Bohomolets Microbiology Lecture #7

Antimicrobial medicines

Principles of chemotherapyAntibiotics

Disinfection

is the process that reduces the number of potential pathogens on a material until they no longer represent a hazard.

Asepsis

asepsis refers to any practice that prevents the entry of infectious agents onto sterile tissues and thus prevent infection

Antisepsis

is the complex of procedures of growth inhibition and reproduction potential pathogenic microorganisms on skin of mucous membrane

Categories antimicrobial agents based on their appsication

Term Description Examples

Disinfec-tant

Agent that kills microorganisms on inanimate objects

Hypochlorite, formaldehyde

Antiseptic Agent that kills of prevents the growth of microorganisms on lining tissues

Soap, hydrogen peroxide, iodine, ethanol

Sanitizer A disinfectant that is used to reduce numbers of bacteria to levels judged safe by public health officials

Ethanol

Preserva-tive

Agents that prevents microbial growth: often added to products such as foods and cosmetics to prevent microbial growth

Lactic acid, benzoic acid, sodium chloride

Antibiotic Agent produced by microorganisms that inhibits or kills other microorganisms

Penicillin, tetracycline

The action of antimicrobial agents

Term Action Examples

Bactericide Agent that kills bacteria Chlorhexidine, ethanol

Biocide Agent that kills living organisms

Hypochlorite

Fungicide Agent that kills fungi Ethanol

Germicide (microbicide)

Chemical agent that specifically kills pathogenic microorganisms

Formaldehyde, silver, mercury

Sporicide Agent that kills bacterial endospores

Glutaraldehyde

Virucide Inactivates viruses so that they lose the ability to replicate

Cationic detergents

Antimicrobial agents

Disinfectants and antiseptics

Can kill or inhibit growth and development majority of microorganisms in space around patient, and microorganisms that are on human body surface

Chemotherapeutic medicines

Can kill or inhibit reproduction of agents of disease in the patient organism. Have selective influence upon microorganisms.

Classification of disinfectants based on their mode of action

Mode of action Type of disinfectant

Coagulate proteins Formaldehyde, glutaraldehyde, alcohols, dyes, mercurials, acids

Oxidize proteins Halogens: iodine, iodophors, chlorine, chlorine compoynds

Destroys cell membrane

Phenolics, quaternary ammonium compounds (surface-active agents)

Chemotherapy

is a method of therapy of infectious disease and cancer with chemical agents – chemotherapeutic medicines

Chemotherapeutic index

Maximal tolerated dose is the most quantity of drug that not cause harmful effect in a patient.

Minimal curative dose is the least dose of drug that kill of inhibit reproduction of microorganisms

Maximal tolerated dose

Minimal curative dose> 3

Paul Ehrlich’s principles of chemotherapy

Receptor interaction of drug and microorganism Changing of chemical structure of drug causes change of its activity Changing of drug structure can occur in microorganism’s cell, therapeutic effect can slacken or intensify during it Microbes can develop drug resistance to medicine The drug can be used only if its chemotherapeutic index is not less three.

Community interactions

Mutualism

Commensalism

Parasitism

Antagonism (competition)

Synergism

Predation

Antagonism (ammensalism)

Antagonism is a form interaction between organisms when one microorganisms inhibits development of others

Mechanisms of antagonism:

Competition for nutrient substrate (different spread of growth)

Excretion of acids, alcohols, ammonia by microorganisms-antagonist

Excretion antibiotics, bacteriocines by microorganisms-antagonist

Predation

Antibiotic

Chemotherapeutic preparation produced by living organisms or their synthetic analogs that can selectively inhibit disease agents or inhibit growth tumor cells in patient organism

Characteristics of successful antimicrobial drugs

Great activity against microbes Selectively toxic to the microbe but nontoxic to host cells Microbicidal rather than mocrobistatic Relatively soluble and functions even when highly diluted

in body fluids Remains potent long enough to act and is not broken down

or excreted prematurely Not subject to the debelopment of antimicrobial resistance Complements or assists the activities of the host’s

defenses Remains active despite the presence of large volumes of

organic materials It is readily delivered to the site of infection Does not disrupt the host’s health by causing allergies or

predisposing the host to other infections

Classification based on type of antibiotic action

Microbistatic (bacteriostatic, fungistatic) agents prevent the growth of microorganisms (bacteria, fungi)

Microbicidal agent (bactericide, virucide, fungicide) kills microorganisms (bacteria, viruses, fungi)

Categories based on group of organisms that produce of antibiotics

Producers Antibiotics

Bacteria Polmyxyn

Fungi Penicillin, cephalosporin

Actinomycetes Streptomycin, tetracycline

Plants Imanin, salvin,

Animals Lysocim

Classification of antibiotics based on spectrum of action

Narrow-spectrum agents are effective against a limited array of different microbial types (examples: bacitracin inhibit certain gram-

positive bacteria)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)

Primary sites of action of antimicrobic drugs

Modes of action of antimicrobial medicines

Mechanism of action Drugs Inhibition of cell wall synthesis Penicilins,

cephalosporins

Inhibition of protein synthesis Chloramphenicol, erythromycin

Inhibition of nucleic acid synthesis

Inhibition of nucleotide synthesis Sulfonamides, trimethoprim

Inhibition of DNA synthesis Quinolones

Inhibition of RNA synthesis Rifampin

Alteration of cell membrane function

Antibacterial activity Polymyxin

Antifungal activity Amphotericin B, nystatin

Types of cell wall synthesis inhibition

Inhibit polymerization of peptidoglican Penicillins Cephalosporins Carbapenems Monobactams

Inhibit the synthesis of dipeptide Cycloserine

Inhibit transport of murein components to the assembly place

Bacitracin

Block the formation of precursors subunit (muramic acid, pentapeptide, and slucosamine)

Vancomycin

Inhibition of cell wall synthesis

Mode of action of antibiotics that inhibit protein synthesis

Mode of action of antibiotics that inhibit protein synthesis Riboso-mal subunit

Mode of action Type of action

Example

30 S Blocks functioning of initiation complex and causes misreading of mRNA

Bactericidal Aminogly-cosides

30 S Blocks tRNA binding to ribosome

Bacteriostatic Tetracyc-lines

50 S Blocks peptidyltransferase Both Chloram-phenicol

50 S Blocks translocation Primarily bacteriostatic

Erythro- mycin

50 S Blocks peptide bond formation

Primarily bacteriostatic

Clindami-cin

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

Synthesis of enzymes that inactivate the drug (a)

Decrease in cell permeability and uptake of the drug Change in the number or affinity of the drug receptor sites

Modification of an essential metabolic pathway (b)

Types of drug resistance

Natural

Acquired Mutation

Recombination

Transferred with plasmids and transposons

Natural selection and drug resistance

Suppression and alteration of the normal microflora by antimicrobics

Method of testing for the drug susceptibility of microorganisms

Qualitative. Diffusion methods

Quantitative. Method of serial dilutions

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 microorganisms.

Antiviral therapy

Virus Medication

Cytomegalovirus Ganciclovir, foscarnet

Hepatitis B or C -interferon

Herpes simplex Acyclovir, foscarnet

Human immunodeficiency

Dideoxyinosine, zidovudine

Influenza A Amantadine

Respiratory syncytial

Ribavarin

Modes of action of antiviral medicines

Medicine Mode of action

Amantadine Prevents assembly of the viral core protein

-interferon Inhibits function of viral mRNA or degrades mRNA

Foscarnet Inhibits reverse transcriptase by attaching to its phosphate receptors

Acyclovir, ribavarin, ganciclovir

Inhibit viral DNA synthesis by reacting with DNA polymerases