Reduced Chance of Hearing Loss Associated with Therapeutic Drug Monitoring of Aminoglycosides in the Treatment of Multidrug-Resistant Tuberculosis

R van Altena, J A Dijkstra, M E van der Meer, J F Borjas Howard, J G W Kosterink, D van Soolingen, T S van der Werf, J W C Alffenaar

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Hearing loss and nephrotoxicity are associated with prolonged treatment duration and higher dosage of amikacin and kanamycin. In our tuberculosis center, we used therapeutic drug monitoring (TDM) targeting preset pharmacokinetic/pharmacodynamic (PK/PD) surrogate endpoints in an attempt to maintain efficacy while preventing (oto)toxicity. To evaluate this strategy, we retrospectively evaluated medical charts of tuberculosis (TB) patients treated with amikacin or kanamycin in the period from 2000 to 2012. Patients with culture-confirmed multiresistant or extensively drug-resistant tuberculosis (MDR/XDR-TB) receiving amikacin or kanamycin as part of their TB treatment for at least 3 days were eligible for inclusion in this retrospective study. Clinical data, including maximum concentration (Cmax), Cmin, and audiometry data, were extracted from the patients' medical charts. A total of 80 patients met the inclusion criteria. The mean weighted Cmax/MIC ratios obtained from 57 patients were 31.2 for amikacin and 12.3 for kanamycin. The extent of hearing loss was limited and correlated with the cumulative drug dose per kg of body weight during daily administration. At follow-up, 35 (67.3%) of all patients had successful outcome; there were no relapses. At a median dose of 6.5 mg/kg, a correlation was found between the dose per kg of body weight during daily dosing and the extent of hearing loss in dB at 8,000 Hz. These findings suggest that the efficacy at this lower dosage is maintained with limited toxicity. A randomized controlled trial should provide final proof of the safety and efficacy of TDM-guided use of aminoglycosides in MDR-TB treatment.

Original languageEnglish
JournalAntimicrobial Agents and Chemotherapy
Volume61
Issue number3
DOIs
Publication statusPublished - Mar 2017

Cite this

@article{9dd372a54c1045c590c0098b41fad082,
title = "Reduced Chance of Hearing Loss Associated with Therapeutic Drug Monitoring of Aminoglycosides in the Treatment of Multidrug-Resistant Tuberculosis",
abstract = "Hearing loss and nephrotoxicity are associated with prolonged treatment duration and higher dosage of amikacin and kanamycin. In our tuberculosis center, we used therapeutic drug monitoring (TDM) targeting preset pharmacokinetic/pharmacodynamic (PK/PD) surrogate endpoints in an attempt to maintain efficacy while preventing (oto)toxicity. To evaluate this strategy, we retrospectively evaluated medical charts of tuberculosis (TB) patients treated with amikacin or kanamycin in the period from 2000 to 2012. Patients with culture-confirmed multiresistant or extensively drug-resistant tuberculosis (MDR/XDR-TB) receiving amikacin or kanamycin as part of their TB treatment for at least 3 days were eligible for inclusion in this retrospective study. Clinical data, including maximum concentration (Cmax), Cmin, and audiometry data, were extracted from the patients' medical charts. A total of 80 patients met the inclusion criteria. The mean weighted Cmax/MIC ratios obtained from 57 patients were 31.2 for amikacin and 12.3 for kanamycin. The extent of hearing loss was limited and correlated with the cumulative drug dose per kg of body weight during daily administration. At follow-up, 35 (67.3{\%}) of all patients had successful outcome; there were no relapses. At a median dose of 6.5 mg/kg, a correlation was found between the dose per kg of body weight during daily dosing and the extent of hearing loss in dB at 8,000 Hz. These findings suggest that the efficacy at this lower dosage is maintained with limited toxicity. A randomized controlled trial should provide final proof of the safety and efficacy of TDM-guided use of aminoglycosides in MDR-TB treatment.",
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author = "{van Altena}, R and Dijkstra, {J A} and {van der Meer}, {M E} and {Borjas Howard}, {J F} and Kosterink, {J G W} and {van Soolingen}, D and {van der Werf}, {T S} and Alffenaar, {J W C}",
note = "Copyright {\circledC} 2017 American Society for Microbiology.",
year = "2017",
month = "3",
doi = "10.1128/AAC.01400-16",
language = "English",
volume = "61",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "3",

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Reduced Chance of Hearing Loss Associated with Therapeutic Drug Monitoring of Aminoglycosides in the Treatment of Multidrug-Resistant Tuberculosis. / van Altena, R; Dijkstra, J A; van der Meer, M E; Borjas Howard, J F; Kosterink, J G W; van Soolingen, D; van der Werf, T S; Alffenaar, J W C.

In: Antimicrobial Agents and Chemotherapy, Vol. 61, No. 3, 03.2017.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Reduced Chance of Hearing Loss Associated with Therapeutic Drug Monitoring of Aminoglycosides in the Treatment of Multidrug-Resistant Tuberculosis

AU - van Altena, R

AU - Dijkstra, J A

AU - van der Meer, M E

AU - Borjas Howard, J F

AU - Kosterink, J G W

AU - van Soolingen, D

AU - van der Werf, T S

AU - Alffenaar, J W C

N1 - Copyright © 2017 American Society for Microbiology.

PY - 2017/3

Y1 - 2017/3

N2 - Hearing loss and nephrotoxicity are associated with prolonged treatment duration and higher dosage of amikacin and kanamycin. In our tuberculosis center, we used therapeutic drug monitoring (TDM) targeting preset pharmacokinetic/pharmacodynamic (PK/PD) surrogate endpoints in an attempt to maintain efficacy while preventing (oto)toxicity. To evaluate this strategy, we retrospectively evaluated medical charts of tuberculosis (TB) patients treated with amikacin or kanamycin in the period from 2000 to 2012. Patients with culture-confirmed multiresistant or extensively drug-resistant tuberculosis (MDR/XDR-TB) receiving amikacin or kanamycin as part of their TB treatment for at least 3 days were eligible for inclusion in this retrospective study. Clinical data, including maximum concentration (Cmax), Cmin, and audiometry data, were extracted from the patients' medical charts. A total of 80 patients met the inclusion criteria. The mean weighted Cmax/MIC ratios obtained from 57 patients were 31.2 for amikacin and 12.3 for kanamycin. The extent of hearing loss was limited and correlated with the cumulative drug dose per kg of body weight during daily administration. At follow-up, 35 (67.3%) of all patients had successful outcome; there were no relapses. At a median dose of 6.5 mg/kg, a correlation was found between the dose per kg of body weight during daily dosing and the extent of hearing loss in dB at 8,000 Hz. These findings suggest that the efficacy at this lower dosage is maintained with limited toxicity. A randomized controlled trial should provide final proof of the safety and efficacy of TDM-guided use of aminoglycosides in MDR-TB treatment.

AB - Hearing loss and nephrotoxicity are associated with prolonged treatment duration and higher dosage of amikacin and kanamycin. In our tuberculosis center, we used therapeutic drug monitoring (TDM) targeting preset pharmacokinetic/pharmacodynamic (PK/PD) surrogate endpoints in an attempt to maintain efficacy while preventing (oto)toxicity. To evaluate this strategy, we retrospectively evaluated medical charts of tuberculosis (TB) patients treated with amikacin or kanamycin in the period from 2000 to 2012. Patients with culture-confirmed multiresistant or extensively drug-resistant tuberculosis (MDR/XDR-TB) receiving amikacin or kanamycin as part of their TB treatment for at least 3 days were eligible for inclusion in this retrospective study. Clinical data, including maximum concentration (Cmax), Cmin, and audiometry data, were extracted from the patients' medical charts. A total of 80 patients met the inclusion criteria. The mean weighted Cmax/MIC ratios obtained from 57 patients were 31.2 for amikacin and 12.3 for kanamycin. The extent of hearing loss was limited and correlated with the cumulative drug dose per kg of body weight during daily administration. At follow-up, 35 (67.3%) of all patients had successful outcome; there were no relapses. At a median dose of 6.5 mg/kg, a correlation was found between the dose per kg of body weight during daily dosing and the extent of hearing loss in dB at 8,000 Hz. These findings suggest that the efficacy at this lower dosage is maintained with limited toxicity. A randomized controlled trial should provide final proof of the safety and efficacy of TDM-guided use of aminoglycosides in MDR-TB treatment.

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KW - Amikacin/adverse effects

KW - Antitubercular Agents/adverse effects

KW - Area Under Curve

KW - Audiometry

KW - Biological Availability

KW - Drug Administration Schedule

KW - Drug Dosage Calculations

KW - Drug Monitoring

KW - Extensively Drug-Resistant Tuberculosis/blood

KW - Female

KW - Hearing Loss/chemically induced

KW - Humans

KW - Kanamycin/adverse effects

KW - Male

KW - Microbial Sensitivity Tests

KW - Mycobacterium tuberculosis/drug effects

KW - Retrospective Studies

U2 - 10.1128/AAC.01400-16

DO - 10.1128/AAC.01400-16

M3 - Article

VL - 61

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

IS - 3

ER -