Amikacin

Amikacin(BAY416651) is a semi-synthetic aminoglycoside antibiotic derived from kanamycin A.

Epithelial-mesenchymal transition, and collective and individual cell migration regulate epithelial changes in the amikacin-damaged organ of Corti.[Pubmed:28365859]

Histochem Cell Biol. 2017 Aug;148(2):129-142.

Characterizing the microenvironment of a damaged organ of Corti and identifying the basic mechanisms involved in subsequent epithelial reorganization are critical for improving the outcome of clinical therapies. In this context, we studied the expression of a variety of cell markers related to cell shape, cell adhesion and cell plasticity in the rat organ of Corti poisoned with Amikacin. Our results indicate that, after severe outer hair cell losses, the cytoarchitectural reorganization of the organ of Corti implicates epithelial-mesenchymal transition mechanisms and involves both collective and individual cell migratory processes. The results also suggest that both root cells and infiltrated fibroblasts participate in the homeostasis of the damaged epithelium, and that the flat epithelium that may emerge offers biological opportunities for late regenerative therapies.

Protective effect of dexpanthenol against nephrotoxic effect of amikacin: An experimental study.[Pubmed:28320109]

Biomed Pharmacother. 2017 May;89:1409-1414.

BACKGROUND: Amikacin has the largest spectrum among aminoglycosides, its nephrotoxic effect limits its utilization. Our purpose in this study is to review the protective effect of dexpanthenol against the nephrotoxic effect of Amikacin, accompanied with histopathological and biochemical parameters. METHODS: 32 rats were randomly separated into four groups with eight in each (Amikacin (1.2mg/kg/day), Amikacin (1.2mg/kg/day)+dexpanthenol (500mg/kg/day), dexpanthenol (500mg/kg/day) and control). In order to assess the oxidative balance and renal damage between groups, biochemical parameters (total antioxidant capacity (TAS), total oxidant stress (TOS), catalase (CAT), paraoxonase (PON), arylesterase (ARES), urea, and creatinin) were studied from the blood samples. At the end of the 14th day, renal tissues were reviewed blindly by a pathologist. RESULTS: TOS and oxidative stress index (OSI) values were significantly lower in the group which was administered with dexpanthenol+Amikacin compared to the group which only received Amikacin (respectively, p=0.001, p=0.002). Antioxidant biochemical parameters (TAS, CAT, PON, and ARES) were significantly higher in the group which was administered with dexpanthenol+Amikacin compared to the group administered only with Amikacin (respectively, p=0.007, p=0.001, p=0.003, p=0.003). Urea and creatitin values were found to be significantly lower in the group which was administered with dexpanthenol+Amikacin compared to the group administered only with Amikacin (respectively, p=0.002, p=0.001). Histopathologic changes such as glomerular and tubular epithelium changes and interstitial edema were clearly observed in the group administered only with Amikacin, such findings were insignificant in the group administered with dexpanthenol+Amikacin. CONCLUSION: It was revealed with biochemical and histopathologic data that nephrotoxic effects created by Amikacin administration can be limited with dexpanthenol by using them together, and further advanced clinical studies are required.

Comparison of Amikacin Pharmacokinetics in Neonates Following Implementation of a New Dosage Protocol.[Pubmed:28337079]

J Pediatr Pharmacol Ther. 2017 Jan-Feb;22(1):33-40.

OBJECTIVES: The primary aim was to compare attainment of goal serum Amikacin concentrations using two dosage regimens in patients admitted to a neonatal intensive care unit. Secondary objectives included comparison of percentages of supratherapeutic trough concentrations, and subtherapeutic and supratherapeutic peak concentrations. METHODS: This was an Institutional Review Board-approved, retrospective study of neonates receiving Amikacin during January-December 2013 (group 1) and January-December 2014 (group 2). Group 1 received Amikacin dosage consistent with published recommendations, whereas group 2 was dosed using a modified protocol that was based on postmenstrual and postnatal age. Goal serum Amikacin peak concentration was defined as 20 to 35 mg/L; hence, subtherapeutic and supratherapeutic peak concentrations were defined as <20 mg/L and >35 mg/L, respectively. Supratherapeutic trough concentrations were >8 mg/L. Between-group analysis was performed using Wilcoxon-Mann-Whitney test, Student t-test or chi(2), or Fisher exact analysis as appropriate with a p value <0.05. RESULTS: A total of 278 neonates were included (group 1: n = 144; group 2: n = 134). Most patients were male (60%) and were admitted for prematurity or respiratory distress (77%). The median gestational age in group 1 was 34.4 weeks (range, 30.0-37.9 weeks) versus group 2 at 36.9 weeks (range, 31.4-38.9 weeks), whereas the postnatal age was similar between both groups at 4 days. There was a significant increase in attaining goal peak Amikacin concentrations between groups 1 and 2, 34% versus 84%, p < 0.001, and decrease in supratherapeutic peak concentrations, 65% versus 12%, p < 0.001. There was no significant difference in subtherapeutic peak or supratherapeutic trough concentrations. CONCLUSIONS: A modified neonatal Amikacin dosage protocol resulted in increased peak Amikacin serum concentration compared with published dosage recommendations. Future research should focus on determination of the optimal dosage regimen in neonates.

Increased activity of colistin in combination with amikacin against Escherichia coli co-producing NDM-5 and MCR-1.[Pubmed:28333193]

J Antimicrob Chemother. 2017 Jun 1;72(6):1723-1730.

Objectives: Colistin and carbapenem are two lines of last-resort antibiotics against lethal infections caused by MDR Gram-negative pathogens. The emergence of carbapenemase-positive Escherichia coli with colistin resistance poses a serious threat to public health worldwide. Here we report, for the first time (to the best of our knowledge), a novel combination therapy used for the treatment of E. coli co-producing MCR-1 and NDM-5. Methods: The MICs of colistin were determined alone and with 1-4 mg/L Amikacin. A 7-by-4 time-kill array of colistin (0, 0.5, 1, 2, 4, 8 and 16 mg/L) and Amikacin (0, 1, 2 and 4 mg/L) over 48 h was designed to characterize the in vitro activity of these agents alone and in combination against each E. coli isolate at an inoculum of 10 6 and 10 8 cfu/mL. The sigmoid E max model was utilized for better delineation of the concentration-effect relationship of each combination. In vivo effectiveness was investigated using a mouse model (combination therapy with intraperitoneal colistin plus Amikacin compared with monotherapy). Results: For colistin-resistant isolates, the addition of Amikacin demonstrated augmented susceptibility, reducing colistin MICs below the current susceptibility breakpoint. A concentration-dependent decrease in the EC 50 values of colistin was observed for all study isolates in the presence of increasing Amikacin concentrations. Further in vivo treatment experiments demonstrated that this combination could achieve 1.5-2.8 log 10 killing after 24 h of therapy, while monotherapy was unable to achieve such a killing effect. Conclusions: The combination of colistin and Amikacin may be a promising therapeutic option for the treatment of lethal infections caused by NDM-5-bearing MCR-1-positive superbugs.