RESISTENSI ANTIBIOTIK DIPENGARUHI OLEH BIOFILM PADA PENGOBATAN OTITIS MEDIA AKUT: TINJAUAN NARATIF
BIOFILM-MEDIATED ANTIBIOTIC RESISTANCE IN ACUTE OTITIS MEDIA TREATMENT: A NARRATIVE REVIEW
Abstract
Otitis media akut (OMA) adalah infeksi telinga yang umum terjadi pada anak-anak dengan gejala seperti rasa sakit, demam, dan gangguan pendengaran yang dapat mempengaruhi kualitas hidup. Meskipun antibiotik telah menjadi pilihan pengobatan utama selama ini, banyak kasus yang tidak sembuh sepenuhnya. Salah satu penyebab masalah ini adalah adanya biofilm, yaitu kumpulan bakteri yang terorganisir dalam lapisan pelindung membuatnya kebal terhadap antibiotik dan sistem kekebalan tubuh inang. Penelitian terbaru menunjukkan bahwa biofilm berperan penting dalam kegagalan terapi dan kekambuhan OMA. Mekanisme yang terlibat meliputi penghalang penetrasi obat, keberadaan sel persister, heterogenitas metabolik bakteri, dan transfer gen resistensi. Dampak klinis meliputi infeksi yang sering terjadi kembali, otitis media kronis, perforasi membran timpani, hingga gangguan perkembangan bicara dan kognitif pada anak-anak. Keterbatasan terapi antibiotik mendorong pengembangan pendekatan baru, seperti penggunaan agen antibiofilm non-antibiotik (misalnya N-asetilsistein), terapi faga, penghantaran obat menggunakan nanopartikel, serta pendekatan imunomodulasi. Selain itu, inovasi dalam diagnostik non-invasif dan terapi berbasis cahaya juga menunjukkan potensi yang menjanjikan. Dengan pemahaman yang lebih baik tentang peran biofilm, pengelolaan OMA perlu beralih dari sekadar mengandalkan antibiotik menjadi pendekatan multimodal yang lebih menyeluruh. Penerapan terapi inovatif diharapkan dapat mengurangi angka kekambuhan dan meningkatkan kualitas hidup anak-anak yang terdampak.
References
Akyıldız İ, Take G, Uygur K, Kızıl Y, Aydil U. Bacterial Biofilm Formation in the Middle-Ear Mucosa of Chronic Otitis Media Patients. Indian J Otolaryngol Head Neck Surg. 2013;65(S3):557-561. doi:10.1007/s12070-012-0513-x
Abu Bakar M, McKimm J, Haque M. Otitis media and biofilm: An overview. Int J Nutr Pharmacol Neurol Dis. 2018;8(3):70. doi:10.4103/ijnpnd.ijnpnd_28_18
Daniel M, Chessman R, Al-Zahid S, et al. Biofilm Eradication With Biodegradable Modified-Release Antibiotic Pellets: A Potential Treatment for Glue Ear. Arch Otolaryngol Neck Surg. 2012;138(10):942. doi:10.1001/archotol.2013.238
Empitu M, Kadariswantiningsih I, Shakri N. Pharmacological strategies for targeting biofilms in otorhinolaryngologic infections and overcoming antimicrobial resistance (Review). Biomed Rep. 2025;22(6):1-13. doi:10.3892/br.2025.1973
Gebreyohannes G, Nyerere A, Bii C, Sbhatu DB. Challenges of intervention, treatment, and antibiotic resistance of biofilm-forming microorganisms. Heliyon. 2019;5(8):e02192. doi:10.1016/j.heliyon.2019.e02192
Thornton RB, Rigby PJ, Wiertsema SP, et al. Multi-species bacterial biofilm and intracellular infection in otitis media. BMC Pediatr. 2011;11(1):94. doi:10.1186/1471-2431-11-94
Mueller SK. The Role of Exosomes in the Pathophysiology of Chronic Rhinosinusitis. Front Cell Infect Microbiol. 2022;11:812920. doi:10.3389/fcimb.2021.812920
Nithyanand P, Boya BR, Lee J, Lee J. Polymicrobial Biofilms: Interkingdom Interactions, Resistance and Therapeutic Strategies. Microb Biotechnol. 2025;18(8):e70218. doi:10.1111/1751-7915.70218
Hall CW, Mah TF. Molecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria. FEMS Microbiol Rev. 2017;41(3):276-301. doi:10.1093/femsre/fux010
Sharma S, Mohler J, Mahajan SD, Schwartz SA, Bruggemann L, Aalinkeel R. Microbial Biofilm: A Review on Formation, Infection, Antibiotic Resistance, Control Measures, and Innovative Treatment. Microorganisms. 2023;11(6):1614. doi:10.3390/microorganisms11061614
Li H, Staxäng K, Ladak HM, Agrawal S, Rask-Andersen H. Middle ear biofilm and sudden deafness - a light and transmission electron microscopy study. Front Neurol. 2024;15:1495893. doi:10.3389/fneur.2024.1495893
Shree P, Singh CK, Sodhi KK, Surya JN, Singh DK. Biofilms: Understanding the structure and contribution towards bacterial resistance in antibiotics. Med Microecol. 2023;16:100084. doi:10.1016/j.medmic.2023.100084
Almatroudi A. Biofilm Resilience: Molecular Mechanisms Driving Antibiotic Resistance in Clinical Contexts. Biology. 2025;14(2):165. doi:10.3390/biology14020165
Habashi N, Marom T, Steinberg D, Zacks B, Tamir SO. Biofilm distribution on tympanostomy tubes: An ex vivo descriptive study. Int J Pediatr Otorhinolaryngol. 2020;138:110350. doi:10.1016/j.ijporl.2020.110350
Prasad SV, Piktel E, Depciuch J, et al. Targeting Bacteria Causing Otitis Media Using Nanosystems Containing Nonspherical Gold Nanoparticles and Ceragenins. Nanomed. 2021;16(30):2657-2678. doi:10.2217/nnm-2021-0370
Ioannidis A, Chatzipanagiotou S, Vassilaki N, et al. Biofilm-Forming Bacteria Implicated in Complex Otitis Media in Children in the Post-Heptavalent Pneumococcal Conjugate Vaccine (PCV7) Era. Microorganisms. 2023;11(3):545. doi:10.3390/microorganisms11030545
Michaelis C, Grohmann E. Horizontal Gene Transfer of Antibiotic Resistance Genes in Biofilms. Antibiotics. 2023;12(2):328. doi:10.3390/antibiotics12020328
Jotic A, Savic Vujovic K, Cirkovic A, et al. Antibiofilm Effects of Novel Compounds in Otitis Media Treatment: Systematic Review. Int J Mol Sci. 2024;25(23):12841. doi:10.3390/ijms252312841
Ko YS, Gi EJ, Lee S, Kim HC, Cho HH. Dual red and near-infrared LED therapy inhibits MRSA biofilm in otitis media. Biofilm. 2025;10:100314. doi:10.1016/j.bioflm.2025.100314
Lewis K. Persister cells. Annu Rev Microbiol. 2010;64:357-372. doi:10.1146/annurev.micro.112408.134306
Niedzielski A, Chmielik LP, Stankiewicz T. The Formation of Biofilm and Bacteriology in Otitis Media with Effusion in Children: A Prospective Cross-Sectional Study. Int J Environ Res Public Health. 2021;18(7):3555. doi:10.3390/ijerph18073555
Orazi G, O’Toole GA. “It Takes a Village”: Mechanisms Underlying Antimicrobial Recalcitrance of Polymicrobial Biofilms. Margolin W, ed. J Bacteriol. 2019;202(1). doi:10.1128/JB.00530-19
Uruén C, Chopo-Escuin G, Tommassen J, Mainar-Jaime RC, Arenas J. Biofilms as Promoters of Bacterial Antibiotic Resistance and Tolerance. Antibiotics. 2020;10(1):3. doi:10.3390/antibiotics10010003
Frost HM, Keith A, Fletcher DR, et al. Clinical Outcomes Associated with Amoxicillin Treatment for Acute Otitis Media in Children. J Pediatr Infect Dis Soc. 2024;13(3):203-210. doi:10.1093/jpids/piae010
Vashistha A, Sharma N, Nanaji Y, et al. Quorum sensing inhibitors as Therapeutics: Bacterial biofilm inhibition. Bioorganic Chem. 2023;136:106551. doi:10.1016/j.bioorg.2023.106551
Roy R, Tiwari M, Donelli G, Tiwari V. Strategies for combating bacterial biofilms: A focus on anti-biofilm agents and their mechanisms of action. Virulence. 2018;9(1):522-554. doi:10.1080/21505594.2017.1313372
Cavallo I, Sivori F, Mastrofrancesco A, et al. Bacterial Biofilm in Chronic Wounds and Possible Therapeutic Approaches. Biology. 2024;13(2):109. doi:10.3390/biology13020109
Wood TK, Knabel SJ, Kwan BW. Bacterial Persister Cell Formation and Dormancy. Appl Environ Microbiol. 2013;79(23):7116-7121. doi:10.1128/AEM.02636-13
Olsen I. Biofilm-specific antibiotic tolerance and resistance. Eur J Clin Microbiol Infect Dis Off Publ Eur Soc Clin Microbiol. 2015;34(5):877-886. doi:10.1007/s10096-015-2323-z
Santa Maria PL, Kaufman AC, Bacacao B, et al. Topical Therapy Failure in Chronic Suppurative Otitis Media is Due to Persister Cells in Biofilms. Otol Neurotol Off Publ Am Otol Soc Am Neurotol Soc Eur Acad Otol Neurotol. 2021;42(9):e1263-e1272. doi:10.1097/MAO.0000000000003222
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