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Published in: BMC Infectious Diseases 1/2014

Open Access 01-12-2014 | Research article

Successful MDR-TB treatment regimens including Amikacin are associated with high rates of hearing loss

Authors: Chawangwa Modongo, Rafal S Sobota, Boikobo Kesenogile, Ronald Ncube, Giorgio Sirugo, Scott M Williams, Nicola M Zetola

Published in: BMC Infectious Diseases | Issue 1/2014

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Abstract

Background

Aminoglycosides are a critical component of multidrug-resistant tuberculosis (MDR-TB) treatment but data on their efficacy and adverse effects in Botswana is scarce. We determined the effect of amikacin on treatment outcomes and development of hearing loss in MDR-TB patients.

Methods

Patients started on MDR-TB treatment between 2006 and 2012 were included. Multivariate analysis was used to determine the effect of amikacin on treatment outcomes and development of hearing loss.

Results

437 MDR-TB patients were included, 288 (66%) of whom were HIV co-infected. 270 (62%) developed hearing loss, of whom 147 (54%) had audiometry. Of the 313 (72%) patients who completed treatment, 228 (73%) had a good outcome (cure or treatment completion). Good outcome was associated with longer amikacin treatment (adjusted OR [aOR] 1.13, 95% CI 1.06 - 1.21) and higher dosage (aOR 1.90, 95% CI 1.12 – 2.99). Longer amikacin duration (aOR 1.98, 95% CI 1.86 – 2.12) and higher dosage per weight per month (aOR 1.15, 95% CI 1.04 – 1.28) were associated with development of hearing loss. Amikacin treatment duration modified the effect of the dosage on the risk of hearing loss, increasing this risk as the duration increased.

Conclusions

Amikacin was effective for MDR-TB treatment, but was associated with a high incidence of hearing loss especially in our study population. Total treatment duration and average monthly amikacin dose were associated with improved outcomes; however these were also associated with development of hearing loss.
Literature
1.
go back to reference Caminero JA: Guidelines for the Clinical and Operational Management of Drug-Resistant Tuberculosis. 2013, 68 boulevard St Michel, 75006 Paris, Franc: International Union Against Tuberculosis and Lung Disease (The Union) Caminero JA: Guidelines for the Clinical and Operational Management of Drug-Resistant Tuberculosis. 2013, 68 boulevard St Michel, 75006 Paris, Franc: International Union Against Tuberculosis and Lung Disease (The Union)
2.
go back to reference Organization WH: Guidelines for the Programmatic Management of Drug-Resistant Tuberculosis: 2011 Update. 2011, Geneva: WHO/HTM/TB/2011.6 Organization WH: Guidelines for the Programmatic Management of Drug-Resistant Tuberculosis: 2011 Update. 2011, Geneva: WHO/HTM/TB/2011.6
3.
go back to reference Health FJCNTCaCDoP: Drug-Resistant Tuberculosis: A Survival Guide for Clinicians. 2008, 2 Health FJCNTCaCDoP: Drug-Resistant Tuberculosis: A Survival Guide for Clinicians. 2008, 2
4.
go back to reference World Health O: Multidrug-resistant tuberculosis (MDR-TB) October 2013 Update. 2013 World Health O: Multidrug-resistant tuberculosis (MDR-TB) October 2013 Update. 2013
5.
go back to reference Program BNT: National Tuberculosis Manual. 2011, Ministry of Health: Gaborone, 7 Program BNT: National Tuberculosis Manual. 2011, Ministry of Health: Gaborone, 7
6.
go back to reference Pandya A, Xia X, Radnaabazar J, Batsuuri J, Dangaansuren B, Fischel-Ghodsian N, Nance WE: Mutation in the mitochondrial 12S rRNA gene in two families from Mongolia with matrilineal aminoglycoside ototoxicity. J Med Genet. 1997, 34 (2): 169-172. 10.1136/jmg.34.2.169.CrossRefPubMedPubMedCentral Pandya A, Xia X, Radnaabazar J, Batsuuri J, Dangaansuren B, Fischel-Ghodsian N, Nance WE: Mutation in the mitochondrial 12S rRNA gene in two families from Mongolia with matrilineal aminoglycoside ototoxicity. J Med Genet. 1997, 34 (2): 169-172. 10.1136/jmg.34.2.169.CrossRefPubMedPubMedCentral
7.
go back to reference Fischel-Ghodsian N, Prezant TR, Chaltraw WE, Wendt KA, Nelson RA, Arnos KS, Falk RE: Mitochondrial gene mutation is a significant predisposing factor in aminoglycoside ototoxicity. Am J Otolaryngol. 1997, 18 (3): 173-178. 10.1016/S0196-0709(97)90078-8.CrossRefPubMed Fischel-Ghodsian N, Prezant TR, Chaltraw WE, Wendt KA, Nelson RA, Arnos KS, Falk RE: Mitochondrial gene mutation is a significant predisposing factor in aminoglycoside ototoxicity. Am J Otolaryngol. 1997, 18 (3): 173-178. 10.1016/S0196-0709(97)90078-8.CrossRefPubMed
8.
go back to reference Fischel-Ghodsian N, Prezant TR, Fournier P, Stewart IA, Maw M: Mitochondrial mutation associated with nonsyndromic deafness. Am J Otolaryngol. 1995, 16 (6): 403-408. 10.1016/0196-0709(95)90078-0.CrossRefPubMed Fischel-Ghodsian N, Prezant TR, Fournier P, Stewart IA, Maw M: Mitochondrial mutation associated with nonsyndromic deafness. Am J Otolaryngol. 1995, 16 (6): 403-408. 10.1016/0196-0709(95)90078-0.CrossRefPubMed
9.
go back to reference Fischel-Ghodsian N, Prezant TR, Bu X, Oztas S: Mitochondrial ribosomal RNA gene mutation in a patient with sporadic aminoglycoside ototoxicity. Am J Otolaryngol. 1993, 14 (6): 399-403. 10.1016/0196-0709(93)90113-L.CrossRefPubMed Fischel-Ghodsian N, Prezant TR, Bu X, Oztas S: Mitochondrial ribosomal RNA gene mutation in a patient with sporadic aminoglycoside ototoxicity. Am J Otolaryngol. 1993, 14 (6): 399-403. 10.1016/0196-0709(93)90113-L.CrossRefPubMed
10.
go back to reference Smith CR, Lipsky JJ, Laskin OL, Hellmann DB, Mellits ED, Longstreth J, Lietman PS: Double-blind comparison of the nephrotoxicity and auditory toxicity of gentamicin and tobramycin. N Engl J Med. 1980, 302 (20): 1106-1109. 10.1056/NEJM198005153022002.CrossRefPubMed Smith CR, Lipsky JJ, Laskin OL, Hellmann DB, Mellits ED, Longstreth J, Lietman PS: Double-blind comparison of the nephrotoxicity and auditory toxicity of gentamicin and tobramycin. N Engl J Med. 1980, 302 (20): 1106-1109. 10.1056/NEJM198005153022002.CrossRefPubMed
11.
go back to reference Smith CR, Lipsky JJ, Lietman PS: Relationship between aminoglycoside-induced nephrotoxicity and auditory toxicity. Antimicrob Agents Chemother. 1979, 15 (6): 780-782. 10.1128/AAC.15.6.780.CrossRefPubMedPubMedCentral Smith CR, Lipsky JJ, Lietman PS: Relationship between aminoglycoside-induced nephrotoxicity and auditory toxicity. Antimicrob Agents Chemother. 1979, 15 (6): 780-782. 10.1128/AAC.15.6.780.CrossRefPubMedPubMedCentral
12.
go back to reference Moore RD, Smith CR, Lietman PS: The association of aminoglycoside plasma levels with mortality in patients with gram-negative bacteremia. J Infect Dis. 1984, 149 (3): 443-448. 10.1093/infdis/149.3.443.CrossRefPubMed Moore RD, Smith CR, Lietman PS: The association of aminoglycoside plasma levels with mortality in patients with gram-negative bacteremia. J Infect Dis. 1984, 149 (3): 443-448. 10.1093/infdis/149.3.443.CrossRefPubMed
13.
go back to reference Moore RD, Smith CR, Lipsky JJ, Mellits ED, Lietman PS: Risk factors for nephrotoxicity in patients treated with aminoglycosides. Ann Intern Med. 1984, 100 (3): 352-357. 10.7326/0003-4819-100-3-352.CrossRefPubMed Moore RD, Smith CR, Lipsky JJ, Mellits ED, Lietman PS: Risk factors for nephrotoxicity in patients treated with aminoglycosides. Ann Intern Med. 1984, 100 (3): 352-357. 10.7326/0003-4819-100-3-352.CrossRefPubMed
14.
go back to reference Peloquin CA, Berning SE, Nitta AT, Simone PM, Goble M, Huitt GA, Iseman MD, Cook JL, Curran-Everett D: Aminoglycoside toxicity: daily versus thrice-weekly dosing for treatment of mycobacterial diseases. Clin Infect Dis. 2004, 38 (11): 1538-1544. 10.1086/420742.CrossRefPubMed Peloquin CA, Berning SE, Nitta AT, Simone PM, Goble M, Huitt GA, Iseman MD, Cook JL, Curran-Everett D: Aminoglycoside toxicity: daily versus thrice-weekly dosing for treatment of mycobacterial diseases. Clin Infect Dis. 2004, 38 (11): 1538-1544. 10.1086/420742.CrossRefPubMed
15.
go back to reference Matz GJ: Aminoglycoside cochlear ototoxicity. Otolaryngol Clin North Am. 1993, 26 (5): 705-712.PubMed Matz GJ: Aminoglycoside cochlear ototoxicity. Otolaryngol Clin North Am. 1993, 26 (5): 705-712.PubMed
16.
go back to reference Fausti SA, Frey RH, Henry JA, Olson DJ, Schaffer HI: Early detection of ototoxicity using high-frequency, tone-burst-evoked auditory brainstem responses. J Am Acad Audiol. 1992, 3 (6): 397-404.PubMed Fausti SA, Frey RH, Henry JA, Olson DJ, Schaffer HI: Early detection of ototoxicity using high-frequency, tone-burst-evoked auditory brainstem responses. J Am Acad Audiol. 1992, 3 (6): 397-404.PubMed
17.
go back to reference Fausti SA, Henry JA, Schaffer HI, Olson DJ, Frey RH, McDonald WJ: High-frequency audiometric monitoring for early detection of aminoglycoside ototoxicity. J Infect Dis. 1992, 165 (6): 1026-1032. 10.1093/infdis/165.6.1026.CrossRefPubMed Fausti SA, Henry JA, Schaffer HI, Olson DJ, Frey RH, McDonald WJ: High-frequency audiometric monitoring for early detection of aminoglycoside ototoxicity. J Infect Dis. 1992, 165 (6): 1026-1032. 10.1093/infdis/165.6.1026.CrossRefPubMed
18.
go back to reference Rizzi MD, Hirose K: Aminoglycoside ototoxicity. Curr Opin Otolaryngol Head Neck Surg. 2007, 15 (5): 352-357. 10.1097/MOO.0b013e3282ef772d.CrossRefPubMed Rizzi MD, Hirose K: Aminoglycoside ototoxicity. Curr Opin Otolaryngol Head Neck Surg. 2007, 15 (5): 352-357. 10.1097/MOO.0b013e3282ef772d.CrossRefPubMed
19.
go back to reference Selimoglu E: Aminoglycoside-induced ototoxicity. Curr Pharm Des. 2007, 13 (1): 119-126. 10.2174/138161207779313731.CrossRefPubMed Selimoglu E: Aminoglycoside-induced ototoxicity. Curr Pharm Des. 2007, 13 (1): 119-126. 10.2174/138161207779313731.CrossRefPubMed
20.
21.
go back to reference Gandhi NR, Shah NS, Andrews JR, Vella V, Moll AP, Scott M, Weissman D, Marra C, Lalloo UG, Friedland GH, Tugela Ferry Care and Research (TF CARES), et al: HIV coinfection in multidrug- and extensively drug-resistant tuberculosis results in high early mortality. Am J Respir Crit Care Med. 2010, 181 (1): 80-86. 10.1164/rccm.200907-0989OC.CrossRefPubMed Gandhi NR, Shah NS, Andrews JR, Vella V, Moll AP, Scott M, Weissman D, Marra C, Lalloo UG, Friedland GH, Tugela Ferry Care and Research (TF CARES), et al: HIV coinfection in multidrug- and extensively drug-resistant tuberculosis results in high early mortality. Am J Respir Crit Care Med. 2010, 181 (1): 80-86. 10.1164/rccm.200907-0989OC.CrossRefPubMed
22.
go back to reference Small PM, Shafer RW, Hopewell PC, Singh SP, Murphy MJ, Desmond E, Sierra MF, Schoolnik GK: Exogenous reinfection with multidrug-resistant Mycobacterium tuberculosis in patients with advanced HIV infection. N Engl J Med. 1993, 328 (16): 1137-1144. 10.1056/NEJM199304223281601.CrossRefPubMed Small PM, Shafer RW, Hopewell PC, Singh SP, Murphy MJ, Desmond E, Sierra MF, Schoolnik GK: Exogenous reinfection with multidrug-resistant Mycobacterium tuberculosis in patients with advanced HIV infection. N Engl J Med. 1993, 328 (16): 1137-1144. 10.1056/NEJM199304223281601.CrossRefPubMed
23.
go back to reference Zetola NM, Olabiyi B, Ramogola-Masire D, Modongo C: Measuring stigma: are we looking in the right places?. Int J Tuberc Lung Dis. 2012, 16 (8): 1130-1131. 10.5588/ijtld.11.0824.CrossRefPubMedPubMedCentral Zetola NM, Olabiyi B, Ramogola-Masire D, Modongo C: Measuring stigma: are we looking in the right places?. Int J Tuberc Lung Dis. 2012, 16 (8): 1130-1131. 10.5588/ijtld.11.0824.CrossRefPubMedPubMedCentral
24.
go back to reference Zetola NM, Modongo C, Kip EC, Gross R, Bisson GP, Collman RG: Alcohol use and abuse among patients with multidrug-resistant tuberculosis in Botswana. Int J Tuberc Lung Dis. 2012, 16 (11): 1529-1534. 10.5588/ijtld.12.0026.CrossRefPubMedPubMedCentral Zetola NM, Modongo C, Kip EC, Gross R, Bisson GP, Collman RG: Alcohol use and abuse among patients with multidrug-resistant tuberculosis in Botswana. Int J Tuberc Lung Dis. 2012, 16 (11): 1529-1534. 10.5588/ijtld.12.0026.CrossRefPubMedPubMedCentral
25.
go back to reference Modongo C, Zetola NM: Prevalence of hypothyroidism among MDR-TB patients in Botswana. Int J Tuberc Lung Dis. 2012, 16 (11): 1561-1562. 10.5588/ijtld.12.0403.CrossRefPubMedPubMedCentral Modongo C, Zetola NM: Prevalence of hypothyroidism among MDR-TB patients in Botswana. Int J Tuberc Lung Dis. 2012, 16 (11): 1561-1562. 10.5588/ijtld.12.0403.CrossRefPubMedPubMedCentral
26.
go back to reference Organization WH: 2011 Global Tuberculosis Control. 2011, 258- Organization WH: 2011 Global Tuberculosis Control. 2011, 258-
27.
go back to reference Botswana Ministry of Health, Office of Statistics: Final report: Botswana AIDS Impact Survey III (BAIS III - 2008). 2009, Gaborone, Botswana Botswana Ministry of Health, Office of Statistics: Final report: Botswana AIDS Impact Survey III (BAIS III - 2008). 2009, Gaborone, Botswana
28.
go back to reference Cruciani M, Scarparo C, Malena M, Bosco O, Serpelloni G, Mengoli C: Meta-analysis of BACTEC MGIT 960 and BACTEC 460 TB, with or without solid media, for detection of mycobacteria. J Clin Microbiol. 2004, 42 (5): 2321-2325. 10.1128/JCM.42.5.2321-2325.2004.CrossRefPubMedPubMedCentral Cruciani M, Scarparo C, Malena M, Bosco O, Serpelloni G, Mengoli C: Meta-analysis of BACTEC MGIT 960 and BACTEC 460 TB, with or without solid media, for detection of mycobacteria. J Clin Microbiol. 2004, 42 (5): 2321-2325. 10.1128/JCM.42.5.2321-2325.2004.CrossRefPubMedPubMedCentral
29.
go back to reference Madison B, Gross W, George I, Sloutsky A, Washabaugh G, Robinson-Dunn B, Lipman H, Metchock B, Mazurek G, Ridderhof J: Multicenter evaluation of a nonweekend reading schedule for radiometric pyrazinamide susceptibility testing of Mycobacterium tuberculosis. J Clin Microbiol. 2002, 40 (10): 3753-3756. 10.1128/JCM.40.10.3753-3756.2002.CrossRefPubMedPubMedCentral Madison B, Gross W, George I, Sloutsky A, Washabaugh G, Robinson-Dunn B, Lipman H, Metchock B, Mazurek G, Ridderhof J: Multicenter evaluation of a nonweekend reading schedule for radiometric pyrazinamide susceptibility testing of Mycobacterium tuberculosis. J Clin Microbiol. 2002, 40 (10): 3753-3756. 10.1128/JCM.40.10.3753-3756.2002.CrossRefPubMedPubMedCentral
30.
go back to reference Madison B, Robinson-Dunn B, George I, Gross W, Lipman H, Metchock B, Sloutsky A, Washabaugh G, Mazurek G, Ridderhof J: Multicenter evaluation of ethambutol susceptibility testing of mycobacterium tuberculosis by agar proportion and radiometric methods. J Clin Microbiol. 2002, 40 (11): 3976-3979. 10.1128/JCM.40.11.3976-3979.2002.CrossRefPubMedPubMedCentral Madison B, Robinson-Dunn B, George I, Gross W, Lipman H, Metchock B, Sloutsky A, Washabaugh G, Mazurek G, Ridderhof J: Multicenter evaluation of ethambutol susceptibility testing of mycobacterium tuberculosis by agar proportion and radiometric methods. J Clin Microbiol. 2002, 40 (11): 3976-3979. 10.1128/JCM.40.11.3976-3979.2002.CrossRefPubMedPubMedCentral
31.
go back to reference Government of Botswana MoH: 2012 Botswana National HIV & AIDS Treatment Guidelines. 2012, Gaborone Government of Botswana MoH: 2012 Botswana National HIV & AIDS Treatment Guidelines. 2012, Gaborone
32.
go back to reference Organization WH: Definitions and reporting framework for tuberculosis– 2013 revision. 2013 Organization WH: Definitions and reporting framework for tuberculosis– 2013 revision. 2013
33.
go back to reference Nevins M, Bright M: Cockcroft-Gault formula for diagnosing moderate kidney failure. J Am Geriatr Soc. 2008, 56 (4): 774-CrossRefPubMed Nevins M, Bright M: Cockcroft-Gault formula for diagnosing moderate kidney failure. J Am Geriatr Soc. 2008, 56 (4): 774-CrossRefPubMed
34.
go back to reference Shoker A, Hossain MA, Koru-Sengul T, Raju DL, Cockcroft D: Performance of creatinine clearance equations on the original Cockcroft-Gault population. Clin Nephrol. 2006, 66 (2): 89-97.CrossRefPubMed Shoker A, Hossain MA, Koru-Sengul T, Raju DL, Cockcroft D: Performance of creatinine clearance equations on the original Cockcroft-Gault population. Clin Nephrol. 2006, 66 (2): 89-97.CrossRefPubMed
35.
go back to reference Froissart M, Rossert J, Jacquot C, Paillard M, Houillier P: Predictive performance of the modification of diet in renal disease and Cockcroft-Gault equations for estimating renal function. J Am Soc Nephrol. 2005, 16 (3): 763-773. 10.1681/ASN.2004070549.CrossRefPubMed Froissart M, Rossert J, Jacquot C, Paillard M, Houillier P: Predictive performance of the modification of diet in renal disease and Cockcroft-Gault equations for estimating renal function. J Am Soc Nephrol. 2005, 16 (3): 763-773. 10.1681/ASN.2004070549.CrossRefPubMed
36.
go back to reference Poggio ED, Wang X, Greene T, Van Lente F, Hall PM: Performance of the modification of diet in renal disease and Cockcroft-Gault equations in the estimation of GFR in health and in chronic kidney disease. J Am Soc Nephrol. 2005, 16 (2): 459-466. 10.1681/ASN.2004060447.CrossRefPubMed Poggio ED, Wang X, Greene T, Van Lente F, Hall PM: Performance of the modification of diet in renal disease and Cockcroft-Gault equations in the estimation of GFR in health and in chronic kidney disease. J Am Soc Nephrol. 2005, 16 (2): 459-466. 10.1681/ASN.2004060447.CrossRefPubMed
37.
go back to reference Rastogi N, Labrousse V, Goh KS: In vitro activities of fourteen antimicrobial agents against drug susceptible and resistant clinical isolates of Mycobacterium tuberculosis and comparative intracellular activities against the virulent H37Rv strain in human macrophages. Curr Microbiol. 1996, 33 (3): 167-175. 10.1007/s002849900095.CrossRefPubMed Rastogi N, Labrousse V, Goh KS: In vitro activities of fourteen antimicrobial agents against drug susceptible and resistant clinical isolates of Mycobacterium tuberculosis and comparative intracellular activities against the virulent H37Rv strain in human macrophages. Curr Microbiol. 1996, 33 (3): 167-175. 10.1007/s002849900095.CrossRefPubMed
38.
go back to reference de Jager P, van Altena R: Hearing loss and nephrotoxicity in long-term aminoglycoside treatment in patients with tuberculosis. Int J Tuberc Lung Dis. 2002, 6 (7): 622-627.PubMed de Jager P, van Altena R: Hearing loss and nephrotoxicity in long-term aminoglycoside treatment in patients with tuberculosis. Int J Tuberc Lung Dis. 2002, 6 (7): 622-627.PubMed
39.
go back to reference Harris T, Bardien S, Schaaf HS, Petersen L, De Jong G, Fagan JJ: Aminoglycoside-induced hearing loss in HIV-positive and HIV-negative multidrug-resistant tuberculosis patients. S Afr Med J. 2012, 102 (6 Pt 2): 363-366.PubMed Harris T, Bardien S, Schaaf HS, Petersen L, De Jong G, Fagan JJ: Aminoglycoside-induced hearing loss in HIV-positive and HIV-negative multidrug-resistant tuberculosis patients. S Afr Med J. 2012, 102 (6 Pt 2): 363-366.PubMed
40.
41.
go back to reference Barza M, Lauermann MW, Tally FP, Gorbach SL: Prospective, randomized trial of netilmicin and amikacin, with emphasis on eighth-nerve toxicity. Antimicrob Agents Chemother. 1980, 17 (4): 707-714. 10.1128/AAC.17.4.707.CrossRefPubMedPubMedCentral Barza M, Lauermann MW, Tally FP, Gorbach SL: Prospective, randomized trial of netilmicin and amikacin, with emphasis on eighth-nerve toxicity. Antimicrob Agents Chemother. 1980, 17 (4): 707-714. 10.1128/AAC.17.4.707.CrossRefPubMedPubMedCentral
42.
go back to reference Govaerts PJ, Claes J, van de Heyning PH, Jorens PG, Marquet J, De Broe ME: Aminoglycoside-induced ototoxicity. Toxicol Lett. 1990, 52 (3): 227-251. 10.1016/0378-4274(90)90033-I.CrossRefPubMed Govaerts PJ, Claes J, van de Heyning PH, Jorens PG, Marquet J, De Broe ME: Aminoglycoside-induced ototoxicity. Toxicol Lett. 1990, 52 (3): 227-251. 10.1016/0378-4274(90)90033-I.CrossRefPubMed
43.
go back to reference Mills CD, Loos BM, Henley CM: Increased susceptibility of male rats to kanamycin-induced cochleotoxicity. Hear Res. 1999, 128 (1–2): 75-79.CrossRefPubMed Mills CD, Loos BM, Henley CM: Increased susceptibility of male rats to kanamycin-induced cochleotoxicity. Hear Res. 1999, 128 (1–2): 75-79.CrossRefPubMed
44.
go back to reference Wu WJ, Sha SH, McLaren JD, Kawamoto K, Raphael Y, Schacht J: Aminoglycoside ototoxicity in adult CBA, C57BL and BALB mice and the Sprague-Dawley rat. Hear Res. 2001, 158 (1–2): 165-178.CrossRefPubMed Wu WJ, Sha SH, McLaren JD, Kawamoto K, Raphael Y, Schacht J: Aminoglycoside ototoxicity in adult CBA, C57BL and BALB mice and the Sprague-Dawley rat. Hear Res. 2001, 158 (1–2): 165-178.CrossRefPubMed
Metadata
Title
Successful MDR-TB treatment regimens including Amikacin are associated with high rates of hearing loss
Authors
Chawangwa Modongo
Rafal S Sobota
Boikobo Kesenogile
Ronald Ncube
Giorgio Sirugo
Scott M Williams
Nicola M Zetola
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2014
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-14-542

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