Final Exam Study Guide Lectures 26 and 27 Antimicrobial Drugs Chemotherapy use of drugs to treat a disease Antimicrobial drugs interfere with growth of microbes within a host Antibiotic substance produced by a microbe that in small amounts inhibits another microbe Selective toxicity drug that kills harmful microbes without damaging host o Selective toxicity of antibiotics Affect only target organism but not humans Drug should affect microbial physiology that does not exist or is greatly modified in humans o Peptidoglycan o Differences in ribosome structure o Biochemical pathways absent in human May have side effects at high concentration o Chloramphenicol interferes with eukaryotic ribosome At high levels interferes with RBC development o Some may cause allergic response Antibiotics are foreign substances in our bodies Spectrum of activity o Broad spectrum effective against many species o Narrow spectrum effective against few or a single species o Source of antibiotics Most discovered as natural products Often modified by artificial means Increase efficacy decrease toxicity to humans Bactericidal vs bacteriostatic o Bactericidal antibiotics kill target organism Many drugs only affect growing cells Inhibitors of cell wall synthesis o Only effective if organism is building new cell wall Ex penicillin o Bacteriostatic antibiotics Prevent growth of organism Cannot kill organism Immune system removes infection Action of antimicrobial drugs Penicillins o Inhibition of cell wall synthesis penicillins cephallosporins bacitracin vancomycin Natural penicillins and semisynthetic penicillins Penicilinase resistant penicillins Extended spectrum penicillins Penicillins beta lactamase inhibitors augmentin Cephalosporins Polypeptide antibiotics 2nd 3rd and 4th generations more effective against gram negatives Bacitracin topical application against gram positives Vancomycin glycopeptide that is an important last line against antibiotic resistant S aureus Antimycobacterial antibiotics Isoniazid INH inhibits mycolic acid synthesis Ethambutol inhibits incorporation of mycolic acid o Inhibition of protein synthesis chloramphenicol erythromycin tetracyclines streptomycin Chloramphenicol binds to 50S portion and inhibits formation of peptide bond broad spectrum Broad spectrum Tetracyclines interfere with attachment of tRNA to mRNA ribosome complex Streptomycin changes shape of 30S portion causing code on mRNA to be read incorrectly broad spectrum Neomycin and gentamycin broad spectrum and change shape of 30S subunit Hearing loss side effect Macrolides gram positives Bind 50S prevents translocation Oxazolidinones linezolid Gram positives binds 50S subunit prevents formation of 70S ribosome o Inhibition of nucleic acid replication and transcription quinolones rifamycin Rifamycin inhibits RNA synthesis and is antituberculosis Quinolones nad fluoroquinolones Ciprofloxacin Inhibits DNA gyrase anti anthrax urinary tract infections o Injury to plasma membrane polymyxin B Topical combines with bacitracin neomycin in over the counter prep Neosporin o Inhibition of synthesis of essential metabolites sulfanilamide trimethoprim Sulfonamides sulfa drugs Inhibit folic acid synthesis broad spectrum First antibiotic o 1928 Fleming discovered penicillin produced by Penicillium o 1940 Howard Florey and Ernst Chain performed first clinical trials of penicillin Testing antibiotic efficacy o Kirby Bauer disk diffusion test test strain sensitivity to multiple antibiotics Multiple disks with different antibiotics Size of cleared zones reflects relative sensitivity o E test determines MIC Gradient of antibiotic in paper strip Drug must be above MIC in tissue in order to be effective o Broth dilution test Antibiotic resistance variety of mutations can lead to antibiotic resistance o Resistance genes are often on plasmids or transposons that can be transferred between bacteria o Mechanisms of resistance Inactivating enzymes Blocking entry Alteration of target molecule Efflux of antibiotic o Misuse of antibiotics selects for resistance mutants Using outdated or weakened antibiotics Using antibiotics for common cold and other inappropriate conditions Failing complete the prescribed regimen Using someone else s leftover prescription Using antibiotics in animal feed Antiviral drugs nucleoside and nucleotide analogs o Protease inhibitors Indinavir HIV o Inhibit attachment Oseltamivir Tamiflu Zanamivir neuraminidase inhibitor for Influenza CCR5 inhibitor for HIV Fusion inhibitor for HIV o Inhibit uncoating Amantadine Influenza o Interferons prevent spread of viruses to new cells viral hepatitis Lecture 28 Microbial diseases of the skin and eyes Skin anatomy o Structure and function Epidermis stratus corneum and keratin Dermis secretions by perspiration and sebum and portals of entry by follicles and ducts Subcutaneous layer Skin inhospitable to most microbes o Dry o Perspiration and sebum contain nutrients salt inhibits microbes o Lysozyme hydrolyzes peptidoglycan o Fatty acids inhibit some pathogens o Defensins are antimicrobial peptides Mucous membrane o Line body cavities o Epithelial cells are attached to an extracellular matrix o Cells secrete mucous and some cells have cilia Skin flora o Normal flora Gram positive bacterial Staphylococcus low GC o Coagulase enzyme clots fibrin in blood o Majority of skin flora consists of coagulase S epidermidis o All pathogenic S aureus are coagulase Also produce extracellular enzymes and toxins o Cause Folliculitis furuncles boils carbuncles Folliculitis infection of hair follicles Sty e folliculitis of eyelash Furuncles abscess pus surrounded by inflamed tissue Carbuncle inflammation of tissue under skin Toxemias occur when toxins in bloodstream Scalded skin syndrome Toxic shock syndrome Streptococcus low GC many prophages carry virulence factors o Hemolysins beta alpha and gamma hemolysis o Classified into groups according to hemolytic enzymes and surface antigens Group A most important Steptokinases hyaluronidase exotoxin A superantigen cellulitis necrotizing fasciitis flesh eating Group B C O o Many virulence factors M protein extracellular enzymes and toxins o M protein on surface anti complement anti phagocytosis o Cause Impetigo isolated pustles and erysipelas Diphtheroids coryneforms high GC anaerobic inhabit hair follicles Can withstand drying fatty acids low pH high salt Some yeasts Psuedomonase aeruginosa dermatitis and others Gram negative aerobic rods o 5 groups o Unusual
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