterial, nasal
Glaxo Smith Kline (GSK) Bldg. Chino Roces Ave., Makati City, Philippines October 21, 2009 and 14th Asian Research corticosteroids, allergic rhinitis, acute bacterial rhinosinusitis Symposium on Rhinology, New World Hotel, Ho Chi Minh Philipp J Otolaryngol Head Neck Surg 2010; 25 (1): 13-16 c Philippine Society of Otolaryngology – Head and Neck Surgery, Inc.
PhiliPPine Journal of otolaryngology-head and neck Surgery PhiliPPine Journal of otolaryngology-head and neck Surgery Vol. 25 no. 1 January – June 2010 Health care experts estimate that in the United States, acute and freshly prepared Mueller-Hinton Agar (S. aureus, P. aeruginosa, and E.
chronic rhinosinusitis affects an estimated 14% of the population.1 coli), Sheep Mueller-Hinton Agar (S. pneumoniae, and S. viridans), and Unfortunately, there is no precise local information.
commercially prepared Chocolate Agar Plate (H. influenza).
Although nasal corticosteroids are generally not used in acute Disc diffusion susceptibility testing using the Kirby Bauer inoculation infections because of adverse effects, their adjunct use in acute sinusitis method was performed.8 Using a micropipette, 0.15 ml of commercially has been proposed because of their decongestant and anti-inflammatory prepared intranasal corticosteroids were applied on separate 6.0 mm properties.3 Double-blind study data have shown that the addition of sterile blank paper discs (Becton, Dickenson & Company, Sparks MD topical corticosteroids to oral antibiotics have a positive effect in the 21152 USA). The preparations used were Mometasone Furoate 0.05% treatment of acute exacerbations of chronic rhinosinusitis.4 (Nasonex™, Merck & Co), Fluticasone Propionate 0.05% (Flixotide™, In addition to decongestant and anti-inflammatory properties, recent GlaxoSmithKline) and Fluticasone Furoate 27.5 µg/actuation (Avamys™, data suggest that corticosteroids may also demonstrate antibacterial GlaxoSmithKline).
properties against common ear, nose, and throat pathogens. In a recent The discs were placed individual y and distributed evenly into each in vitro study, viability of S. pyogenes was reduced by 99.00% by 0.01% plate. A blank paper disc was included to serve as a control. The plates Mometasone Furoate (MF), by 99.90% by 0.1% MF, and by 99.99% by were placed in a CO incubator (Memmert model TV50U, Bavaria, Germany) 0.5% MF after 24 hours of incubation.2 In a similar study, Dexamethasone set to 35 to 37 °C within 15 minutes after the discs were applied. (0.1%) killed S. milleri and A. flavus after incubation periods of 24 to Following 24 and 48 hours of incubation, the diameter of each 48 hours.5 This added property may modify the heretofore adjunct zone of inhibition was measured with a ruler from the edges of the last therapeutic role of topical corticosteroids in the management of acute visible colony-forming growth. The results were recorded in millimeters sinusitis and other common ENT infections. A literature search of Ovid, (mm).
PubMed and HERDIN databases using the terms “Mometasone Furoate,” Data was verified and tabulated using Excel, version 2007 (Microsoft “Fluticasone Propionate,” “Fluticasone Furoate” yielded no other studies Corporation), then analyzed using SPSS for Windows version 16.0.2.
on the possible antibiotic properties of other intranasal corticosteroids such as Fluticasone Propionate (FP) and Fluticasone Furoate (FF).
This study aims to investigate the antimicrobial activity of locally After 24 hours of incubation, plates with S. pneumoniae, S. viridians available commercial nasal corticosteroid preparations containing and S. aureus, showed inhibition zones to MF, FP, and FF. Plates with H. Mometasone Furoate (MF), Fluticasone Propionate (FP) and Fluticasone Influenzae, P aeruginosa and E coli were negative for inhibition (Table 1). Furoate (FF), against common bacteria causing bacterial sinusitis.6 S. aureus with FP showed the highest difference from baseline (3mm). Consistently, across other specimens, discs containing FP had the Specific Objectives:
largest zones of inhibition at 24 hours (Table 2). To measure the zone of inhibition from nasal corticosteroid After 48 hours of incubation, plates with S. pneumoniae, S. viridans, preparations containing MF, FP and FF on S. pneumoniae, S. viridans, S. and S. aureus showed inhibition zones to MF, FP, and FF. Plates with H. aureus, H. influenza, P. aeruginosa and E. coli at 24 and 48 hours; and Influenzae, P aeruginosa and E coli were negative for inhibition (Table 1). To determine if there is a significant difference among the S. viridans showed the largest inhibition zone regardless of the steroid. inhibition zones of S. pneumoniae, S. viridans, S. aureus, H. influenza, P. Consistently, FP registered the largest reaction to S. pneumoniae, S. aeruginosa and E. coli produced by the three preparations containing viridians and S. aureus (Table 2).
MF, FP and FF.
At 24 hours, ANOVA detected significant differences among the specimens regardless of the corticosteroid preparation (P-value 0.00). Post hoc (Multiple Comparison) test showed H. influenza, P. aeruginosa, Bacterial strains from clinical isolates were inoculated and evaluated E. coli and the control were similar to each other, but significantly using the Vitek 2 Compact System (BioMerieux, Inc. Durham, NC, USA) different from the group S. pneumoniae and S. viridians, and that both to verify the identity of the bacteria. groups were significantly different from S. aureus.
Guided by the Manual on Antibacterial Susceptibility Testing7 At 48 hours, ANOVA detected significant differences among the each organism was inoculated on three separate plates, to allow for specimens (P-value 0.00). Post hoc test showed that S. viridans has the randomization.2 Inoculation was done onto the following media: highest reaction to the corticosteroid preparations at 48 hours, followed PhiliPPine Journal of otolaryngology-head and neck Surgery PhiliPPine Journal of otolaryngology-head and neck Surgery Vol. 25 no. 1 January – June 2010 Table 1. Average size of inhibition zones of the steroid preparations on the
DISCUSSION
different bacterial specimens after 24 and 48 hours of incubation
Nasal corticosteroids have been a mainstay of therapy for Average Size (in mm)
allergic rhinitis with persistent symptoms.9 The use of nasal steroids (particularly with intramaxillary instillation) may be beneficial in chronic Aureus Viridans Pneumoniae Influenzae Aeruginosa Coli rhinosinusitis, with no side effects or increased signs of infection.4 While it is common practice to treat acute bacterial rhinosinusitis empirically with antibiotics,2 the idea that steroids may play a role in controlling infection as an adjunctive or first-line treatment is novel. Such a role may find application in treating patients suffering from allergic rhinitis and bacterial sinusitis as well as in other ENT infections.
Several locally available, commonly prescribed nasal corticosteroid sprays currently used for allergic rhinitis include MF, FP and FF. This study suggests that these preparations may possess antimicrobial properties against S. pneumoniae, S. viridans, and S. aureus. Although the mechanism of action of steroids on bacteria is Table 2 - Average difference of inhibition zones from the baseline of 6mm (blank
relatively unknown, the results of this, as well as other studies paper disc diameter). The table shows FP registered the largest reaction to S.
suggest susceptibility of streptococcus and staphylococcus species to pneumoniae, S. viridians and S. aureus at 24 and 48 hours (indicated by an asterisk)
corticosteroids. This may be due to the general effects of corticosteroids.3 Average Difference from the Baseline of 6mm (in mm)
A recent study on dexamethasone suggests that it may have to do with Aureus Viridans Pneumoniae Influenzae Aeruginosa Coli the steroid’s action on the cell wall or cytoplasmic membrane, as well as the transcription and translation machinery of the microorganisms.5 To the best of our knowledge, no other studies have investigated the antibacterial properties of FP or FF.
All three preparations tested contain Benzalkonium chloride as an excipient. Benzalkonium chloride is a quarternary ammonium compound commonly used to prevent bacterial contamination as an antimicrobial additive, rendering solutions bacteriostatic or bactericidal according to concentration. Since 1982, Benzalkonium chloride has been approved by the US Food and Drug Administration as an “inactive ingredient” for prescription drugs.14 It is not clear whether the antibacterial properties exhibited by all by S. aureus, then S. pneumoniae. However H. influenzae, P. aeruginosa, E. three preparations of intranasal corticosteroids can be attributed to the coli and the control did not show any difference at 48 hours.
steroids, the excipient, or both. While the study shows the preparations At 24 hours, ANOVA did not detect a significant difference among the themselves have antibacterial properties, further studies testing their inhibition zones regardless of the specimen (P-value 0.161). Although components separately are in order. FP descriptively registered the highest reaction from the baseline (followed by MF then FF), Post-hoc test showed that the differences were not significant.
At 48 hours, ANOVA did not detect a significant difference among the preparations (P-value 0.390). The post-hoc test also showed that the difference among the three corticosteroid preparations was not significant.
PhiliPPine Journal of otolaryngology-head and neck Surgery PhiliPPine Journal of otolaryngology-head and neck Surgery Vol. 25 no. 1 January – June 2010 ACKNOWLEDGEMENT
The authors wish to thank Dr. German B. Castillo, Sr., Chair of the Department of Laboratories of The Medical City, and the staff of the section of microbiology for the use of the equipment and REFERENCES
1. Ryan D. Management of acute rhinosinusitis in primary care: changing paradigms and the emerging role of intranasal corticosteroids. Prim Care Respir J. 2008 Sep;17(3):148-55.
2. Benninger MS, Sedory Holzer SE, Lau J. Diagnosis and treatment of uncomplicated acute bacterial rhinosinusitis: Summary of the Agency for Health Care Policy and Research evidence- based report. Otolaryngology Head and Neck Surgery. 2000 Jan; 122(1):1-7.
3. Neher A, Gstöttner M, Scholtz A, Nagl M. Antibacterial activity of Mometasone Furoate. Arch Otolaryngol Head Neck Surg. 2008 May;134(5):519-21.
4. Parikh A, Scadding GK, Darby Y, Baker RC. Topical corticosteroids in chronic rhinosinusitis: a randomized double-blind, placebo-controlled trial using Fluticasone Furoate aqueous nasal spray. Rhinology. 2001 Jun; 39(2)75-9.
5. Neher A, Arnitz R, Gstöttner M, Schäfer D, Kröss EM, Nagl M. Antimicrobial activity of dexamethasone and its combination with N-chlorotaurine Arch Otolaryngol Head Neck Surg. 6. Wald ER., Microbiology of acute and chronic sinusitis in children and adults. Am J Med Sci. 1998 7. Lalitha MK. Manual on Antimicrobial susceptibility testing. 1st ed. Vellore, Tamil Nadu: Department of Microbiology, Christian Medical College: 2008. pp.10-13.
8. Bauer AW, Kirby WM, Sherris JC, Turck M. 1966. Antibiotic susceptibility testing by a standardized single disk method. Am. J. Clin. Pathol. 45:493-496. 9. Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen Allergy. 2008 Apr;63 Suppl 86:8-160.
10. Graf P. Benzalkonium chloride as a preservative in nasal solutions: re-examining the data. Respir 11. Marple B, Roland P, Benninger M., Safety review of benzalkonium chloride used as a preservative in intranasal solutions: An overview of conflicting data and opinions, Otolaryngol Head Neck 12. Patarca R, Rosenzwei JA, Zuniga AA, Fletcher MA Benzalkonium salts: effects on G protein- mediated processes and surface membranes. Crit Rev Oncog. 2000;11(3-4):255-305.
13. Seymour SB. Disinfection, sterilization, and preservation. 5th illustrated ed. Philadelphia (PA) Lippincott Williams & Wilkins; 2001. pp311.
14. Graf P. Adverse Effects of Benzalkonium Chloride on the Nasal Mucosa: Allergic Rhinitis and Rhinitis Medicamentosa, Clin Ther. 1999 Oct; 21(10):1749-55.
PhiliPPine Journal of otolaryngology-head and neck Surgery

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