MCB2004 Exam 4 Study Guide Lecture 26 27 Antimicrobial drug I II Terminology Basis for 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 Peptidoglycan Differences in ribosome structure Biochemical pathways absent in human May have side effects at high concentration Chloramphenicol interferes with eukaryotic ribosome At high levels interferes with red blood cell development Some may cause allergic response Antibiotics are foreign substances in our bodies Bactericidal and bacteriostatic antibiotics Most antibiotics come from the group Actinomycetes Spectrum of activity Broad spectrum Effective against many species Narrow spectrum Effective against few or a single species Source of antibiotics Most discovered as natural products Often modified by artificial means Increase efficacy decrease toxicity to humans The first antibiotic penicillin history and derivatives 1928 Fleming discovered penicillin produced by Penicillium 1940 Howard Florey and Ernst Chain performed first clinical trials of penicillin used for gram positive bacteria The actions modes or targets of antimicrobial drugs Inhibition of Nucleic acid replication and transcription Inhibition of cell wall synthesis Inhibition of protein synthesis Inhibition of synthesis of essential metabolites Injury to the plasma membrane Inhibitors of nucleic acid replication and transcription Rifamycin Quinolones Fluoroquinolones Ciprofloxacin Inhibitors of cell wall synthesis Inhibitors of protein synthesis Cephalosporins Bacitracin Vancomycin Isoniazid thambutol Chloramphenicol Aminoglycosides Tetracyclines Macrolides Oxazolidinones Inhibitors of synthesis of essential metabolites Sulfonamides Trimethroprim Injury to plasma membrane Polymyxin B Testing Antibiotic Efficacy Disk diffusion test E test Broth dilution test Kirby Bauer disk diffusion test Test strain sensitivity to multiple antibiotics Multiple disks with different antibiotics Size of cleared zones reflects relative sensitivity E test determines Minimum inhibitory concentration Gradient of antibiotic in paper strip Drug must be above MIC Minimum Inhibitory Concentration in tissue in order to be effective Broth Dilution Test Can dilute the bacteria to determine what concentration of bacteria can be inhibited by antibiotics Antibiotic Resistance Mechanisms and causes A variety of mutations can lead to antibiotic resistance Resistance genes are often on plasmids or transposons that can be transferred between bacteria Nature of resistance comes from DNA mutation Misuse of antibiotics selects for resistance mutants Misuse includes Using outdated or weakened antibiotics Using antibiotics for the 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 used to target viruses Protease inhibitors o Oseltamivir Tamiflu Zanamivir neuraminidase inhibitor for o Indinavir HIV Inhibit attachment Influenza o CCR5 inhibitor for HIV o Fusion inhibitor for HIV Inhibit uncoating o Amantadine Influenza Interferons prevent spread of viruses to new cells Viral hepatitis Lecture 28 Microbial Disease of the skin and eyes Structure and function of the skin and mucous membrane Normal skin microbiota Staphylococcus Streptococcus Diphtheroids and some yeast Normal flora 1 Gram positive bacteria 1 Staphylococcus Low GC Gram 2 Streptococcus Low GC Gram 3 Diphtheroids coryneforms eg Propionibacterium acnes High GC Gram anaerobic inhabit hair follicles Can withstand drying fatty acids low pH high salt 2 Some yeasts Staphylococcus Gram low GC cocci in clusters Coagulase an enzyme clots fibrin in blood majority of skin flora consists of coagulase S epidrmidis all pathogenic S aureus are Coagulase Pathogenic S aureus also produce extracellular enzymes and toxins Staphylococcus skin infections Cause Folliculitis furuncles boils carbuncles Toxemias occur when toxins enter bloodstream Scalded skin syndrome Toxic shock syndrome Streptococcus 1 Gram Low GC cocci in chains 2 Hemolysins beta alpha and gamma hemolysis 3 Classified into groups according hemolytic enzymes and surface antigens 1 Group A most important 2 Groups B C O 4 Many virulence factors M protein extracellular enzymes and toxins 5 M protein on surface anti complement anti phagocytosis 6 Cause 1 2 Erysipelas Impetigo isolated pustules Streptococcus skin infections Streptokinases Hyaluronidase Exotoxin A superantigen Cellulitis Necrotizing fasciitis flesh eating Pseudomonas and skin infections 1 Gram negative aerobic rods 1 Five groups 2 Unusual metabolism grow on traces of organic substance in soap liner adhesive 2 Environmental soils and water 3 Opportunists medical devices contact solutions 4 Cause 1 Dermatitis self limiting 2 wks swimming pool sauna hot tub 2 Wound and skin infections 3 Otitis externa swimmer s ear 4 Burn patient infections 5 Infections have a characteristic of blue green pus Pyocyanin Viral skin infections warts cold sores chickenpox shingles smallpox measles rubella Warts Papilloma virus Fever blisters herpes simplex Herpes Latency Recurrent lesions Chickenpox shingles VZV Herpes Latency Painful dermal infections dermatomes Smallpox Variola virus Pox Paramyxovirus rubeola Measles Togavirus rubella German measles Herpes Viruses Varicella zoster virus VZV Transmitted by the respiratory route Causes pus filled vesicles Virus may remain latent in dorsal root ganglia Herpes Simplex Virus 1 HSV 1 and HSV 2 Human herpes virus 1 and HHV 2 Cold sores or fever blisters vesicles on lips HSV 1 can remain latent in trigeminal nerve ganglia HSV 2 can remain latent in sacral nerve ganglia Shingles Reactivation of latent VZV releases viruses that move along peripheral nerves to skin Postherpetic neuralgia Prevention Live attenuated vaccine Measles Rubeloa Measles virus Paramyxoviruses Transmitted by respiratory route Prevented by vaccination MMR Rubella German Measle Rubella virus Togavirus Macular rash and fever Prevented by vaccination MMR Bacterial Diseases of the eye Conjunctivitis An inflammation of the conjunctiva Also called pinkeye or red eye Commonly caused by Haemophilus influenzae Eye infections Neisseria gonorrhoeae o Gram negative o Transmitted to a newborn s eyes during passage through the birth canal o Prevent by ophthalmic ointment antibiotics at birth
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