The Prevalens of Ototoxicity in Drug Resistance Tuberculosis Patients and The Associated Factors at Persahabatan General Central Hospital

Ismulat Rahmawati, Fathiyah Isbaniah, Heidy Agustin, Raden Ena Sarikencana


Background: The treatment of drug resistance tuberculosis needs second line injection antituberculosis drug that associated with irreversible ototoxic. The aim of this study is to know the prevalence of ototoxicity in tuberculosis drug resistance patients and the contributing factors.
Methods: This is a cross sectional study among drug resistance TB patients who receive kanamysin or capreomycin as a part of drug regimen during intensive phase in January to September 2017 at Persahabatan hospital. Ototoxic defined according to American Speech Language and Hearing Association (ASHA) 1994 criteria by comparing baseline audiometric examination before treatment with current result.
Results: Seventy-two patients were included in this study. The prevalence of ototoxicity was found in 34 patients (47,2%). Ototoxic found in 5 subjects (14,7%) during the first month of treatment and 19 subjects (56%) without hearing disturbance complain. Ototoxic in kanamisin group (47,9%) is more frequent compared with capreomisin (36,8%). Ototoxicity was associated with age, the risk increases 5% every 1 year older p=0,029 aOR:1,050 IK95% (1,005-1,096). The prevalences of ototoxicity are higher in diabetes and increasing serum creatinin patients but statistically not significance. Sex, body mass index, the history of using injectable antiTB drug, HIV status and total dosis were not associated with ototoxicity.
Conclusion: Ototoxicity is common in intensive phase of drug resistance tuberculosis treatment. Further study needed to determine the association of contributing factors. (J Respir Indo. 2019; 39(3):180-95)


Ototoxicity; second line injectable antituberculosis drugs; drug resistant tuberculosis

Full Text:



World Health Organization. Global tuberculosis report 2015. Geneva: World Health Organization;2015. p. 54-68

World Health Organization. WHO treatment guidelines for drug resistant tuberculosis 2016 update. Geneva: World Health Organization;2016. p.19-24.

World Health Organization.Companion handbook to the WHO guidelines for the programmatic management of drug resistant tuberculosis. Geneva: World Health Organization; 2014. p.7-12.

Kementerian Kesehatan Republik Indonesia. Alur dan prinsip pengobatan paduan standar jangka pendek. Jakarta: Kementerian Kesehatan Republik Indonesia;2017. p.1.

Chung DK, Revilla MA, Guillen BS, Velez SE, Soria MA, Ez-Garbin AN, et al. Factors associated with anti-tuberculosis medication adverse effects: a case-control study in lima, peru. Plosone. 2011;6(11):1-5.

Schellack N, Naude A. An overview of pharmacotherapy induced ototoxicity. S Afr Fam Pract. 2013;55(4):357-65.

Kementerian Kesehatan Republik Indonesia. Peraturan menteri kesehatan nomor 67 tahun 2016 tentang penanggulangan tuberkulosis. Jakarta: Kementerian Kesehatan Republik Indonesia; 2016. p.19-81.

Shin SS, Pasechnikov AD, Gelmanova IY, Peremitin GG, Strelis AK, Mishustin S, et al. Adverse reactions among patients being treated for MDR-TB in Tomsk, Russia. Int J Tuberc Lung Dis. 2007;11(12):1314-20.

Petersen L, Rogers C. Aminoglycoside-induced hearing deficits – a review of cochlear ototoxicity. S Afr Fam Pract. 2015;57(2):77-82.

Duggal P, Sarkar M. Audiologic monitoring of multidrug resistant tuberculosis patients on aminoglycoside treatment with long term follow up. BMC Ear Nose and Throat Disord. 2007;7(5):1-7.

Seddon JA, Godfrey-Faussett P, Jacobs K, Ebrahim A, Hesselingan AC, Schaaf HS. Hearing loss in patients on treatment for drug-resistant tuberculosis. Eur Respir J. 2012;40:1277-86.

Harris T, Bardien S, Schaaf HS, Petersen L, Jong Gd, Fagan JJ. Aminoglycoside-induced hearing loss in HIV-positive and HIVnegative multidrug-resistant tuberculosis patients. S Afr Med J 2012;106(6):363-6.

Peloquin CA, Berning SE, Nitta AT, Simone PM, Goble M, Huitt GA, et al. Aminoglycoside toxicity: daily versus thrice weekly dosing for treatment of mycobacterial diseases. CID. 2004;38:1538-44.

Sharma V, Bhagat S, Verma B, Singh R, Singh S. Audiological evaluation of patients taking kanamycin for multidrug resistant tuberculosis. Iran J Otorhinolar. 2016;28(3):203-8.

Sagwa EL, Ruswa N, Mavhunga F, Rennie T, GMLeufkens H, Teeuwisse AKM. Comparing amikacin and kanamycin induced hearing loss in multi drug resistant tuberculosis treatment under programmatic condition in a namibian retrospective cohort. BMC Pharmacol Toxicol. 2015;16(36):1-9

Hopewell PC, Maeda MK. Tuberculosis. In: Mason RJ, Braddus C, Martin TR, King TE, Schraufnagel DE, Murray JF, editors. Textbook of respiratory medicine. 5th ed. Philadelphia: Saunders elsevier;2010. p. 754-65.

Librianty N. Faktor yang mempengaruhi lama konversi pada pasien tuberkulosis multidrug resistant.[Tesis].[Jakarta]: Universitas Indonesia;2015.

Bhardwaj P, Deshkar AM, Verma R. Side effects encountered in treatment of multidrug resistant tuberculosis: a 3 year experience at first dots plus site of Chattisgarh. IJSS. 2015;3(5):104-6.

Rathod KB, Borkar MS, Avinash R Lamb SLS, Surwade GA, Pandey VR. Adverse events among patients of multi drug resistant tuberculosis receiving second line anti TB treatment. Int J Sci Rep. 2015;1(6):253-7.

Sturdy A, Goodman A, Jose RJ, Loyse A, O’Donoghue M, Kon OM, et al. Multidrug-resistant tuberculosis (MDR-TB) treatment in the UK: a study of injectable use and toxicity in practice. J Antimicrob Chemother. 2011;66:1-6.

Din MATE, Maraghy AAE, Hay AHRA. Adverse reactions among patients being treated for multi-drug resistant tuberculosis at Abbassia Chest Hospital. Egypt J of Chest Dis Tuberc. 2015;64:939-52.

Anggraeni DH. Kekerapan kejadian gangguan elektrolit dan faktor-faktor yang berhubungan pada pasien tuberkulosis multidrug resistan di RSUP Persahabatan Jakarta.[Tesis].[Jakarta]: Universitas Indonesia; 2017.

Shinde MP, Halasawadekar NR, Ramanand SJ, Pore SM, Ramanand JB, Patil PT, et al. A study of adverse drug reactions in patients receiving treatment for multi-drug resistant tuberculosis. Int J Basic Clin Pharmacol. 2017;6(2):354-8.

Neyrolles O, Murci LQ. Sexual inequality in tuberculosis. Plosmed. 2009;6(12):1-6.

Tiwari M, Roy AK, Shamaliya K, Yadav SK. Ototoxicity associated with the usage of injectable kanamycin in multi-drug resistant tuberculosis patients during intensive phase of category IV treatment on DOTS-plus therapy. Journal of Dental and Medical Sciences. 2016;15(2):12-6.

Reviono, Kusnanto P, Eko V, Pakiding H, Nurwidiasih D. Multidrug resistant tuberculosis (MDR TB): tinjauan epidemiologi dan faktor risiko efek samping obat anti tuberkulosis. MKB. 2014;46(4).

Kaffah S. Prevalens acute kidney injury pada pasien tuberculosis multidrug resistant yang diobati dengan paduan standar pada fase awal dan faktor-faktor yang mempengaruhi di RSUP Persahabatan.[Tesis].[Jakarta]: Universitas Indonesia; 2017.

Jager PD, Altena RV. Hearing loss and nephrotoxicity in long term aminoglycoside treatment in patients with tuberculosis. Int JTuberc Lung Dis. 2002;6(7):622-7.

Nathella PK, Babu S. Influence of diabetes mellitus on immunity to human tuberculosis. Immunology. 2017;152:13-24.

Durrant JD, Campbell K, Fausti S, Guthrie On, Jacobson G, Martin BLL, et al. American academy of audiology position statement and clinical practice guidelines ototoxicity monitoring. 2009. p.3-15.

Asri DA, Soepandi PZ, Burhan E, Widyahening I. Gambaran efek tidak diinginkan dan tatalaksana pada pasien tuberkulosis multidrug resistant dengan pemberian obat antituberkulosis regimen standar di RS Persahabatan.[Tesis].[Jakarta]: Universitas Indonesia; 2012.

Yulianti, Mahdiani S. Gangguan pendengaran penderita tuberkulosis multidrug resistant. ORLI. 2015;45(2):83-9.

Ramma L, Ibekwe TS. Cochleo-vestibular clinical findings among drug resistant Tuberculosis Patients on therapy-a pilot study. Int Arch Med. 2012;5(3):1-5.

Javadi MR, Abtahib B, Gholamia K, Moghadamb BS, Tabarsic P, Salamzadehb J. The incidence of amikacin ototoxicity in multidrug-resistant tuberculosis patients. Iran J Pharm Res. 2011;10(4):905-11.

Nizamuddin S, Khan FA, Khan AR, Kamaal CM. Assessment of hearing loss in multi-drug resistant tuberculosis (MDR-TB) patients undergoing aminoglycoside treatment. Int J Res Med Sci. 2015;3(7):1734-40.

Arnold A, Cooke GS, Kon OM, Dedicoat M, Lipman M, Loyse A, et al. Adverse effects and choice between the injectable agents amikacin and capreomycin in multidrug resistant tuberculosis. Antimicrob Agents Chemother. 2017;61(9):1-12.

Appana D, Joseph L, Paken J. An audiological profile of patients infected with multi-drug resistant tuberculosis at a district hospital in KwaZulu-Natal. South African Journal of Communication Disorders. 2016:1-12.

Harris T, Heinze B. Tuberculosis, aminoglycoside and HIV related hearing loss. UCT. 2013:1-17.

Khoza-Shangasea K, Stirka M. Audiological testing for ototoxicity monitoring in adults with tuberculosis in state hospitals in Gauteng, South Africa. South Afr J Infect Dis. 2016;31(2):44-9.

Huth ME, Ricci AJ, Cheng AG. Mechanisms of aminoglycoside ototoxicity and targets of hair cell protection. Int J Otolaryngol. 2011;2011:1-19.

KNCV foundation. Audiometry in the management of drug resistant tuberculosis. Washington DC. 2017. p. 1-23.

Ribeiro L, Sousa C, Sousa A, Ferreira C, Duarte R, Almeida AFE, et al. Evaluation of hearing in patients with multiresistant tuberculosis. Acta Med Port. 2015;28(1):87-91.

Bardien S, deJong G, Schaaf HS, Harris T, Fagan J, Petersen L. Aminoglycoside induced hearing loss: south africans at risk. S Afr Med J. 2009;99(6):440-1.

Kamogashira T, Fujimoto C, Yamasoba T. Reactive oxygen species, apoptosis, and mitochondrial dysfunction in hearing loss. BioMed Res Int. 2015:1-4.

Gatell JM, Ferran F, Araujo V, Bonet M, Soriano E, Traserra J, et al. Univariate and multivariate analyses of risk factors predisposing to auditory toxicity in patients receiving aminoglycosides. Antimicrob agent chemother. 1987;31(9):1383-7.

Sogebi OA, Adefuye BO, Adebola SO, Oladeji SM, Adedeji TO. Clinical predictors of aminoglycoside-induced ototoxicity in drug-resistant tuberculosis patients on intensive therapy. Auris Nasus Larynx. 2017;44:404-10.

Rizzi MD, Hirose K. Aminoglycoside ototoxicity. Curr Opin Otolaryngol Head Neck Surg. 2007;15:352-7.

Torrico MM, Luna JC, Migliori GB, Ambrosio LD, Alduenda JC, Velarde HV, et al. Diabetes is associated with severe adverse events in multidrug resistant tuberculosis. Arch Bronconeumol. 2017;53(5):245-50.

Heysell S, Ahmed S, Rahman M. Hearing loss with kanamycin treatment for multidrug-resistant tuberculosis in Bangladesh. Eur Respir J. 2018;51:1-3.



  • There are currently no refbacks.

Copyright (c) 2019 Ismulat Rahmawati, Fathiyah Isbaniah, Heidy Agustin, Raden Ena Sarikencana

Jurnal Respirologi Indonesia
pISSN: 0853-7704 - eISSN: 2620-3162
Address: Jalan Cipinang Bunder No. 19, Cipinang, Pulogadung, Jakarta Timur, DKI Jakarta 13240, Indonesia
Phone: +62-21-2247-4845

An official publication by
the Indonesian Society of Respirology (ISR)

Creative Commons License
Creative Commons Attribution-NonCommercial 4.0 International License