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株细菌金葡菌12（ MRSA3）CoNS6 （ MR3）中性葡萄球菌2链球菌1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 15.8%金葡 10.4%肠球菌 6.0%溶葡 3.3%其他 15.3%神经外科术后颅内感染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 41 CoNS 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o19972007年，50 例颅内感染，23例在 感染前有 1次颅内手 术金葡菌18MR 2MS 10CoNS 6 链球菌 2Shervin R Dashti,et al.Operative intracranial infection following craniotomy. Neurosurg Focus.2008,24 (6):E10,1-5 原则：Treatment of Bacterial Meningitiso在腰穿后尽快开始抗生素治疗o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CSF中有较高浓度的杀菌剂o必要时应用激素o当病原菌确定后，选择更有针对性的抗生素o必要时复查CSF。Bactericidal vs Bacteristatic AgentsoBactericidal agentsnB-LactamsnGlycopeptideoBacteriostatic agents (i.e. Clindamycin or TCN) n Inadequate for meningitisIndication for bacteriocidal antibioticsoMeningitisoEndocarditisoOsteomyelitis ?oFebrile neutropeniaCSF Antibiotic LevelsoMost drugs achieve peak concentrations in the CSF equal to 10-20% of serum levelsoCSF inflammation increases drug penetrationEmpiric TreatmentoOptimal concentration of antibiotic for killing is 30 times the MBC (animal models)o3rd Generation CephalosporinsnCeftriaxonenCefotaximenActivity against major pathogens (except Listeria and resistant PNC and GNRs) oGlycopeptidenResistant gram positive organismsoAmpicillinnListeriaTissue PenetrationTissue Penetration Tissue/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. 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 MeningitisoCombination with -lactam for community-acquired meningitisoMonotherapy for G(+) shunt infectionIn vitro activities of ceftriaxone and teicoplanin against S. pneumoniae at 6h and 24hDrugs (fold MIC)Difference log cfu/ml at 6 h24 h TEL (8)-0.5-4.2 TEL (2)11.4 TEL (1)2.60.8 TEL (1/2)2.51.0 CRO (2)-2.1-4.5 CRO (1)-2.2-4.4 CRO (1/2)0.50.9 CRO (1/4)1.90.3Journal of Antimicrobial Chemotherapy (2005) 55, 7883In vitro activities of ceftriaxone and teicoplanin against S. pneumoniae at 6h and 24hDrugs (fold MIC)Difference log cfu/ml at 6 h24 h CRO (1) + TEL (2)-2.9-4.4 CRO (1) + TEL (1)-2.5-4.4 CRO (1) + TEL (1/2)-2.7-4.4 CRO (1/2) + TEL (2)-2.8-4.4 CRO (1/2) + TEL (1)-2.8-4.1 CRO (1/2) + TEL (1/2)-1.6-4.9 CRO (1/4 )+ TEL (2)-2.4-4.4CRO (1/4 )+ TEL (1)-0.21.3 CRO (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%) 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 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 + DEXCSFmax1.090.930.320.22CSFmin0.250.170.050.07log 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 activityoCSF bacteria killing ratenT MBClinear correlationnCpeak/MBCnonlinear correlationnAUC/MBC nonlinear correlationAntimicrobial 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时间依赖性与时间有关，但抗菌活性持续时间较长与时间有关，但抗菌活性持续时间较长浓度依赖性浓度依赖性对致病菌的杀菌作对致病菌的杀菌作 用取决于峰浓度用取决于峰浓度抗菌作用与同细菌抗菌作用与同细菌 接触时间密切相关接触时间密切相关时间依赖且时间依赖且PAEPAE或或T T1/21/2较长较长 氨基糖苷类、氟喹诺酮类氨基糖苷类、氟喹诺酮类 、酮内酯类、两性霉素、酮内酯类、两性霉素B B 、daptomycindaptomycin、甲硝唑、甲硝唑多数多数-内酰胺类、大环内酯内酰胺类、大环内酯类、林可霉素类、恶唑烷酮类、林可霉素类、恶唑烷酮 类、氟胞嘧啶类、氟胞嘧啶链阳霉素、四环素、阿齐链阳霉素、四环素、阿齐 霉素、碳青霉烯类、霉素、碳青霉烯类、糖肽糖肽 类类、唑类抗真菌药、唑类抗真菌药 主要参数主要参数T TMICMIC和和 AUCAUCMICMIC主要参数主要参数T TMICMIC 和 AUC/MIC AUC/MIC 主要参数主要参数AUCAUC0-240-24/MIC /MIC (AUIC) (AUIC) CmaxCmax/MIC /MIC 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