利奈唑胺治疗耐多药肺结核的临床观察

目的观察利奈唑胺（LZD）治疗耐多药结核病（MDR-TB）的临床疗效和安全性。方法采用含LZD为主的化疗方案治疗12例MDR-TB住院患者。LZD用法：治疗开始时应用600 mg,静脉滴注或口服,每天1次,强化治疗6个月后,可用600mg,每天1次;或300mg口服,每天1次,疗程至少9个月。结果 12例患者应用LZD疗程1～12个月;治疗9～12个月3例完成疗程并治愈,最短为1个月;12例患者除1例症状没有改善,其余11例临床症状均有不同程度改善,平均改善时间18天;除2例治疗失败病例外,其余10例空洞缩小时间平均为1.5个月;痰菌涂片阴转时间最短7天1例,最长120天1例,2例仍阳性;痰培养阴转时间14天1例,21天3例,60天3例,3例仍阳性;1例治疗1个月因严重四肢麻木而停药;1例治疗1个月出现严重呕吐、失眠、心悸,后将LZD改为300mg,每天1次,1个月后症状无好转而停药;1例治疗9个月出现视物模糊停药,随访符合治愈标准;1例治疗10个月出现视物模糊,减为300mg每天1次,治疗至12个月治愈停药。结论 LZD600mg,每天1次的剂量可以明显改善MDR-TB患者临床症状,缩短痰菌阴转时间和空洞闭合时间,药物不良反应小,疗程至少9个月。     

利奈唑胺全身给药后在人非炎性玻璃体中的药动学

利奈唑胺为全合成嚼唑烷酮类（oxazolidinones）抗菌药,对甲氧西林耐药金葡菌和凝固酶阴性葡萄球菌具良好抗菌作用。文献报道该药在人体非炎性房水中穿透性良好,但其对玻璃体穿透性的资料则甚少。本文作者研究了利奈唑胺全身给药后在人体非炎性玻璃体中的穿透性。该研究在24例接受玻璃体摘除术患者中进行。     

利奈唑胺对结核性脑膜炎患者脑脊液指标水平及预后的影响

目的：探讨利奈唑胺对结核性脑膜炎患者脑脊液指标水平及预后的影响。方法：选择2017年1月~2018年9月接受治疗的结核性脑膜炎患者84例,以随机数字表法分为对照组和观察组各42例。对照组采用抗结核治疗,观察组在对照组基础上加用利奈唑胺治疗。比较两组患者脑脊液指标、后遗症及不良反应发生情况。结果：观察组治疗后脑脊液葡萄糖含量高于对照组,白细胞计数、蛋白定量低于对照组（P＜0.05）;观察组后遗症发生率低于对照组（P＜0.05）;两组不良反应发生率比较,差异无统计学意义（P＞0.05）。结论：利奈唑胺可改善结核性脑膜炎患者的脑脊液指标水平及预后,且不会明显增加不良反应。     

咔哒唑胺与利奈唑胺对艰难梭菌的敏感性实验

目的 比较咔哒唑胺与利奈唑胺对不同基因和毒素型别的艰难梭菌的抑菌效果,以及咔哒唑胺对艰难梭菌芽孢形成的影响。方法 采用咔哒唑胺与利奈唑胺对10株不同基因型别的艰难梭菌、1株产气荚膜梭菌和1株脆弱拟杆菌进行药物敏感性实验,获得各菌株测试药物对应的最低抑菌浓度（MIC）值。选取其中1株艰难梭菌ATCC BAA-1803,核糖体027型高毒株,试验咔哒唑胺对菌株芽孢形成的影响,从而对药物进行评价。结果 艰难梭菌咔哒唑胺MIC为0.25 g/ml（0.03~0.25 g/ml）,利奈唑胺MIC为4.0 g/ml（0.5~16.0 g/ml）,艰难梭菌咔哒唑胺MIC值低于利奈唑胺16倍。2种抗生素对不同基因型别与毒素型别的艰难梭菌均具有良好抑菌效果,同时对产气荚膜梭菌也具有抑菌效果。咔哒唑胺对脆弱拟杆菌不产生抑菌效果,利奈唑胺对其有抑菌效果。咔哒唑胺能抑制艰难梭菌芽孢形成。结论 临床常见的不同基因型和毒素型别的艰难梭菌对咔哒唑胺敏感,咔哒唑胺可用于治疗艰难梭菌感染。     

含利奈唑胺方案治疗耐多药结核病期间利奈唑胺调整的危险因素分析

目的 探讨使用含利奈唑胺方案治疗耐多药结核病(MDR-TB)期间,利奈唑胺因不良事件调整的危险因素。方法 回顾性分析2018年3月—2021年11月成都市公共卫生临床医疗中心接受含利奈唑胺方案抗结核并已完成疗程的MDR-TB患者73例,根据药物是否因不良事件调整利奈唑胺治疗(包括停药或降低剂量)分为2组,调整组47例,未调整组26例。收集并比较两组患者的性别、年龄、抗结核治疗方案、结核治疗史、体质量指数、合并症等临床资料,探讨需要调整利奈唑胺的危险因素。结果 单因素logistic回归显示,调整组利奈唑胺初始使用剂量>600 mg/d的患者明显多于未调整组(P=0.016)。多因素logistic回归分析显示,利奈唑胺使用初始剂量>600 mg/d是其治疗MDR-TB期间因不良事件调整用药的独立危险因素(OR=4.229,95%CI：1.251～14.293,P=0.020)。结论 在使用含利奈唑胺方案治疗MDR-TB期间,因不良事件而进行治疗调整较常见,利奈唑胺使用初始剂量>600 mg/d是需要调整的独立危险因素,临床使用时需注意该药治疗方案的选择。     

利奈唑胺治疗老年院内获得性肺炎临床观察

目的:观察利奈唑胺与万古霉素老年院内获得性肺炎的疗效与安全性.方法:回顾性分析应用利奈唑胺(68例)与万古霉素(56例)治疗老年院内获得性肺炎患者的临床资料,比较两组患者临床总有效率、细菌清除率及不良反应情况.结果:利奈唑胺和万古霉素治疗院内获得性肺炎临床有效率分别为73.5%、51.8%(P＜0.05),对病原菌的清除率分别达70.1%、72.1%(P＞0.05),两组患者药品不良反应发生率无统计学差异,但万古霉素治疗组出现肾毒性9例,较利奈唑胺不良反应严重.结论:利奈唑胺治疗老年院内获得性肺炎安全可靠.     

利奈唑胺不敏感肠球菌的耐药机制及分子分型

目的 了解利奈唑胺不敏感肠球菌(linezolid-insensitive Enterococcus,LISE)检出率及分布特点,分析LISE的主要耐药机制和分子分型,为LISE医院感染精准预防与控制提供理论依据。方法 回顾性分析2018—2019年福建医科大学附属泉州第一医院临床分离肠球菌属细菌药敏试验数据,对经仪器法检测出的LISE采用肉汤微量稀释法和纸片法进行确认,采用多位点序列分型(MLST)分析LISE菌株的同源性。采用PCR法检测23S rRNA、rplC、rplD、rplV、optrA、poxtA、cfr、cfr(B)利奈唑胺耐药相关基因。结果 2018—2019年共分离鉴定肠球菌522株,检测出LISE共44株(均为粪肠球菌),检出率为8.4%(44/522),其中利奈唑胺中介粪肠球菌(linezolid-intermediate Enterococcus faecalis,LIEf)占3.1%(16/522);利奈唑胺耐药粪肠球菌(linezolid-resistant Enterococcus faecalis,LREf)占5.4%(28/522)。利奈唑胺对28株...     

头孢曲松联合利奈唑胺治疗成人化脓性脑膜炎的疗效

目的:探讨头孢曲松联合利奈唑胺治疗成人化脓性脑膜炎疗效评价.方法:将确诊为化脓性脑膜炎成人案例65例随机分为两组:36例为对照组即单用头孢曲松静脉点滴抗炎治疗组;29例为实验组即应用头孢曲松静脉点滴抗炎治疗,3d后加用利奈唑胺静脉点滴治疗组.选取体温恢复正常天数,外周白细胞恢复正常天数,1周后复查腰穿,脑脊液恢复正常例数作为观察指标,观察对照组与实验组疗效差异.结果:实验组与对照组相比,体温恢复正常时间缩短约3.1d,外周血象恢复正常时间缩短约3.3 d,两组间治疗效果对比具有差异,并具有统计学意义(P＜0.05);1周后复查腰穿,脑脊液白细胞恢复正常例数实验组多于对照组,两组间治疗效果对比具有差异,并具有统计学意义(P＜0.05).结论:应用头孢曲松联合利奈唑胺治疗成人化脓性脑膜炎疗效优于单用头孢曲松治疗疗效.     

利奈唑胺在耐药肺结核治疗中的应用效果

目的 探究利奈唑胺对耐药肺结核患者血清降钙素原(PCT)、C-?反应蛋白(CRP)及红细胞沉降率(ESR)水平的影响及安全性,为提升耐药肺结核的临床治疗效果提供参考和依据.方法 按照随机数字表法将吉林省结核病医院(吉林省传染病医院)于2018年1月至2020年10月收治的63例耐药肺结核患者分为对照组(31例,采用丙硫...     

利奈唑胺致粒细胞缺乏1例报告并文献复习

利奈唑胺是一种(嚷)唑烷酮类抗生素,主要用于严重的革兰阳性球菌感染,包括万古霉素耐药的肠球菌感染;由金黄色葡萄球菌(金葡菌)、化脓性链球菌或无乳链球菌引起的皮肤感染;由葡萄球菌或肺炎链球菌引起的院内肺炎;由甲氧西林敏感的葡萄球菌或青霉素敏感的肺炎链球菌引起的社区获得性肺炎[1].利奈唑胺的作用机制是通过与核糖体rRNA的50S亚单位结合,阻止细菌蛋白质的合成.利奈唑胺进入临床后,在带来良好治疗效果的同时,其毒副作用也逐渐显现.现报告1例使用利奈唑胺后出现粒细胞缺乏患者的临床资料,并结合相关文献进行复习,以期提高对该药血液系统副作用的认识.     

Pharmacokinetics,toxicity and clinical efficacy of linezolid in Japanese pediatric patients

ObjectivesThe aims of the present study were (a) to evaluate the pharmacokinetics of linezolid, and (b) to assess the toxicity and clinical efficacy of linezolid in Japanese pediatric patients.Patients and methodsRoutine clinical data including serum linezolid total and unbound concentrations were collected from 15 pediatric patients (0–13 years old). Pharmacokinetics of linezolid was assumed to follow one-compartment with the first-order absorption model. The relationship between risk for thrombocytopenia and linezolid concentrations, and the variations in C-reactive protein (CRP) concentrations and body temperatures were evaluated as clinical efficacy assessment.ResultsBody weight (WT) and maturation of body function were significant covariates for pharmacokinetics of linezolid in pediatric patients. The elimination half-life of linezolid in a pediatric patient with a WT of 9.9 kg and age of 24 months (median of this study) was 3.0 h. Thrombocytopenia was detected in three patients (21.4%), and the minimum concentrations (C_min) in these patients were significantly higher than those in patients without thrombocytopenia (P < 0.05). The CRP concentrations decreased more than 50% in all pediatric patients after the treatment with linezolid, however body temperatures at the end of treatment were higher than 37.5 °C in 6 patients (42.9%).ConclusionsAlthough dose adjustment based on body size was performed for pediatric patients, thrombocytopenia was detected in 21.4% of pediatric patients, and higher C_min was associated with the risk of thrombocytopenia. These results encourage the implementation of individual dose adjustment based on linezolid serum concentrations for safe and appropriate treatment with linezolid.     

Some glycolytic enzymes in normal cerebrospinal fluid, brain tissue and blood plasma of infants.

The activities of several glycolytic enzymes (hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase) as well as glycerol-1-phosphate dehydrogenase and (Mg2+)ATPase in normal cerebrospinal fluid (CSF) and blood plasma samples, from 12 healthy infants, aged 2-18 months, and in supernatants from brain tissue slices, taken during neurosurgical operations from infants of the same range of age were estimated. The values obtained confirm the high activity of the above enzymes found in animal brains, and indicate an independence of these activities in blood plasma and CSF. The origin of the activities of the investigated enzymes in CSF seems to be mainly, if not, exclusively, from brain tissue. This might be useful for detection of brain tissue damage as was earlier proven with LDH activity in CSF.     

Pharmacokinetics of florfenicol in cerebrospinal fluid and plasma of calves.

Florfenicol, a fluorinated analog of thiamphenicol, is of great value in veterinary infectious diseases that formerly responded favorably to chloramphenicol. In view of the treatment of meningitis in calves, we studied its pharmacokinetics in the cerebrospinal fluid (CSF) and plasma of six animals. To this end, a new high-performance liquid chromatography method was developed which, unlike previous ones, uses solid-phase instead of double-phase extraction to isolate the drug. After a single intravenous dose of 20 mg/kg of body weight, a maximum concentration in CSF of 4.67 +/- 1.51 microg/ml (n = 6) was reached, with a mean residence time of 8.7 h. The decline of florfenicol in both CSF and plasma fitted a biexponential model with elimination half-lives of 13.4 and 3.2 h, respectively. Florfenicol penetrated well into CSF, as evidenced from an availability of 46% +/- 3% relative to plasma. The levels remained above the MIC for Haemophilus somnus over a 20-h period. Our results provide evidence indicating the effectiveness of florfenicol in the treatment of bacterial meningitis of calves.     

Pharmacokinetics of repeated dosing of linezolid in a hemodialysis patient with chronic renal failure

Linezolid (LZD) is thought not to require dose adjustment in patients with renal dysfunction, making it a drug of choice for these patients. However, in the current study we show LZD accumulation occurring with repeated dosing during hemodialysis in a 64-year-old man receiving hemodialysis treatment. In this patient, methicillin-resistant Staphylococcus aureus (MRSA) caused an abscess under the abdominal wall due to wound infection after colon cancer surgery. Treatment was initiated with intravenous LZD (600 mg) every 12 h. However, pancytopenia and liver dysfunction occurred during the LZD administration period. A high trough level, of 15–20 μg/ml, during LZD administration was determined from stored blood biochemistry samples, and pharmacokinetic parameters, estimated by the Bayesian nonlinear least squares method, were as follows: clearance (CL), 1.56 l/h; clearance during hemodialysis (CL_HD), 2.23 l/h; volume of distribution (Vd), 18.69 l; and area under the curve (AUC), 384.07 μg/ml · h. Simulation of the serum concentration-time profile from the estimated pharmacokinetic parameters gave a trough level about four to five times higher than that in healthy individuals in the early administration period, indicating LZD accumulation in blood. These findings suggest a causal relationship between the high LZD level and the adverse effects. The cause of the high LZD level is unclear, but the findings indicate that careful monitoring and dose adjustment of LZD is necessary in hemodialysis patients.     

The effect of phenethylhydrazine on plasma,cerebrospinal fluid and brain tissue amino acid distribution in guinea pigs

An experimental study on 200 guinea pigs was carried out to analyze the amino acid pattern and their distribution among plasma, cerebrospinal fluid and brain tissue in acute phenethylhydrazine poisoning. The amino acid pattern in the various fluids and tissues was strongly modified and the free amino acid distribution between plasma and cerebrospinal fluid, plasma and brain tissue, and brain tissue and cerebrospinal fluid differed significantly from control values. Hypotheses about the particular cerebral metabolic pathways involved are presented.     

肠球菌对利奈唑胺耐药的分子机制研究进展

肠球菌属细菌为院内感染的重要病原菌之一,不仅可引起尿路感染、皮肤软组织感染,还可引起危及生命的腹腔感染、败血症及心内膜炎。万古霉素耐药肠球菌(vancomycin resistant Enterococci,VRE)的出现给临床治疗带来了挑战,利奈唑胺作为VRE治疗的最后一道防线,其耐药分布及分子机制应该引起医务工作者的重视。该文从国内外耐药现状和耐药机制两方面进行阐述,尤其对23S rRNA的V区突变,L3、L4核糖体蛋白氨基酸突变,多重耐药基因cfr介导的耐药以及近来研究逐渐增多的optrA基因介导的耐药机制进行了分析,为减缓耐药形成、耐药相关基因及时检出、早期干预提供一定的理论依据。     

Pharmacokinetics of cefsulodin in rat cerebrospinal fluid during experimental Pseudomonas aeruginosa meningitis

Experimental meningitis was induced in rats with Pseudomonas aeruginosa. Bacteria were inoculated in the second ventricle. Twenty hours later cefsulodin penetration was studied in CSF by on-line cannula system which permitted sampling of CSF in the third ventricle. Comparison with healthy animals indicated breakdown of the blood-CSF barrier and high concentrations of cefsulodin were found in CSF.     

Pharmacokinetics of dideoxypurine nucleoside analogs in plasma and cerebrospinal fluid of rhesus monkeys.

The pharmacokinetics of 2',3'-dideoxyadenosine (ddA), didanosine, 2',3'-dideoxyguanosine (ddG), and 6-halogenated prodrugs of ddG, 6-chloro-ddG and 6-iodo-ddG, in plasma and cerebrospinal fluid (CSF) were studied in a non-human primate model. ddA was rapidly and completely deaminated to didanosine, such that didanosine concentration profiles in plasma and CSF were identical following administration of ddA and didanosine. The mean clearance of didanosine was 0.50 liters/h/kg, the terminal half-life was 1.8 h, and the CSF-to-plasma ratio was 4.8%. The disposition of ddG was similar, with a clearance of 0.70 liters/h/kg and a half-life of 1.7 h. The adenosine deaminase-mediated conversion of the 6-halogenated-ddG prodrugs to ddG was rapid but incomplete (48% for 6-chloro-ddG and 29% for 6-iodo-ddG). The CSF-to-plasma ratios of ddG with equimolar doses of ddG, 6-chloro-ddG, and 6-iodo-ddG were 8.5, 24, and 17%, respectively, but the actual ddG exposures in CSF (area under the CSF concentration-time curve) were comparable for ddG (12.1 microM.h) and the 6-halogenated-ddG prodrugs (18.8 microM.h for 6-chloro-ddG, 9.3 microM.h for 6-iodo-ddG).6-Chloro-ddG was not detectable in plasma or CSF, and the CSF-to-plasma ratio of 6-iodo-ddG was 9.4%, so the higher CSF-to-plasma ratios of ddG with the administration of the 6-halogenated-ddG prodrugs does not appear to be the result of enhanced penetration of the prodrug and subsequent dehalogenation to ddG. The penetration of ddG into CSF exceeds that of didanosine and is enhanced by administration of the 6-halogenated prodrugs, although the mechanism of this enhanced penetration is unclear.     

Neurotoxicity of benzylpenicillin: correlation to concentrations in serum, cerebrospinal fluid and brain tissue fluid in rabbits

The neurotoxic potential of benzylpenicillin, administered as continuous intravenous infusion, was studied in rabbits. Thirteen animals were killed at the onset of epileptogenic EEG activity (seven) or convulsions (six). Benzylpenicillin levels were determined in serum, cerebrospinal fluid (CSF) and brain tissue fluid. High doses of benzylpenicillin were required to induce neurotoxicity; epileptogenic (EEG) changes were seen at serum levels of 510-960 mg/l and convulsions at 920-1902 mg/l. Neurotoxicity correlated well with levels of benzylpenicillin in brain tissue fluid, calculated as 10 x the concentration in whole brain tissue. The correlation of neurotoxic reactions to levels of benzylpenicillin in CSF was poor and the CSF levels were consistently lower than those in brain tissue fluid. The technique used was found to be a satisfactory, though laborious, way to study neurotoxicity of drugs.