替考拉宁治疗脑膜炎

1、替考拉宁治疗替考拉宁治疗g+颅内感染的疗效颅内感染的疗效 浙江省中医院icu 江荣林开颅手术后颅内感染细菌28例38株细菌金葡菌金葡菌12（mrsa3）cons6 （mr3）中性葡萄球菌中性葡萄球菌2链球菌链球菌1肠球菌肠球菌4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）：208-209nicu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）：53-54cons 17.5%表葡表葡 15.8%金葡金葡 10.4%肠球菌肠球菌 6.0%溶葡溶葡 3.3%其他其他 15.3%神经外科术后颅内

2、感染cons 7金葡 5屎肠球菌 3其他肠球菌 3其他 3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o 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%）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

3、following craniotomy. neurosurg focus.2008,24 (6):e10,1-5 颅脑手术后感染o 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 2shervin r dashti,et al.operative intracranial infection following craniotomy. neurosurg focus.2008,24 (6):e10,1-5 原则：原则：treatment of bacterial meningitiso 在腰穿后尽快开始抗生素治疗在腰穿后尽

4、快开始抗生素治疗o 经验性应用抗生素治疗前作血培养经验性应用抗生素治疗前作血培养o 经验性应用抗生素应选择在经验性应用抗生素应选择在csf中中有较高浓度有较高浓度的的杀菌杀菌剂剂o 必要时应用必要时应用激素激素o 当病原菌确定后，选择更有针对性的抗生素当病原菌确定后，选择更有针对性的抗生素o 必要时复查必要时复查csf。 bactericidal vs bacteristatic agentso bactericidal agentsn b-lactamsn glycopeptideo bacteriostatic agents (i.e. clindamycin or tcn) n inad

5、equate for meningitisindication for bacteriocidal antibioticso meningitiso endocarditiso osteomyelitis ?o febrile neutropeniacsf antibiotic levelso most drugs achieve peak concentrations in the csf equal to 10-20% of serum levelso csf inflammation increases drug penetrationempiric treatmento optimal

6、 concentration of antibiotic for killing is 30 times the mbc (animal models)o 3rd generation cephalosporinsnceftriaxonencefotaximenactivity against major pathogens (except listeria and resistant pnc and gnrs) o glycopeptidenresistant gram positive organismso ampicillinnlisteriatissue/serum (%)61%40%

7、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. georges 1997; 5. lamer 1993; 6. daschner 1987; 7. blevins 1984; 8. wilson

8、 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 meningitiso combination with -lactam for community-acquired meningitiso monotherapy for g(+) shunt infectionin vitro activities of ceftriaxon

9、e and teicoplanin against s. pneumoniae at 6h and 24hdrugs (fold mic)difference log cfu/ml at6 h24 htel (8)-0.5-4.2tel (2)11.4tel (1)2.60.8tel (1/2)2.51.0cro (2)-2.1-4.5cro (1)-2.2-4.4cro (1/2)0.50.9cro (1/4)1.90.3journal of antimicrobial chemotherapy (2005) 55, 7883in vitro activities of ceftriaxon

10、e and teicoplanin against s. pneumoniae at 6h and 24hdrugs (fold mic)difference log cfu/ml at6 h24 hcro (1) + tel (2)-2.9-4.4cro (1) + tel (1)-2.5-4.4cro (1) + tel (1/2)-2.7-4.4cro (1/2) + tel (2)-2.8-4.4cro (1/2) + tel (1)-2.8-4.1cro (1/2) + tel (1/2)-1.6-4.9cro (1/4 )+ tel (2)-2.4-4.4cro (1/4 )+ t

11、el (1)-0.21.3cro (1/4 )+ tel (1/2)1.5-0.9journal of antimicrobial chemotherapy (2005) 55, 7883steroid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 modelantibioticscsf/serum peak csf/serum troughceftriaxone without dmx 5.5/275 (2.1%) 2.7/28 (13.8%)

12、with dmx 5.6/228 (2.5%) 2.1/29 (7.9%)vancomycin without dmx 1.6/29 (5.3%) 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;38:1320-4effect of dexamethasone on

13、therapy of experimental penicillin- and cephalosporin-resistant pneumococcal meningitisantimicrobial agents and chemotherapy 1994;38:1320-4experimental study of teicoplanin alone in the therapy of resistant pneumococcal meningitisteicoplanintecicoplanin + dexcsfmax1.090.930.320.22csfmin0.250.170.050

14、.07log cfu/ml 6h-2.660.66-2.750.82log cfu/ml 24h-3.390.55-4.010.69journal of antimicrobial chemotherapy (2005) 55, 7883pharmacodynamic parameter and csf bactericidal activityo csf bacteria killing rate n t mbclinear correlationn cpeak/mbcnonlinear correlationn auc/mbc nonlinear correlationantimicrob

15、ial agents and chemotherapy 1997;41:2414-2417根据pk/pd特性的抗菌药物分类 和替考拉宁：替考拉宁： long serum half life (88182 hrs)teicoplanin plus ceftazidime in the treatment of bacterial meningitis - a case reporto 男性，37岁，非何杰金氏恶性淋巴瘤（侵犯纵膈，肝，肺，颈淋巴结）o 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o 数日后病人出现呕吐，发热39，癫痫大发作；2天后幻觉，急躁易怒。o 怀疑颅内浸润，

16、腰穿：淋巴细胞少，中性粒细胞多，o 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)：255o 治疗：替考拉宁0.4 q12h，一天后0.2 q12h +头孢他啶3.0 q12h ivo 次日症状改善，3天后退热o 疗程15天，颅内感染治愈teicoplanin plus ceftazidime in the treatment of bacterial meningitis - a case reportkrcmery v jr,et al.infec

17、tion.1991;19(4)：255替考拉宁为替考拉宁为g+細菌性細菌性脑脑膜炎治疗首膜炎治疗首选选o 不受激素之影响而降低杀菌力o 为長效型药物，最符合治疗脑膜炎之药物动力学要求o 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颅内感染：万古霉素治疗失败后的替考拉宁挽救性治疗o 3例儿童患者，颅内分流装置术后出现感染o 2例表皮葡萄球菌，1例肠球菌o 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。o 再改用： teicoplanin 负荷量6 mg/kg，继而 12 mg/k

18、g/day，iv，14天。o 替考拉宁快速有效，耐受性好。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 meningitis2