Comparing amikacin and kanamycin-induced hearing loss in multidrug-resistant tuberculosis treatment under programmatic conditions in a Namibian retrospective cohort

Abstract

BackgroundAmikacin and kanamycin are mainly used for treating multidrug-resistant tuberculosis (MDR-TB), especially in developing countries where the burden of MDR-TB is highest. Their protracted use in MDR-TB treatment is known to cause dose-dependent irreversible hearing loss, requiring hearing aids, cochlear implants or rehabilitation. Therapeutic drug monitoring and regular audiological assessments may help to prevent or detect the onset of hearing loss, but these services are not always available or affordable in many developing countries. We aimed to compare the cumulative incidence of hearing loss among patients treated for MDR-TB with amikacin or kanamycin-based regimens, and to identify the most-at-risk patients, based on the real-life clinical practice experiences in Namibia.MethodsWe conducted a retrospective cohort study of patients treated with amikacin or kanamycin-based regimens in four public sector MDR-TB treatment sites in Namibia between June 2004 and March 2014. Patients were audiologically assessed as part of clinical care. The study outcome was the occurrence of any hearing loss. Data were manually extracted from patients’ treatment records. We compared proportions using the Chi-square test; applied stratified analysis and logistic regression to study the risk of hearing loss and to identify the most-at-risk patients through effect-modification analysis. A P-value < 0.05 was statistically significant.ResultsAll 353 patients had normal baseline hearing, 46 % were HIV co-infected. Cumulative incidence of any hearing loss was 58 %, which was mostly bilateral (83 %), and mild (32 %), moderate (23 %), moderate-severe (16 %), severe (10 %), or profound (15 %). Patients using amikacin had a greater risk of developing the more severe forms of hearing loss than those using kanamycin (adjusted odds ratio (OR) = 4.0, 95 % CI: 1.5–10.8). Patients co-infected with HIV (OR = 3.4, 95 % CI: 1.1–10.6), males (OR = 4.5, 95 %1.5–13.4) and those with lower baseline body weight (40–59 kg, OR = 2.8, 95 % CI: 1.1–6.8), were most-at-risk of developing hearing loss.ConclusionAmikacin use in the long-term MDR-TB treatment led to a higher risk of occurrence of the more severe forms of hearing loss compared to kanamycin use. Males, patients with low baseline body weight and those co-infected with HIV were most-at-risk. MDR-TB treatment programmes should consider replacing amikacin with kanamycin and strengthen the routine renal, serum therapeutic drug levels and audiometric monitoring in the most-at-risk patients treated with aminoglycosides.Electronic supplementary materialThe online version of this article (doi:10.1186/s40360-015-0036-7) contains supplementary material, which is available to authorized users.

Adverse Effects and Choice between the Injectable Agents Amikacin and Capreomycin in Multidrug-Resistant Tuberculosis

“…Kanamycin is closely related to amikacin and is more commonly used worldwide. The level of ototoxicity of 55% found in our study is similar to the findings of others using intense monitoring and aminoglycosides at 15 mg/kg (7,12,13,15,16). A retrospective cohort analysis suggests that the use of kanamycin is associated with less ototoxicity than the use of amikacin (16).…”

Increased risk of aminoglycoside-induced hearing loss in MDR-TB patients with HIV coinfection

“…All eight studies were published between 2012 and 2016. 13,24,30–35 Most were prospective and retrospective cohort studies; one study retrospectively collected study outcomes from medical records and then compared these to cross-sectional patient interview outcomes. 24 The studies were conducted in specialist TB hospitals (n=7) 13,24,30,32–35 and community-based HIV-TB clinical settings (n=1).…”

“…13,24,30–35 Most were prospective and retrospective cohort studies; one study retrospectively collected study outcomes from medical records and then compared these to cross-sectional patient interview outcomes. 24 The studies were conducted in specialist TB hospitals (n=7) 13,24,30,32–35 and community-based HIV-TB clinical settings (n=1). 31 Seven studies had a cohort sample of adults aged ≥14 years; 13,24,31–35 only one study had a sample of children aged <15 years.…”

“…24 The studies were conducted in specialist TB hospitals (n=7) 13,24,30,32–35 and community-based HIV-TB clinical settings (n=1). 31 Seven studies had a cohort sample of adults aged ≥14 years; 13,24,31–35 only one study had a sample of children aged <15 years. 30 Sample size was between 50 and 99 individuals in four studies, 30–32,34 between 100 and 299 in two studies, 13,24 and >300 in two studies.…”

Current therapies for the treatment of multidrug-resistant tuberculosis in children in India

“…There is some evidence to suggest that capreomycin has less ototoxicity than amikacin [34]. A retrospective study on a Namibian cohort of adult MDR-TB patients showed that odds ratio of developing hearing loss with amikacin was 4.0 (95% CI: 1.5–10.8) as compared to kanamycin in similar setting [35]. …”