Antimicrobial medicines   Principles of chemotherapy Antibiotics
Disinfection  <ul><li>is the process that reduces the number of potential pathogens on a material until they no longer rep...
Asepsis  <ul><li>asepsis refers to any practice that prevents the entry of infectious agents onto sterile tissues and thus...
Antisepsis  <ul><li>is the complex of procedures of growth inhibition and reproduction potential pathogenic microorganisms...
Categories antimicrobial agents based on their appsication  Antibiotic Preserva-tive  Sanitizer  Antiseptic Disinfec-tant ...
The action of antimicrobial agents  Cationic detergents  Inactivates viruses so that they lose the ability to replicate Vi...
Antimicrobial agents Can kill or inhibit reproduction of agents of disease in the patient organism. Have selective influen...
Classification of disinfectants based on their mode of action Phenolics, quaternary ammonium compounds (surface-active age...
Chemotherapy  <ul><li>is a method of therapy of infectious disease and cancer with chemical agents – chemotherapeutic medi...
Chemotherapeutic index  <ul><li>Maximal tolerated dose   is the most quantity  of drug that not cause harmful effect  in a...
Paul Ehrlich’s principles of chemotherapy  <ul><li>Receptor interaction of drug and microorganism </li></ul><ul><li>Changi...
Community interactions   Mutualism  Commensalism  Parasitism  Antagonism (competition) Synergism   Predation
Antagonism (ammensalism)  Antagonism  is a form interaction between organisms when one microorganisms inhibits development...
Antibiotic   <ul><li>Chemotherapeutic preparation produced by living organisms  or their synthetic analogs that can select...
Characteristics of successful antimicrobial drugs  <ul><li>Great activity against microbes  </li></ul><ul><li>Selectively ...
Classification based on type of antibiotic action  <ul><li>Microbistatic (bacteriostatic, fungistatic) agents prevent the ...
Categories based on group of organisms that produce of antibiotics   Polmyxyn  Bacteria  Lysocim  Animals  Imanin, salvin,...
Classification of antibiotics based on spectrum of action  <ul><li>Narrow-spectrum   agents are effective against a limite...
Primary sites of action of antimicrobic drugs
Modes of action of antimicrobial medicines  Amphotericin B, nystatin  Antifungal activity  Polymyxin  Antibacterial activi...
Types of cell wall synthesis inhibition <ul><li>Inhibit polymerization of peptidoglican  </li></ul><ul><ul><li>Penicillins...
Inhibition of cell wall synthesis
Mode of action of antibiotics that inhibit protein synthesis
Mode of action of antibiotics that inhibit protein synthesis  Clindami-cin  Primarily bacteriostatic Blocks peptide bond f...
Alteration of cell membrane function  Polymyxin  Cytoplasm  Membrane   The detergent action of polymyxin
Microbial resistance to drugs  is a possibility of microorganisms to grow and in presence of antibiotic
Specific mechanisms of drug resistance <ul><li>Synthesis of enzymes that inactivate the drug (a) </li></ul><ul><li>Decreas...
Types of drug resistance <ul><ul><li>Natural  </li></ul></ul><ul><ul><li>Acquired  </li></ul></ul><ul><ul><ul><li>Mutation...
Natural selection and drug resistance
Suppression and alteration of the normal microflora by antimicrobics
Method of testing for the drug susceptibility of microorganisms  <ul><li>Qualitative. Diffusion methods  </li></ul><ul><li...
Diffusion test for investigation of susceptibility of microorganisms to antibiotics
Tube dilution test  Minimal inhibitory dose (MID)  is a lowest concentration of drug that inhibits the growth  of the micr...
Antiviral therapy Ribavarin  Respiratory syncytial  Amantadine  Influenza A Dideoxyinosine, zidovudine Human immunodeficie...
Modes of action of antiviral medicines Inhibit viral DNA synthesis by reacting with DNA polymerases  Acyclovir, ribavarin,...
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Bohomolets Microbiology Lecture #7

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  • Disinfection is complex of measures that are directed to prevention spread of microorganisms which can be agent of disease. Disinfection, refers to the use of a physical process or a chemical agent (a disinfectant) to destroy vegetative pathogens but not bacterial endospores. It is important to note that disinfectants are normally used only on inanimate objects because, in the concentration required to be effective, they can be toxic to human and other animal tissue.
  • Aseptic techniques commonly practiced in health care range from sterile methods that exclude all microbes to antisepsis.
  • In antisepsis, chemical agents called antiseptics are applied directly to exposed body surfaces (skin and mucous membrane), wounds, and surgical incisions to destroy or inhibit vegetative pathogens. Examples of antisepsis include preparing the skin before surgical incision with iodine compounds
  • Antimicrobial agents used to control microbial growth and prevent infections. A disinfectant is a chemical used for disinfection of inanimate objects, whereas an antiseptics is a disinfectant that is nontoxic enough to be used on human tissue. Washing hands with soap for prevention of microorganisms penetration into organism. Applying antiseptic to wound for prevention of sepsis. To clean skin surfaces with ethanol before giving injections to prevent infection through breaks in the skin Sanitization. Может ли в норме содержать ( contain) питьевая вода мо ?
  • A germicide can be used on inanimate (nonliving) materials or on living tissue, but it ordinarily cannot kill resistant microbial cells.
  • Surface-active agents (detergents) like soap reduce the surface tension of liquids. They act against many vegetative bacteria by attacking the cytoplasmic membrane.
  • As a characteristic of the quality of medicinal preparation, Paul Ehrlich introduced the chemotherapeutic index which is the ratio of the maximal tolerated dose to the minimal therapeutic (curative) dose. The chemotherapeutic index should not be less than 3.
  • Paul Ehrlich have provided principled of chemotherapy.
  • Whenever complex mixtures of organisms associate, they develop various dynamic interrelationships based on nutrition and shared habitant. Community interactions that have beneficial, harmful, or neutral effects. When mutualism two members required each other for survival. In contrast, commensalism is one-side and independent. It second microorganism take benefit, first microorganism receives no profit. Parasitism is an intimate relationship whereby a parasite derives its nutrients and habitant or kill susceptible species sharing its habitat. In synergism , two organisms that are usually independent cooperate to break down a nutrient neither one could have metabolized alone. A predator is a form of consumer that actively seeks out and ingests live prey (protozoa that prey on algae and bacteria).
  • Antagonism occurs when one population produces a substance inhibitory to another population. The production of antibiotics, for example, can give the antibiotic-producing population an advantage over a sensitive strain when competing for the same nutrient resources.
  • Antibiotics are substances produced by the natural metabolic processes of some microorganisms that can inhibit or destroy other microorganisms. Other antimicrobial substances, termed synthetic drugs, are derived in the laboratory from dyes or other organic compounds. Although separation into these 2 categories has bee traditional, they tend to overlap, because many antibiotics are now chemically altered in the laboratory. There are semisynthetic antibiotics.
  • Peptidoglican (murein) Drugs such as penicillins and cephalospirins reach with one or more of the enzymes required to complete process of peptidoglycan synthesize, causing the cell to develop weak points at growth sites and to become osmotically fragile. Most of these antibiotics are active only in young, actively growing cells, because old, inactive cells do not synthesize murein.
  • Chloramphenicol can be either bactericidal or bacteriostatic, depending on the organism
  • After passing through the cell wall of gram-negative bacteria, polymyxin binds to the cell membrane and disrupts its structure.
  • In general, a microorganism loses its sensitivity to a drug by expressing genes that stop the action of the drug. Gene expression takes the form of:…….. beta-lactamases hydrolyze the beta-lactam ring structure of some penicillins and cephalosporins. The resistance of some bacteria can be due to a mechanism that prevents the drug from entering the cell and acting on its target. For example, the outer membrane of the cell wall of certain gram-negative bacteria is a natural blockade for some of the penicillin drugs. Resistance to the tetracyclines can arise from plasmid-encoded proteins that pump the drug out of the cell. Because most drugs act on a specific target such as protein, RNA, DNA, or membrane structure, microbes can circumvent drugs by altering the nature of this target. Erythromycin and clindamycin resistance is associated with an alteration on the 5OS ribosomal binding site. The action of antimetabolites can be circumvented if a microbe develops an alternative metabolic pathway or enzyme Some bacteria can become resistant indirectly by lapsing into dormancy, or, in the case of penicillin, by converting to a cell-wall-deficient form (L-form) that penicillin cannot affect.
  • Natural resistance depends on absence of target for antibiotic. For ins. Mycoplasma is not sensitive to penicillin because do not have cell wall with murein. Mutation, recombination and plasmid- and transponos-mediated resistance are based on changes in genetic material and can be transferred from one bacterium to another. Chromosomal resistance is due to a mutation is the gene that codes for either the target of the drug or the transport system in the membrane that controls the uptake of the drug. The frequency of spontaneous mutations usually is one mutational cell among to billion of intact cells. It is much lower than the frequency of plasmid-mediated resistance. Therefore, chromosomal resistance is less of a clinical problem than is plasmid-mediated resistance.
  • Any large population of microbes is likely to contain a few individual cells that are already drug-resistant because of prior mutations or transfer of plasmids ( a). As long as the drug is not present in the habitat, the numbers of these resistant forms will remain low because they have no particular growth advantage. But if the population is subsequently exposed to this drug ( b), sensitive individuals are inhibited or destroyed, and resistant forms survive and proliferate. During subsequent population growth, all offspring of these resistant microbes will inherit this drug resistance. In time, the population will become completely resistant (figure c). In ecological terms, the environmental factor (in this case, the drug) has put selection pressure on the population, allowing the more &amp;quot;fit&amp;quot; mi­crobe (the drug-resistant one) to survive, and the population has evolved to a condition of drug resistance. Natural selection for drug-resistant forms is apparently a common phenomenon. It takes place most frequently in various natural habitats, laboratories, and medical environments, but it occasionally occurs within the bodies of humans and animals during drug therapy
  • Most normal, healthy body surfaces, such as the skin, large intestine, oral cavity provide numerous habitats for a virtual &amp;quot;garden&amp;quot; of microorganisms. These normal colonists or residents, called the flora* or microflora, consist mostly of harmless or beneficial bacteria, but some can be potential pathogens. If a broad-spectrum antimicrobic is introduced into the host to treat infection, it will destroy microbes regardless of their roles in the ecological balance, affecting not only the targeted infectious agent but also many others in sites far removed from the original infection. In some cases, the result of this therapy is the destruction of beneficial resident species and the subsequent survival and overgrowth of opportunistic residents or contaminants that can be agent of disease.
  • The Kirby-Bauer technique is an agar diffusion test that provides useful semiquantitative data on antimicrobic susceptibility. In this test, the surface of a plate of special medium is covered completely with the test bacterium, and small discs containing a antimicrobic are dispensed onto the bacterial lawn. After 18 to 24 hours of incubation at 37°C, the zone of inhibition surrounding the discs is measured and compared with a standard for each drug . The profile of antimicrobic sensitivity, or antibiogram, provides data for drug selection. An advantage of the Kirby-Bauer procedure is that many drugs can be tested simulta­neously in a single plate.
  • More sensitive and quantitative results can be obtained with tube dilution tests. First the antimicrobic is diluted serially in containers of broth, and then each tube is inoculated with a small uniform sample of pure culture. After incubation for 18-24 hours, the tubes are examined for growth. The smallest concentration of drug that visibly inhibits growth is called the minimum inhibitory concentration, or MIC.
  • Bohomolets Microbiology Lecture #7

    1. 1. Antimicrobial medicines Principles of chemotherapy Antibiotics
    2. 2. Disinfection <ul><li>is the process that reduces the number of potential pathogens on a material until they no longer represent a hazard. </li></ul>
    3. 3. Asepsis <ul><li>asepsis refers to any practice that prevents the entry of infectious agents onto sterile tissues and thus prevent infection </li></ul>
    4. 4. Antisepsis <ul><li>is the complex of procedures of growth inhibition and reproduction potential pathogenic microorganisms on skin of mucous membrane </li></ul>
    5. 5. Categories antimicrobial agents based on their appsication Antibiotic Preserva-tive Sanitizer Antiseptic Disinfec-tant Term Penicillin, tetracycline Agent produced by microorganisms that inhibits or kills other microorganisms Lactic acid, benzoic acid, sodium chloride Agents that prevents microbial growth: often added to products such as foods and cosmetics to prevent microbial growth Ethanol A disinfectant that is used to reduce numbers of bacteria to levels judged safe by public health officials Soap, hydrogen peroxide, iodine, ethanol Agent that kills of prevents the growth of microorganisms on lining tissues Hypochlorite, formaldehyde Agent that kills microorganisms on inanimate objects Examples Description
    6. 6. The action of antimicrobial agents Cationic detergents Inactivates viruses so that they lose the ability to replicate Virucide Glutaraldehyde Agent that kills bacterial endospores Sporicide Formaldehyde, silver, mercury Chemical agent that specifically kills pathogenic microorganisms Germicide (microbicide) Ethanol Agent that kills fungi Fungicide Hypochlorite Agent that kills living organisms Biocide Chlorhexidine, ethanol Agent that kills bacteria Bactericide Examples Action Term
    7. 7. Antimicrobial agents Can kill or inhibit reproduction of agents of disease in the patient organism. Have selective influence upon microorganisms. Chemotherapeutic medicines Can kill or inhibit growth and development majority of microorganisms in space around patient, and microorganisms that are on human body surface Disinfectants and antiseptics
    8. 8. Classification of disinfectants based on their mode of action Phenolics, quaternary ammonium compounds (surface-active agents) Destroys cell membrane Halogens: iodine, iodophors, chlorine, chlorine compoynds Oxidize proteins Formaldehyde, glutaraldehyde, alcohols, dyes, mercurials, acids Coagulate proteins Type of disinfectant Mode of action
    9. 9. Chemotherapy <ul><li>is a method of therapy of infectious disease and cancer with chemical agents – chemotherapeutic medicines </li></ul>
    10. 10. Chemotherapeutic index <ul><li>Maximal tolerated dose is the most quantity of drug that not cause harmful effect in a patient . </li></ul><ul><li>Minimal curative dose is the least dose of drug that kill of inhibit reproduction of microorganisms </li></ul>Maximal tolerated dose Minimal curative dose > 3
    11. 11. Paul Ehrlich’s principles of chemotherapy <ul><li>Receptor interaction of drug and microorganism </li></ul><ul><li>Changing of chemical structure of drug causes change of its activity </li></ul><ul><li>Changing of drug structure can occur in microorganism’s cell, therapeutic effect can slacken or intensify during it </li></ul><ul><li>Microbes can develop drug resistance to medicine </li></ul><ul><li>The drug can be used only if its chemotherapeutic index is not less three. </li></ul>
    12. 12. Community interactions Mutualism Commensalism Parasitism Antagonism (competition) Synergism Predation
    13. 13. Antagonism (ammensalism) Antagonism is a form interaction between organisms when one microorganisms inhibits development of others <ul><li>Mechanisms of antagonism: </li></ul><ul><li>Competition for nutrient substrate (different spread of growth) </li></ul><ul><li>Excretion of acids, alcohols, ammonia by microorganisms-antagonist </li></ul><ul><li>Excretion antibiotics, bacteriocines by microorganisms-antagonist </li></ul><ul><li>Predation </li></ul>
    14. 14. Antibiotic <ul><li>Chemotherapeutic preparation produced by living organisms or their synthetic analogs that can selectively inhibit disease agents or inhibit growth tumor cells in patient organism </li></ul>
    15. 15. Characteristics of successful antimicrobial drugs <ul><li>Great activity against microbes </li></ul><ul><li>Selectively toxic to the microbe but nontoxic to host cells </li></ul><ul><li>Microbicidal rather than mocrobistatic </li></ul><ul><li>Relatively soluble and functions even when highly diluted in body fluids </li></ul><ul><li>Remains potent long enough to act and is not broken down or excreted prematurely </li></ul><ul><li>Not subject to the debelopment of antimicrobial resistance </li></ul><ul><li>Complements or assists the activities of the host’s defenses </li></ul><ul><li>Remains active despite the presence of large volumes of organic materials </li></ul><ul><li>It is readily delivered to the site of infection </li></ul><ul><li>Does not disrupt the host’s health by causing allergies or predisposing the host to other infections </li></ul>
    16. 16. Classification based on type of antibiotic action <ul><li>Microbistatic (bacteriostatic, fungistatic) agents prevent the growth of microorganisms (bacteria, fungi) </li></ul><ul><li>Microbicidal agent (bactericide, virucide, fungicide) kills microorganisms (bacteria, viruses, fungi) </li></ul>
    17. 17. Categories based on group of organisms that produce of antibiotics Polmyxyn Bacteria Lysocim Animals Imanin, salvin, Plants Streptomycin , tetracycline Actinomycetes Penicillin , cephalosporin Fungi Antibiotics Producers
    18. 18. Classification of antibiotics based on spectrum of action <ul><li>Narrow-spectrum agents are effective against a limited array of different microbial types ( examples: bacitracin inhibit certain gram-positive bacteria ) </li></ul><ul><li>Broad-spectrum agents are active against a wider range of different microbes ( example – tetracycline that affect upon gram-positive and gram-negative bacteria, rickettsias, mycoplasmas) </li></ul>
    19. 19. Primary sites of action of antimicrobic drugs
    20. 20. Modes of action of antimicrobial medicines Amphotericin B, nystatin Antifungal activity Polymyxin Antibacterial activity Alteration of cell membrane function Rifampin Inhibition of RNA synthesis Quinolones Inhibition of DNA synthesis Sulfonamides, trimethoprim Inhibition of nucleotide synthesis Inhibition of nucleic acid synthesis Chloramphenicol, erythromycin Inhibition of protein synthesis Penicilins, cephalosporins Inhibition of cell wall synthesis Drugs Mechanism of action
    21. 21. Types of cell wall synthesis inhibition <ul><li>Inhibit polymerization of peptidoglican </li></ul><ul><ul><li>Penicillins </li></ul></ul><ul><ul><li>Cephalosporins </li></ul></ul><ul><ul><li>Carbapenems </li></ul></ul><ul><ul><li>Monobactams </li></ul></ul><ul><li>Inhibit the synthesis of dipeptide </li></ul><ul><ul><li>Cycloserine </li></ul></ul><ul><li>Inhibit transport of murein components to the assembly place </li></ul><ul><ul><li>Bacitracin </li></ul></ul><ul><li>Block the formation of precursors subunit (muramic acid, pentapeptide, and slucosamine) </li></ul><ul><ul><li>Vancomycin </li></ul></ul>
    22. 22. Inhibition of cell wall synthesis
    23. 23. Mode of action of antibiotics that inhibit protein synthesis
    24. 24. Mode of action of antibiotics that inhibit protein synthesis Clindami-cin Primarily bacteriostatic Blocks peptide bond formation 50 S Erythro- mycin Primarily bacteriostatic Blocks translocation 50 S Chloram-phenicol Both Blocks peptidyltransferase 50 S Tetracyc-lines Bacteriostatic Blocks tRNA binding to ribosome 30 S Aminogly-cosides Bactericidal Blocks functioning of initiation complex and causes misreading of mRNA 30 S Example Type of action Mode of action Riboso-mal subunit
    25. 25. Alteration of cell membrane function Polymyxin Cytoplasm Membrane The detergent action of polymyxin
    26. 26. Microbial resistance to drugs is a possibility of microorganisms to grow and in presence of antibiotic
    27. 27. Specific mechanisms of drug resistance <ul><li>Synthesis of enzymes that inactivate the drug (a) </li></ul><ul><li>Decrease in cell permeability and uptake of the drug </li></ul><ul><li>Change in the number or affinity of the drug receptor sites </li></ul><ul><li>Modification of an essential metabolic pathway (b) </li></ul>
    28. 28. Types of drug resistance <ul><ul><li>Natural </li></ul></ul><ul><ul><li>Acquired </li></ul></ul><ul><ul><ul><li>Mutation </li></ul></ul></ul><ul><ul><ul><li>Recombination </li></ul></ul></ul><ul><ul><ul><li>Transferred with plasmids and transposons </li></ul></ul></ul>
    29. 29. Natural selection and drug resistance
    30. 30. Suppression and alteration of the normal microflora by antimicrobics
    31. 31. Method of testing for the drug susceptibility of microorganisms <ul><li>Qualitative. Diffusion methods </li></ul><ul><li>Quantitative. Method of serial dilutions </li></ul>
    32. 32. Diffusion test for investigation of susceptibility of microorganisms to antibiotics
    33. 33. Tube dilution test Minimal inhibitory dose (MID) is a lowest concentration of drug that inhibits the growth of the microorganisms.
    34. 34. Antiviral therapy Ribavarin Respiratory syncytial Amantadine Influenza A Dideoxyinosine, zidovudine Human immunodeficiency Acyclovir, foscarnet Herpes simplex  -interferon Hepatitis B or C Ganciclovir, foscarnet Cytomegalovirus Medication Virus
    35. 35. Modes of action of antiviral medicines Inhibit viral DNA synthesis by reacting with DNA polymerases Acyclovir, ribavarin, ganciclovir Inhibits reverse transcriptase by attaching to its phosphate receptors Foscarnet Inhibits function of viral mRNA or degrades mRNA  -interferon Prevents assembly of the viral core protein Amantadine Mode of action Medicine

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