替考拉寧治療腦膜炎

1、替考拉寧治療G+顱內(nèi)感染的療效,浙江省中醫(yī)院ICU 江榮林,開顱手術(shù)后顱內(nèi)感染細(xì)菌,28例38株細(xì)菌,趙崗等，28例開顱術(shù)后顱內(nèi)感染病原學(xué)分析和臨床治療，第三軍醫(yī)大學(xué)學(xué)報，2011；33（2）：208-209,NICU顱內(nèi)感染細(xì)菌,183株細(xì)菌,舒凱等，神經(jīng)外科重癥監(jiān)護病房顱內(nèi)感染的臨床調(diào)查，中華醫(yī)院感染學(xué)雜志2010，20（1）：53-54,神經(jīng)外科術(shù)后顱內(nèi)感染,裘天侖,等，神經(jīng)外科術(shù)后顱內(nèi)感染相關(guān)因素分析與預(yù)防對策，中華醫(yī)院感染

2、學(xué)雜志，2009，19（19）：2553-2555,開顱手術(shù)后顱內(nèi)感染,薈萃分析國內(nèi)36篇文章，43766例，顱內(nèi)感染1137例，617株細(xì)菌（陽性率55.41%）,金葡菌 159表葡 41CoNS 29腸球菌 3肺炎鏈球菌 7鏈球菌 4,靳桂明等，開顱手術(shù)后顱內(nèi)感染流行病學(xué)調(diào)查的薈萃分析，中國臨床神經(jīng)外科雜志，2007，12（3）：149-151,顱腦手術(shù)后感染,Shervin R Da

3、shti,et al.Operative intracranial infection following craniotomy. Neurosurg Focus.2008,24 (6):E10,1-5,顱腦手術(shù)后感染,1997~2007年，50例顱內(nèi)感染，23例在感染前有﹥1次顱內(nèi)手術(shù),金葡菌18 MR 2 MS 10 CoNS 6鏈球菌 2,Shervin R Dashti,et al.Operative intrac

4、ranial infection following craniotomy. Neurosurg Focus.2008,24 (6):E10,1-5,原則：Treatment of Bacterial Meningitis,在腰穿后盡快開始抗生素治療經(jīng)驗性應(yīng)用抗生素治療前作血培養(yǎng)經(jīng)驗性應(yīng)用抗生素應(yīng)選擇在CSF中有較高濃度的殺菌劑必要時應(yīng)用激素當(dāng)病原菌確定后，選擇更有針對性的抗生素必要時復(fù)查CSF。,Bactericidal v

5、s Bacteristatic Agents,Bactericidal agentsB-LactamsGlycopeptideBacteriostatic agents (i.e. Clindamycin or TCN) Inadequate for meningitis,Indication for bacteriocidal antibiotics,MeningitisEndocarditisOsteomyelitis

6、 ?Febrile neutropenia,CSF Antibiotic Levels,Most drugs achieve peak concentrations in the CSF equal to 10-20% of serum levelsCSF inflammation increases drug penetration,Empiric Treatment,Optimal concentration of antibi

7、otic for killing is 30 times the MBC (animal models)3rd Generation CephalosporinsCeftriaxoneCefotaximeActivity against major pathogens (except Listeria and resistant PNC and GNRs) GlycopeptideResistant gram positi

8、ve organismsAmpicillinListeria,Tissue PenetrationTissue/Serum (%),61%,~40%,~20%,Peritoneal dialysis fluid,94%,~40%,~30%,Muscle,104%,77%,20~30%,Inflammatory blister fluid,415%,,11%–17%,ELF,70%,~10%,0%–18%,CSF,60%,~50%–

9、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、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 β-lactam for community-acquired

11、 meningitisMonotherapy for G(+) shunt infection,In vitro activities of ceftriaxone and teicoplanin against S. pneumoniae at 6h and 24h,Journal of Antimicrobial Chemotherapy (2005) 55, 78–83,In vitro activities of ceftri

12、axone and teicoplanin against S. pneumoniae at 6h and 24h,Journal of Antimicrobial Chemotherapy (2005) 55, 78–83,Steroid對抗生素穿透腦膜及腦膜內(nèi)殺菌能力之影響,Steroid effect on antibiotics CSF penetration a rabbit pneumococcal meningitis

13、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

14、/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%),,,,Antimicr

15、obial Agents and Chemotherapy 1994;38:1320-4,,Effect of dexamethasone on therapy of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis,Antimicrobial Agents and Chemotherapy 1994;38:1320-4,Experi

16、mental study of teicoplanin alone in the therapy of resistant pneumococcal meningitis,Journal of Antimicrobial Chemotherapy (2005) 55, 78–83,Pharmacodynamic parameter and CSF bactericidal activity,CSF bacteria killing ra

17、te T> MBClinear correlationCpeak/MBCnonlinear correlationAUC/MBCnonlinear correlation,Antimicrobial Agents and Chemotherapy 1997;41:2414-2417,根據(jù)PK/PD特性的抗菌藥物分類,時間依賴性,與時間有關(guān)，但抗菌活性持續(xù)時間較長,濃度依賴性,,,,,,,對致病菌的殺菌作用取決

18、于峰濃度,抗菌作用與同細(xì)菌接觸時間密切相關(guān),時間依賴且PAE或T1/2較長,,,,,,,氨基糖苷類、氟喹諾酮類、酮內(nèi)酯類、兩性霉素B、daptomycin、甲硝唑,多數(shù)β-內(nèi)酰胺類、大環(huán)內(nèi)酯類、林可霉素類、惡唑烷酮類、氟胞嘧啶,鏈陽霉素、四環(huán)素、阿齊霉素、碳青霉烯類、糖肽類、唑類抗真菌藥,,,,主要參數(shù)T>MIC和AUC>MIC,主要參數(shù)T>MIC 和AUC/MIC,主要參數(shù)AUC0-24/MIC (AUIC)

19、 Cmax/MIC,替考拉寧： Long serum half life (88~182 hrs),Teicoplanin plus Ceftazidime in the Treatment of Bacterial Meningitis - A Case Report,男性，37歲，非何杰金氏惡性淋巴瘤（侵犯縱膈，肝，肺，頸淋巴結(jié)）為預(yù)防顱內(nèi)病灶，鞘內(nèi)注射氨甲嘌呤、胞密啶、激素5次+頭顱放療數(shù)日后病人出現(xiàn)嘔吐，發(fā)熱39℃，癲癇

20、大發(fā)作；2天后幻覺，急躁易怒。懷疑顱內(nèi)浸潤，腰穿：淋巴細(xì)胞少，中性粒細(xì)胞多，培養(yǎng)：腸球菌（萬古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,治療：替考拉寧0.4 q12h，一天后0.2 q12h +頭孢他啶3.0 q12h IV次日癥狀改善，3天后退熱療程15天，顱內(nèi)感染治愈,Tei

21、coplanin plus Ceftazidime in the Treatment of Bacterial Meningitis - A Case Report,Krcmery V Jr,et al.Infection.1991;19(4)：255,替考拉寧為G+細(xì)菌性腦膜炎治療首選,不受激素之影響而降低殺菌力為長效型藥物，最符合治療腦膜炎之藥物動力學(xué)要求與頭孢三代合并使用有相乘之殺菌效果,G+顱內(nèi)感染：萬古霉素治療失敗后的替考

22、拉寧挽救性治療,3例兒童患者，顱內(nèi)分流裝置術(shù)后出現(xiàn)感染2例表皮葡萄球菌，1例腸球菌先：vancomycin負(fù)荷量15 mg/kg，繼而 50 mg/kg/day，iv，治療7~10天，臨床和微生物學(xué)均無效。再改用： teicoplanin 負(fù)荷量6 mg/kg，繼而 12 mg/kg/day，iv，14天。替考拉寧快速有效，耐受性好。,Jourdan C, et al. Adequate intrathecal diffusio

23、n 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 expe

24、rimental MRSA meningitis,,,,,20 mg/kg vancomycin q12h，6 mg/kg teicoplanin q12h,Oguz Resat Sipahi，et al. International Journal of Antimicrobial Agents 26 (2005) 412–415,Vancomycin versus teicoplanin in the therapy of expe

25、rimental MRSA meningitis,Oguz Resat Sipahi，et al. International Journal of Antimicrobial Agents 26 (2005) 412–415,Meningitis due to methicillin-resistant Staphylococcus aureus(MRSA): Review of 10 cases

26、 (療程：23.5±18.8 days 【range, 3–60 days】）,Bilgin Arda,et al. International Journal of Antimicrobial Agents 25 (2005) 414–418,替考拉寧治療MRSA腦膜炎優(yōu)勢總結(jié),長效藥物、殺菌劑，符合腦膜炎治療要求不受激素影響而降低療效（研究表明萬古霉素可能會受到影響）藥物聯(lián)合使用可以提高藥效（多篇文獻報道替考拉寧+