Evidence suggests that otologic injury from ototopical aminoglycoside preparations is infrequent when used to treat ear infections with an intact tympanic membrane. Meanwhile, parenteral administration of aminoglycosides, is well known to be associated with a significant incidence of cochlear and vestibular damage. The discrepancy between topical and parenteral ototoxic effects is thought to result from a combination of factors, including the protective function of debris overlying the round window membrane, low antibiotic concentrations of topical antibiotic preparations, length of exposure and inability to detect subtle hearing or vestibular changes. Herein, we present a case of acute vestibulopathy following a 2-week course of topical gentamicinotic drops. Awareness of vestibulotoxicity following topical gentamicin therapy is prudent as vestibulopathic symptoms can be severely debilitating.
Aminoglycosides ; Ototoxicity

Nature, a rich source of bioactive natural products, serves as a massive pool of drug candidates for the pharmaceutical industry. However, the supply of these structurally complex chemicals is costly as most of the natural products are scarce in nature, thus requiring de novo synthesis. The supply chain issue hinders the development of novel therapeutic agents from natural products. Microbial synthesis, based on the expression of biosynthetic genes in a suitable microbial host to produce certain chemicals, is a sustainable strategy to produce complex natural products. However, this strategy requires gaining insights into the biosynthesis of target molecules. Most natural products are biosynthetically unknown or not fully elucidated; thus, the sole application of microbial synthesis strategy to produce a given molecule is challenging. In this review, we highlight a strategy that combines microbial and chemical syntheses to tackle the supply chain issue in developing drugs from natural products. We believe this strategy can revive the drug development pipeline for natural products.
Biological Products/chemistry* ; Aminoglycosides

BACKGROUND: High-level gentamicin and streptomycin disks are not easily available, despite their critical role in detection of high-level resistance to aminoglycosides in enterococci. Therefore, the possibility of applicating home-made disks to test high-level resistance of enterococci to aminoglycosides was evaluated. METHODS: The disk diffusion method using home-made disks was compared with minimal inhibitory concentrations(MIC) in 53 clinical isolates of enterococci, and, the stability of the disks were also evaluated by disk diffusion testing, biweekly, for 14 weeks. RESULTS: The high-level resistance rates to gentamicin(GM) and streptomycin(SM) were 60% and 43%, respectively. Thirty eight % of the enterococci were highly resistant in both GM and SM. The results of the disk diffusion method were consistent with the MIC until 10 weeks after production of the disks. After 12 weeks, the inhibition zones of GM- or SM-susceptible strains decreased by 2.9-3.9 mm, and the discrepancy rates were 5-24% between the results of the MIC and disk diffusion method. The storage temperature of -20degrees C versus -70degrees C showed no difference in the inhibition zone. CONCLUSION: It has been demonstrated that home-made high-level GM and SM disks are stable at -20degrees C for 10 weeks, and the results of disk diffusion method on the disks show they are applicable for the test of susceptibility of aminoglycosides to enterococci.
Aminoglycosides ; Diffusion ; Enterococcus ; Gentamicins ; Streptomycin

As an important aminoglycosides antibiotic, gentamicin has been used clinically over decades. With the development in modern biological technology, the mechanisms of gentamicin action and resistance, its biosynthesis and structural modification were studied in great depth. Meanwhile, its emerging novel bioactivities and potential applications are also under extensive exploration. Here we summarize the latest progresses and prospects towards the future development of gentamicin for more efficient and effective uses.
Aminoglycosides ; biosynthesis ; chemistry ; Gentamicins ; biosynthesis ; chemistry

Since the characteristics of aminoglycoside ototoxicity is typically bilaterally symmetric progression of cochlea-vestibular dysfunction, a unilateral involvement has rarely been reported. However, ototoxicity can be asymmetric or focal after systemic aminoglycoside treatment. The authors report 2 cases of asymmetric or focal audiovestibular deficits in patients treated with systemic aminoglycoside. In such cases, further investigations are also necessary to rule out other possible causes of unilateral sensorineural hearing loss such as cerebellopontine angle tumors.
Aminoglycosides ; Hearing Loss, Sensorineural ; Humans ; Neuroma, Acoustic

We analysed retrospectively pharmacokinetic parameters of gentamicin and amikacin in 44 and 58 Korean pediatric patients, respectively, with normal renal function. Pharmacokinetic parameters were calculated from two concentrations in serum by method of Sawchuck. There was wide individual variation in peak serum concentrations of gentamicin and amikacin, Administration of the usually recommended doses yielded subtherapeutic concentrations in 47% and 82%, respectevely, of patients in the peak concentrations of gentamicin and amikacin. The volumes of distribution of gentamicin and amikacin in children of over 1 year of age were 0.37+/-0.13L/kg and 0.41+/-0.13L/kg which are greater than those reported from the western countries. We conclude that the wide individual variation and high frequency of subtherapeutic levels in the peak concentrations of gentamicin and amikacin obtained by usually recommended dosage as well as the narrow safety margin of these drugs necessitate monitoring of serum concentration and adjustment of individual dosage regimen early in the course of treatment with aminoglycosides.
Amikacin* ; Aminoglycosides ; Child* ; Gentamicins* ; Humans ; Pharmacokinetics* ; Retrospective Studies

Amikacin is a semisynthetic derivative of kanamycin and primarily active against aerobic Gram-negative-pathogens with limited activity against Gram-positive bacteria. Meager study was reported on pharmacokinetic data on multi-days administration of amikacin. Hence, pharmacokinetics study was done in five clinically healthy goats (n = 5), after intravenous bolus injection of amikacin sulfate at the dose rate of 10 mg/kg body weight daily for three consecutive days. The amikacin concentrations in plasma and pharmacokinetics-parameters were analyzed by using microbiological assay technique and noncompartmental open-model, respectively. The mean peak plasma concentrations (Mean +/- SD) of amikacin at time zero (Cp0) was 114.19 +/- 20.78 and 128.67 +/- 14.37 microg/mL, on day 1st and 3rd, respectively. The mean elimination half-life (t(1/2)ke) was 1.00 +/- 0.28 h on day 1st and 1.22 +/- 0.29 h on day 3rd. Mean of area under concentration-time curve (AUC(0-->infinity)) was 158.26 +/- 60.10 and 159.70 +/- 22.74 microg.h/mL, on day 1st and 3rd respectively. The total body clearance (ClB) and volume of distribution at steady state (Vdss) on day 1st and 3rd were ClB = 0.07 +/- 0.02 and 0.06 +/- 0.01 L/h.kg and Vdss = 0.10 +/- 0.03 and 0.11 +/- 0.05 L/kg, respectively. No-significant difference was noted in both drug-plasma concentration and pharmacokinetics-parameters, respectively. Amikacin concentration in plasma was found higher up-to 4 h and 6 h onward on down-ward trends favour to reduce toxicity. Which also support the pharmacokinetic-pharmacodynamic way of dosing of aminoglycosides and hence, amikacin may be administered 10 mg/kg intravenously daily to treat principally Gram-negative pathogens and limitedly Gram-positive-pathogens.
Amikacin ; Aminoglycosides ; Body Weight ; Goats ; Gram-Positive Bacteria ; Half-Life ; Injections, Intravenous ; Kanamycin ; Plasma

BACKGROUND: The aim of this study was to evaluate antibiotic consumption by adult patients at a single university hospital in Korea between 2001 and 2012. METHODS: We used the 2004 World Health Organization Anatomical Therapeutic Chemical Classification System definition of defined daily doses (DDD) per 1,000 patient-days to calculate the annual antibiotic consumption for 18 antibiotic groups. Chi-square linear-by-linear analysis was performed to evaluate antibiotic consumption trends for each group. RESULTS: Average annual antibiotic consumption during 2001-2012 was 644.6 DDD/1,000 patient-days (standard deviation, 33.3 DDD/1,000 patient-days). Although no statistically significant change was observed during the study period, consumption of first- and second-generation cephalosporins, and aminoglycosides was significantly decreased, while that of beta-lactam/beta-lactamase inhibitors, fourth-generation cephalosporins, carbapenem, glycopeptide, linezolid, colistin, and quinolone increased significantly. CONCLUSION: The total amount of prescribed antibiotics did not change, but the use of broad-spectrum antibiotics increased during the study period.
Adult ; Aminoglycosides ; Anti-Bacterial Agents ; Cephalosporins ; Classification ; Colistin ; Hospitals, University ; Humans ; Korea ; World Health Organization ; Linezolid

Multidrug-resistant tuberculosis(MDR-TB), resistant to at least the two main TB drugsisoniazid and rifampicin, has been a threat to TB control because the treatment requires more toxic drugs and longer period with poor treatment outcomes. Recently, more serious concerns have been raised about extensively drug resistant-tuberculosis (XDR-TB), which shows resistance to fluoroquinolones and aminoglycosides in addition to isoniazid and rifampicin. XDR-TB is a serious global health threat because the cure is very difficult as few sensitive anti-TB drugs remain. XDR-TB develops when first-and second-line anti-TB drugs are misused during the course of treatment, most commonly due to poor compliance of the patients to the treatment regimen. People with XDR-TB can pass the XDR-TB bacteria to other people. Thus, every effort should be made to prevent the development of XDR-TB by establishing an effective TB control program maximizing patient adherence to prescribed anti-TB regimen and minimizing contact of XDR-TB patients with other people to prevent the spread of XDR-TB.
Aminoglycosides ; Bacteria ; Compliance ; Extensively Drug-Resistant Tuberculosis ; Fluoroquinolones ; Humans ; Isoniazid ; Patient Compliance ; Rifampin ; Tuberculosis

Aminoglycosides are one of the clinically relevant antibiotics. They kill bacteria by binding to bacterial 30S subunit of ribosome. Resistance to aminoglycosides occurs by three different mechanisms: 1. Production of an enzyme that modifies aminoglycosides, 2. Impaired entry of aminoglycoside into the cell by altering the OMP permeability, decreasing inner membrane transport, or active efflux, 3. The receptor protein on the 30S ribosomal subunit may be deleted or altered as a result of a mutation. By far, enzymatic modification has been the most important mechanism. In this review, the mechanisms of action and resistance, and the prevalence of resistance due to acquisition of enzymes are briefly described.
Aminoglycosides ; Anti-Bacterial Agents ; Bacteria ; Membranes ; Permeability ; Prevalence ; Ribosome Subunits ; Ribosomes