Significance of fungal flora in chronic suppurative otitis media

Introduction: Chronic suppurative otitis media (CSOM) is defined as infection of the middle ear that lasts for >3 months and is accompanied by tympanic membrane perforation. The incidence is higher in developing countries, especially among the low socioeconomic strata of the society. Many authors have focused their attention on the bacterial flora of CSOM, but very little is known about the mycological aspects of these, the importance of which has been increasing in the recent years. Objective: The present study was aimed to speculate the etiological fungal flora responsible for the cases of CSOM among patients who attended the Ear, Nose, and Throat Department of our hospital a tertiary care center in Uttarakhand. Materials and Methods: The total of 107 patients (both males and females) who were clinically diagnosed with CSOM and were on any antibiotics (oral, topical or systemic) for >14 days and still persisted with symptoms were included in this study. Results: Among the 107 cases of CSOM studied, fungi were isolated in 83 (77.57%). Majority of the patients were in second and third decades of life (62.62%). Of the 83 fungal culture positive cases, the predominantly isolated fungi were Aspergillus species (47%), Candida species (41%), and Penicillium species (9.6%). Among the Aspergillus, the predominant species were Aspergillus flavus (17 isolates) and Aspergillus niger (12 isolates). Candida albicans (19 isolates) and Candida tropicalis (9 isolates) were the commonly isolated species of Candida. Conclusion: A definite search for fungal etiology is desirable in all cases of CSOM. Prolonged use of topical antibiotics or antibiotics-steroids ear drops may cause suppression of bacterial flora and the subsequent emergence of fungal flora. This probably increases the incidence of fungal superinfection. Otologists should suspect mycotic otitis media in patients with continuous otorrhea and who do not respond to the antibacterial treatment.

Keywords: Antibiotics, Aspergillus, Candida, Chronic otitis media, Otomycosis

Chronic suppurative otitis media (CSOM) is commonly encountered chronic inflammation of the middle ear and mastoid process caused by dysfunction of  Eustachian tube ^{More Details} followed by microbial infection. ^[1] The disease is capable of causing severe destruction sequelae with the manifestation of deafness, discharge and a permanent perforation. ^[2] CSOM is defined as infection of the middle ear that lasts for >3 months and is accompanied by tympanic membrane perforation. ^[3] It is one of the most common diseases of all age groups, especially of childhood. The incidence of CSOM is higher in developing countries, especially among the low socioeconomic strata of the society (with an urban-rural ratio of 1:2) because of poor nutrition, improper hygiene, and lack of health education. ^[4] The disease is highly prevalent in tropical regions including South Asia. ^[5]

Many authors have focused their attention on the bacterial flora of CSOM but very little is known about the mycological aspects of these, the importance of which has been increasing in the recent years because of the excessive use of broad-spectrum antibiotics, corticosteroids, and cytotoxic chemotherapy and an increase in the number of immune deficiency conditions. Fungal infections superimposed over CSOM are suspected when the discharging ear does not respond to the local antibiotic ear drops. However, information on the exact prevalence of such CSOM cases with secondary fungal infections is conspicuously lacking. Apart from bacteria, CSOM can be caused by wide variety of fungi, most of which are saprobe, occurring in diverse type of environmental material. ^[6] Fungi are abundant in soil which contains decaying vegetable matter. Fungal spores get suspended in the air as small dust particles and also carried by water vapors, a fact that correlates the higher rates of infection in monsoon when relative humidity rises to 80%. In the recent years, opportunistic fungal infections are gaining greater importance in human medicine as a result of possibly huge number of immunocompromised patients, so early diagnosis and treatment of mycotic otitis media are important to minimize the serious complications such as mastoid abscess, hearing loss, facial nerve paralysis, lateral sinus thrombosis, temporal bone infection, meningitis, and intracranial abscesses. ^[6],[7]

The present study was aimed to speculate the etiological fungal flora responsible for the cases of CSOM, who attended the Ear, Nose, and Throat Department of our hospital a tertiary care center in Uttarakhand.

The study was conducted for a period of 1 year (July 2011 to June 2012) in a tertiary care hospital of Uttarakhand state, India and was approved by our Institutional Ethics Committee. The study group included a total of 107 patients (both males and females) who were clinically diagnosed with CSOM. Inclusion criteria included patients presenting with tympanic perforation and ear discharge of >2 months. Only those patients who were on any antibiotics (oral, topical or systemic) and/or steroid ear drops for >14 days and still persisted with symptoms formed the subjects of this study. Informed consent from patients was obtained at enrollment.

The sample collection procedure was innocuous bringing the patient no risk. Three sterile cotton swabs after being thoroughly soaked with the exudates through the tympanic perforation were collected and sent to the microbiology laboratory for microscopic examination and fungal culture.

In the laboratory, the samples were examined microscopically (in 10% KOH preparations and Giemsa stained smears) for the presence of pus cells, budding yeast cells, fungal hyphae (septate or aseptate) and spores, etc. Special stains such as periodic acid-Schiff and Gomori’s methanamine silver were used whenever needed. Swabs were inoculated on two sets of Sabouraud’s dextrose agar slants with 0.05 mg/ml of chloramphenicol and incubated at 35°C and 28°C, respectively. The culture tubes were examined daily for 1 ^st week and then twice a week for next 3 weeks for the growth of any yeast or mycelial fungi. The specimens were considered positive for fungus when (i) both smears and culture were positive, (ii) smear negative but culture significant (heavy to confluent growth per slope) or repeatedly positive for same fungus, and (iii) smear-positive although culture were sterile.

The isolates were identified based on colonial appearance, microscopic morphology in lactophenol cotton blue mount, slide culture preparation, and biochemical characters according to Lodder and Kreger-Van Rij ^[8] and Rippon. ^[9]

Among the 107 cases of CSOM studied, fungi were isolated in 83 (77.57%). No fungal growth was seen in 24 (22.43%) cases. Majority of the patients were in second and third decades of life (62.62%). There was a predominance of males over females (1.5:1), and the duration of the illness was >3 months in 79 (73.83%) patients. Out of total 107 patients, six were known diabetics and nine patients were on antitubercular therapy. [Table 1] depicts the age and sex distribution of the patients.

As indicated in [Table 2], all the cases had a history of local treatment in the form of antibiotic (topical or systemic) or steroid ear drops for the treatment of presumed bacterial otitis media. Ciprofloxacin, gentamicin, and neomycin-polymyxin B-hydrocortisone were the most frequently prescribed.

Of the 83 fungal culture positive cases, the predominantly isolated fungi were Aspergillus species (47%), Candida species (41%), and Penicillium species (9.6%). Among the Aspergillus, the predominant species were Aspergillus flavus (17 isolates) and Aspergillus niger (12 isolates). Candida albicans (19 isolates) and Candida tropicalis (9 isolates) were the commonly isolated species of Candida. [Table 3] depicts the characterization of various fungal species isolated.

In the past, there were controversies regarding the existence of fungal etiology in CSOM but now it is considered to be a definitive clinical entity and an increasing problem ^[10] as the incidence of the mycotic infections and the diversity of pathogenic fungi have increased dramatically in the recent years due to continuously increasing number of immunocompromised patients. ^[11] Conditions such as diabetes, chemotherapy, malignancy, steroid administration, HIV infection, and prolonged antibiotic use (topical or systemic) renders the individual more susceptible to fungal infections of the middle ear. ^[12]

There are few studies available regarding fungal etiology in CSOM. ^{[4],[12],[13]} In the present study, the fungal isolation rate is very high among the patients who did not respond to antibiotic therapy, clearly suggesting that definite search for fungi is desirable in all cases of CSOM. The highest incidence of fungal CSOM was noted in second and third decades of life (62.62%), and this observation was concurrent to the studies conducted by various other authors. ^[12],[14] Higher incidence in young adults may be attributed to the fact that they are more exposed to the fungal spores whereas extreme age groups are not. ^[15]

Among the fungal etiology in CSOM, the most commonly isolated organisms are Aspergillus species and Candida species. ^[16] In the present study, Aspergillus species comprised of 47% of the total fungal isolates, whereas 41% of the isolates were Candida species. Most commonly involved Aspergillus species were A. flavus (20.5%) and A. niger (14.5%), among the Candida species, the most common isolates were C. albicans (23%) and C. tropicalis (10.8%). Earlier study from India, ^[12] reported higher isolation rate of Aspergillus species (60.2%) as compared to Candida species (17.6%). A recent study by Aneja et al. ^[17] from India reported Aspergillus in 86.8% of patients with A. niger (39.8%) and A. flavus (16.6%) to be the most common species. They also reported Aspergillus luchuensis as a causative agent of otomycosis for the first time. In contrast various other authors reported Candida to be the most commonly isolated fungi followed by Aspergillus. ^[13],[18] The difference in the various studies could be due to the difference in the patient population studied and geographical variation.

Aspergillus is one of the most predominant fungal etiologies in CSOM, so invasive Aspergillosis is not very uncommon in such patients. Invasive Aspergillus otomastoiditis is being found with increased frequency in immunocompromised hosts. Strauss and Fine ^[19] reported two cases of Aspergillus otomastoiditis caused by A. fumigatus. This mold has been considered more pathogenic than A. niger as A. fumigatus produces a hemolytic exotoxin which has the ability to alter skin resistance. ^[20] Aspergillus is a saprophytic mold and is one of the primary colonizers of the manmade substrata. Its rapid growth and production of a large number of small, dry, easily aerosolized conidia make it a significant contaminant with regards to air quality and potential human exposure-related illness. ^[17] Aspergilli are common in airborne dust, and their growth is aided by cerumen and the slightly acidic pH of the ear canal. ^[21] Pseudallescheria boydii is a saprophytic fungus capable of causing invasive fungal infections in humans. This fungus is morphologically similar to Aspergillus but is resistant to conventional systemic antifungal therapy with amphotericin B. ^[22] Infections with Candida can be more difficult to detect clinically due to its lack of characteristic appearance like Aspergillus and can present as otorrhea not responding to aural antimicrobials and are often identified by fungal culture. ^[23] This substantiates the essentiality of fungal cultures for diagnosis.

Penicillium species was isolated in eight cases (9.6%). A study by Talwar et al. ^[12] found Penicillium in 11.8% of the cases whereas a study by Aneja et al. ^[17] reported the same in 2.7% of cases. Mucor species was isolated in two cases (2.4%), and both the patients were known diabetics. Mucor has a propensity to invade arterial walls in immunocompromised patients, especially in uncontrolled diabetes mellitus patients. Haruna et al. ^[24] reported a case of invasive fungal temporal bone infection caused by Mucor, leading to meningoencephalitis. It was interesting to note that even the less virulent fungal isolates (including nonalbicans Candida) are gaining importance in ear infections.

The distribution of fungi is not only affected geographically but also changes with time and season. In the present study, higher incidence of the fungal infections was seen during the rainy season followed by summer season. This could be attributed to the hot and humid climate and the presence of dust in the environment which facilitates the fungal growth. Prevalence of fungal infections of the ear during moist and humid conditions has been reported previously by several authors. ^{[25],[26],[27]} One of the important environmental factors which may be responsible for a high incidence of fungal infections in this area is increased content of suspended dust particles in the air. The various dams as a part of hydroelectricity power projects are under construction on Alaknanda river (tributary of river Ganges) nearby from past few years which has increased the content of dust particles in the surrounding air to many folds and may be a contributory predisposing factor for higher incidence of fungal infection especially due to Aspergilli in this part of the country.

We suggest a definite search for fungi is desirable in all cases of CSOM. Prolonged use of topical antibiotics or antibiotics-steroids ear drops may cause suppression of bacterial flora and the subsequent emergence of fungal flora. This probably increases the incidence of fungal superinfection and even the less virulent fungi become more opportunistic. Otologists should elevate the suspicion of mycotic otitis media in patients with continuous otorrhea and patients who did not respond to the antibacterial treatment. The diagnosis based on microbiological findings should be prompt. We believe that at the onset of the CSOM, use of topical antibiotics should be avoided, and treatment in the form of local aural toilet should be considered. This not only will decrease the incidence of fungal CSOM but will also prevent the emergence of drug resistance to an extent.

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1755-6783.146400

[Table 1], [Table 2], [Table 3]