Variability and predictability of the plasma concentration of ampicillin and kanamycin in new-born infants

Summary The variability and predictability of the plasma concentration of ampicillin and kanamycin in new-born infants being treated for infections are discussed. For kanamycin a standard dose regimen of 7.5 mg/kg/12 h is recommended.     

Pharmacokinetic aspects of therapy with ampicillin and kanamycin in new-born infants

Summary Standard dose-blood level relationships and pharmacokinetic parameters were determined for ampicillin in 34 neonates and for kanamycin in 27 neonates. The parameters were correlated with the postmenstrual age, the postnatal age of the newborns and with the plasma creatinine clearance.     

Kanamycin and bumetanide ototoxicity: Anatomical,physiological and behavioral correlates

Severe hair-cell degeneration and cochlear dysfunction was observed in chinchillas examined at 60 days (or longer) after administration of a single injection of 150 mg/kg kanamycin, followed 2 h later by a single injection of 20 mg/kg bumetanide. Outer hair cells in the cochlear base were most severely affected. While inner and outer hair-cell loss was common, some animals showed large regions along the basilar membrane where almost all inner hair cells were present and almost all outer hair cells were absent. Wherever areas of complete degeneration of the organ of Corti occurred, a small, diffuse population of nerve fibers within the spiral lamina was always present. Single-unit tuning curves correlated best with anatomical observations, compared with the other functional measures of auditory sensitivity that were obtained (behavioral audiogram and compound action potential thresholds). Results indicated that behavioral detection of auditory stimuli is relatively independent of innervation density as long as a few inner hair cells are present. Thus, the cross-fiber threshold envelope of the single-unit tuning curves appeared very similar to the behavioral audiogram.     

A recombinant probiotic for treatment and prevention of cholera

BACKGROUND & AIMS: We have developed a therapeutic strategy based on molecular mimicry of host receptors for bacterial toxins on the surface of harmless gut bacteria. In the present study, this has been applied to the development of a recombinant probiotic for treatment and prevention of cholera, caused by Vibrio cholerae. METHODS: We expressed glycosyltransferase genes from Neisseria gonorrhoeae and Campylobacter jejuni in a harmless Escherichia coli strain, resulting in production of a chimeric lipopolysaccharide terminating in a mimic of the ganglioside GM(1). RESULTS: The recombinant bacterium was capable of binding cholera toxin, a sine qua non of virulence, with high avidity; when tested with purified cholera toxin, it was capable of adsorbing >5% of its own weight of toxin in vitro. Administration of the GM(1)-expressing probiotic also protected infant mice against challenge with virulent V cholerae, even when treatment was delayed until after establishment of infection. When treatment commenced 1 hour after challenge, 12 of 12 mice given the probiotic survived, compared with only 1 of 12 for control mice (P < .00001). CONCLUSIONS: Toxin-binding probiotics such as that described here have considerable potential for prophylaxis and treatment of cholera in humans.     

Viability of Human Melanocytes HEMa-LP Exposed to Amikacin and Kanamycin

Aminoglycosides, such as amikacin and kanamycin, are powerful broad-spectrum antibiotics used for the treatment of many bacterial infections. The widely used aminoglycosides have the unfortunate side effects of targeting sensory hair cells of the inner ear, so that treatment often results in permanent hair cell loss. The aim of the study was to evaluate the influence of incubation time and drug concentration on viability of melanocytes cultured in the presence of amikacin or kanamycin. The normal human melanocytes HEMa-LP and the different concentrations of amikacin (0.075, 0.75 and 7.5 mmol/l) and kanamycin (0.06, 0.6 and 6.0 mmol/l), were used. The estimations were performed after 24, 48 and 72 h. The observed decrease in melanocytes viability may be an explanation for the mechanisms involved in aminoglycosides toxicity on pigmented tissues during high-dose and/or long-term therapy.     

Alteration of the Liver in Rats with Experimental Dysbiosis

We evaluated the relationship between pathological changes in the liver and the state of intestinal microflora in rats with experimental dysbiosis. Changes in the intestinal microflora were accompanied by alteration of the morphological structure in the liver. Enhanced proliferation of Ito cells served as an indirect evidence of damage to the liver. Ito cells did not undergo transformation into myofibroblasts that excluded the possibility of fibrosis.     

豚鼠硫酸卡那霉素急性致聋研究进展

耳聋是最为常见的健康问题之一,据估计全世界约有近十分之一人群有不同程度的听力下降〔1〕。2005年WHO估计双耳中到重度听力损失的有2.78亿。药物性聋是致聋的常见原因之一,3%～4%的发展中国家的成人和儿童以及相当数量发达国家的成人耳聋患者由药物(尤其氨基苷类抗生素)所致〔2〕。氨基苷类抗生素耳毒性的机制至今仍     

卡那霉素耳中毒后雏鸡耳蜗神经纤维的透射电镜观察

目的探讨卡那霉素对鸟类耳蜗神经纤维有无损伤。方法将雏鸡连续肌注卡那霉素10d[2O0mg/(kg     

Nontoxic concentration of kanamycin and gentamicin for intravitreal use — evaluated by in vitro ERG

The effects of kanamycin (KM) and gentamicin (GM) on the in-vitro electroretinogram of the albino rabbit were studied. The b-wave and oscillatory potentials (OPs) were unchanged by 0.1 mM KM. The photopic b-wave and OPs were slightly suppressed by 0.4 mM. The b-wave and OPs were not deteriorated by 23 µg/ml (approximately 0.05 mM) GM. The photopic b-wave and OPs were slightly suppressed by 46 µg/ml (approximately 0.1 mM) GM. The minimum concentration affecting the ERG was tentatively defined as the mean of the minimum concentration needed to change the ERG and the maximum concentration which induced no discernible changes in the ERG. The minimum concentration of KM and GM affecting the ERG were 0.25mM (approximately 150 g/ml) and 35 g/ml (approximately 0.075 mM) respectively. The minimum concentration of KM affecting the ERG was higher than its minimum inhibitory concentration against Staphylococcus aureus and Streptococcus pneumoniae. The minimum concentration of GM affecting the ERG was higher than its mimimum inhibitory concentration against Staphylococcus aureus, Streptococcus pneumoniae and Pseudomonas aeruginosa.     

Efficacy of the cat deafening method: Co-administration of ethacrynic acid and kanamycin

Objective: This study was designed to determine if hearing status monitoring during intravenous infusion of EA reduces individual variability and to evaluate the correlation between EA dose and Bwt.

Materials and methods: Twenty-five cats with the mean age of 24?±?3.7 weeks (range?=?20.6–28.3) and a mean weight of 3.21?±?0.84?kg (range?=?1.9–5.1) were administered a subcutaneous injection of KM (300?mg/kg) followed by an intravenous infusion of EA (1?mg/min). Click-evoked auditory brainstem responses (ABRs) were recorded to monitor hearing during the infusion. When ABR thresholds exceeded a 90 dB sound pressure level, the infusion of EA was terminated. Histopathology forapex, middle, and base sections of the cochlea were examined after 6 months.

Results: The dose of EA was optimized for deafening through simultaneous ABR measurements. Bwt was positively correlated with EA dose (mg) (p?R²?=?0.548), which was different from a study previously reported. Cochlear histopathology assessments revealed an absence of organ of Corti in the majority of cochleae.

Conclusion: Co-administration of kanamycin (KM) and ethacrynic acid (EA) was an easy and effective method for deafening procedures in adult animals. Body weight (Bwt) was positively correlated with EA dose (mg) and an optimal EA dose can be calculated.