Background: Use of inappropriate amikacin dose is one of the most important factors in inducing toxicity, prolonged hospitalization as well as in increasing patient’s mortality. Objective: The aims of this study are ...Background: Use of inappropriate amikacin dose is one of the most important factors in inducing toxicity, prolonged hospitalization as well as in increasing patient’s mortality. Objective: The aims of this study are the analysis of amikacin dose, serum level and the examination of the effectiveness of the clinical pharmacologist (CP) therapeutic drug monitoring (TDM) intervention to guarantee the safety of amikacin use. Methods: This is a one-year retrospective observational chart review study, which evaluates amikacin dose, serum drug level, development of adverse effects in patients on amikacin with or without CP TDM consultation. Results: Amikacin was prescribed for 393 complex patients, with median age 83. Amikacin group (AG) included 140 (32%) courses with CP consultation (AG1) and 292 (68%) courses without CP consultation (AG2). The distribution of most study characteristics in both groups was similar including amikacin dose (9-10 mg/kg/day), renal failure (14%) and mortality (12%). Acceptance for CP consultation was in 46% of amikacin courses and dose changes were done in 63% after CP intervention. Prolonged antibiotic course (4.6 ± 1.5 vs 3.8 ± 1.6 days, p < 0.0001) and the patient’s hemodynamic instability (15% vs 7%, p = 0.01) were more frequent in the AG1 compared to the AG2. There was a strong association between CP consultation and prolonged hospitalization (p = 0.005), while no association between it and amikacin adverse effects, renal failure or mortality. Conclusions: There was no trend to reducing amikacin toxicity, days of hospitaliza tion or mortality in patients with CP consultation. CP TDM intervention was more in the management of complicated clinical situations. However, it is necessary to optimize it.展开更多
Aim: To assess the efficacy and safety of anal submucosal injection (ASI) of amikacin in chronic bacterial prostatitis (CBP). Methods: Fifty male outpatients with CBP were randomly divided into two groups. Thirty case...Aim: To assess the efficacy and safety of anal submucosal injection (ASI) of amikacin in chronic bacterial prostatitis (CBP). Methods: Fifty male outpatients with CBP were randomly divided into two groups. Thirty cases of ASI group were given amikacin 400 mg daily by ASI for ten times and the other twenty cases of intramuscular injection (IM) group were given the same drug dally by IM. All patients were evaluated with NIH-Chronic prostatitis symptom index (NIH-CPSI), the bacteria culture of the expressed prostate secretion (EPS), proctoscopic examination, rectal biopsy and the clinical manifestation were checked at pretreatment and on day 7 and 90 after cessation of therapy. Results: The cure rate, apparent effective rate and effective rate of ASI group and IM group were 33.3% vs 5% (P<0.05), 43.3% vs 10% (P<0.05) and 16.7% vs 20% (P>0.05), respectively. The score of NIH-CPSI in both of ASI group and IM group decreased significantly 7 days after cessation of therapy, both ASI and IM of amikacin could relieve symptoms within a short time. However, 3 months after cessation of therapy the score of NIH-CPSI in ASI group continued down in spite of no significant differences compared with 7 days after cessation of therapy, but the score of IM group was rebound nearly closed to level of pretreatment at 23.8±8.5 and significantly higher than that of ASI group. The amount of white blood cell (WBC) of EPS in ASI group increased slightly at 7 days after cessation of therapy without significant difference with pretreatment (P>0.05), but it significantly decreased at 3 months after cessation of therapy, the amount of WBC of EPS in ASI group was lower than that of IM group at 3 months after cessation of therapy (P<0.05). Proctoscopic examination of anal canal were normal after ASI therapy and the rectum biopsy showed no obvious histopathologic abnormality at the site of injection except mild focal submucosal infiltration of lymphocytes and plasma cells at 7 days after cessation of therapy which disappeared on 3 months after cessation of therapy. All patients had no evident complications. Conclusion: ASI could be recommended as a new safe, effective, painless method of antibiotics administration in the treatment of CBP.展开更多
AIM: To compare the efficacy and safety of single daily amikacin vs. cefotaxime in the 5-d treatment of spontaneous bacterial peritonitis (SBP).METHODS: Thirty-seven cirrhotic patients with SBP,19 in group A and 18 in...AIM: To compare the efficacy and safety of single daily amikacin vs. cefotaxime in the 5-d treatment of spontaneous bacterial peritonitis (SBP).METHODS: Thirty-seven cirrhotic patients with SBP,19 in group A and 18 in group B, were studied. Group A received 1 g of cefotaxime every 6 h, and group B received 500 mg of amikacin qd. Both antibiotics were administered up to 5 d and the responses were compared.RESULTS: Infection was cured in 15 of 19 patients (78.9%) treated with cefotaxime and in 11 of 18 (61.1%)treated with amikacin. Four patients of the Cefotaxime group (21.1%) and five patients of the Amikacin group (27.8%) died. Two in each group (10.5% vs 11.1%)had renal impairment during study period. One in each group (5.3% vs 5.6%) may be considered to suffer from nephrotoxicity due to increased urinary β2-microglobulin concentration.CONCLUSION: In this study, single daily doses of amikacin in the treatment of SBP in cirrhotics were not associated with an increased incidence of renal impairment or nephrotoxicity. However, a 5-d regimen of amikacin is less effective than a 5-d regimen of cefotaxime in the SBP treatment.展开更多
The quantitative estimation of amikacin （AMK） in AMK sulfate injection samples is reported using FTIR-derivative spectrometric method in a continuous flow system. Fourier transform of mid-IR spectra were recorded wi...The quantitative estimation of amikacin （AMK） in AMK sulfate injection samples is reported using FTIR-derivative spectrometric method in a continuous flow system. Fourier transform of mid-IR spectra were recorded without any sample pretreatment. A good linear calibration （r40.999, %RSDo 2.0） in the range of 7.7-77.0 mg/mL was found. The results showed a good correlation with the manufacturer＇s and overall they all fell within acceptable limits of most pharmacopoeial monographs on AMK sulfate.展开更多
In a weak acid medium, potassium ferrioxalate（PF） can react with some aminoglycoside（AGs） antibiotics, such as amikacin（AMK）, kanamycin（KANA）, tobramycin（TOB） and gentamicin（GEN）, to form ion-association c...In a weak acid medium, potassium ferrioxalate（PF） can react with some aminoglycoside（AGs） antibiotics, such as amikacin（AMK）, kanamycin（KANA）, tobramycin（TOB） and gentamicin（GEN）, to form ion-association complexes. It results in the enhancement of resonance light scattering（RLS） in different degrees. The maximum scattering peaks are all located at 345 nm. Among them, the relative scattering intensity（AIRLs） of AMK system is much higher than that of KANA, TOB or GEN. Therefore the method is more propitious to the determination of trace amounts of AMK. The optimum reaction conditions, influencing factors, and the relationship between scattering intensity and concentration of antibiotics were investigated by means of the proposed method. The enhancement of RLS signals is directly proportional to the concentration of antibiotics in a certain range of concentration. A new resonance light scattering method for the determination of AMK and other aminoglycoside antibiotics with [Fe（C2O4）3]^3- as a probe is thus established based on it. The method exhibits high sensitivity and good selectivity. The detection limit（3σ） for AMK is 1.8 ng/mL. The method can be applied to the determination of AMK in clinical serum samples. The reaction mechanism and the reasons for RLS enhancement are discussed in this paper.展开更多
A new method to determine the concentration of amikacin （AMK） using methyl blue （MB） as electrochemical probe was developed in this paper. In pH 4.5 Britton-Robinson （B-R） buffer solution, the MB reacted with AM...A new method to determine the concentration of amikacin （AMK） using methyl blue （MB） as electrochemical probe was developed in this paper. In pH 4.5 Britton-Robinson （B-R） buffer solution, the MB reacted with AMK to form ion association complexes, which led to the reductive peak current of MB at -0.275 V （versus SCE） to decrease, and the decreases were linear with the concentration of AMK in the range of 1.0-60.0 mg/L, the regression of equation is AIp （hA） = -8.48 ＋ 102.36c （rag/L）, correlation coefficient yis 0.997. The conditions for determining the concentration of AMK using linear sweep voltammetry （SLV） were optimized. The method was used to determine the content of amikacin commercially available with satisfactory results.展开更多
A novel chemiluminescence （CL） reaction was based on the oxidizing reaction of luminol by the trivalent copper-periodate complex （Ks[Cu（HIO6）2], DPC） in alkaline medium. The CL intensity could be enhanced in the...A novel chemiluminescence （CL） reaction was based on the oxidizing reaction of luminol by the trivalent copper-periodate complex （Ks[Cu（HIO6）2], DPC） in alkaline medium. The CL intensity could be enhanced in the presence of amikacin sulfate （AKS）. A new CL method was developed for the determination of AKS by coupling with flow injection （FI） technology. Because of the distinctive oxidative effect of DPC, the luminol-based CL reaction could occur at a low concentration of 10-7 M. The relative CL intensity was proportional to the concentration of AKS in the range of 4.0 x 10-9-4.0 x 10-6 g/mL with the detection limit of 1.2 x 10-9 g/mL. The relative standard deviation was 2.1% for 8.0xl0-9g/mL AKS （n=9）. The proposed method was successfully applied to the direct determination of AKS at the level of ng/mL in serum samples. The recovery varied from 97.0% to 106.3%. A possible mechanism of the CL reaction was discussed in detail by relating to the CL kinetic characteristics and electrochemical activities of the oxidant DPC.展开更多
Objective: To characterize amikacin pharmacokinetics in serum and in blister fluid of severe burn patients to guide optimal treatment timing. Methods: Patients (N = 32) were divided into four groups based on amikacin ...Objective: To characterize amikacin pharmacokinetics in serum and in blister fluid of severe burn patients to guide optimal treatment timing. Methods: Patients (N = 32) were divided into four groups based on amikacin administration timing and groups received drug minutes to hours after injury. In Groups A, B, C, and D, amikacin (400 mg, IV) was administered 3 - 4, 10, 20 and 30 h post burn injury, respectively (N = 8 for all groups). Next blister fluid and venous blood samples from 9 patients were obtained at 0, 0.25, 0.5, 1, 2, 3, 4, 5, 6, and 7 h after drug infusion. Amikacin concentrations were measured with a fluorescent polarization immunoassay and pharmacokinetics was deduced using DAS3.2.5. Statistical analyses performed with SPSS13.0. Results: Compared with normal values, t1/2z of amikacin from burn patients was shortened in serum but amikacin half-lives in blister fluid was significantly greater than serum half-life values (p < 0.05). Groups A and B had greater pharmacokinetic values at each time point, and Group D did not achieve antibacterial concentrations of amikacin. Conclusion: Early amikacin administration in severe burn patients offers greater concentrations of drug in serum and blister fluids.展开更多
Morphology of spiral ganglion neurons （SGNs） in Sprague-Dawley rats before and after amikacin treatment was observed by transmission electron microscopy. Amikacin induced cochlear SGN apoptosis. Immunohistochemical ...Morphology of spiral ganglion neurons （SGNs） in Sprague-Dawley rats before and after amikacin treatment was observed by transmission electron microscopy. Amikacin induced cochlear SGN apoptosis. Immunohistochemical staining and RT-PCR revealed a decrease in Bcl-2 protein ex-pression, and an increase in Bax protein, caspase-3 protein and caspase-6 mRNA expression fol-lowing amikacin treatment. （-）-Epigallocatechin-（3）-gallate （EGCG） inhibited SGN Bax protein, caspase-3 protein and caspase-6 mRNA expression, and enhanced Bcl-2 protein expression, thereby decreasing SGN apoptosis. Results demonstrated that EGCG can protect SGNs against amikacin-induced injury.展开更多
Silver nitrate could inhibit the clinical multidrug resistant isolates at high concentrations（with minimal inhibitory concentrations（MICs） from 32 μM to 64 μM）. The activities of amikacin in the presence of sub-...Silver nitrate could inhibit the clinical multidrug resistant isolates at high concentrations（with minimal inhibitory concentrations（MICs） from 32 μM to 64 μM）. The activities of amikacin in the presence of sub-lethal silver nitrate（15 μM） were tested for the combinational effects against multidrug resistant clinical isolates in vitro. Silver nitrate restored the susceptibility of drug-resistant Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus to amikacin. It lowered the MICs of amikacin from 〉128 μg/mL to（2–16） μg/mL and 32 μg/mL, respectively, and lowered the MICs of amikacin on extended spectrum β-lactamase-producing Pseudomonas aeruginosa and Escherichia coli from（16–32） μg/mL and 16 μg/mL to（〈1–4） μg/mL and 〈1 μg/mL, respectively.展开更多
Background： Aerosolized amikacin （AA） is a current option for the management of ventilator-associated pneumonia （VAP） caused by multidrug-resistant Gram-negative bacteria （MDR-GNB）, as it is reported that AA co...Background： Aerosolized amikacin （AA） is a current option for the management of ventilator-associated pneumonia （VAP） caused by multidrug-resistant Gram-negative bacteria （MDR-GNB）, as it is reported that AA could increase the alveolar level of the drug without increasing systemic toxicity. This study aimed to evaluate the efficacy and safety of AA as an adjunctive therapy for VAP caused by MDR-GNB. Methods： In this single-center, double-blind study conducted in a 36-bed general Intensive Care Unit （ICU） in a tertiary hospital from June 2014 to June 2016, 52 ICU patients with confirmed MDR-GNB VAP were randomized to two groups （AA group, n - 27 and placebo group, n = 25）. Amikacin （400 rag, q8h） or saline placebo （4 ml, q8h） was aerosolized for 7 days. The attending physician determined the administration of systemic antibiotics for VAP. Patients were tbllowed up for 28 days. Bacteriological eradication, clinical pulmonary infection score （CP1S）, and serum creatinine were assessed on day 7 of therapy. New resistance to amikacin, cure rate of VAP, weaning rate, and mortality were assessed on day 28. Results： The baseline characteristics of patients in both groups were similar. At the end of the treatment, 13 of the 32 initially detected bacterial isolates were eradicated in AA group, compared to 4 of 28 in placebo group （41% vs. 14%, P - 0.024）. As for patients, 11 of 27 patients treated with AA and 4 of 25 patients treated with placebo have eradication （41% vs. 16%, P = 0.049）. The adjunction of AA reduced CPIS （4.2 ± 1.6 vs. 5.8 ± 2.1, P = 0.007）. New drug resistance to amikacin and the change in serum creatinine were not detected in AA group. No significant differences in the clinical cure rate in survivors （48% vs. 35%, P = 0.444）, weaning rate （48% vs. 32%, P = 0.236）, and mortality （22% vs. 32%, P = 0.427） were detected between the two groups on day 28. Conclusions： As an adjunctive therapy of MDR-GNB VAP, AA successfully eradicated existing MDR organisms without inducing new resistance to amikacin or change in serum creatinine. However, the improvement of mortality was not found.展开更多
The interaction between congo red (CR) and amikacin (AMK) was studied by resonance Rayleigh scattering (RRS), frequency doubling scattering (FDS) and second-order scattering (SOS) combining with absorption spectrum. I...The interaction between congo red (CR) and amikacin (AMK) was studied by resonance Rayleigh scattering (RRS), frequency doubling scattering (FDS) and second-order scattering (SOS) combining with absorption spectrum. In a weak acidic medium, CR combined with AMK to form an ion association complex with the composition ratio of 1∶1 by electrostatic interaction, hydrophobicity and charge transferring effect. As a result, the new spectra of RRS, FDS, and SOS appeared and their intensities were enhanced greatly. The maximum wavelengths of RRS, FDS and SOS were located at 563 nm, 475 nm and 940 nm, and the scattering intensities were proportional to the concentration of AMK. These three methods have very high sensitivities, and the detection limits were 4.0 ng·mL?1 for RRS, 3.6 ng·mL?1 for FDS and 1.9 ng·mL?1 for SOS, respectively. At the same time, the methods have better selectivity. A new method for the determination of trace amounts of AMK with congo red by resonance scattering technique has been developed. The recovery for the determination of AMK in blood serum and urine sample was between 95.5% and 105.5%. In this study, the properties, such as enthalpy of formation, charge distribution and mean polarizability, were calculated by AM1 quantum chemistry method. In addition, the reaction mechanism and the reasons for the enhancement of scattering spectra were discussed.展开更多
文摘Background: Use of inappropriate amikacin dose is one of the most important factors in inducing toxicity, prolonged hospitalization as well as in increasing patient’s mortality. Objective: The aims of this study are the analysis of amikacin dose, serum level and the examination of the effectiveness of the clinical pharmacologist (CP) therapeutic drug monitoring (TDM) intervention to guarantee the safety of amikacin use. Methods: This is a one-year retrospective observational chart review study, which evaluates amikacin dose, serum drug level, development of adverse effects in patients on amikacin with or without CP TDM consultation. Results: Amikacin was prescribed for 393 complex patients, with median age 83. Amikacin group (AG) included 140 (32%) courses with CP consultation (AG1) and 292 (68%) courses without CP consultation (AG2). The distribution of most study characteristics in both groups was similar including amikacin dose (9-10 mg/kg/day), renal failure (14%) and mortality (12%). Acceptance for CP consultation was in 46% of amikacin courses and dose changes were done in 63% after CP intervention. Prolonged antibiotic course (4.6 ± 1.5 vs 3.8 ± 1.6 days, p < 0.0001) and the patient’s hemodynamic instability (15% vs 7%, p = 0.01) were more frequent in the AG1 compared to the AG2. There was a strong association between CP consultation and prolonged hospitalization (p = 0.005), while no association between it and amikacin adverse effects, renal failure or mortality. Conclusions: There was no trend to reducing amikacin toxicity, days of hospitaliza tion or mortality in patients with CP consultation. CP TDM intervention was more in the management of complicated clinical situations. However, it is necessary to optimize it.
文摘Aim: To assess the efficacy and safety of anal submucosal injection (ASI) of amikacin in chronic bacterial prostatitis (CBP). Methods: Fifty male outpatients with CBP were randomly divided into two groups. Thirty cases of ASI group were given amikacin 400 mg daily by ASI for ten times and the other twenty cases of intramuscular injection (IM) group were given the same drug dally by IM. All patients were evaluated with NIH-Chronic prostatitis symptom index (NIH-CPSI), the bacteria culture of the expressed prostate secretion (EPS), proctoscopic examination, rectal biopsy and the clinical manifestation were checked at pretreatment and on day 7 and 90 after cessation of therapy. Results: The cure rate, apparent effective rate and effective rate of ASI group and IM group were 33.3% vs 5% (P<0.05), 43.3% vs 10% (P<0.05) and 16.7% vs 20% (P>0.05), respectively. The score of NIH-CPSI in both of ASI group and IM group decreased significantly 7 days after cessation of therapy, both ASI and IM of amikacin could relieve symptoms within a short time. However, 3 months after cessation of therapy the score of NIH-CPSI in ASI group continued down in spite of no significant differences compared with 7 days after cessation of therapy, but the score of IM group was rebound nearly closed to level of pretreatment at 23.8±8.5 and significantly higher than that of ASI group. The amount of white blood cell (WBC) of EPS in ASI group increased slightly at 7 days after cessation of therapy without significant difference with pretreatment (P>0.05), but it significantly decreased at 3 months after cessation of therapy, the amount of WBC of EPS in ASI group was lower than that of IM group at 3 months after cessation of therapy (P<0.05). Proctoscopic examination of anal canal were normal after ASI therapy and the rectum biopsy showed no obvious histopathologic abnormality at the site of injection except mild focal submucosal infiltration of lymphocytes and plasma cells at 7 days after cessation of therapy which disappeared on 3 months after cessation of therapy. All patients had no evident complications. Conclusion: ASI could be recommended as a new safe, effective, painless method of antibiotics administration in the treatment of CBP.
文摘AIM: To compare the efficacy and safety of single daily amikacin vs. cefotaxime in the 5-d treatment of spontaneous bacterial peritonitis (SBP).METHODS: Thirty-seven cirrhotic patients with SBP,19 in group A and 18 in group B, were studied. Group A received 1 g of cefotaxime every 6 h, and group B received 500 mg of amikacin qd. Both antibiotics were administered up to 5 d and the responses were compared.RESULTS: Infection was cured in 15 of 19 patients (78.9%) treated with cefotaxime and in 11 of 18 (61.1%)treated with amikacin. Four patients of the Cefotaxime group (21.1%) and five patients of the Amikacin group (27.8%) died. Two in each group (10.5% vs 11.1%)had renal impairment during study period. One in each group (5.3% vs 5.6%) may be considered to suffer from nephrotoxicity due to increased urinary β2-microglobulin concentration.CONCLUSION: In this study, single daily doses of amikacin in the treatment of SBP in cirrhotics were not associated with an increased incidence of renal impairment or nephrotoxicity. However, a 5-d regimen of amikacin is less effective than a 5-d regimen of cefotaxime in the SBP treatment.
基金the CDCHTA of the University of Los Andes for providing financial support through several approved projectsthe National Fund for Science, Technology and Innovation (FONACIT) of Venezuelan Ministry of Science and Technology for providing financial support, SPE 112–370 and Project G-2005000641
文摘The quantitative estimation of amikacin （AMK） in AMK sulfate injection samples is reported using FTIR-derivative spectrometric method in a continuous flow system. Fourier transform of mid-IR spectra were recorded without any sample pretreatment. A good linear calibration （r40.999, %RSDo 2.0） in the range of 7.7-77.0 mg/mL was found. The results showed a good correlation with the manufacturer＇s and overall they all fell within acceptable limits of most pharmacopoeial monographs on AMK sulfate.
基金Supported by the National Natural Science Foundation of China(No.20875078) Chongqing Municipal Key Laboratory on Luminescence and Real-Time Analysis, Southwest University, China(No.2006CA8006)
文摘In a weak acid medium, potassium ferrioxalate（PF） can react with some aminoglycoside（AGs） antibiotics, such as amikacin（AMK）, kanamycin（KANA）, tobramycin（TOB） and gentamicin（GEN）, to form ion-association complexes. It results in the enhancement of resonance light scattering（RLS） in different degrees. The maximum scattering peaks are all located at 345 nm. Among them, the relative scattering intensity（AIRLs） of AMK system is much higher than that of KANA, TOB or GEN. Therefore the method is more propitious to the determination of trace amounts of AMK. The optimum reaction conditions, influencing factors, and the relationship between scattering intensity and concentration of antibiotics were investigated by means of the proposed method. The enhancement of RLS signals is directly proportional to the concentration of antibiotics in a certain range of concentration. A new resonance light scattering method for the determination of AMK and other aminoglycoside antibiotics with [Fe（C2O4）3]^3- as a probe is thus established based on it. The method exhibits high sensitivity and good selectivity. The detection limit（3σ） for AMK is 1.8 ng/mL. The method can be applied to the determination of AMK in clinical serum samples. The reaction mechanism and the reasons for RLS enhancement are discussed in this paper.
基金The work was supported by the National Natural Science Foundation of China （No. 20375020）.
文摘A new method to determine the concentration of amikacin （AMK） using methyl blue （MB） as electrochemical probe was developed in this paper. In pH 4.5 Britton-Robinson （B-R） buffer solution, the MB reacted with AMK to form ion association complexes, which led to the reductive peak current of MB at -0.275 V （versus SCE） to decrease, and the decreases were linear with the concentration of AMK in the range of 1.0-60.0 mg/L, the regression of equation is AIp （hA） = -8.48 ＋ 102.36c （rag/L）, correlation coefficient yis 0.997. The conditions for determining the concentration of AMK using linear sweep voltammetry （SLV） were optimized. The method was used to determine the content of amikacin commercially available with satisfactory results.
基金supported by the National Natural Science Foundation of China(No.21105133 and No.21127008)the Key Program of Guangdong Provincial Natural Science Foundation(No.9251027501000004)
文摘A novel chemiluminescence （CL） reaction was based on the oxidizing reaction of luminol by the trivalent copper-periodate complex （Ks[Cu（HIO6）2], DPC） in alkaline medium. The CL intensity could be enhanced in the presence of amikacin sulfate （AKS）. A new CL method was developed for the determination of AKS by coupling with flow injection （FI） technology. Because of the distinctive oxidative effect of DPC, the luminol-based CL reaction could occur at a low concentration of 10-7 M. The relative CL intensity was proportional to the concentration of AKS in the range of 4.0 x 10-9-4.0 x 10-6 g/mL with the detection limit of 1.2 x 10-9 g/mL. The relative standard deviation was 2.1% for 8.0xl0-9g/mL AKS （n=9）. The proposed method was successfully applied to the direct determination of AKS at the level of ng/mL in serum samples. The recovery varied from 97.0% to 106.3%. A possible mechanism of the CL reaction was discussed in detail by relating to the CL kinetic characteristics and electrochemical activities of the oxidant DPC.
文摘Objective: To characterize amikacin pharmacokinetics in serum and in blister fluid of severe burn patients to guide optimal treatment timing. Methods: Patients (N = 32) were divided into four groups based on amikacin administration timing and groups received drug minutes to hours after injury. In Groups A, B, C, and D, amikacin (400 mg, IV) was administered 3 - 4, 10, 20 and 30 h post burn injury, respectively (N = 8 for all groups). Next blister fluid and venous blood samples from 9 patients were obtained at 0, 0.25, 0.5, 1, 2, 3, 4, 5, 6, and 7 h after drug infusion. Amikacin concentrations were measured with a fluorescent polarization immunoassay and pharmacokinetics was deduced using DAS3.2.5. Statistical analyses performed with SPSS13.0. Results: Compared with normal values, t1/2z of amikacin from burn patients was shortened in serum but amikacin half-lives in blister fluid was significantly greater than serum half-life values (p < 0.05). Groups A and B had greater pharmacokinetic values at each time point, and Group D did not achieve antibacterial concentrations of amikacin. Conclusion: Early amikacin administration in severe burn patients offers greater concentrations of drug in serum and blister fluids.
文摘Morphology of spiral ganglion neurons （SGNs） in Sprague-Dawley rats before and after amikacin treatment was observed by transmission electron microscopy. Amikacin induced cochlear SGN apoptosis. Immunohistochemical staining and RT-PCR revealed a decrease in Bcl-2 protein ex-pression, and an increase in Bax protein, caspase-3 protein and caspase-6 mRNA expression fol-lowing amikacin treatment. （-）-Epigallocatechin-（3）-gallate （EGCG） inhibited SGN Bax protein, caspase-3 protein and caspase-6 mRNA expression, and enhanced Bcl-2 protein expression, thereby decreasing SGN apoptosis. Results demonstrated that EGCG can protect SGNs against amikacin-induced injury.
基金Peking Union Medical College(PUMC)Youth Fund and the Fundamental Research Funds for the Central Universities,China(Grant No.333203084)
文摘Silver nitrate could inhibit the clinical multidrug resistant isolates at high concentrations（with minimal inhibitory concentrations（MICs） from 32 μM to 64 μM）. The activities of amikacin in the presence of sub-lethal silver nitrate（15 μM） were tested for the combinational effects against multidrug resistant clinical isolates in vitro. Silver nitrate restored the susceptibility of drug-resistant Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus to amikacin. It lowered the MICs of amikacin from 〉128 μg/mL to（2–16） μg/mL and 32 μg/mL, respectively, and lowered the MICs of amikacin on extended spectrum β-lactamase-producing Pseudomonas aeruginosa and Escherichia coli from（16–32） μg/mL and 16 μg/mL to（〈1–4） μg/mL and 〈1 μg/mL, respectively.
文摘Background： Aerosolized amikacin （AA） is a current option for the management of ventilator-associated pneumonia （VAP） caused by multidrug-resistant Gram-negative bacteria （MDR-GNB）, as it is reported that AA could increase the alveolar level of the drug without increasing systemic toxicity. This study aimed to evaluate the efficacy and safety of AA as an adjunctive therapy for VAP caused by MDR-GNB. Methods： In this single-center, double-blind study conducted in a 36-bed general Intensive Care Unit （ICU） in a tertiary hospital from June 2014 to June 2016, 52 ICU patients with confirmed MDR-GNB VAP were randomized to two groups （AA group, n - 27 and placebo group, n = 25）. Amikacin （400 rag, q8h） or saline placebo （4 ml, q8h） was aerosolized for 7 days. The attending physician determined the administration of systemic antibiotics for VAP. Patients were tbllowed up for 28 days. Bacteriological eradication, clinical pulmonary infection score （CP1S）, and serum creatinine were assessed on day 7 of therapy. New resistance to amikacin, cure rate of VAP, weaning rate, and mortality were assessed on day 28. Results： The baseline characteristics of patients in both groups were similar. At the end of the treatment, 13 of the 32 initially detected bacterial isolates were eradicated in AA group, compared to 4 of 28 in placebo group （41% vs. 14%, P - 0.024）. As for patients, 11 of 27 patients treated with AA and 4 of 25 patients treated with placebo have eradication （41% vs. 16%, P = 0.049）. The adjunction of AA reduced CPIS （4.2 ± 1.6 vs. 5.8 ± 2.1, P = 0.007）. New drug resistance to amikacin and the change in serum creatinine were not detected in AA group. No significant differences in the clinical cure rate in survivors （48% vs. 35%, P = 0.444）, weaning rate （48% vs. 32%, P = 0.236）, and mortality （22% vs. 32%, P = 0.427） were detected between the two groups on day 28. Conclusions： As an adjunctive therapy of MDR-GNB VAP, AA successfully eradicated existing MDR organisms without inducing new resistance to amikacin or change in serum creatinine. However, the improvement of mortality was not found.
基金This work was supported by the National Natural Science Foundation of China (Grant No. 20475045) the Municipal Science Foundation of Chongqing City.
文摘The interaction between congo red (CR) and amikacin (AMK) was studied by resonance Rayleigh scattering (RRS), frequency doubling scattering (FDS) and second-order scattering (SOS) combining with absorption spectrum. In a weak acidic medium, CR combined with AMK to form an ion association complex with the composition ratio of 1∶1 by electrostatic interaction, hydrophobicity and charge transferring effect. As a result, the new spectra of RRS, FDS, and SOS appeared and their intensities were enhanced greatly. The maximum wavelengths of RRS, FDS and SOS were located at 563 nm, 475 nm and 940 nm, and the scattering intensities were proportional to the concentration of AMK. These three methods have very high sensitivities, and the detection limits were 4.0 ng·mL?1 for RRS, 3.6 ng·mL?1 for FDS and 1.9 ng·mL?1 for SOS, respectively. At the same time, the methods have better selectivity. A new method for the determination of trace amounts of AMK with congo red by resonance scattering technique has been developed. The recovery for the determination of AMK in blood serum and urine sample was between 95.5% and 105.5%. In this study, the properties, such as enthalpy of formation, charge distribution and mean polarizability, were calculated by AM1 quantum chemistry method. In addition, the reaction mechanism and the reasons for the enhancement of scattering spectra were discussed.
