Archives of Medicine and Health Sciences

: 2021  |  Volume : 9  |  Issue : 1  |  Page : 140--144

Role of biofilms in otorhinolaryngological Diseases

Harsh Suri1, Neha Vijay Haswani2, Gangadhara Somayaji1,  
1 Department of Otorhinolaryngology, Yenepoya Medical College and Hospital, Deralakatte, Mangalore, Karnataka, India
2 Department of Microbiology, Yenepoya Medical College and Hospital, Deralakatte, Mangalore, Karnataka, India

Correspondence Address:
Dr. Neha Vijay Haswani
Department of Microbiology, Yenepoya Medical College and Hospital, Deralakatte, Mangalore - 575 018, Karnataka


Biofilms over the years have been implicated to play a major role in the development of various diseases particularly Otorhinolaryngology. It is one of the topics with great interest within the field of medicine. A thorough review of the literature reveals the association of various infectious conditions of ENT practice is associated with biofilm-producing bacteria. Infections associated with biofilms are usually chronic due to the resilience of bacteria, to the innate and acquired immune system of the host and antibiotic therapy. This review article is written to evaluate and understand various aspects of biofilm-related infections in ENT.

How to cite this article:
Suri H, Haswani NV, Somayaji G. Role of biofilms in otorhinolaryngological Diseases.Arch Med Health Sci 2021;9:140-144

How to cite this URL:
Suri H, Haswani NV, Somayaji G. Role of biofilms in otorhinolaryngological Diseases. Arch Med Health Sci [serial online] 2021 [cited 2022 Jan 22 ];9:140-144
Available from:

Full Text


The first biofilms were observed in the year 1674 on human tooth samples with a help of a simple microscope by a Dutch scientist, Antonie van Leeuwenhoek who later went on to become the Father of Microbiology.[1]

Biofilms are defined as “groups of bacteria embedded in extracellular polymeric substance with increased resistance to antibiotics and host defense mechanisms as compared to their free counterparts.”[2],[3]

Bacterial resistance is a growing phenomenon in terms of increased social and economic factors which occur due to increased hospital stay and duration of treatment. Commonly used antimicrobial drugs, antiseptics, and biocides carry a high degree of resistance.[4],[5],[6]

A biofilm is a three-dimensional physical barrier formed by various bacterial communities which hinders the diffusional penetration of antimicrobials.[7] This, along with restricted antimicrobial transmission and the environmental factors provide a more hostile environment and leads to widespread resistance and tolerance to organisms.[8]

Biofilm formation is known to occur not only in Otorhinolaryngologic infections but also in the vast majority of the other infectious conditions.[9],[10] The chronic nature of such diseases is usually attributed to several factors such as reduced metabolic activity and transmission of resistance genes, etc. All these factors result in the development of antibiotic-resistant nature of biofilm-producing organism.[11]

Nearly (99.9%) of micro-organisms have the tendency to form biofilm on various surfaces both biological and inert surfaces [Table 1]. They are known to attach itself to mucosal surfaces and also to indwelling medical devices. The capability to form biofilms has been reported in the large number of organisms such as Pseudomonas aeruginosa, Staphylococcus epidermidis, Escherichia coli species, Staphylococcus aureus, Enterobacter cloacae, Klebsiellapneumonia etc.[12]{TAble 1}

 Biofilm Formation and its Role in Pathogenesis

Biofilm formation is a highly complex process, in which microorganism cells transform from planktonic to the sessile mode of growth.[14] The process of biofilm formation occurs through a series of events leading to adaptation under diverse nutritional and environmental conditions.[15],[16]

This is a multi-step process in which the microorganisms undergo certain changes after adhering to a surface. (a) attachment initially to a surface (b) formation of micro-colony (c) three-dimensional structure formation (d) biofilm formation, maturation, and detachment[17] [Figure 1].{Figure 1}

Biofilms being ubiquitous in nature, have a large impact on human health in both beneficial and detrimental manner. The beneficial effect is seen in the case of biofilm produced by commensals like S. epidermidis, which can stimulate the host immune defense mechanisms and prevent the adhesion of the bacteria, thereby hindering the colonization by potential pathogens.[18]

The race between the human immune system and the bacterial strategies of evading them is a never-ending one. The extrapolymeric substance is made up of various proteins like fibrinogen, elastin, fibronectin, etc., play a key role in the adherence of bacteria to surfaces within the host's body. The adhesion further triggers the release of enzymes which promote the formation of polysaccharides that help in colonization. The organisms which are suspended in this polysaccharide matrix even resist phagocytosis, resulting in “frustrated phagocytes.” These phagocytes then cause the release of various proinflammatory cytokines and enzymes leading to inflammation and destruction of nearby tissues.[18]

 Biofilms in Otolaryngologic Disease States

In otorhinolaryngology, biofilms have been first reported in a case of otitis media with effusion (OME)[19] usually attributing to biofilm presence in patients with chronic adeno-tonsillitis and are also reported in patients with chronic otitis media with cholesteatoma, chronic rhinosinusitis (CRS), and on some prosthetic devices, such as tympanostomy tubes and cochlear implants.[5],[20]

 Chronic Rhinosinusitis

It is a condition characterized by a minimum of two of the following symptoms which include nasal congestion, nasal discharge, postnasal drip, hyposmia, headache, and facial pain.[21] It is one of the most common ENT conditions requiring long-term treatment with antibiotics and also due to its recalcitrant nature. This disease affects the nose and paranasal sinuses and significantly effects the quality of life of the individual suffering from it.

The first report suggesting the presence of biofilm in CRS emerged in 2004.[22] However, recent studies have indicated that biofilms are known to play a major role in the pathogenesis of recurrent CRS. Patients with biofilm positive CRS were reported to have poorer quality of life at 6 months post functional endoscopic sinus surgery (FESS) compared to biofilm negative patients.[23]

Jung et al. evaluated and established the relationship between CRS and the presence of biofilm by scanning electron microscopy (SEM). They detected biofilms in 13 (50%) out of 26 samples of maxillary sinus mucosa from patients undergoing septoplasty and only one (14.3%) from the control group.[24]

Dlugaszewska et al. also studied the pathophysiological role of biofilms with nasal concha mucosal samples taken during FESS. SEM of these samples revealed biofilm in 23 samples (76.7%) of patients undergoing FESS for CRS.[25]

 Chronic Adenoiditis

Chronic adenoiditis is a frequent infection seen in children, commonly between the age group of 3–7 years, characterized by mouth breathing and snoring with typical facial features. It usually results in the development of chronic or recurrent infections of the middle ear such as acute otitis media (AOM) or serous otitis media.[26]

The presence of biofilms in adenoid tissue samples has been reported with numerous studies showing a strong correlation between biofilm formation and adenoiditis. Hundred percentage biofilm production was seen in a study aimed to establish a strong relationship between adenoid biofilm and frequency of upper respiratory tract infections in the pediatric population as adenoid acts as a reservoir for microorganisms leading to chronic infections.[13]

Two studies conducted to demonstrate biofilm production in patients with adenoid hypertrophy with or without OME and established adenoiditis as a common cause of chronic infection with higher grades of biofilm formation in patients with OME than without OME.[27],[28]

Lin et al. conducted a study on children with S. aureus adenoiditis and studied their biofilm-forming capability by dividing patients into methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus group.[29]

Adenoidectomy has proved successful in children with CRS and OME in preventing recurrent infections and the recent knowledge in this regard helps us in understanding the disease process better.

 Chronic Tonsillitis

Chronic/recurrent tonsillitis involves repeated occurrences of repeated tonsillar infection causing fever, throat pain, and painful swallowing impacting the patient's quality of life.[30],[31]

It most commonly affects school-going children between the age group of 5 and 15 years of age and is commonly caused by Group A Streptococci with an average prevalence of 15.9%.[32]

Tonsillar infections have developed more resistance to antibiotics due to the exsistance of bacterial biofilms. Alasil et al. processed 140 tonsil samples from 70 patients who underwent tonsillectomy and found S. aureus (39.65%) to be the most recovered isolate followed by haemophilus influenzae (18.53%) with the highest susceptibility to cotrimoxazole. Bacterial biofilms were seen in 60% of patients proving presence of biofilms in tonsil tissues.[33]

Chole and Faddis also confirmed the presence of biofilms in tonsils, with 70.8% of samples showing biofilm formation as evidenced by confocal SEM with double fluorescent staining.[34]

 Cochlear Implants

Patients who undergo various implantations of exogenous materials such as prostheses or devices in their body are usually prone to the risk of postoperative infection which often causes prolonged hospital stay and increases morbidity.

Although infections are reported to be low in cochlear implant surgeries,[35],[36] there are however some reports which have visualized the growth of biofilms on various implants including different types of material leading to failure of the device or re-implantation.

A study that analyzed the ability of S. aureus and P. aeruginosa using SEM, showed the greatest formation of biofilms on metal implants, whereas the highest rate of biofilm production was seen on polystyrene surfaces indicating biofilm formation differs from materials composition of the implant.[37]

There have been several reports of the removal of cochlear implant devices due to persistent chronic infection, which also revealed biofilms on those implants.[38],[39]

Although, nonimplanted control devices have shown no biofilm production but only planktonic bacteria. Infected implants require long-standing antibiotics which are usually resistant resulting in failure of the device and extraction. 5% tea tree oil has been used as a novel treatment of infected cochlear implants with the presence of MRSA which was resistant to all antimicrobials but eradicated completely within 1 h of exposure.[40]

 Otitis Media

Otitis media is a common pathology of the middle ear cleft, characterized by ear discharge and hearing loss. This spectrum includes acute to the chronic stage of the disease and is a primary cause of hearing loss in children and adults. Otitis media was the first disease entity where in the role of biofilms was established in otolaryngological infections.[41]

Using confocal laser scanning microscopy examination, fluorescence in situ hybridization, and immunohistochemical staining it was demonstrated that bacterial biofilm formation was found on the middle ear mucosa of children with both OME and recurrent otitis media. Post JC et al. reported biofilm producing growth in 92% middle ear mucosa specimens, supporting the concept that biofilms play a role in chronic ear infections.[20]

Hoa et al.[19] demonstrated that adenoid tissue may act as a reservoir for recurrent infection of chronic otitis media in children. The planktonic bacteria existing in the antibiotic-resistant adenoid biofilms may pass into the middle ear during viral infection of upper airway tract may be an important factor causing recurrent otitis media.

Gu et al. observed the presence of biofilms in various types of Chronic Otitis media. Middle ear samples were obtained from 38 patients who had undergone tympanoplasty or tympanomastoid surgery. Furthermore, 38 middle ear discharge samples were obtained for routine bacterial culture analysis. They found that bacterial biofilm formation was seen in 85% of patients with middle ear cholesteatoma.[42]

Lampikoski et al. studied the Mastoid biofilms in Chronic Otitis Media. They harvested 29 Mastoid tissue samples and studied them with multiplex polymerase chain reaction and with CSLM using Baclight live/Dead stain. Biofilms were identified in 42% CSOM patients and 82% of cholesteatoma patients.[43]

With such a high burden of the disease, it becomes necessary to look into the host-pathogen interactions for a better treatment modality.

 Treatment of Biofilms

Various treatment modalities have been studied against biofilms for many years which include antimicrobial agents such as mupirocin, honey, and surfactant such as baby shampoo and citric acid, and quorum sensing inhibitory agents such as macrolide therapy.[4],[34],[44],[45],[46],[47],[48] Surgical modalities mechanically disrupt the biofilms resulting in increased host defense mechanism. Topical antibiotics may be more superior than systemic as they require a lower dose to achieve the desired effect. Krespi et al.[47] formulated a nonpharmacologic method for the treatment of MRSA biofilm disruption using two different lasers.

 Vaccination and Newer Treatment Modalities

CSOM is a multifactorial disease and various other preventive and novel adjuvant treatments have been developed over the years. Vaccination has been developed to eliminate the colonization of common bacterial nasopharyngeal and otopathogens such as Streptococcus pneumoniae. PCV-7, a vaccine developed in the early 2000s against seven serotypes of S. pneumoniae was included in the universal vaccination at 2,4,6 months and booster dose at 12–15 months with 29% reduction in cases of AOM in America and European countries. A decade later, PCV-13 was made available with further reduction in AOM and associated complications.[49]

Other treatment modalities of promise include transcutaneous immunization (TCI) and intranasal immunization. TCI is a noninvasive method to elicit a host immune response over the skin's dermis and epidermis inducing both mucosal and systemic immunological responses. It is more desirable due to needleless delivery mechanisms, less hazardous, cheaper, and increased patient compliance. Successful trials on animal models have been conducted showing the vaccine efficacy of 64%–77%. Intranasal vaccination is being developed with an aim to reduce pneumococcal colonization in the nasopharynx and thus preventing AOM.[50]

Other novel adjuvant treatments have been tested with an aim to enhance the repair of tympanic membrane by using biomolecules to stimulate the growth of perforated edges and bioengineered scaffolds.[51] Drug delivery mechanisms like electromagnetic, ultrasonic, and phototherapy hold the good potential to eliminate biofilms and need further exploration.[49]

Future directions

Due to increasing antibiotic resistance, the current research should shift its focus from targeting the bacterial cell towards the more novel and practical approaches like dispersal of biofilms by using quorum sensing inhibitors and reengineering of surfaces like implants and catheters.[14] Further research is needed despite the promising potential advances in the treatment of biofilm-associated diseases. Due to the noncultivable nature of the viable organisms in the biofilm, it becomes imperative to have an alternative diagnostic method for the detection of biofilms in otorhinolaryngology.

Financial support and sponsorship


Conflicts of Interest

There are no conflicts of interest.


1Slavkin HC. Biofilms, microbial ecology and Antoni van Leeuwenhoek. J Am Dent Assoc 1997;128:492-5.
2Donné J, Dewilde S. The challenging world of biofilm physiology. Adv Microb Physiol 2015;67:235-92.
3Donlan RM. Biofilms: Microbial life on surfaces. Emerg Infect Dis 2002;8:881-90.
4Hentzer M, Givskov M. Pharmacological inhibition of quorum sensing for the treatment of chronic bacterial infections. J Clin Invest 2003;112:1300-7.
5Chole RA, Faddis BT. Evidence for microbial biofilms in cholesteatomas. Arch Otolaryngol Head Neck Surg 2002;128:1129-33.
6Stewart PS. Antimicrobial tolerance in biofilms. Microbiol Spectr 2015;3:10.
7Stoodley P, Sauer K, Davies DG, Costerton JW. Biofilms as complex differentiated communities. Annu Rev Microbiol 2002;56:187-209.
8Abu Bakar M, McKimm J, Haque SZ, Majumder MA, Haque M. Chronic tonsillitis and biofilms: A brief overview of treatment modalities. J Inflamm Res 2018;11:329-37.
9Develioglu ON, Kulekci M. Biofilms in otolaryngology. JAREM 2013;3:1-4.
10Chen HH, Liu X, Ni C, Lu YP, Xiong GY, Lu YY, et al. Bacterial biofilms in chronic rhinosinusitis and their relationship with inflammation severity. Auris Nasus Laryn×2012;39:169-74.
11Bayazian G, Sayyahfar S, Safdarian M, Kalantari F. Is there any association between adenoid biofilm and upper airway infections in pediatric patients? Turk Pediatri Ars 2018;53:71-7.
12Jamal M, Tasneem U, Hussain T, Andleeb S. Bacterial biofilms: Its composition, Formation and Role in Human infections. Research & Reviews: Journal of Microbiology and biotechnology. 2015:4;1-14.
13Vestby LK, Grønseth T, Simm R, Nesse LL. Bacterial biofilm and its role in the pathogenesis of disease. Antibiotics (Basel) 2020;9:59.
14Okada M, Sato I, Cho SJ, Iwata H, Nishio T, Dubnau D, et al. Structure of the Bacillus subtilis quorum-sensing peptide pheromone ComX. Nat Chem Biol 2005;1:23-4.
15Hentzer M, L.Eberl, M Givskov. Transcriptome analysis of Pseudomonas aeruginosa biofilm development: Anaerobic respiration and iron limitation. Biofouling 2005;2:37-61.
16Rajan S, Saiman L. Pulmonary infections in patients with cystic fibrosis. Semin Respir Infect 2002;17:47-56.
17Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: A common cause of persistent infections. Science 1999;284:1318-22.
18Hollman B, Perkins M,Walsh D. Biofilm and their Role in Pathogenesis. Bitesized Immunology, Pathogens and Disease Published by British Society for Immunology.
19Hoa M, Tomovic S, Nistico L, Hall-Stoodley L, Stoodley P, Sachdeva L, et al. Identification of adenoid biofilms with middle ear pathogens in otitis-prone children utilizing SEM and FISH. Int J Pediatr Otorhinolaryngol 2009;73:1242-8. doi: 10.1016/j.ijporl.2009.05.016.
20Post JC, Hiller NL, Nistico L, Stoodley P, Ehrlich GD. The role of biofilms in otolaryngologic infections: Update 2007. Curr Opin Otolaryngol Head Neck Surg 2007;15:347-51.
21Al-Mutairi D, Kilty SJ. Bacterial biofilms and the pathophysiology of chronic rhinosinusitis. Curr Opin Allergy Clin Immunol 2011;11:18-23.
22Kilty SJ, Desrosiers MY. The role of bacterial biofilms and the pathophysiology of chronic rhinosinusitis. Curr Allergy Asthma Rep 2008;8:227-33.
23Zhang Z, Linkin DR, Finkelman BS, O'Malley BW Jr., Thaler ER, Doghramji L, et al. Asthma and biofilm-forming bacteria are independently associated with revision sinus surgeries for chronic rhinosinusitis. J Allergy Clin Immunol 2011;128:221-3.e1.
24ung JH, Cha HE, Kang IG, Kim ST. Clinical characteristics of biofilms in patients with chronic rhinosinusitis: a prospective case-control study. Indian J Otolaryngol Head Neck Surg 2015;67:1-6.
25Dlugaszewska J, Leszczynska M, Lenkowski M, Tatarska A, Pastusiak T, Szyfter W. The pathophysiological role of bacterial biofilms in chronic sinusitis. Eur Arch Otorhinolaryngol 2016;273:1989-94.
26Torretta S, Drago L, Marchisio P, Ibba T, Pignataro L. Role of biofilms in children with chronic adenoiditis and middle ear disease. J Clin Med 2019;8:671.
27Saafan ME, Ibrahim WS, Tomoum MO. Role of adenoid biofilm in chronic otitis media with effusion in children. Eur Arch Otorhinolaryngol 2013;270:2417-25.
28Galli J, Calò L, Ardito F, Imperiali M, Passali GC, Carnevale N, et al. Bacterial biofilm identification in the rhinopharingeal mucosa of children with recurrent infection of the upper respiratory tract and otitis media. Pediatr Med Chir 2008;30:31-4.
29Lin CD, Tsai MH, Lin CW, Ho MW, Wang CY, Tsou YA, et al. Association of adenoid hyperplasia and bacterial biofilm formation in children with adenoiditis in Taiwan. Eur Arch Otorhinolaryngol 2012;269:503-11.
30American Academy of Otolaryngology. Tonsillitis; 2018. Available from: [Last accessed on 2018 Jan 06].
31Hayes K. Chronic and Recurrent Tonsillitis: What to Know; 2017. Available from: [Last acessed on 2018 Jan 06].
32Pichichero ME, Casey JR. Defining and dealing with carriers of Group A streptococci. Contemp Pediatr 2003;20:46-53.
33Alasil SM, Omar R, Ismail S, Yusof MY, Dhabaan GN, Abdulla MA. Evidence of bacterial biofilms among infected and hypertrophied tonsils in correlation with the microbiology, histopathology, and clinical symptoms of tonsillar diseases. Int J Otolaryngol 2013;2013:408238.
34Chole RA, Faddis BT. Anatomical evidence of microbial biofilms in tonsillar tissues: A possible mechanism to explain chronicity. Arch Otolaryngol Head Neck Surg 2003;129:634-6.
35Kalejaiye A, Ansari G, Ortega G, Davidson M, Kim HJ. Low surgical complication rates in cochlear implantation for young children less than 1 year of age. Laryngoscope 2017;127:720-4.
36Cunningham CD 3rd, Slattery WH 3rd, Luxford WM. Postoperative infection in cochlear implant patients. Otolaryngol Head Neck Surg 2004;131:109-14.
37Kirchhoff L, Arweiler-Harbeck D, Arnolds J, Hussain T, Hansen S, Bertram R, et al. Imaging studies of bacterial biofilms on cochlear implants-bioactive glass (BAG) inhibits mature biofilm. PLoS One 2020;15:e0229198.
38Pawlowski KS, Wawro D, Roland PS. Bacterial biofilm formation on a human cochlear implant. Otol Neurotol 2005;26:972-5.
39Antonelli PJ, Lee JC, Burne RA. Bacterial biofilms may contribute to persistent cochlear implant infection. Otol Neurotol 2004;25:953-7.
40Brady AJ, Farnan TB, Toner JG, Gilpin DF, Tunney MM. Treatment of a cochlear implant biofilm infection: A potential role for alternative antimicrobial agents. J Laryngol Otol 2010;124:729-38.
41Abu Bakar MB, McKimm J, Haque M. Otitis media and biofilm: An overview. Int J Nutr Pharmacol Neurol Dis 2018;8:70-8.
42Gu X, Keyoumu Y, Long L, Zhang H. Detection of bacterial biofilms in different types of chronic otitis media. Eur Arch Otorhinolaryngol 2014;271:2877-83.
43Lampikoski H, Aarnisalo AA, Jero J, Kinnari TJ. Mastoid biofilm in chronic otitis media. Otol Neurotol 2012;33:785-8.
44Zuliani G, Carron M, Gurrola J, Coleman C, Haupert M, Berk R, et al. Identification of adenoid biofilms in chronic rhinosinusitis. Int J Pediatr Otorhinolaryngol 2006;70:1613-7.
45Hoa M, Tomovic S, Nistico L, Hall-Stoodley L, Stoodley P, Sachdeva L, et al. Identification of adenoid biofilms with middle ear pathogens in otitis-prone children utilizing SEM and FISH. Int J Pediatr Otorhinolaryngol 2009;73:1242-8.
46Desrosiers M, Bendouah Z, Barbeau J. Effectiveness of topical antibiotics on Staphylococcus aureus biofilm in vitro. Am J Rhinol 2007;21:149-53.
47Krespi YP, Kizhner V, Nistico L, Hall-Stoodley L, Stoodley P. Laser disruption and killing of methicillin-resistant Staphylococcus aureus biofilms. Am J Otolaryngol 2011;32:198-202.
48Alandejani T, Marsan J, Ferris W, Slinger R, Chan F. Effectiveness of honey on Staphylococcus aureus and Pseudomonas aeruginosa biofilms. Otolaryngol Head Neck Surg 2009;141:114-8.
49Marom T, Tan A, Wilkinson GS, Pierson KS, Freeman JL, Chonmaitree T. Trends in otitis media-related health care use in the United States, 2001-2011. JAMA Pediatr 2014;168:68-75.
50Mittal R, Parrish JM, Soni M, Mittal J, Mathee K. Microbial otitis media: Recent advancements in treatment, current challenges and opportunities. J Med Microbiol 2018;67:1417-25.
51Hong P, Bance M, Gratzer PF. Repair of tympanic membrane perforation using novel adjuvant therapies: A contemporary review of experimental and tissue engineering studies. Int J Pediatr Otorhinolaryngol 2013;77:3-12.