1、“The future is not what it used to be”-Yogi Berra細菌抗藥性產生有效治療病人Chinese Emperor Shen Nung(神農氏)wrote a treatise on the use of chang shan(常山）in fever.2735 BC發燒、休克意識不清感染？不需使用抗生素細菌、病毒細菌、病毒黴菌或其他黴菌或其他感染部位？泌尿道、呼吸道取得適當檢體做培養Urine,Blood,Sputum.有抗微生物藥劑可有效治療？選擇適當抗微生物藥劑否是是否Pattern of Activity Antibiotics Goal of T
2、herapy PK/PD Parameter Type IConcentration-dependent killing andProlonged persistent effects AminoglycosidesDaptomycinFluoroquinolonesKetolides Maximize concentrations 24h-AUC/MICPeak/MIC Type IITime-dependent killing and Minimal persistent effects CarbapenemsCephalosporinsErythromycinLinezolidPenic
3、illins Maximize duration of exposure TMIC Type IIITime-dependent killing andModerate to prolonged persistent effects.AzithromycinClindamycinOxazolidinonsTetracyclinesVancomycin Maximize amount of drug 24h-AUC/MISNOOOOCH2OCCH3SONCONHHNH2COSultamicillinNSNH2CHCONHHCH3CH3COOHOAmpicillinNSOOCH3CH3COOHOS
4、ulbactamEsterase1.Campoli-Richards DM,Brogden RN.Drugs 1987;33:577609.2.Friedel HA et al.Drugs 1989;37:491522.CH3COCH3CH3HWilliams JD.Int J Antimicrob Agents 1999;12(Suppl 1):S3S7.Inhibitor inactivates-lactamase-Lactam can reach penicillin-binding protein(PBP)-Lactam alone may be degraded by-lactama
5、se PBPPBPPBPWith inhibitorWithout inhibitor-Lactam-Lactamase inhibitor-Lactamase1.Marshall SA et al.Diagn Microbiol Infect Dis 1995;21:15368.2.Johnson DM et al.Diagn Microbiol Infect Dis 1996;25:13741.3.Cullman W.J Chemother 1995;7:215.1.Smayevsky J et al.Diagn Microbiol Infect Dis 2000;37:2614.2.Ma
6、rshall SA et al.Diagn Microbiol Infect Dis 1995;21:15368.Peptostreptococcusspp.81A/S,ampicillin/sulbactamaMIC90 based on ampicillin concentrationEdnie LM et al.Antimicrob Agents Chemother 1998;42:5962.NOONHCOCH3FNOH5Morpholino group enhances pharmacokinetic profile&improves water solubilityStrategic
7、ally located fluorine atom improves activityC-5 acylaminomethyl group essential5-(S)-configuration necessaryN-Aryl group requiredInitiation Factors30S ribosomemRNA50S ribosome30S+mRNAfMet-tRNAElongation Factors70S Initiation ComplexPeptide ProductElongationAminoglycosidesMacrolides StreptograminsLin
8、ezolid blocks formation of the initiation complexLinezolid MIC(mg/L)SpeciesN0.1250.250.5124S.aureus (oxacillin-R)958834S.aureus (oxacillin-S)15521449CoNS(oxacillin-R)104346541CoNS(oxacillin-S)6932937E.faecalis150221442E.faecium392361SPNE(penicillin-S)14941685431SPNE(penicillin-I)1305177632SPNE(penic
9、illin-R)481819191Streptococcus spp.80240317Conclusions:There was no difference in linezolid susceptibility betweencountries or between multiresistant and susceptible strains.Resistance tolinezolid was not detected in more the 2,000 clinical isolates in the WesternPacific.Asia-Pacific ZAPSOral bioavailability100%(based on AUC)Food effectNo effect on extent Slight decrease in rateVolume of distribution50 litersPlasma protein binding31%Elimination half-life6 hoursZyvoxTM (linezolid)Package Insert 2001
