9-controlofmicrobialgrowth-antimicrobialagents-210802195340.pptx

this presentation gives you the agents for antimicrobial growth

1. Definitions Chemotherapy treatment of a disease by a chemical compound selectively directed against invading microbes or abnormal cells. Or u se of drugs to treat infections and malignancy. (Antimicrobials and Antineoplastic agents). Antimicrobial any agent that kills or inhibits growth of a susceptible organism. Antibiotic a microbial product or its derivative that kills or inhibits growth of a susceptible organism. All antibiotics are antimicrobials but all antimicrobials are not antibiotics

2. Antimicrobial Drugs Antimicrobial therapy takes advantage of the biochemical differences between microorganisms and humans. Antimicrobial drugs should have selective toxicity towards the invading microorganism without harming the cells of the host. This selective toxicity is usually relative rather than absolute, requiring careful control of the drug concentration.

3. Antimicrobial Drugs Antibiotic producing microbes include: Gram-Positive Rods: - Bacillus subtilis: Bacitracin - Bacillus polymyxa : Polymyxin Fungi: - Penicillium notatum: Penicillin - Cephalosporium spp.: Cephalothin Actinomycetes: - Streptomyces venezuelae : Chloramphenicol - Streptomyces griseus: Streptomycin - Streptomyces nodosus : Amphotericin B - Micromonospora purpurea: Gentamycin

4.   Antibacterials : Relatively easy to develop and find with low toxicity because procaryotic cells are very different from host cells. Antihelminthic , antiprotozoan , and antifungal drugs: More difficult to develop because eucaryotic cells resemble human cells. Antivirals : Most difficult to develop because virus reproduces using host cell enzymes and machinery.

5. Spectrum of Antibiotic Activity Narrow Spectrum Antibiotics : Effective against a subset of bacteria (either gram positive and negative). Examples: Penicillin, Isoniazid (Mycobacteria only). Broad Spectrum Antibiotics : Effective against many different types of bacteria (e.g.: both gram positive and negative). Examples: Tetracyclin .

6. The Action of Antibiotic Drugs Bactericidal Kill microbes directly. Bacteriostatic Prevent microbes from growing.

7. Mechanisms of Antimicrobial Action Bacteria have their own enzymes for: Cell wall formation Protein synthesis DNA replication RNA synthesis Synthesis of essential metabolites. Viruses use host enzymes inside host cells. Fungi and protozoa have own eukaryotic enzymes. The more similar the pathogen and host enzymes, the more side effects the antimicrobials will have.

8. The Action of Antimicrobial Drugs Antimicrobial mechanisms of action include: Inhibition of Cell Wall Synthesis : Interfere with peptidoglycan synthesis. E.g.: Penicillin and vancomycin. Inhibition of Protein Synthesis : Interfere with procaryotic (70S) ribosomes. E.g.: Tetracyclin and erythromycin.  Injury to the Plasma Membrane : Cause changes in membrane permeability. Result in loss of metabolites and/or cell lysis. E.g.: Polymyxin B (antibacterial) or miconazole (antifungal). Inhibition of Nucleic Acid (DNA/RNA) Synthesis : Interfere with DNA replication and transcription. May be toxic to human cells. E.g.: Rifampin and quinolones. Inhibition of Synthesis of Essential Metabolites : Involve competitive inhibition of key enzymes. Closely resemble substrate of enzyme. E.g.: Sulfa drugs inhibit the synthesis of folic acid which is necessary for DNA and RNA synthesis.

9. Selection of antimicrobial agents Selection of the most appropriate antimicrobial agent requires knowing: 1) the organism’s identity 2) the organism’s susceptibility to antimicrobial agent 3) the site of the infection 4) patient factors 5) the safety of the antimicrobial agent. 6) the cost of therapy.

10. Selection of antimicrobial agents Patient factors taken into consideration when selecting an antimicrobial agent Immune system Renal dysfunction Hepatic dysfunction Poor perfusion Age Pregnancy Lactation

11. Routes of administration Oral route is chosen for mild infections, and is favorable for outpatients. Parenteral route is used for more serious infections, or when the anti-microbial agent of choice has poor GI absorption such as vancomycin, amphotericin B and aminoglycosides.

12. Determination of rational dosing Pharmacodynamics of the drug (the relationship of drug concentrations to antimicrobial effects): Concentration dependent killing Rate of microbial killing increases as the concentration increases e.g. aminoglycosides like tobramycin. Time dependent (concentration-independent) killing Increasing concentration does not increase the rate of killing e.g. β-lactams, glycopeptides, macrolides, clindamycin.

13. Drug resistance Bacteria is resistant to an antibiotic if the maximal level of the antibiotic does not stop their growth. Some organisms are inherently resistant to antibiotics Ex. Gram negative bacteria are inherently resistant to vancomycin. Or maybe due t o absent of mechanism to transport the drug into the cell or do not contain antibiotic’s target process or protein Microbial species that are normally responsive to a particular drug may develop more virulent or resistant strains through spontaneous mutation or acquired resistance by genes passing from resistant to non-resistant strain or by gene transfer mechanisms: Conjugation. Transduction. Transformation. Some organisms may become resistant to more than one antibiotic.

14. Mechanisms of Antimicrobial Resistance Modification of target sites : Alteration of an antibiotic's target site through mutation can confer organismal resistance to one or more related antibiotics. For example, S. pneumoniae . Decreased uptake or increased efflux: of an antibiotic can confer resistance, because the drug is unable to attain access to the site of its action in sufficient concentrations to injure or kill the organism Enzymic inactivation : The ability to destroy or inactivate the antimicrobial agent can also confer resistance on microorganisms.

15. Factors Promote Antimicrobial Resistance If a patient taking a course of antibiotic treatment does not complete it Or forgets to take the doses regularly. Exposure to microbes carrying resistance genes. The use of antibiotics also promotes antibiotic resistance in non-pathogens ,These non-pathogens may later pass their resistance genes into pathogens. Use of antibiotics in foods. Antibiotics for viral infections Spread of resistant microbes in hospitals due to lack of hygiene and using it extensively.

16. Prophylactic antibiotics Antibiotics use for prevention is restricted to situations where the benefit outweighs the risks of bacterial resistance and superinfections such as: Prevention of tuberculosis or meningitis among individuals who are in close contact with infected patients. Treatment prior to most surgical procedures to decrease the incidence of infection afterwards.

17. Complications of antimicrobial therapy Hypersensitivity : Penicillins can cause serious hypersensitivity problems ranging from urticaria (hives) to anaphylactic shock Direct toxicity : Aminoglycosides can cause ototoxicity by interfering with membrane function in the cells. Superinfections :Drug therapy especially broad spectrum antimicrobials can lead to alterations to the normal flora of the upper respiratory, intestinal and genitourinary tracts permitting overgrowth of opportunistic organisms like fungi or resistant bacteria.

18. Antiviral drugs Because viruses are obligate intracellular parasites, antiviral agents must be capable of inhibiting viral function without damaging the host. In general antiviral agents are very limited because of their toxicity. Antiviral chemotherapy should be chosen in such a way that they affect on the steps of replication of the virus either they inhibit entry of the virus in to the host cells or they prevent replication of the virus by inhibiting certain peptides which are responsible for viral replication.

19. Antiviral drugs Mechanisms of action include: • inhibition of virus adsorption • inhibition of virus-cell fusion • inhibition of the HIV integrase (HIV) • inhibition of viral DNA or RNA synthesis • viral protease inhibition • viral neuraminidase inhibition (influenza)

20. Antifungal drugs Also called antimycotic drugs Used to treat two types of fungal infections: superficial fungal infections skin or mucus membrane Systemic fungal infections Lungs or central nervous system

21. Antifungal drugs Groups : Polyenes :amphotericin B, Nystatin. Antimetabolic antifungal : Flucytosine Imidazoles : ketoconazole, miconazole, clotrimazole. Griseofulvin Antifungals generally kill fungi by disrupting the synthesis or function of fungal cellular membranes or by interference with intracellular functions .

22. Antihelmentic drugs According the mechanism of action Anthelmintics are divided into: 1) Cellular poisons – Tetrachloroethylene. 2) Disturbing the function of the neuromuscular apparatus in nematodes – Piperazine adipinate and Ditrazin . 3) Paralyzing neuromuscular system predominantly of flatworms (cestodes) and damaging their coating tissues –Praziquantel andNiclosamide . 4) Affecting predominantly the energy processes – Mebendazole and Levamisole.

23. Antihelmentic drugs Anthelmintics must be selectively toxic to the parasite. This is usually achieved by inhibiting metabolic processes that are vital to the parasite but not vital to or absent in the host. While the precise mode of action of many anthelmintics is not fully understood, the sites of action and biochemical mechanisms of many of them are generally known. The pharmacologic basis of the treatment for helminths generally lead to starvation, paralysis, and expulsion or digestion of the parasite.