Clinical Uses of Antimicrobial AgentsClinical Uses of Antimicrobial AgentsSan- San-HuaHua FangFang, PhD, PhD方三华方三华Dept. of Pharmacology, Dept. of Pharmacology, School of Medicine, Zhejiang UniversitySchool of Medicine, Zhejiang Universityfshfbzxhqzju.edu.cnfshfbzxhqzju.edu.cn1. 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 principlesBasic principlesEmpiricEmpiricTherapyTherapy Vast majority of all antimicrobial therapyVast majority of all antimicrobial therapy Should be approached rationallyShould be approached rationally SyndromeSyndrome Likely pathogensLikely pathogens Known resistance patternsKnown resistance patterns Host factorsHost factorsIdentification of Infecting OrganismIdentification of Infecting Organism Staining of clinical specimensStaining of clinical specimens Gram stain, Acid-fast stain, silver stains Antigen detection (e.g. ELISA)Antigen detection (e.g. ELISA) Nucleic acid detection (e.g. PCR)Nucleic acid detection (e.g. PCR) Culture methodsCulture methods Obtain culture material prior to antimicrobial therapy, if possiblei in brothn brothpharmacological factors include: A. 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 principlesBasic principlesBactericidal vs Bacterostatichost factors include: A. Site of infection B. the age and pregnancy status C. Hepatic or renal function D. The functional state of host defense mechanism E. Individual variationBasic principlesBasic principlesHost FactorsHost Factors Site of infectionSite of infection Adequate concentrations of antimicrobials must be delivered to the site of infection Local concentrations greater than MIC ExcretionExcretion Urine Aminoglycosides, fluoroquinolones Bile Ceftriaxone(头孢曲松头孢曲松) Penetration into various sitesPenetration into various sites Central nervous system Lung BoneHost FactorsHost Factors AgeAge 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 growthHost FactorsHost 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 ImmunocompromiseResistance Patterns Antibiograms Local patterns of susceptibility Hospital, state, countryProportion of invasion S. Proportion of invasion S. aureusaureus isolatesresistantisolatesresistant to to oxacillinoxacillin(or equivalent) EARSS,2004 (or equivalent) EARSS,2004A. Formulate a clinical diagnosis of microbial infection B. Obtain specimens for laboratory examination C. Formulate a microbiologic diagnosis D. Determine the necessity for empirical therapy E. Institute treatmentTherapeutic applications of Anti- infectivesThe uses of antimicrobial agents is strictly controlled in: A. Viral infections B. Fever caused by unidentified reasons C. Topical applications D. Antimicrobial prophylaxis E. 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 infectionsProphylaxis use of Anti-infectives Surgical prophylaxisNational 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) AppendectomyProphylaxis use of Anti-infectivesAntimicrobial agents combinationsAntimicrobial agents combinations?Antimicrobial agents combinationsAntimicrobial agents combinationsAccordi