11.Antimicrobialagents ppt for microbiology.pptx

It's microbiology

1. CHAPTER 11 ANTIMICROBIAL AGENTS DR SONAL SAXENA DR ARPITA SAXENA

2. ANTIBIOTICS AND ANTIMICROBIALS ‘ Antimicrobial ’ is a broad term that is used for all agents that act against different types of microorganisms, namely bacteria (antibacterial), viruses (antiviral), fungi (antifungal), and parasites (antiparasitic). Antibiotics refer to compounds that are produced by microorganisms and act against other microorganisms F our major sites in the bacterial cell that antibiotics act on: - Cell wall - Cell membrane - Nucleic acid - Ribosome

3. ANTIBIOTICS Bactericidal An antibiotic, which in optimum dose, kills the target bacteria Bacteriostatic An antibiotic, which in appropriate dose, inhibits the growth of bacteria but does not kill them

4. MECHANISMS OF ACTION OF ANTIBIOTICS ON BACTERIAL CELL Sites and targets of antimicrobial action on bacterial cells ( Source: Image 14. 9. https://openstax.org/books/microbiology/ pages/14-3-mechanisms-of-antibacterial-drugs)

5. MECHANISMS OF ACTION OF ANTIBIOTICS ON BACTERIAL CELL 1. Inhibition of cell wall synthesis 2. Inhibition of protein synthesis 3. Inhibition of nucleic acid synthesis i ) Inhibition of precursor synthesis ii) Inhibition of DNA synthesis iii) Inhibition of mRNA synthesis 4. Action on bacterial cell membrane

6. Table 11.2 Common antibiotics used in clinical practice

7. Table 11.2 Common antibiotics used in clinical practice

8. Intrinsic resistance Property shared universally within a bacterial species. It is independent of previous antibiotic exposure and is not related to horizontal gene transfer. It occurs due to reduced permeability of the outer membrane and due to the natural activity of efflux pumps in bacteria .

9. ANTIMICROBIAL RESISTANCE 2. Acquired resistance: B y mutation/acquisition of resistance genes from other organisms - Production of enzymes that destroy the antibacterial d rug - Expression of efflux systems - Reduction of permeability of (mutation of porin proteins) - Modification of the drug’s target site - Production of an alternative metabolic pathway

10. ANTIMICROBIAL RESISTANCE Fig. 11.3 Mechanisms of antibiotic resistance by a bacterium ( Source: image 14.18: https://openstax.org/books/microbiology/ pages/14-5-drug-resistance

11. GENETIC MECHANISMS OF DRUG RESISTANCE IN BACTERIA 1. Mutation 2. Genetic transfer 3. Physical mechanisms Decreased permeability to the drug Development of alternative metabolic pathways Production of enzymes that inactivate the drugs Table 11.4 Comparison of mutational and transferable drug resistance

12. GENETIC MECHANISMS OF DRUG RESISTANCE IN BACTERIA Mutational resistance i ) Stepwise mutation: penicillin ii) ‘ One-step’ mutation : streptomycin Clinical implication- mutational resistance: tuberculosis Genetic t ransfer 1. Vertical gene transfer 2. Horizontal gene transfer: i ) Conjugation ii) Transformation iii) Transduction iv) Transposons v) Plasmids

13. GENETIC MECHANISMS OF DRUG RESISTANCE IN BACTERIA Plasmid-mediated transferable drug resistance - Mediated by the R factor - Due to the production of degrading enzymes - L evel of resistance is usually high - Multiple drug resistance

14. ANTIBIOTIC SENSITIVITY TESTS Diffusion tests - Kirby–Bauer disc diffusion method - Stokes disc diffusion method - E-test Dilution tests - Broth dilution method - Agar dilution method Automated systems

15. ANTIBIOTIC SENSITIVITY TESTS DIFFUSION TESTS A ntibiotic is allowed to diffuse through a solid medium D isc diffusion method uses filter paper discs, 6.0 mm in diameter, impregnated with appropriate concentrations of the antibiotic Fig. 11.4 Antibiotic sensitivity tests

16. ANTIBIOTIC SENSITIVITY TESTS Kirby–Bauer method Most used Zones of inhibition around the discs are recorded and interpreted G uidelines issued by - Clinical and Laboratory Standards Institute ( CLSI ) - European Committee on Antimicrobial Susceptibility Testing ( EUCAST ) Fig. 11.4 Zones of inhibition around antibiotic discs on the lawn culture of the test bacterium: (a) sensitive strain (b) resistant strain ( Source: Department of Microbiology, Pondicherry Institute of Medical Sciences, Puducherry) and (c) schematic diagram of the Kirby–Bauer disc diffusion test ( Source: https://commons.wikimedia.org/wiki/File:Zones_of_Inhibition.png)

17. ANTIBIOTIC SENSITIVITY TESTS Stokes method Comparison of zone of inhibition of control with test bacteria susceptible bacteria Intermediately susceptible Resistant bacteria E-test Quantitative diffusion gradient M inimum inhibitory concentration (MIC) - lowest concentration of the gradient at which the bacterial growth has been inhibited , is obtained Fig. 11.5 Diffusion of an antibiotic disc in a medium

18. ANTIBIOTIC SENSITIVITY TESTS Fig. 11.6 Stokes method of testing for antibiotic susceptibility Fig. 11.7 MIC of colistin by E-test for Pseudomonas aeruginosa —the ellipsoidal zone of inhibition has a cut-off where the zone meets the strip incorporated with gradient concentration of the antibiotic (MIC is 1.5 μ g /mL) ( Source: Department of Microbiology, Pondicherry Institute of Medical Sciences, Puducherry)

19. ANTIBIOTIC SENSITIVITY TESTS

20. ANTIBIOTIC SENSITIVITY TESTS AUTOMATED METHODS TO DETECT ANTIBIOTIC SUSCEPTIBILITY Automated microtitre plates ii) VITEK system Fig. 11.9 VITEK system for rapid identification of bacteria and determining the MIC levels of a set of antibiotics for an organism ( Source: Centre for Virology and Molecular Biology, Pushpagiri Institute of Medical Sciences and Research Centre, Thiruvalla , Kerala)

21. ANTIBIOTIC POLICY G uides the treating physician on the most appropriate antibiotic to be used empirically in a particular infection P olicy should be based on: - Data of the susceptibility patterns of common - pathogens causing infection in the hospital - periodic antibiogram pattern - Information regarding the emergence of resistance to a particular antibiotic

22. ANTIBIOTIC STEWARDSHIP T he optimal selection, dosage, and duration of antimicrobial treatment that results in the best clinical outcome for the treatment or prevention of infection, with minimal toxicity to the patient and minimal impact on subsequent resistance . T o reduce inappropriate treatment Core elements of the antibiotic stewardship programme - Management support - Physician - Pharmacist

23. ANTIBIOTIC STEWARDSHIP ‘Antibiotic time-out’ after 48 hours Tracking—monitoring antibiotic prescription and resistance patterns Calculating the antibiotic utilisation/consumption Reporting Educating clinicians regarding resistance and optimal prescription Strategies of antibiotic stewardship 1. The front-end or pre-prescription approach 2. Back-end or post-prescription approach

24. STRATEGY FOR INITIATING ANTIMICROBIAL TREATMENT Empiric therapy Therapy is initiated when the microorganism causing the infection is not known Definitive (targeted) therapy T reatment is organism-specific Prophylaxis P reventing an infection

25. ANTIVIRAL AGENTS TARGETS FOR DRUG ACTION Attachment of virus to host cells Uncoating of the viral genome Viral nucleic acid synthesis Synthesis of viral proteins Assembly of the virus Release of virus particles Fig. 11.11 Target sites of action of antiviral drugs on the viral cell ( Source: https://openstax.org/books/microbiology/ pages/14-4-mechanisms-of-other-antimicrobial-drugs)

26. ANTIVIRAL AGENTS Table 11.8 Common antiviral agents and their sites of action

27. ANTIVIRAL AGENTS MECHANISMS OF ACTION 1. Inhibition of nucleic acid synthesis i) Viral nucleoside and nucleotide analogues- inhibit nucleic acid synthesis ii) Reverse transcriptase 2. Inhibition of protein synthesis by protease inhibitors Other mechanisms include: (i) prevention of entry of virus into the cell and (ii) inhibition via interferons, which prevent viral replication

28. ANTIVIRAL AGENTS TYPES OF ANTIVIRAL AGENTS

29. INTERFERONS P roteins—members of the cytokine family—that are coded by the host and that inhibit viral replication - Produced very quickly (within hours) in response to viral infection - Non-specific defence - Acts protective to other cells (not synthesising cell) - Host species-specific Virus mechanisms to counteract interferons - Block the induction of expression of IFN - Block IFN -included signal transduction - Neutralise IFN - l

30. RESISTANCE TO ANTIVIRAL AGENTS an emerging problem Eg : resistance of HIV to antiretroviral therapy - necessitated the use of multiple drugs and the maintainance of a first line and a second line of antiretroviral therapy (ART). If the viral load remains static or goes up despite treatment, it is inferred that the antiviral agent is ineffective against that virus

31. ANTIFUNGAL AGENTS Table 11.9 Common antifungal agents used to treat fungal infections

32. ANTIFUNGAL AGENTS Fig. 11.12 Antifungal agents and their modes of action ( Source: https://openstax.org/books/microbiology/ pages/14-4-mechanisms-of-other-antimicrobial-drugs)

33. ANTIFUNGAL AGENTS Susceptibility testing is done for some yeasts and moulds by the following methods: - Disc diffusion tests - Microbroth dilution methods - E-test (gradient MIC)

34. ANTIPARASITIC DRUGS Table 11.10 Common parasitic infections and the preferred treatment

35. ANTIPROTOZOAL DRUGS 1. Antiamoebic and Antigiardial Agents Lumina l amoebicides act on parasites in the lumen: iodoquinol, paromomycin and diloxanide furoate Systemic amoebicides (metronidazole and tinidazole) : Management of extra-intestinal Amoebiasis Mixed amoebicides : M etronidazole and tinidazole

36. ANTIMALARIAL AGENTS Chloroquine: It acts by inhibiting nucleic acid synthesis and heme detoxification; treatment of uncomplicated malaria Quinine: Complicated P. falciparum malaria Artemisinin derivatives: C hloroquine-resistant uncomplicated P. falciparum malaria Amodiaquine: C hloroquine-resistant uncomplicated P. falciparum malaria Atovaquone-proguanil, Pyrimethamine- sulfadoxine

37. ANTIPARASITIC DRUGS 3. Antileishmanials and Trypanocidal Agents Sodium stibogluconate Meglumine antimoniate Benznidazole Nifurtimox Pentamidine Suramin Eflornithine Melarsoprol

38. ANTIHELMINTHIC AGENTS Albendazole and mebendazole Diethylcarbamazine: Pyrantel pamoate Ivermectin Praziquantel

39. OTHER AGENTS WITH ANTIPARASITIC ACTIVITY Table 11.11 Antibacterial agents and their use in parasitic diseases