丁胺卡那对肾功能早期损害的实验室指标研究

目的探讨丁胺卡那对肾功能早期损害的实验室指标的临床价值。方法检测145例尿蛋白定性阴性的细菌感染患者应用丁胺卡那前后肾功能损害的实验室指标:尿素氮(BUN)、肌酐(Scr)、半胱氨酸蛋白酶抑制剂C(Cys-C)、N-乙酰-β-D-氨基葡萄糖苷酶(NAG)、微量清蛋白(MAU),β2-微球蛋白(β2-M)的变化,并与100例健康体检者作对照。结果应用丁胺卡那后,尿Cys-C、NAG、MAU水平明显高于应用前,其差异有统计学意义(P<0.01)。BUN、Scr、β2-M水平在应用丁胺卡那前后变化差异无统计学意义(P>0.05)。结论尿蛋白定性阴性,BUN、Scr正常不能排除丁胺卡那对肾脏的早期损伤作用,尿Cys-C、NAG、MAU是诊断肾脏早期损伤的灵敏、可靠的实验室指标,尿β2-M可能不适宜用于细菌感染患者应用丁胺卡那后的肾功能早期损害监测。     

The safety and tolerability of the second-line injectable antituberculosis drugs in children

ABSTRACT

Introduction: A growing number of children globally are being treated for multidrug-resistant tuberculosis (MDR-TB). The second-line injectable antituberculosis medications amikacin, kanamycin and capreomycin, traditionally a mainstay of MDR-TB treatment, cause important adverse effects including permanent sensorineural hearing loss, nephrotoxicity, electrolyte abnormalities, injection pain and local injection site complications.

Areas covered: To characterize the safety and tolerability of the second-line injectables in children treated for MDR-TB, we reviewed data on the mechanism of injectable associated adverse effects, risk factors for their development, and the incidence of injectable-associated adverse effects in adults and children treated for MDR-TB.

Expert opinion: Despite a substantial evidence base in adults demonstrating the frequent and potentially serious adverse effects of second-line injectables, important knowledge gaps remain. Improved characterization of the incidence of injectable-associated adverse effects will inform rational guidance on monitoring children with TB on injectables. Eliminating the need for injectables in MDR-TB treatment regimens is a high priority, and will rely on the use of novel antituberculosis TB drugs. Strategies to reduce the risk of adverse effects of injectables, if used, deserve evaluation. This includes evaluation of potentially otoprotective medications N-acetylcysteine or aspirin, high frequency hearing screening for earlier detection of ototoxicity and therapeutic drug monitoring.     

柱前衍生化高效液相色谱法检测硫酸阿米卡星注射液中卡那霉素含量的改进

目的 改进柱前衍生化-HPLC方法用于定量测定硫酸阿米卡星注射液中已知杂质卡那霉素。方法 采用更低浓度的样品检测溶液,色谱柱:Agilent ZORBAX SB-C₁₈柱 (4.6 mmá150 mm,5 μm);流动相:0.27%磷酸二氢钾溶液(用2.2%的氢氧化钾溶液调节pH值至6.5)-甲醇(30:70);检测波长:340 nm;进样量:50 μl;流速:1.0 ml/min;柱温:30℃。结果 卡那霉素在2~80 μg/ml(r=0.999 8)浓度范围内呈线性关系,平均回收率为(93.08±9.65)%,样品稳定性提高。结论 本法专属性强,灵敏度高,准确度好,为硫酸阿米卡星注射液的安全性评价提供了一个新的角度。     

Ceftriaxone plus Amikacin in a Single Daily Dose as Empiric Antibiotic Therapy in Granulocytopenic Patients

Summary

In our study ceftriaxone plus amikacin were employed as empirical antibiotic therapy. This antibiotic treatment allows for a once daily administration and has a broad spectrum of activity. 21 febrile episodes were treated with an antibiotic regimen of ceftriaxone 50 mg/kg/day and amikacin 30-35 mg/kg/day i.v. An earlier pilot study was carried out in which 47 febrile episodes were treated with an antibiotic regimen of ceftriaxone 80-100 mg/kg/day i.v. and amikacin 30-35 mg/kg/day i.v. in a single dose.

The overall response rate was 76% (16/21) and 79% (37/47) for the pilot study.

During the treatment no side effects were observed and aminoglycoside related toxicity did not occur.

In conclusion, this empiric antibiotic therapy gives a high response rate and allows for a single daily administration.     

40株伤寒杆菌对常用抗生素和8种中草药的敏感性试验

本文报导了1987年省内分离的40株伤寒杆菌对常用抗生素的敏感率以及五味子、血盆草、来江藤、盐肤木、黄柏、黄连、仙鹤草、板兰根8种中草药对40株菌株的体外抗菌试验,结果表明五味子对各株伤寒杆菌均有较强的抗菌作用。     

Pulse therapy with amikacin and dapsone for the treatment of actinomycotic foot: a case report

Actinomycetoma is a chronic disease caused by aerobic actinomycetes and affecting the skin, subcutaneous tissue, and bones. It causes significant morbidity and clinically manifests as abscesses and sinus/fistulae with or without granules. Early diagnosis is based on the color, size, histopathology of the granules; culture and metabolic studies are used for further species differentiation. Although sulfamethoxazole-trimethoprim alone or in combination with dapsone for a variable period of time are used as first line agents for treatment, slow response to the therapy and high relapse rates have led to increasing usage of alternative agents like gentamycin, amikacin and cefotaxime. We report a case of actinomycetoma foot who had complete treatment failure with a sulfamethoxazole-trimethoprim-dapsone combination and was successfully treated with combination therapy of amikacin and dapsone without any side effects.     

Hemodialyzer clearances of gentamicin,kanamycin, tobramydn,amikacin, ethambutol. procainamide,and flucytosine,with a technique for planning therapy

Hemodialyzer clearance studies have been undertaken on the following drugs: gentamicin, kanamycin, tobramycin, amikacin, ethambutol, procainamide, and flucytosine. The following hemodialyzers were tested: Dow model 4, Kiil, Travenol UF II, and the Extracorporeal EX-03. The studies were predominantly undertaken in vitro,permitting direct comparison between drug clearances on the same dialyzer. Protein binding studies for gentamicin, kanamycin, procainamide, and ethambutol are also reported. Nomograms to facilitate the prediction of drug dosage regimens in dialysis patients are included.This work was supported in part by a grant from the General Clinical Research Centers Program (RR-133) of the Division of Research Resources, National Institutes of Health, and by a research contract (2-2219) from the Artificial Kidney-Chronic Uremia Program of the National Institute of Arthritis, Metabolism, and Digestive Diseases, National Institutes of Health.This paper was presented in part at the American Society of Nephrology meeting, 1974.     

Amikacin treatment for Mycobacterium marinum infection

This report describes a case of Mycobacterium marinum skin infection. A granulomatous plaque on the dorsum of the left hand of a 71-year-old man who kept a tank of tropical fish was followed by erythema and induration on the left forearm of the lymphocutaneous type. The lesion was successfully treated with 6 weeks of administration of amikacin (28 intramuscular injections) a total of 3500 mg. The isolated M. marinum strain was sensitive in vitro to amikacin at 0.78 μg/ml. Furthermore, another 15 clinical strains of M. marinum showed high sensitivity in vitro to this drug (93% of the 16 strains were sensitive to between 0.78 and 1.56 μg/ml).     

Population pharmacokinetics of amikacin in intensive care unit patients studied by NPEM algorithm

Summary— The population pharmacokinetics of amikacin was studied in 40 intensive care unit patients (212 plasma concentrations) by NPEM algorithm using a one-compartment model. The population was best characterized by the following pharmacokinetic parameters: renal clearance relative to creatinine clearance (C_s = 0.96 ± 0.33), and either the total volume of distribution (V_d = 23.9 ± 7.0 I) or the volume of distribution relative to body weight (V_s = 0.36 ± 0.10 1·kg⁻¹. The volume of distribution was increased with respect to the usual value of 0.25 1·kg⁻¹. The statistical distribution of these pharmacokinetic parameters was approximately gaussian, with no significant correlation between volume of distribution and clearance. The medians and standard deviations of C_s and V_s were used as reference population values to estimate the pharmacokinetics of amikacin in a second group of 29 patients by the bayesian method, with two blood samples per patient. For each patient, the fitted parameters were able to predict the plasma concentrations of amikacin during the next 72 h with no significant bias and good precision (2.9 mg·1⁻¹ for peaks and 0.5 mg·1⁻¹ for troughs). This study confirms the ability of the NPEM algorithm to provide reference population values for use in bayesian monitoring of aminoglycoside therapy.     

健康者和急性白血病患者体内苯唑西林对阿米卡星药代动力学的影响

目的 :对阿米卡星 (AMK)与苯唑西林 (OXA)合用健康者和急性白血病患者体内药代动力学进行研究。方法 :微量微生物法测定AMK血、尿药浓度。结果 :单用与合用AMK的药时曲线均符合二房室模型 ,健康者体内AMK单用与合用药代动力学参数分别为 :K10 ( 0 .5 5± 0 .2 2 )和 ( 0 .4 2± 0 .0 3 )h-1(P <0 .0 5 ) ,t1/ 2 β( 2 .1 1± 0 .1 6)和 ( 3 .0 0± 0 .4 1 )h(P <0 .0 1 ) ;AUC( 5 4 .7± 3 .90 )和 ( 69.1 5± 4 .91 ) μg·h·ml-1(P <0 .0 0 1 ) ;急性白血病患者体内 ,AMK单用与合用药代动力学参数分别为 :K12( 0 .0 6± 0 .2 6)和 ( 1 .0 6± 0 .1 0 )h-1(P <0 .0 5 ) ,K2 1( 1 .4 7± 0 .64 )和 ( 1 .84± 0 .2 2 )h-1(P <0 .0 5 )。K10 ( 0 .71± 0 .0 5 )和 ( 0 .5 4± 0 .0 4 )h-1(P <0 .0 5 ) ,t1/ 2 β( 1 .62± 0 .1 9)和 ( 2 .2 2± 0 .0 9)h(P <0 .0 1 ) ,AUC( 3 9.92± 4 .2 0 )和 ( 5 1 .5 3± 3 .0 0 ) μg·h·ml-1(P<0 .0 0 1 )。结论 :健康者和急性白血病患者体内OXA对AMK的药代动力学均有显著的影响。