抗菌药(Clinical_Uses_of_Antimicrobial Agents——方三华

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Clinical Uses of Antimicrobial Agents,San-,Hua,Fang,PhD,方三华,Dept.of Pharmacology,School of Medicine,Zhejiang University,1.Formulating a pathogenic diagnosis early,which depends on clinical diagnosis,microbiologic diagnosis and testing results,in vitro,.,2.Choiceness of antimicrobial agents depends on pharmacological factors and host factors.,3.The uses of antimicrobial agents is strictly controlled in some situations.,Basic principles,Empiric,Therapy,Vast majority of all antimicrobial therapy,Should be approached rationally,Syndrome,Likely pathogens,Known resistance patterns,Host factors,Identification of Infecting Organism,Staining of clinical specimens,Gram stain,Acid-fast stain,silver stains,Antigen detection(e.g.ELISA),Nucleic acid detection(e.g.PCR),Culture methods,Obtain culture material prior to antimicrobial therapy,if possible,i,n broth,pharmacological factors include:,kinetics of absorption,distribution,and elimination;,Bacteriostatic,vs,bactericidal activity,concentration-dependent killing,(,eg,.,aminoglycosides,and,quinolones,),time-dependent killing,(,eg,.,b,-lactams,and,vancomycin,);,C.the potential toxicity of an agent;,D.,pharmacodynamic,or pharmacokinetic interaction with other drugs.,Basic principles,Bactericidal,vs,Bacterostatic,host factors include:,Site of infection,the age and pregnancy status,Hepatic or renal function,The functional state of host defense mechanism,Individual variation,Basic principles,Host Factors,Site of infection,Adequate concentrations of antimicrobials must be delivered to the site of infection,Local concentrations greater than MIC,Excretion,Urine,Aminoglycosides,fluoroquinolones,Bile,Ceftriaxone,(,头孢曲松,),Penetration into various sites,Central nervous system,Lung,Bone,Host Factors,Age,Gastric acidity low in young children and elderly,Renal,hepatic function vary with age,Dose adjustment for,creatinine,clearance and hepatic dysfunction is critical to avoid toxicities,Developing bone and teeth,Tetracyclines,stain teeth,Quinolones,may impair bone and cartilage growth,Host Factors,Genetic and metabolic abnormalities,Isoniazid,acetylation,varies greatly,G-6-PD deficiency and risk of,hemolysis,Sulfonamides,nitrofurantoin,Pregnancy,Teratogenicity,and other toxicity to the fetus,Other toxic reactions(lactic acidosis,pancreatitis),Excretion in breast milk,Immunocompromise,Resistance Patterns,Antibiograms,Local patterns of,susceptibility,Hospital,state,country,Proportion of invasion S.,aureus,isolatesresistant,to,oxacillin,(or equivalent)EARSS,2004,Formulate a clinical diagnosis of microbial infection,Obtain specimens for laboratory examination,Formulate a microbiologic diagnosis,Determine the necessity for empirical therapy,Institute treatment,Therapeutic applications of,Anti-,infectives,The uses of antimicrobial agents is strictly controlled in:,Viral infections,Fever caused by unidentified reasons,Topical applications,Antimicrobial prophylaxis,Antimicrobial agents combinations,Therapeutic applications of,Anti-,infectives,Nonsurgical prophylaxis,1)Rheumatic fever(,风湿热,),2)Meningococcal infection,3)Tuberculosis,4)Newborn,ophthalmia,(,新生儿眼炎,),5)Malaria(,疟疾,),6)Urinary tract infections,Prophylaxis use of,Anti-,infectives,Surgical prophylaxis,National research council expected infection,wound classification criteria rate,Clean 2%,Clean contaminated 10%,Contaminated about 20%,Dirty about 40%,Prophylaxis use of,Anti-,infectives,Surgical prophylaxis,1)Cardiac operation,2),Noncardiac,thoracic operation,3)Vascular(abdominal and lower extremity),operation,4)Head and neck operation,5),Gastroduodenal,or,biliary,operation,6)Orthopedic,operation(with,hardware insertion),7)Penetrating trauma,8)Burn wound,9)Colorectal operation,10)Appendectomy,Prophylaxis use of,Anti-,infectives,Antimicrobial agents combinations,?,Antimicrobial agents combinations,According to their actions,antimicrobial agents,can be classified:,bactericidal,agents for growing bacteria,bactericidal,agents for resting bacteria,fast,b,acteriostatic,agents,slow,b,acteriostatic,agents,Antimicrobial agents combinations,According to their actions,antimicrobial agents,can be classified:,bactericidal,agents for growing bacteria,bactericidal,agents for resting bacteria,fast,b,acteriostatic,agents,slow,b,acteriostatic,agents,+:synergism,+:antagonism,+:addition or indifference,+:addition,Mechanism of synergistic action:,Blockade of sequential steps in a metabolic sequence,Inhibition of enzymatic inactivation,Enhancement of antimicrobial agent uptake,Inhibition of different resistant strain respectively,Two is better than one?,Empiric therapy,Polymicrobial,infection,Increase efficacy-synergism,Prevent emergence of resistance,Combination therapy,Mycobacterium tuberculosis,HIV,Pseudomonas,aeruginosa,?Invasive,aspergillosis,（,侵入性曲霉菌病,）,Antimicrobial agents combinations,Antimicrobial agents dosing in patients with hepat