1、替考拉宁治疗G+颅内感染的疗效,浙江省中医院ICU 江荣林,开颅手术后颅内感染细菌,28例38株细菌,赵岗等，28例开颅术后颅内感染病原学分析和临床治疗，第三军医大学学报，2011；33（2）：208-209,NICU颅内感染细菌,183株细菌,舒凯等，神经外科重症监护病房颅内感染的临床调查，中华医院感染学杂志2010，20（1）：53-54,神经外科术后颅内感染,裘天仑,等，神经外科术后颅内感染相关因素分析与预防对策，中华医院感染学杂志，2009，19（19）：2553-2555,开颅手术后颅内感染,荟萃分析国内36篇文章，43766例，颅内感染1137例，617株细菌（阳性率55.41%）
2、,金葡菌 159表葡 41CoNS 29肠球菌 3肺炎链球菌 7链球菌 4,靳桂明等，开颅手术后颅内感染流行病学调查的荟萃分析，中国临床神经外科杂志，2007，12（3）：149-151,颅脑手术后感染,Shervin R Dashti,et al.Operative intracranial infection following craniotomy. Neurosurg Focus.2008,24 (6):E10,1-5,颅脑手术后感染,19972007年，50例颅内感染，23例在感染前有1次颅内手术,金葡菌18 MR 2 MS 10 CoNS 6链球菌 2,Shervin R Dash
3、ti,et al.Operative intracranial infection following craniotomy. Neurosurg Focus.2008,24 (6):E10,1-5,原则：Treatment of Bacterial Meningitis,在腰穿后尽快开始抗生素治疗经验性应用抗生素治疗前作血培养经验性应用抗生素应选择在CSF中有较高浓度的杀菌剂必要时应用激素当病原菌确定后，选择更有针对性的抗生素必要时复查CSF。,Bactericidal vs Bacteristatic Agents,Bactericidal agentsB-LactamsGlycopept
4、ideBacteriostatic agents (i.e. Clindamycin or TCN) Inadequate for meningitis,Indication for bacteriocidal antibiotics,MeningitisEndocarditisOsteomyelitis ?Febrile neutropenia,CSF Antibiotic Levels,Most drugs achieve peak concentrations in the CSF equal to 10-20% of serum levelsCSF inflammation incre
5、ases drug penetration,Empiric Treatment,Optimal concentration of antibiotic for killing is 30 times the MBC (animal models)3rd Generation CephalosporinsCeftriaxoneCefotaximeActivity against major pathogens (except Listeria and resistant PNC and GNRs) GlycopeptideResistant gram positive organismsAmpi
6、cillinListeria,Tissue PenetrationTissue/Serum (%),61%,40%,20%,Peritoneal dialysis fluid,94%,40%,30%,Muscle,104%,77%,2030%,Inflammatory blister fluid,415%,11%17%,ELF,70%,10%,0%18%,CSF,60%,50%60%,7%13%,Bone,Linezolid,Teicoplanin,Vancomycin,Tissue,1. Graziani 1988; 2. Matzke 1986; 3. Albanese 2000; 4.
7、Georges 1997; 5. Lamer 1993; 6. Daschner 1987; 7. Blevins 1984; 8. Wilson 2000; 9. Stahl 1987; 10. Wise 1986; 11. Frank 1997; 12. Lovering 2002; 13. SmPC; 14. Gee 2001; 15. Gendjar 2001.,132%,Role of Glycopeptide in the Treatment of Meningitis,Combination with -lactam for community-acquired meningit
8、isMonotherapy for G(+) shunt infection,In vitro activities of ceftriaxone and teicoplanin against S. pneumoniae at 6h and 24h,Journal of Antimicrobial Chemotherapy (2005) 55, 7883,In vitro activities of ceftriaxone and teicoplanin against S. pneumoniae at 6h and 24h,Journal of Antimicrobial Chemothe
9、rapy (2005) 55, 7883,Steroid对抗生素穿透脑膜及脑膜內杀菌能力之影响,Steroid effect on antibiotics CSF penetration a rabbit pneumococcal meningitis model,AntibioticsCSF/serum peak CSF/serum troughCeftriaxone without DMX 5.5/275 (2.1%) 2.7/28 (13.8%) with DMX 5.6/228 (2.5%) 2.1/29 (7.9%)Vancomycin without DMX 1.6/29 (5.3
10、%) 1.7/4.5 (53.1%) with DMX 1.1/34 (3.4%) 1.3/3.6 (39.3%)Rifampin without DMX 0.14/7.1 (2.0%) 0.08/2.7 (4.3%) with DMX 0.23/7.3 (3.1%) 0.09/1.8 (5.4%),Antimicrobial Agents and Chemotherapy 1994;38:1320-4,Effect of dexamethasone on therapy of experimental penicillin- and cephalosporin-resistant pneum
11、ococcal meningitis,Antimicrobial Agents and Chemotherapy 1994;38:1320-4,Experimental study of teicoplanin alone in the therapy of resistant pneumococcal meningitis,Journal of Antimicrobial Chemotherapy (2005) 55, 7883,Pharmacodynamic parameter and CSF bactericidal activity,CSF bacteria killing rate
12、T MBClinear correlationCpeak/MBCnonlinear correlationAUC/MBCnonlinear correlation,Antimicrobial Agents and Chemotherapy 1997;41:2414-2417,根据PK/PD特性的抗菌药物分类,时间依赖性,与时间有关，但抗菌活性持续时间较长,浓度依赖性,对致病菌的杀菌作用取决于峰浓度,抗菌作用与同细菌接触时间密切相关,时间依赖且PAE或T1/2较长,氨基糖苷类、氟喹诺酮类、酮内酯类、两性霉素B、daptomycin、甲硝唑,多数-内酰胺类、大环内酯类、林可霉素类、恶唑烷酮类、氟胞
13、嘧啶,链阳霉素、四环素、阿齐霉素、碳青霉烯类、糖肽类、唑类抗真菌药,主要参数TMIC和AUCMIC,主要参数TMIC 和AUC/MIC,主要参数AUC0-24/MIC (AUIC) Cmax/MIC,替考拉宁： Long serum half life (88182 hrs),Teicoplanin plus Ceftazidime in the Treatment of Bacterial Meningitis - A Case Report,男性，37岁，非何杰金氏恶性淋巴瘤（侵犯纵膈，肝，肺，颈淋巴结）为预防颅内病灶，鞘内注射氨甲嘌呤、胞密啶、激素5次+头颅放疗数日后病人出现呕吐，发热3
14、9，癫痫大发作；2天后幻觉，急躁易怒。怀疑颅内浸润，腰穿：淋巴细胞少，中性粒细胞多，培养：肠球菌（万古MIC 0.5 mg/l），表皮葡萄球菌（ceftazidime MIC 0.25 mg/l）,Krcmery V Jr,et al.Infection.1991;19(4)：255,治疗：替考拉宁0.4 q12h，一天后0.2 q12h +头孢他啶3.0 q12h IV次日症状改善，3天后退热疗程15天，颅内感染治愈,Teicoplanin plus Ceftazidime in the Treatment of Bacterial Meningitis - A Case Report,Kr
15、cmery V Jr,et al.Infection.1991;19(4)：255,替考拉宁为G+細菌性脑膜炎治疗首选,不受激素之影响而降低杀菌力为長效型药物，最符合治疗脑膜炎之药物动力学要求与头孢三代合并使用有相乘之杀菌效果,G+颅内感染：万古霉素治疗失败后的替考拉宁挽救性治疗,3例儿童患者，颅内分流装置术后出现感染2例表皮葡萄球菌，1例肠球菌先：vancomycin负荷量15 mg/kg，继而 50 mg/kg/day，iv，治疗710天，临床和微生物学均无效。再改用： teicoplanin 负荷量6 mg/kg，继而 12 mg/kg/day，iv，14天。替考拉宁快速有效，耐受性好。
16、,Jourdan C, et al. Adequate intrathecal diffusion of teicoplanin after failure of vancomycin, administered in continuous infusion in three cases of shunt associated meningitis.Pathol Biol (Paris). 1996;44(5):389-92.,Vancomycin versus teicoplanin in the therapy of experimental MRSA meningitis,20 mg/k
17、g vancomycin q12h，6 mg/kg teicoplanin q12h,Oguz Resat Sipahi，et al. International Journal of Antimicrobial Agents 26 (2005) 412415,Vancomycin versus teicoplanin in the therapy of experimental MRSA meningitis,Oguz Resat Sipahi，et al. International Journal of Antimicrobial Agents 26 (2005) 412415,Meni
18、ngitis due to methicillin-resistant Staphylococcus aureus(MRSA): Review of 10 cases (疗程：23.518.8 days 【range, 360 days】）,Bilgin Arda,et al. International Journal of Antimicrobial Agents 25 (2005) 414418,替考拉宁治疗MRSA脑膜炎优势总结,长效药物、杀菌剂，符合脑膜炎治疗要求不受激素影响而降低疗效（研究表明万古霉素可能会受到影响）药物联合使用可以提高药效（多篇文献报道替考拉宁+第三代头孢）,谢谢,
