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 Table of Contents  
Year : 2021  |  Volume : 9  |  Issue : 1  |  Page : 140-144

Role of biofilms in otorhinolaryngological Diseases

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

Date of Submission02-Nov-2020
Date of Decision28-Apr-2021
Date of Acceptance30-Apr-2021
Date of Web Publication26-Jun-2021

Correspondence Address:
Dr. Neha Vijay Haswani
Department of Microbiology, Yenepoya Medical College and Hospital, Deralakatte, Mangalore - 575 018, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/amhs.amhs_291_20

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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.

Keywords: Bacterial communities, biofilms, chronic infection, otorhinolaryngology

How to cite this article:
Suri H, Haswani NV, Somayaji G. Role of biofilms in otorhinolaryngological Diseases. Arch Med Health Sci 2021;9:140-4

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 Aug 11];9:140-4. Available from: https://www.amhsjournal.org/text.asp?2021/9/1/140/319388

  Introduction Top

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 More Details coli species, Staphylococcus aureus, Enterobacter cloacae, Klebsiellapneumonia etc.[12]
Table 1: Biofilm affecting various organs of the body[13]

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  Biofilm Formation and its Role in Pathogenesis Top

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: The life cycle of biofilm occurs in three steps: attachment, growth of colonies (micro-colony formation and formation of three-dimensional structures) and detachment in clumps[17]

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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 Top

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 Top

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 Top

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 Top

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 Top

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 Top

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 Top

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 Top

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.

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  [Figure 1]

  [Table 1]

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