The synthesis of 3- and 6- aminosugars from the old route requires many synthetic steps and is challenging. An alternative approach is to utilize acid-catalyzed hydrolysis of kanamycin derivatives. The 3-and 6 aminosugar donor was synthesized in just two steps with excellent yield and cost-effective. The acidic hydrolysis of these aminoglycosides provided not only the 3-and 6-aminosugars, but the direct chemical glycosylation of these aminosugars was proven feasible using isopropanol and octanol as the acceptor.

Amphiphilic kanamycin is one of the promising class of compounds for the treatment of fungal infections in plants and animal. Factor that lead to the restricting of compounds for commercialization includes, the higher cost of production and poor stability of the compound. However, the new lead, identified from the synthesis and biological testing, can be synthesized on a large scale with a cost comparable to commercial antifungals. The newly reported lead is stable at the acidic and basic conditions. Additionally, this compound has an excellent activity towards Candida auris, a multidrug-resistant superbug. Heart disease is the leading cause of death in the United States most of which are caused by cardiac ischemia and arrhythmias. Abnormal opening of Cx43 hemichannel can damage the heart muscles and lead to these conditions. A compound which can selectively inhibit the opening of Cx43 hemichannel may pave the way to reducing the mortality rate of heart disease. A selective inhibitor towards Cx43 hemichannel is explored from the synthesis and biological testing of kanamycin derivatives. The synthesis of the new inhibitor is scalable and cost-effective.

On the verge of entering the post-antibiotic era, numerous efforts are in place to regain the losing potential of antibiotics which are proving ineffective against common bacterial infections. Engineered nanomaterials, especially gold nanoparticles (GNPs) capped with antibacterial agents are proving to be an effective and novel strategy against multi-drug resistant (MDR) bacteria. In this study, we report a one-step synthesis of kanamycin-capped GNPs (20 ± 5 nm) utilizing the combined reducing and capping ability of the aminoglycoside antibiotic, kanamycin. Antibacterial assays showed dosedependent broad spectrum activity of Kan-GNPs against Gram-positive (Staphylococcus epidermidis and Enterococcus durans), Gram-negative (Escherichia coli and Enterobacter aerogenes) and Kan-resistant and MDR bacterial strains. A significant reduction in the minimum inhibitory concentration (MIC) of Kan-GNPs was observed as compared to free kanamycin against all the sensitive and resistant bacterial strains tested. Mechanistic studies using TEM and fluorescence microscopy showed that Kan- GNPs exerted their bactericidal action through disrupting the cellular membrane resulting in leakage of cytoplasmic content and death of bacterial cells. Results of this study provide a novel method in the development of antibiotic capped GNPs as potent next-generation antibacterial agents.

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Magister Pharmaceuticae - MPharm / The aim of the study was to determine firstly, kanamycin plasma concentrations using liquid chromatography coupled with mass spectrometry (LC/MS); secondly, to investigate the PK parameters of kanamycin in patients infected with MDR-TB and in patients co-infected with MDR-TB and HIV; thirdly, to assess the influence of HIV infection and renal impairment on the PK of kanamycin and fourthly, to find out whether there is any interaction between antiretroviral drugs and kanamycin.

No description available.

Background: Fourteen thousand (14, 000) people fell ill with Multi-Drug Resistant (MDR) or Rifampicin-Resistant (RR) Tuberculosis (TB) in South Africa (SA) in 2019. Aminoglycosides, which are commonly used anti-tuberculosis drugs in the treatment for RR/MDR-TB patients, are associated with ototoxicity (cochlear or vestibular). Aminoglycoside-induced cochleotoxicity is characterised by permanent, bilateral, highfrequency (HF) sensorineural hearing loss (SNHL). The impact of hearing loss (HL) due to aminoglycoside-induced cochleotoxicity can influence a patient's communication, psychological, physical functioning and overall well-being negatively and lead to a reduced quality of life (QoL). To reduce the risk of aminoglycoside-induced cochleotoxicity, patients' hearing thresholds are monitored (i.e., cochleotoxicity monitoring) when they are being treated with cochleotoxic aminoglycosides. Cochleotoxicity monitoring is performed to detect a significant threshold shift (STS) early and prevent further deterioration of hearing thresholds and avoid hearing loss which may end up affecting frequencies that are important for speech perception. When a STS or hearing loss is detected during cochleotoxicity monitoring, there are various intervention strategies that can be implemented by the treating medical personnel to avoid further deterioration of patient's hearing thresholds. These strategies may include discontinuing the aminoglycoside, changing the aminoglycoside to a less cochleotoxic alternative in the regimen or changing the frequency of administration of the aminoglycoside. This study, therefore, aimed to determine the effectiveness of different strategies used when a STS in hearing occurred during cochleotoxicity monitoring to prevent further deterioration in hearing thresholds. Methodology: A descriptive prospective repeated-measures design was used in this study. Patients who underwent RR/MDR-TB treatment with Kanamycin, a cochleotoxic aminoglycoside, at Brooklyn Chest Tuberculosis Hospital (BCH) between June to December 2016 were recruited to participate in the study. Only patients (n= 69) with normal hearing thresholds (i.e., pure tone average (PTA) at 500 Hz, 1 kHz and 2 kHz ≤ 25 dB HL) at baseline and age 18 – 55 years were included. Patients who were receiving two aminoglycosides, were retreatment patients or had active middle ear (ME) pathology were excluded from this study. Participants were sampled via a purposive sampling strategy. All audiological testing was performed in a sound-treated booth and participants underwent the following types of assessment; baseline, periodic monitoring, and diagnostic assessment (when indicated). The following tests were performed at baseline: case history, otoscopy (OT), tympanometry (TYMP), conventional pure tone audiometry (cPTA) including air conduction (AC) and bone conduction (BC), and ultra-high frequency audiometry (UHFA). Follow-up monitoring assessment occurred monthly if there was no significant change in hearing thresholds, and biweekly if an STS was detected. The ASHA criteria were used to determine STS. The degree of hearing loss was described as mild, moderate, moderately-severe, severe or profound and the type of hearing loss was either conductive, sensorineural, or mixed. Both descriptive and inferential (Chi-squared, Mann-Whitney U and Kruskal-Wallis) statistical tests were used for data analysis. Results: A total of sixty-nine (69) patients who were undergoing treatment for RR/MDR-TB were recruited to participate in this study. Five participants dropped out of the study due to various reasons, therefore, leaving 64 participants in the study. There was 38 males and 26 females. The median age was 31 [range; 18 - 55] years old. An aminoglycoside-induced cochleotoxicity incidence of 90.6% (58/64) was found in this study. There were no statistically significant associations between the occurrence of STS and age (p = 0.487), sex (p = 0.329) and HIV status (p = 0.764). Three types of intervention strategies were used when a participant experienced an STS: (i) discontinue Kanamycin (Strategy A), (ii) modify the frequency of Kanamycin administration (Strategy B), (iii) and leave the regimen unchanged, i.e., no intervention (Strategy C). A smaller proportion of participants, 12 out of 33, experienced further deterioration of hearing thresholds after intervention strategy A (discontinue Kanamycin) was used, when compared to participants who underwent intervention strategies B and C, but the difference was not statistically significant (p = 0.056). Conclusion: This study found a high incidence of cochleotoxicity among patients receiving Kanamycin treatment for RR/MDR-TB. The results showed that discontinuing Kanamycin led to fewer participants developing further deterioration of hearing thresholds, although not statistically significant. There were no statistically significant associations between the occurrence of STS and age, sex, and HIV status. This study had some limitations; only cochlear hearing loss was investigated, participants were not followed up beyond six months, and genetic testing was not performed. Nonetheless, this study revealed that fewer participants had further significant threshold shifts after discontinuing Kanamycin, and for those patients who still receive regimens containing aminoglycosides, these findings are relevant.

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