|
 
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| REVIEW ARTICLE |
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| Year : 2022 | Volume
: 10
| Issue : 2 | Page : 67-72 |
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Microbiology of chronic otitis media—A review
Santosh K Swain1, Smarita Lenka1, Debasmita Dubey2, Pragnya P Jena3
1 Department of Otorhinolaryngology and Head and Neck Surgery, IMS and SUM Hospital, Siksha “O” Anusandhan University, Bhubaneswar, Odisha, India
2 Medical Research Laboratory, IMS and SUM Hospital, Siksha “O” Anusandhan University, Bhubaneswar, Odisha, India
3 Department of Microbiology, IMS and SUM Hospital, Siksha “O” Anusandhan University, Bhubaneswar, Odisha, India
| Date of Submission | 24-Jul-2022 |
| Date of Decision | 15-Sep-2022 |
| Date of Acceptance | 20-Sep-2022 |
| Date of Web Publication | 16-Nov-2022 |
Correspondence Address:
Santosh K Swain
Department of Otorhinolaryngology and Head and Neck Surgery, IMS and SUM Hospital, Siksha “O” Anusandhan University, K8, Kalinga Nagar, Bhubaneswar 751003, Odisha
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/DYPJ.DYPJ_55_22
Chronic otitis media (COM) is a major health problem in the world, particularly in the underdeveloped and developing countries. COM is typically persistent, insidious in onset, and usually capable to manifest deafness and otorrhea. The common microorganisms isolated from COM include Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Bacteroides. Otorrhea and healing of the tympanic membrane perforation in COM is a virtuous circle of events detected by the classic sequence of acute inflammatory change. In COM, a vicious circle occurs when incomplete healing predisposes the ear to further acute episodes, and these occur so frequently that they merge and are seen as continuous and chronic. Conservative medical treatment of COM is required to control active otorrhea. Effective treatment of COM needs a thorough knowledge of causative microorganisms and their antibacterial sensitivity. The appropriate identification of microorganisms and timely administration of antibiotics in COM patients ensure prompt clinical recovery and avoid possible complications. Bacterial predominance and sensitivity to antibiotics have changed over time, so these need periodic surveillance for guiding the appropriate antibacterial therapy. Early and effective treatment is based on the knowledge of causative microorganisms, and their antimicrobial sensitivity that ensures the prompt clinical recovery and possible complications of COM. The objective of this review article is to discuss the prevalence, bacteriology, treatment, and bacterial resistance in COM. Keywords: Anaerobes, chronic otitis media, Pseudomonas aeruginosa, Staphylococcus aureus
How to cite this article:
Swain SK, Lenka S, Dubey D, Jena PP. Microbiology of chronic otitis media—A review. D Y Patil J Health Sci 2022;10:67-72 |
| Introduction | |  |
Chronic otitis media (COM) is a frequently encountered infection of the middle ear cleft.[1] COM is defined as the chronic inflammation of the middle ear cleft that manifests with ear discharge or otorrhea, tympanic membrane perforation, and hearing impairment.[1] COM is caused by bacteria, fungi, and viruses resulting in the inflammation of the mucosal linings of the middle ear cleft.[2] The bacteriology in COM includes both aerobes and anaerobes such as Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Bacteroides.[3] The foul smell of chronic ear discharge and higher frequency of anaerobic bacteria in intracranial infections favor that anaerobe is a common occurrence in COM.[4] However, aerobes are commonly isolated bacteria in the COM. Recurrent otitis media may cause damage to the ossicles, facial nerve, and cochlea, leading to permanent hearing loss.[5] COM is classified into two types, namely, tubotympanic and atticoantral depending on the basis of the disease process affecting the pars tensa or pars flaccida of the tympanic membrane.[6] Tubotympanic type is a safe type of COM as there are no serious complications, whereas the atticoantral type is considered an unsafe type because of its association with complications.[7] In COM, infection from the middle ear cleft can spread to different vital structures such as the labyrinth, facial nerve, lateral sinus, meninges, and brain resulting in deafness, lateral sinus thrombosis, meningitis, and brain abscess.[8] The treatment of COM is often controversial and subject to change in the developing countries. The recent misuse and overuse of antibiotics have caused alterations in major bacterial strains and their sensitivity to antibiotics, resulting in this situation making it more difficult to treat. The prevalence and antibiogram of the microorganisms in COM have been reported to change with time and geographical area, probably because of the indiscriminate use of antibiotics.[9] So, the periodic update of prevalence and antibiogram of the microorganisms for COM would be useful for the treatment of the patients. Currently, early microbiological diagnosis ensures prompt and effective treatment and is also helpful to avoid complications.
| Methods of Literature Search | | |
Multiple systematic methods were used to find current research publications on the microbiology of COM. We started by searching the Scopus, PubMed, Medline, and Google Scholar databases online. A search strategy using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines was developed. This search strategy recognized the abstracts of published articles, whereas other research articles were discovered manually from the citations. Randomized controlled studies, observational studies, comparative studies, case series, and case reports were evaluated for eligibility. There were a total number of 58 articles (14 case reports, 18 cases series, and 26 original articles) [Figure 1]. This article focuses only on the microbiology of COM. This review article describes the prevalence, bacteriology, biofilm, etiological agents other than bacteria, treatment, and antibiotic resistance. This analysis provides a better understanding of the microbiology of COM, which will provide prompt treatment. It will also serve as a catalyst for additional study into a newer diagnostic and treatment protocol for the microbiology of COM.
| Prevalence | | |
COM is a major public health problem in the developing and underdeveloped countries. The incidence of COM is higher in the developing countries particularly among low socioeconomic societies because of overcrowding, malnutrition, passive smoking, poor health care, and recurrent upper respiratory tract infection.[10] The urban to the rural ratio of COM is 1:2, and poor rural areas have a higher prevalence.[10] There is the high prevalence of COM in the pediatric age group, which may be attributed to more prone to upper respiratory tract infections. The global burden of illness by COM is estimated to affect 65–330 million individuals with otorrhea, 60% (39–200 million) of whom suffer from hearing impairment.[11] More than 90% of the burden is borne by the developing countries in Africa, Southeast Asia, and Western Pacific region.[11] One study showed that 39% of the patients showed aerobic bacteria and 11% showed anaerobic organisms.[12] Another study showed that the most common etiological organism isolated was Pseudomonas aeruginosa (33.3%) and Staphylococcus aureus (33.3%) followed by coagulase-negative Staphylococcus (21.1%). Fungi accounted for 8.8% of the isolates, whereas 6.6% of cases showed anaerobic bacteria.[13]
| Microorganisms in Middle Ear Cleft | | |
In COM, the microorganisms can reach the middle ear cleft either from the nasopharynx through the eustachian tube or from the external auditory canal via a nonintact tympanic membrane.[14] The most common microorganisms detected in COM are Pseudomonas aeruginosa, Staphylococcus aureus, Proteus mirabilis, Klebsiella pneumonia, Escherichia coli, Aspergillus species, and Candida species, but these microorganisms vary in different geographical region.[5] The aerobic microorganisms most frequently isolated in COM are Pseudomonas aeruginosa (18%–67%), Staphylococcus aureus (14%–33%), Gram-negative organisms such as Proteus species, Klebsiella species, and Escherichia species (4%–43%), and Haemophilus influenza (1%–11%).[15] The most commonly isolated anaerobic organisms are Bacteroides species (1%–91%) and Fusobacterium species (4%–15%).[15] In COM, the middle ear cleft environment is thought to be more tolerant to the usual microorganisms such as Pseudomonas aeruginosa, Staphylococcus aureus, and anaerobes; it is still uncertain whether these bacteria are true pathogens for COM or may reflect secondary invaders or contamination from the external auditory canal.[16] Fungi are also thought to play a role in COM, particularly Aspergillus spp. and Candida spp.[17] In population, especially those staying in hot, humid regions where fungi may flourish, fungi are detected in 50% of cases of COM.[17] Recently, concerns are rising for secondary fungal overgrowth due to complications of quinolone ear drops.[18]
| Biofilms | | |
Biofilms are defined as communities of microorganisms attaching to the surface. Biofilms can be a single microbial species or multiple microbial species, which can form on a range of abiotic or biotic surfaces.[19] Recently, bacterial biofilm has received attention as a source of chronic infections. A biofilm is a population of bacterial cells growing on the surface, enclosed in an exopolysaccharide matrix; being difficult to eliminate, they could be a source of chronic infections.[20] Biofilms may be attached to injured tissues such as exposed osteitic bone and ulcerated middle ear mucosa, or otologic implants such as grommets, and are so thought to cause persistent infection in COM.[21]
| Com and Bacteriology | | |
COM is classified into noncholesteatomatous and cholesteatomatous based on the absence or presence of cholesteatoma. Long-standing inflammatory alterations of the middle ear and mastoid cavity are important features of the COM, but the mechanism of transition from acute to chronic infection has not yet been established.[22] Patients who do not recover from the acute infections of the middle ear cleft show an increase in mucosal edema and effusion fluid so enhancing the secretary capacity of mucosal glands. Because of mucosal edema and discharge, the narrow pathway of the aditus that connects the middle ear to the mastoid cavity is obstructed, and normal ventilation becomes difficult. At the same time, the circulation of blood decreases, which inhibits the availability of topical and systemic antibiotics and anti-inflammatory agents. These changes can induce a change in bacterial strain.[23] Poor hygiene and unorthodox method of treatment like the application of oil and honey into the middle ear may initiate the proliferation of opportunistic pathogens resulting in the blockage of the eustachian tube.[19] The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and other resistant bacteria, as well as changes in antibiotic sensitivity within identical strains, require continuous and periodic bacteriological surveys.
Staphylococcus aureus
The predominant bacterial etiology (aerobic) of COM is Staphylococcus aureus (48.69%).[24] One study from Iran showed that predominant bacterial etiology (aerobic) of COM was Staphylococcus aureus (31.1%).[25] Another study from India showed that 36% of the bacterial etiology of COM was Staphylococcus aureus.[26] One study from Pakistan revealed the prevalent microorganism of COM was Pseudomonas.[27] In another study, Pseudomonas contributes 19.89% of cases of COM.[28] However, Pseudomonas is the most common cause of COM in the tropical region. It usually does not inhabit the upper respiratory tract, and its presence in the middle ear cleft cannot be ascribed to an invasion via the eustachian tube and is considered a secondary invader gaining access to the middle ear through a defect in the tympanic membrane.[24] Coliforms including Klebsiella pneumoniae and Escherichia coli were identified at 9.42% and 7.33%, respectively.[24]
Pseudomonas aeruginosa
Pseudomonas aeruginosa is a Gram-negative bacilli and common inhabitant of soil, freshwater, and marine environment.[29] It is an opportunist pathogen that causes human disease. Pseudomonas aeruginosa was the most prevalent bacteria in COM.[30]Pseudomonas can grow in the absence of special nutrition and proliferates at room temperature. It is highly resistant to the antibiotic, making it difficult to treat. Antibiotic is preferable for the treatment of COM, depending on the type of causative agent and the age of the patient. Different bacterial strains isolated from COM are given in [Table 1].[30]
Fungal agents
Fungal infections of the middle ear cleft are common as fungi thrive well in moist pus.[31] The most common fungi found are Aspergillus species and Candida species.[32] This study showed that 12.25% of cases of COM presented fungal etiology, out of which 29.17% were Candida species and 70.83% were Aspergillus species.[32] One study from India showed that 15% of the COM cases were due to fungal etiology, out of which 60% were Candida species and 40% were Aspergillus species.[6] Another study showed 33.3% of the fungal etiology in COM by Candida species and 8.8% cases due to Aspergillus species.[33] These findings may be due to the environmental effects on the COM cases, which were studied in this region.[34]
| Bacteriological Study | | |
Bacteriological studies of patients with COM have been used as guidelines for getting appropriate antibiotics. The increasing prevalence of MRSA and other resistant bacteria and changes in antibiotic sensitivity within identical strains indicate the requirement for continuous and periodic bacterial study or surveys. The incidence of mixed strains of bacteria is higher in COM than in acute ones, with both aerobic and anaerobic bacteria found in chronic cases. The etiological agents emphasize the importance of using the most appropriate antibiotics in their appropriate doses. Sometimes, the bacteria are not detected from the aural discharge, and it accounts for 3.1%–20% of cases.[35] The absence of bacterial growth in ear discharge from COM patients has been due to the overuse of diverse antibiotics before performing the bacteriological culture. So, the bacteriological culture should be ideally performed before the empirical use of antibiotics. One study showed that normal bacterial flora in patients of external otitis media includes predominantly Staphylococcus epidermis, Staphylococcus auricularis, Staphylococcus capitis, and Corynebacterium.[36] In another study, Pseudomonas, MRSA, and methicillin-sensitive Staphylococcus aureus (MSSA) were isolated most commonly, indicating that contamination from the external auditory canal occurred rarely.[30]
| Treatment | | |
Antimicrobial treatment of COM is used to eliminate the bacterial agents causing the infections in the middle ear cleft. However, many times, the microorganisms develop resistance. In the developing countries, this problem is rapidly increasing because of the misuse of antibiotics. Early and effective treatment is essential to eradicate such morbid infections of the middle ear. Untreated cases of COM can result in a broad range of complications. The complications of COM occur due to the spread of bacteria to the adjacent structures of the middle ear, and the complications include persistent otorrhea, mastoiditis, labyrinthitis, and facial nerve paralysis to more life-threatening complications such as intracranial abscess or thromboses. So treatment needs to be instituted early and effectively for avoiding such complications. The mainstay of treatment in uncomplicated COM is two-fold: meticulous aural toilet (with suction/mopping up of ear debris and discharge) and instillation of topical antimicrobial agent. The therapeutic use of antibiotics is often started empirically before getting the microbiological culture reports. The selection of any antibiotic is important for a clinician because of its efficacy, resistance to bacteria safety, risk of toxicity, and cost. The clinicians should know the microorganism pattern and the antibiotic sensitivity for effective and cost-effective treatment. The knowledge of the local pattern of the infection is required to enable efficacious treatment of the COM. In COM, treatment failure and disease complications are caused by the development of antibiotic-resistant strains, such as MRSA, vancomycin-resistant Enterococcus, and vancomycin-resistant Staphylococcus aureus.[37]Pseudomonas aeruginosa was found to be sensitive to ciprofloxacin, ceftazidime, piperacillin, and amikacin, whereas Staphylococcus aureus was sensitive to cloxacillin, cephalexin, and Bactrim. The third most commonly isolated bacteria were coagulase-negative Staphylococcus, which may represent skin flora contamination and not be a true pathogen. They were usually sensitive to clindamycin, erythromycin, and cloxacillin. Anaerobic bacteria are not a significant pathogen in COM. Similarly, fungi are a highly uncommon pathogen for resulting COM. One study in South Korea showed that in adult patients with COM, ciprofloxacin-resistant Pseudomonas aeruginosa was seen.[38] However, another study showed that 85% of Pseudomonas aeruginosa was found to be sensitive to ciprofloxacin.[27] It was also reported that more than 90% of isolates were sensitive to ciprofloxacin.[39] It shows that ciprofloxacin is very effective for COM. There is a concern that the overuse of quinolones group of antibiotics such as ciprofloxacin and ofloxacin can lead to the emergence of resistance especially in Pseudomonas aeruginosa, Staphylococcus aureus, and some Enterobacteriaceae.[40] Cephalosporins are the most commonly prescribed group of antibiotics and show an extended gram-negative spectrum of bacteria. If Pseudomonas aeruginosa has become resistant to one, cephalosporin is usually resistant to other beta-lactam anti-Pseudomonas agents as well as other antibiotics.[41] Imipenem belongs to the carbapenem group of antibacterial agents and bonds to different penicillin-binding proteins. It is the most active drug against Pseudomonas aeruginosa seen in COM.[39] Aztreonam is a monobactam antibiotic with no Gram-positive activity but shows good Gram-negative activity. It is active against beta-lactamase-producing organisms. One study showed that Pseudomonas aeruginosa was sensitive to aztreonam.[5]
| Antibiotic Resistance | | |
The important factors associated with antibiotic resistance in COM include poor hospital hygiene, overcrowding, a lack of personnel trained in controlling infections in hospitals, and a lack of resources for infection control.[42] Antibiotic resistance can be natural or acquired.[43] There is a certain mechanism for the development of antibiotic resistance such as the presence of enzymes that inactivates the antimicrobial agents and the mutation in the antimicrobial agent’s targets, which decrease the binding of the antimicrobial agents and decreased uptake of the antimicrobial agents and overproduction of targets of antimicrobial agents.[44]
| Conclusions | | |
COM is caused by bacteria, fungi, and viruses leading to inflammation of the mucosal lining of the middle ear cleft. Antimicrobial treatment is usually used to eradicate the bacterial agents causing COM, but most of the microorganisms are acquiring antibiotic resistance. Bacteriological studies of patients with COM have been used as guidelines for the selection of the appropriate antibiotics. Pseudomonas aeruginosa and Staphylococcus aureus are common bacteria isolated from COM. Proper understanding of the bacterial pattern prevalent in the community is vital for effective treatment of the COM. It is highly essential to use antibiotics in the proper way to prevent resistance.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Justin R, Tumweheire G, Kajumbula H, Ndoleriire C Chronic suppurative otitis media: Bacteriology, susceptibility and clinical presentation among ENT patients at Mulago Hospital, Uganda. South Sudan Med J 2018;11:31-5.  |
| 2. | Sahoo S, Swain SK, Samal S, Sahu MC Surveillance of organisms associated with CSOM and otomycosis at a tertiary care teaching hospital. Indian J Public Health Res Dev 2018;9:2205-13. |
| 3. | Swain SK, Behera IC, Sahu MC Role of betadine irrigation in chronic suppurative otitis media: Our experiences in a tertiary care teaching hospital of East India. Int J Health Allied Sci 2019;8:29-32. |
| 4. | Karma P, Jokippi L, Ojala K, Jokipii AM Bacteriology of the chronically discharging middle ear. Acta Otolaryngol 1978;86:110-4. |
| 5. | Salam AU, Abid SH, Abdulla EM Suppurative otitis in Karachi: An audit of 510 cases. Pak J Otolaryn 1997;13:66-9. |
| 6. | Kumar H, Seth S Bacterial and fungal study of 100 cases of chronic suppurative otitis media. J Clin Diagn Res 2011;5:1224-7. |
| 7. | Rout MR, Mohanty D, Vijaylaxmi Y, Kamalesh B, Chakradhar M Prevalence of cholesteatoma in chronic suppurative otitis media with central perforation. Indian J Otol 2012;18:7-10. |
| 8. | Wiwanitkit S, Wiwanitkit V Pyogenic brain abscess in Thailand. N Am J Med Sci 2012;4:245-8. |
| 9. | Hassan O, Adeyemi RE A study of bacterial isolates in cases of otitis media in patients attending Oautch, Ile-Ife. Afr J Exp Microbiol 2007;8:130-6. |
| 10. | Nwokoye NN, Egwari LO, Coker AO, Olubi OO, Ugoji EO, Nwachukwu SC Predisposing and bacteriological features of otitis media. Afr J Microbiol Res 2012;6:520-5. |
| 11. | Verhoeff M, van der Veen EL, Rovers MM, Sanders EA, Schilder AG Chronic suppurative otitis media: A review. Int J Pediatr Otorhinolaryngol 2006;70:1-12. |
| 12. | Erkan M, Aslan T, Sevük E, Güney E Bacteriology of chronic suppurative otitis media. Ann Otol Rhinol Laryngol 1994;103:771-4. |
| 13. | Loy AH, Tan AL, Lu PK Microbiology of chronic suppurative otitis media in Singapore. Singapore Med J 2002;43:296-9. |
| 14. | Swain SK, Das A, Mohanty JN Acute otitis media with facial nerve palsy: Our experiences at a tertiary care teaching hospital of eastern India. J Acute Dis 2019;8:204-7. |
| 15. | Miró N Controlled multicenter study on chronic suppurative otitis media treated with topical applications of ciprofloxacin 0.2% solution in single-dose containers or combination of polymyxin B, neomycin, and hydrocortisone suspension. Otolaryngol Head Neck Surg 2000;123:617-23. |
| 16. | Brook I Role of anaerobic bacteria in chronic otitis media and cholesteatoma. Int J Pediatr Otorhinolaryngol 1995;31:153-7. |
| 17. | Khanna V, Chander J, Nagarkar NM, Dass A Clinicomicrobiologic evaluation of active tubotympanic type chronic suppurative otitis media. J Otolaryngol 2000;29:148-53. |
| 18. | Swain SK, Debta P, Bishoyi AK, Padhy R Invasive aspergillosis of tympanomastoid cavity. J Sci Soc 2019;46:106-9. |
| 19. | Behera IC, Swain SK, Sahu MC Colonization and antibiotic resistance dynamics of patients at intensive care unit: Our experience. Asian J Pharm Clin Res 2017;10:417-21. |
| 20. | Stewart PS, Costerton JW Antibiotic resistance of bacteria in biofilms. Lancet 2001;358:135-8. |
| 21. | Thi MT, Wibowo D, Rehm BH Pseudomonas aeruginosa biofilms. Int J Mol Sci 2020;21:8671. |
| 22. | da Costa SS, Paparella MM, Schachern PA, Yoon TH, Kimberley BP Temporal bone histopathology in chronically infected ears with intact and perforated tympanic membranes. Laryngoscope 1992;102:1229-36. |
| 23. | Folino F, Ruggiero L, Capaccio P, Coro I, Aliberti S, Drago L, et al. Upper respiratory tract microbiome and otitis media intertalk: Lessons from the literature. J Clin Med 2020;9:2845. |
| 24. | Vishwanath S, Mukhopadhyay C, Prakash R, Pillai S, Pujary K, Pujary P Chronic suppurative otitis media: Optimizing initial antibiotic therapy in a tertiary care setup. Indian J Otolaryngol Head Neck Surg 2012;64:285-9. |
| 25. | Ettehad GH, Refahi S, Nemmati A, Pirzadeh A, Daryani A Microbial and antimicrobial susceptibility patterns from patients with chronic otitis media in Ardebil. Int J Trop Med 2006;1:62-5. |
| 26. | Shyamla R, Reddy SP The study of bacteriological agents of chronic suppurative otitis media–aerobic culture and evaluation. J Microbiol Biotechnol Res 2012;2:152-62. |
| 27. | Mansoor T, Musani MA, Khalid G, Kamal M Pseudomonas aeruginosa in chronic suppurative otitis media: Sensitivity spectrum against various antibiotics in Karachi. J Ayub Med Coll Abbottabad 2009;21:120-3. |
| 28. | Prakash R, Juyal D, Negi V, Pal S, Adekhandi S, Sharma M, et al. Microbiology of chronic suppurative otitis media in a tertiary care setup of Uttarakhand state, India. N Am J Med Sci 2013;5:282-7. |
| 29. | Sahu MC, Swain SK, Kar SK Genetically diversity of Pseudomonas aeruginosa isolated from chronic suppurative otitis media with respect to their antibiotic sensitivity pattern. Indian J Otolaryngol Head Neck Surg 2019;71:1300-8. |
| 30. | Yeo SG, Park DC, Hong SM, Cha CI, Kim MG Bacteriology of chronic suppurative otitis media—A multicenter study. Acta Otolaryngol 2007;127:1062-7. |
| 31. | Swain SK, Behera IC, Sahu MC, Das A Povidone iodine soaked gelfoam for the treatment of recalcitrant otomycosis—Our experiences at a tertiary care teaching hospital of Eastern India. J Mycol Med 2018;28:122-7. |
| 32. | Ibekwe AO, al Shareef Z, Benayam A Anaerobes and fungi in chronic suppurative otitis media. Ann Otol Rhinol Laryngol 1997;106:649-52. |
| 33. | Osazuwa F, Osazuwa E, Osime C, Igharo EA, Imade PE, Lofor P, et al. Etiologic agents of otitis media in Benin City, Nigeria. N Am J Med Sci 2011;3:95-8. |
| 34. | Debta P, Swain SK, Lenka S, Sahu MC Otomycosis: A Comprehensive review. Indian J Forensic Med Toxicol 2020;14:8429-32. |
| 35. | Saini S, Gupta N, Aparna Seema, Sachdeva OP Bacteriological study of paediatric and adult chronic suppurative otitis media. Indian J Pathol Microbiol 2005;48:413-6. |
| 36. | David W, Peter S, Joseph D, Wayne B Microbiology of external auditory canal. Laryngoscope 2001;111:20549. |
| 37. | Swain SK, Jena PP Microbiome of the head-and-neck region. Mustansiriya Med J 2022;21:8-12. |
| 38. | Jang CH, Park SY Emergence of ciprofloxacin-resistant Pseudomonas in chronic suppurative otitis media. Clin Otolaryngol Allied Sci 2004;29:321-3. |
| 39. | Gul AA, Ali L, Rahim E, Ahmed S Chronic suppurative otitis media; frequency of Pseudomonas aeruginosa in patients and its sensitivity to various antibiotics. Professional Med J 2007;14:411-5. |
| 40. | Gilbert DN, Kohlhepp SJ, Slama KA, Grunkemeier G, Lewis G, Dworkin RJ, et al. Phenotypic resistance of Staphylococcus aureus, selected Enterobacteriaceae, and Pseudomonas aeruginosa after single and multiple in vitro exposures to ciprofloxacin, levofloxacin, and trovafloxacin. Antimicrob Agents Chemother 2001;45:883-92. |
| 41. | Carsenti-Etesse H, Cavallo JD, Roger PM, Ziha-Zarifi I, Plesiat P, Garrabé E, et al. Effect of beta-lactam antibiotics on the in vitro development of resistance in Pseudomonas aeruginosa. Clin Microbiol Infect 2001;7:144-51. |
| 42. | Hart CA, Kariuki S Antimicrobial resistance in developing countries. BMJ 1998;317:647-50. |
| 43. | Normark BH, Normark S Evolution and spread of antibiotic resistance. J Intern Med 2002;252:91-106. |
| 44. | Chandra Sahu M, Swain SK Surveillance of antibiotic sensitivity pattern in chronic suppurative otitis media of an Indian teaching hospital. World J Otorhinolaryngol Head Neck Surg 2019;5:88-94. |
[Figure 1]
[Table 1]
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