Low-dose amikacin in the treatment of Multidrug-resistant Tuberculosis (MDR-TB)

Sabur, Natasha F.; Brar, Mantaj S.; Wu, Lisa Dong-Ying; Brode, Sarah K.

doi:10.1186/s12879-021-05947-6

Cited by 16 publications

(10 citation statements)

References 27 publications

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“…A retrospective evaluation in the Netherlands found that TDM-guided low doses of amikacin and kanamycin were associated with a reduced rate of ototoxicity whilst maintaining efficacy when treating MDR TB [105]. These findings were supported in a recent study in Canada in which there were low rates of ototoxicity and nephrotoxicity associated with TDM-guided low-dose amikacin in patients with MDR TB [106]. TDM has also been used to lower the dose of linezolid administered in select MDR TB patients, although the efficacy of doing so remains to be seen [107].…”

Section: Therapeutic Drug Monitoring (Tdm)mentioning

confidence: 82%

Personalised Medicine for Tuberculosis and Non-Tuberculous Mycobacterial Pulmonary Disease

Kumar

Kon

2021

Microorganisms

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Personalised medicine, in which clinical management is individualised to the genotypic and phenotypic data of patients, offers a promising means by which to enhance outcomes in the management of mycobacterial pulmonary infections. In this review, we provide an overview of how personalised medicine approaches may be utilised to identify patients at risk of developing tuberculosis (TB) or non-tuberculous mycobacterial pulmonary disease (NTM-PD), diagnose these conditions and guide effective treatment strategies. Despite recent technological and therapeutic advances, TB and NTM-PD remain challenging conditions to diagnose and treat. Studies have identified a range of genetic and immune factors that predispose patients to pulmonary mycobacterial infections. Molecular tests such as nucleic acid amplification assays and next generation sequencing provide a rapid means by which to identify mycobacterial isolates and their antibiotic resistance profiles, thus guiding selection of appropriate antimicrobials. Host-directed therapies and therapeutic drug monitoring offer ways of tailoring management to the clinical needs of patients at an individualised level. Biomarkers may hold promise in differentiating between latent and active TB, as well as in predicting mycobacterial disease progression and response to treatment.

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Section: Therapeutic Drug Monitoring (Tdm)mentioning

confidence: 82%

Personalised Medicine for Tuberculosis and Non-Tuberculous Mycobacterial Pulmonary Disease

Kumar

Kon

2021

Microorganisms

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“…We found that 9 out of 25 mice (36%) experienced gap detection deficits indicative of tinnitus at some point during the 18 weeks of testing after treatment, and similar to hyperacusis and hearing loss ( Figures 2 , 4D ), the incidence decreased over time ( Figure 6G ). AG-induced tinnitus is thought to have an incidence rate between 12 and 37.5% in CF or tuberculosis patients ( Daud et al, 2014 ; Harruff et al, 2020 ; Sabur et al, 2021 ). The other interesting point to note is that tobramycin treatment caused consistent gap detection deficits.…”

Section: Discussionmentioning

confidence: 99%

“…Physiological examinations such as the ABR or middle-ear muscle reflex should also investigate if ABR wave III/wave I amplitude ratios are altered in patients taking AGs as they have been in noise/age related hearing loss investigations ( Bharadwaj et al, 2019 ; Guest et al, 2019 ; Refat et al, 2021 ). Preclinical work should investigate the neurotoxic effects of AGs using clinically translatable dosing schedules ( Longenecker et al, 2020 ), to parallel what has been reported in AG treated patients ( Segal et al, 1999 ; Daud et al, 2014 ; Harruff et al, 2020 ; Sabur et al, 2021 ). As discussed above, the CBA/Ca mouse would make a good model for researching this question because of its good hearing sensitivity throughout its lifespan.…”

Section: Discussionmentioning

confidence: 99%

Development of Tinnitus and Hyperacusis in a Mouse Model of Tobramycin Cochleotoxicity

Longenecker¹,

Gu²,

Homan³

et al. 2021

Front. Mol. Neurosci.

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Aminoglycosides (AG) antibiotics are a common treatment for recurrent infections in cystic fibrosis (CF) patients. AGs are highly ototoxic, resulting in a range of auditory dysfunctions. It was recently shown that the acoustic startle reflex (ASR) can assess behavioral evidence of hyperacusis and tinnitus in an amikacin cochleotoxicity mouse model. The goal of this study was to establish if tobramycin treatment led to similar changes in ASR behavior and to establish whether ebselen can prevent the development of these maladaptive neuroplastic symptoms. CBA/Ca mice were divided into three groups: Group 1 served as a control and did not receive tobramycin or ebselen, Group 2 received tobramycin (200 mg/kg/s.c.) and the vehicle (DMSO/saline/i.p.) daily for 14 continuous days, and Group 3 received the same dose/schedule of tobramycin as Group 2 and ebselen at (20 mg/kg/i.p.). Auditory brainstem response (ABR) and ASR hearing assessments were collected at baseline and 2, 6, 10, 14, and 18 weeks from the start of treatment. ASR tests included input/output (I/O) functions which assess general hearing and hyperacusis, and Gap-induced prepulse inhibition of the acoustic startle (GPIAS) to assess tinnitus. At 18 weeks, histologic analysis showed predominantly normal appearing hair cells and spiral ganglion neuron (SGN) synapses. Following 14 days of tobramycin injections, 16 kHz thresholds increased from baseline and fluctuated over the 18-week recovery period. I/O functions revealed exaggerated startle response magnitudes in 50% of mice over the same period. Gap detection deficits, representing behavioral evidence of tinnitus, were observed in a smaller subset (36%) of animals. Interestingly, increases in ABR wave III/wave I amplitude ratios were observed. These tobramycin data corroborate previous findings that AGs can result in hearing dysfunctions. We show that a 14-day course of tobramycin treatment can cause similar levels of hearing loss and tinnitus, when compared to a 14-day course of amikacin, but less hyperacusis. Evidence suggests that tinnitus and hyperacusis might be common side effects of AG antibiotics.

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“…A study in Namibian by Sagwa et al, comparing the cumulative incidence of hearing loss between amikacin or kanamycin-based regimen in MDR-TB patients, reported that patients treated with amikacin had a higher risk of a severe form of hearing loss compared to kanamycin (OR=4.0, CI 95% 1.5-10.8) (Ernest et al, 2021). Similarly, a study by Sabur et al, stated that the use of amikacin and impaired renal function was significantly associated with hearing loss compared to capreomycin and streptomycin (Sabur et al, 2021).…”

Section: Key Study Characteristicsmentioning

confidence: 98%

Ototoxicity in Multidrug-Resistant Tuberculosis: A Scoping Review of the Indonesian Studies

Putra

N.H.

Hidayat

et al. 2022

JPS

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A wide variation in ototoxicity or hearing loss due to injectable anti-tubercular drugs in patients with multidrug-resistant tuberculosis (MDR-TB) has been reported globally and in Indonesia. This scoping review assesses the ototoxicity of second-line injectable anti-tubercular drugs in Indonesian patients with MDR-TB. This review was conducted under the recommended PRISMA extension for scoping review (PRISMA-ScR). The Google Scholar and PubMed database were used to search the articles on MDR-TB in the Indonesian population. Seven studies were identified based on the inclusion criteria reporting kanamycin and capreomycin in the management of MDR-TB. Ototoxicity was observed in 39.3% (116/295) MDR-TB patients. Ototoxicity was observed in kanamycin, 38.7% (105/271 patients); capreomycin, 36,8% (7/19 patients); and kanamycin plus capreomycin, 80% (4/5 patients). Only one study reported risk factors ototoxicity in MDR-TB patients. Ototoxicity was significantly associated with older age and the length of kanamycin therapy correlates with hearing loss. This review identified a high prevalence of ototoxicity in Indonesian patients with MDR-TB treated with second-line injectable drugs. Efforts were urgently needed to develop guidelines for monitoring ototoxicity, improving pharmacist and clinician awareness, and educating patients or caregivers to report hearing loss symptoms as a sign of ototoxicity. Keywords: MDR-TB; Ototoxicity, Second-line injectable

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Low-dose amikacin in the treatment of Multidrug-resistant Tuberculosis (MDR-TB)

Cited by 16 publications

References 27 publications

Personalised Medicine for Tuberculosis and Non-Tuberculous Mycobacterial Pulmonary Disease

Personalised Medicine for Tuberculosis and Non-Tuberculous Mycobacterial Pulmonary Disease

Development of Tinnitus and Hyperacusis in a Mouse Model of Tobramycin Cochleotoxicity

Ototoxicity in Multidrug-Resistant Tuberculosis: A Scoping Review of the Indonesian Studies

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