Slide 1

Control of microbial growth Slide 2 Antimicrobial Classes Disinfectants Products aimed at reducing by at least five powers of 10 (99,999 %) the number of microorganisms/virus present on inanimate objects Antiseptics Products aimed at reducing by at least five powers of 10 (99,999 %) the number of microorganisms/virus present on live tissue Slide 3 Antimicrobial Classes (Contd) The drugs Antibiotic or Antibacterial Against bacteria Antifungal Against fungi Antiviral Against viruses Slide 4 Disinfectants and Antiseptics Ideal characteristics Broad action spectrum Powerful; low amounts required for a high efficacy Low toxicity in humans Not corrosive Stable Hydrophilic and hydrophobic Low surface tension No odor or pleasant odor Slide 5 The Drugs: Antibiotics Literal: Anti (against) biotic (life) Old def.: Any compound synthesized by a microorganism that inhibits or kills other bacteria New def.: Any compound that inhibits or kills bacteria Definitions: Slide 6 Desired Characteristics 1.High selective toxicity: Must kill or inhibit the target organism with a minimum of deleterious effects on the host Penicillin: Targets cell wall Cyanide: Target: electron transport of eukaryotes/prokaryotes Slide 7 Desired Characteristics (Contd) 2.High toxic dose (LD50) Concentration of the compound that is toxic to the host Penicillin Cyanide 3.Low therapeutic dose (MIC or MBC) Concentration of the compound required for the clinical treatment of an infection Penicillin Table salt Slide 8 The Therapeutic Index Toxic Dose/Therapeutic dose Want a therapeutic index that is? Slide 9 Action Spectrum Narrow: Efficacy restricted to only a few types of microorganisms Ex. Acts only on Gram - Broad: Efficacy is good for a wide variety of microorganisms Ex. Acts on Gram + and - Slide 10 Antibacterial targets 10 Translation Transcription AB Metabolism Protein synthesis Aminoglycosides Macrolides Tetracyclines Chloramphenicol RNA synthesis Macrolides DNA synthesis Quinolones Cell wall synthesis -lactams Slide 11 Modes of Action Bacteriocidal Kills Irreversible Bacteriolytic Kills Cell lysis Irreversible Time Direct count Viable count # Bacteriostatic: Inhibits growth Non-lethal Reversible Slide 12 The Beta-Lactams Bacteriolytic Inhibit cell wall synthesis Act only on actively growing bacteria! 12 Penicillines Cephalosporins Carbapenems Monobactams They all contain a beta lactam ring Slide 13 Quinolones Bacteriocidal Inhibit DNA synthesis Broad spectrum Side effects: Severe gastrointestinal problems Ex. Ciprofloxacin 13 Slide 14 Tetracyclines Bacteriostatic Inhibits protein synthesis Broad spectrum Side effects: Hepatic toxicity Renal toxicity Vitamin deficiency 14 Slide 15 Macrolides Bacteriostatic Inhibits protein synthesis Narrow spectrum Side effects Diarrhea Hepatic dammages Ex. Erythromycin & Clarithromycin 15 Slide 16 Aminoglycosides Bacteriocide Narrow spectrum Inhibits protein synthesis High level of toxicity Side effects: Allergies Renal dammages Deafness Ex. Gentamycin, streptomycin 16 Slide 17 Antimicrobial Therapies Empirical The infectious agent is unknown Broad spectrum antibiotic is recommended Definitive The infectious agent has been identified A specific therapy is chosen Narrow spectrum antibiotic is recommended Prophylactic Prevent an initial infection or reinfection 17 Slide 18 Kirby-Bauer Disc Diffusion Assay Agar is inoculated with test bacteria Antibiotic impregnated discs are laid on the agar The antibiotic diffuses in the medium creating a gradient Following the incubation the zones of inhibition are measured The sizes of the zones of inhibition are compared to those established to determine whether the organism is sensitive or resistant Slide 19 Inhibitory Diameters Vs Conc. 19 27mm = MIC MIC > 27mm = Conc. < MIC Gradient de concentration + - Slide 20 Determination of Efficacy MIC/MBC Minimal Inhibitory Concentration Cultures with different concentrations of antibiotic 100502512630 Minimal Bacteriocidal Concentration Sub culture without antibiotics MIC=12g/ml MBC=50g/ml Slide 21 E-test Slide 22 In Vivo Susceptibility The in vivo concentration is not constant! Influenced by human physiology A range of concentrations is maintained (C Max -C Min ) The concentration at the infection site must be higher than the MIC IfSlide 23 Sensitivity In Vivo Sensitive pathogen MIC is lower than the lowest conc. maintained in vivo Resistant pathogen MIC is higher than the highest concentration maintained in vivo Intermediate sensitivity pathogen MIC is between the lowest and the highest concentration maintained in vivo A combination of antibiotics is recommended 23 Slide 24 Example Antibiotic A conc. in vivo = 5-40g/ml Thus: MIC 5 g/ml = Sensitive MIC 40g/ml = resistant MIC between 5 -40 g/ml = intermediate sensitivity 24 Slide 25 Decimal Reduction Time D value Time required to kill 90% of microorganisms Time required to reduce the population by a factor of 10 Time required to reduce the population by one log10 Slide 26 26 1 X 10 6 1 X 10 5 1 X 10 4 1 X 10 3 # Bacteria Time (min.) 510152025303540 100 D =12min 1 log 120 D Decimal Reduction Time Slide 27 Problem At 75 o C it takes 18 min. to reduce a population of microorganisms from 10 9 to 10 6 What is the value of D 75 ? 18 minutes to go from 10 9 to 10 6 3 log 3 log = 3D 75 Therefore 3D 75 = 18minutes D 75 =6minutes