抗菌剂化学疗法 （英文ppt）antimicrobial chemotherapy课件

Antimicrobial Chemotherapy Chemotherapy Ehrlich; chemical used to kill pathogens with no harm to host Chemotherapeutic Agents any chemical used in medicine = drugs Antimicrobial Agent special group of drugs used against microbial diseases Antibiotic Waksman chemical produced by microbes to kill or inhibit other microbes ; Synthetic ( lab made) or Semisynthetic ( part lab, part microbe) DO NOT WORK ON VIRUSES Chemotherapy History Egyptians moldy bread wounds Willow Bark aspirin - alleviate pain Foxglove digitalis - heart disease Paul Ehrlich 1st salvarsan 606 ( arsenic compound) syphilis 1910 Domagk sulfa drugs or sulfonamides prontosil Fleming penicillium ( mold) contaminant on petri plates; saw usefulness if mass produced (Chain used WWII Antimicrobial Agent Properties 1. Selective toxicity harm microbe more than host; target cell wall, ribosomes 2. Spectrum of activity Broad spectrum wide range of microbes gram positive used when patient is seriously ill can kill or inhibit normal flora , too Narrow spectrum limited type of microbes; used if microbe known; less loss of normal flora; drug resistance 3. Modes of Action A. Cell wall inhibition B. Disruption of cell membrane function C. Inhibition protein synthesis D. Nucleic acid inhibition E. Antimetabolite 4. Side Effects A. Toxicity chemicals kill microbes, no serious harm to host; (more later) B. Allergy over reaction of immune system to foreign protein; mild rash to severe anaphylactic shock C. Disruption of normal flora broad spectrum antibiotics; superinfections can result- drug resistant 5. Resistance to drugs Microbes once susceptible to antibiotic , no longer affected; many antibiotics bacteriostatic inhibit when present Resistance can be acquired by Nongenetic Evasion microbe hides in tissue , produces progeny , released progeny still susceptible to drug EX. TB Reversion no cell wall; become resistant Genetic Spontaneous mutations 1/10 million to 1/10 billion organisms Antibiotics do not induce mutations BUT can create favorable environment for mutant survival. Genetic resistance changes in bacterial chromosome - DNA mutated, one antibiotic Plasmid (s) acquiring extrachromosomal DNA 1959 Shigella R factor = Resistance plasmids Resistance to multiple antibiotics (6-7) Transferred transduction (most) , conjugation; interspecies or interstrain Mechanisms of Resistance 1. Alteration of target Bacterial ribosomes altered by DNA mutation , antimicrobial agent no longer binds; erythromycin, rifamycin, antimetabolites 2. Alteration membrane permeability Membrane transport or pores; antimicrobials cannot cross; tetracyclines, quinolones, aminoglycosides 3. Development of enzymes Beta lactamase inactivate penicillin Staphylococci, Streptococci, Gonococci Gram negative enzymes against aminoglycosides bacterial infections only, not viral; narrow spectrum ; NO ANTIBIOTICS IN ANIMAL FEED. CDC 50 M of 150 M outpatient prescriptions no need Testing Microbial Sensitivity to Antimicrobial Agents Kirby Bauer method disk diffusion Spread microbe to test over agar plate Place drug impregnated disks on agar surface; incubate; look for ZONES OF INHIBITION ( clear zones) around disks Measure zone diameters, compare to table, determine, sensitivity or resistance of microbe to drug Larger diameter more sensitive to drug Antibacterial Agents 1. INHIBITORS - CELL WALL SYNTHESIS Penicillins G - cidal 1950s S. aureus resistant semisynthetic - methicillin Others ampicillin. amoxicillin, ticarcillin, carbenicillin Choice for Streptococcus, Meningococcus, Pneumococcus, spirochaetes, Clostridia, gram positive , aerobic rods Large doses-toxic to kidney, liver, nervous system Cephalosporin fungus Cephalosporium Semisynthetic ; third generation ceftraxone, cephalexin; nosocomial infections Side effects irritation at injection site; nausea, vomiting, diarrhea Vancomycin soil bacteria actinomycete- Streptomyces orientalis Treat MRSA 5 kinds B topical; c m distorted Works well gram negative bacteria 3. INHIBITORS PROTEIN SYNTHESIS AMINOGLYCOSIDES 70S ribosome; IM or IV not oral Streptomycin Streptomyces damage kidneys, inner ear, dizziness , permanent ringing Synergistic drug with isoniazid bacteriostatic; broad spectrum Aplastic anemia reversible or irreversible Treats typhoid fever, pen. resist meningococci blocks RNA transcription, cidal; broad spectrum; Treat TB interacts with oral contraceptives Quinolones blocks bDNA gyrase DNA no unwind; synthetic Effective Travellers diarrhea bacteriostatic; block folic acid synthesis Nausea, skin rashes Septra UTI Isoniazid Bacteriostatic TB bacterium Antifungal Agents POLYENES Amphotericin B Powerful, binds to ergosterol, disrupts cell membrane glucose C albicans Antiviral Agents Inhibits viral replication but does not kill; nucleic acid synthesis target Most analogues T,A,G Erroneous nucl