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aminoglycoside ototoxicity

Kenneth P Smith, James E Kirby
We evaluated activity of apramycin, a non-ototoxic/non-nephrotoxic aminocyclitol against 141 clinical Enterobacteriaceae isolates, 51% of which were non-susceptible to carbapenems (CRE). Among CRE, 70.8% were apramycin susceptible, which compared favorably to aminoglycosides in current clinical use. Our data suggest that apramycin deserves further investigation as a repurposed, anti-CRE therapeutic.
September 8, 2016: Diagnostic Microbiology and Infectious Disease
Yüksel Olgun, Safiye Aktaş, Zekiye Altun, Günay Kırkım, Deniz Çakır Kızmazoğlu, Ayşe Pınar Erçetin, Banu Demir, Dilek İnce, Kamer Mutafoğlu, Bengü Demirağ, Hülya Ellidokuz, Nur Olgun, Enis Alpin Güneri
OBJECTIVE: The aim of this study was to analyse the genetic and non genetic risk factors for cisplatin ototoxicity. METHODS: This study was conducted on 72 children who received cisplatin based chemotherapy. Brock and Muenster classifications were used to evaluate ototoxicity seen in these children. 6 single nucleotide polymorphisms (SNP); ERCC1 rs 11615, GSTP1 rs1138272, GSTP1 rs1695, LRP2 rs 2075252, TPMT rs 12201199, COMT rs 9332377, were evaluated as genetic factors by real time PCR...
November 2016: International Journal of Pediatric Otorhinolaryngology
M Strupp, K Feil, M Dieterich, T Brandt
The leading symptoms of bilateral vestibulopathy (BVP) are postural imbalance and unsteadiness of gait that worsens in darkness and on uneven ground. There are typically no symptoms while sitting or lying under static conditions. A minority of patients also have movement-induced oscillopsia, in particular while walking. The diagnosis of BVP is based on a bilaterally reduced or absent function of the vestibulo-ocular reflex (VOR). This deficit is diagnosed for the high-frequency range of the angular VOR by a bilaterally pathologic bedside head impulse test (HIT) and for the low-frequency range by a bilaterally reduced or absent caloric response...
2016: Handbook of Clinical Neurology
Peng Jiang, Amrita Ray, Leonard P Rybak, Michael J Brenner
RATIONALE: Oxidative stress plays a critical role in gentamicin-induced hair cell death. Previous work has implicated the cytoplasmic transcription factor signal transducer and activator of transcription 1 (STAT1) as a potential mediator of drug-induced ototoxicity, but role in aminoglycosides is largely unknown. This study investigated aminoglycosides-induced cell death, exploring contributions of reactive oxygen species and STAT1 pathway in injury and protection. METHODS: Neonatal murine organ of Corti explants from 2 to 3 day postnatal pups (n = 96) were treated with gentamicin at (4 μM, 50 μM) for 4 to 72 hours, with/without protectants...
October 2016: Otology & Neurotology
Takayuki Kato, Guanyu Yang, Youjin Teo, Reda Juskeviciene, Déborah Perez-Fernandez, Harish M Shinde, Sumanth Salian, Bruno Bernet, Andrea Vasella, Erik C Böttger, David Crich
Chemistry for the efficient modification of the kanamycin class of 4,6-aminoglycosides at the 4'-position is presented. In all kanamycins but kanamycin B, 4'-O-alkylation is strongly detrimental to antiribosomal and antibacterial activity. Ethylation of kanamycin B at the 4″-position entails little loss of antiribosomal and antibacterial activity, but no increase of ribosomal selectivity. These results are contrasted with those for the 4,5-aminoglycosides, where 4'-O-alkylation of paromomycin causes only a minimal loss of activity but results in a significant increase in selectivity with a concomitant loss of ototoxicity...
October 9, 2015: ACS Infectious Diseases
Ming Guan, Qiaojun Fang, Zuhong He, Yong Li, Fuping Qian, Xiaoyun Qian, Ling Lu, Xiaoli Zhang, Dingding Liu, Jieyu Qi, Shasha Zhang, Mingliang Tang, Xia Gao, Renjie Chai
Hearing loss is a common sensory disorder mainly caused by the loss of hair cells (HCs). Noise, aging, and ototoxic drugs can all induce apoptosis in HCs. Apoptosis repressor with caspase recruitment domain(ARC) is a key factor in apoptosis that inhibits both intrinsic and extrinsic apoptosis pathways; however, there have been no reports on the role of ARC in HC loss in the inner ear. In this study, we used House Ear Institute Organ of Corti 1 (HEI-OC-1) cells, which is a cochlear hair-cell-like cell line, to investigate the role of ARC in aminoglycoside-induced HC loss...
August 20, 2016: Oncotarget
Abi Jenkins, Alison H Thomson, Nicholas M Brown, Yvonne Semple, Christine Sluman, Alasdair MacGowan, Andrew M Lovering, Phil J Wiffen
OBJECTIVES: The objectives of this study were to identify the amikacin dosage regimens and drug concentrations consistent with good outcomes and to determine the drug exposures related to nephrotoxicity and ototoxicity. METHODS: A literature review was conducted in Medline, EMBASE and the Cochrane Central Register of Controlled Trials. Full journal articles reporting randomized controlled trials, controlled clinical trials, interrupted time series trials, and controlled before and after studies involving amikacin therapeutic drug monitoring (TDM) and dose adjustment were considered for inclusion...
October 2016: Journal of Antimicrobial Chemotherapy
Jorrit W van As, Henk van den Berg, Elvira C van Dalen
BACKGROUND: Platinum-based therapy, including cisplatin, carboplatin, oxaliplatin or a combination of these, is used to treat a variety of paediatric malignancies. Unfortunately, one of the most important adverse effects is the occurrence of hearing loss or ototoxicity. There is a wide variation in the reported prevalence of platinum-induced ototoxicity and the associated risk factors. More insight into the prevalence of and risk factors for platinum-induced hearing loss is essential in order to develop less ototoxic treatment protocols for the future treatment of children with cancer and to develop adequate follow-up protocols for childhood cancer survivors treated with platinum-based therapy...
2016: Cochrane Database of Systematic Reviews
Vishal Sharma, Sanjeev Bhagat, Bhimsain Verma, Ravinder Singh, Surinderpal Singh
INTRODUCTION: The incidence of multidrug resistant tuberculosis is increasing in developing countries. Aminoglycosides are an integral part of second-line drugs, however ototoxicity is a major limitation for their use. This study aims to determine the extent of hearing loss in patients taking one of the commonly prescribed drugs for Multidrug resistant tuberculosis (MDR-TB), Kanamycin, at a Government Medical College, Patiala, Punjab, India, which is a 1200 bed tertiary care hospital...
May 2016: Iranian Journal of Otorhinolaryngology
Rania Abusamra, Donna McShane
Aminoglycosides are widely used in cystic fibrosis management. The m.1555A>G mutation predisposes to aminoglycoside ototoxicity. It may cause later onset hearing loss in the absence of aminoglycosides use and gradual hearing loss may be an inevitable consequence of the mutation. Given that aminoglycoside therapy forms the backbone of IV protocols in CF, this article recommends screening for this mutation to allow informed decision-making prior to aminoglycoside administration, to avoid preventable deafness...
August 2016: Paediatric Respiratory Reviews
Zuhong He, Shan Sun, Muhammad Waqas, Xiaoli Zhang, Fuping Qian, Cheng Cheng, Mingshu Zhang, Shasha Zhang, Yongming Wang, Mingliang Tang, Huawei Li, Renjie Chai
Aminoglycosides are ototoxic to the cochlear hair cells, and mitochondrial dysfunction is one of the major mechanisms behind ototoxic drug-induced hair cell death. TRMU (tRNA 5-methylaminomethyl-2-thiouridylate methyltransferase) is a mitochondrial protein that participates in mitochondrial tRNA modifications, but the role of TRMU in aminoglycoside-induced ototoxicity remains to be elucidated. In this study, we took advantage of the HEI-OC-1 cell line to investigate the role of TRMU in aminoglycoside-induced cell death...
2016: Scientific Reports
Yu Ding, Bo-Hou Xia, Qi Liu, Mei-Ya Li, Shui-Xian Huang, Guang-Chao Zhuo
Mutations in mitochondrial 12S rRNA (MT-RNR1) are the important causes of sensorineural hearing loss. Of these mutations, the homoplasmic m.1555A>G or m.1494C>T mutation in the highly conserved A-site of MT-RNR1 gene has been found to be associated with both aminoglycoside-induced and non-syndromic hearing loss in many families worldwide. Since the m.1555A>G and m.1494C>T mutations are sensitive to ototoxic drugs, therefore, screening for the presence of these mutations is important for early diagnosis and prevention of deafness...
October 10, 2016: Gene
Adebolajo A Adeyemo, Odunayo Oluwatosin, Olayemi O Omotade
Hearing impairment is due to various causes including ototoxicity from aminoglycosides. The susceptibility to aminoglycosides increases in the presence of certain mitochondria gene mutations. There is unrestrained use of aminoglycosides in many developing nations which may worsen the burden of hearing impairment in these countries but there is lack of data to drive required policy changes. Streptomycin (an aminoglycoside) is part of the drug regimen in re-treatment of tuberculosis. Exploring the impact of streptomycin ototoxicity in tuberculosis patients provides a unique opportunity to study aminoglycoside ototoxicity within the population thus providing data that can inform policy...
2016: SpringerPlus
A A Akinbodewa, O Okunola
Co-occurrence of aminoglycoside-induced ototoxicity and nephrotoxicity is rare, possibly as a result of divergent mechanisms of tissue damage despite similarities in the anatomy of the inner ear and the proximal renal tubular epithelium. We present the case of a 63-year-old hypertensive woman who developed nonoliguric acute exacerbation of chronic renal failure and sudden onset of sensorineural deafness after receiving daily injections of gentamicin. Coexisting ototoxicity and nephrotoxicity from aminoglycosides can occur, though rare...
July 2016: Nigerian Journal of Clinical Practice
Soha Namazi, Mohammad Mahdi Sagheb, Mohammad Mahdi Hashempour, Arman Sadatsharifi
BACKGROUND: The inappropriate use of aminoglycosides has harmful effects such as the development of resistant pathogens and the incidence of nephrotoxicity and ototoxicity. Therefore, drug utilization evaluation of these drugs may improve their usage remarkably. The aim of this study was to assess the usage pattern of amikacin in an internal medicine ward. METHODS: This cross-sectional study was conducted in the Internal Medicine Ward of Nemazee Teaching Hospital, Shiraz, Iran, in 2011...
May 2016: Iranian Journal of Medical Sciences
Lokman Uzun, Numan Kokten, Osman Halit Cam, M Tayyar Kalcioglu, M Birol Ugur, Muhammet Tekin, Gul Ozbilen Acar
Objectives: Gentamicin is a potent aminoglycoside antibiotic. Ototoxicity and nephrotoxicity are the main side effects which restrict the use of gentamicin. Garlic with its intrinsic antioxidant activity may prove beneficial in prevention from ototoxicity. S-allylmercaptocysteine (SAMC), diallyl disulfide (DD), and S-allylcysteine (SAC) are three active compounds found in garlic. In this study, we investigated the effect of SAMC, DD, and SAC on the ototoxicity induced by gentamicin in rats, by using brainstem evoked response audiometry (BERA)...
May 2, 2016: Clinical and Experimental Otorhinolaryngology
Gerben Sam, Dick Wong Chung, Ruud van der Hoeven, Sjoerd Verweij, Matthijs Becker
Background The intratympanic application of the ototoxic aminoglycoside gentamicin has shown promising results as an ablative treatment for vertigo associated with Ménière's disease. Objective To evaluate the efficacy and safety of intratympanic gentamicin and to specifically analyse the effect of this treatment on high and low hearing frequencies in patients with unilateral definite Ménière's disease. Method Subjects were treated with intratympanic gentamicin and were evaluated on vertigo, tinnitus, mean pure tone audiometry threshold and speech discrimination score...
August 2016: International Journal of Clinical Pharmacy
Nishad Thamban Chandrika, Sylvie Garneau-Tsodikova
Since the discovery of the first aminoglycoside (AG), streptomycin, in 1943, these broad-spectrum antibiotics have been extensively used for the treatment of Gram-negative and Gram-positive bacterial infections. The inherent toxicity (ototoxicity and nephrotoxicity) associated with their long-term use as well as the emergence of resistant bacterial strains have limited their usage. Structural modifications of AGs by AG-modifying enzymes, reduced target affinity caused by ribosomal modification, and decrease in their cellular concentration by efflux pumps have resulted in resistance towards AGs...
2016: MedChemComm
Mun Young Chang, Seon-Hee Byon, Hyeon-Cheol Shin, Song Ee Han, Ju Yeon Kim, Jang Yul Byun, Jong Dae Lee, Moo Kyun Park
OBJECTIVES: Drug-induced ototoxicity from compounds such as aminoglycosides and platinum can damage the inner ear resulting in hearing loss, tinnitus or balance problems and may be caused by the formation of reactive oxygen species (ROS). Dieckol is a phlorotannin polyphenolic compound with strong antioxidant effects found in edible brown algae. This study investigated the protective effects of dieckol on drug-induced ototoxicity in cochlear cultures obtained from neonatal mice. METHODS: Cochlear explants were pretreated with dieckol and exposed to gentamicin for 48h...
April 2016: International Journal of Pediatric Otorhinolaryngology
Yongdong Song, Zhaomin Fan, Xiaohui Bai, Wenwen Liu, Yuechen Han, Lei Xu, Mingming Wang, Jianfeng Li, Qingyin Zheng, Daogong Zhang, Haibo Wang
Conclusion SM-induced dose- and location-dependent cochlear hair cell death in vitro. AIF might be translocated from mitochondria to nucleus and cytoplasm within SM-treated hair cells. The translocation of AIF might be modulated by PARP-1. Objective Streptomycin (SM), one of the widely used aminoglycoside nowadays, is still causing significant permanent sensorineural hearing loss owing to sensory hair cell death. This study was designed to investigate the role of apoptosis-inducing factor (AIF), an important mitochondrial cell death regulator, in SM ototoxicity within neonatal rat cochleae and HEI-OC1 cells...
June 2016: Acta Oto-laryngologica
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