Antimicrobial agents. are chemicals active against microorganisms

Transcription

1 Antimicrobial agents are chemicals active against microorganisms

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3 Antibacterial Agents Are chemicals active against bacteria

4 Antimicrobials Antibacterial Antifungal Antiviral Antiparasitic: -anti protozoan -anti-helmintic

5 Antibacterials include Antibiotics Semisentehetic antibacterials Synthetic(sulfonamids,quinolones)

6 Antibiotic is the natural products of fungi and bacteria that kill or inhibit the growth of microorganisms

7 Selective toxicity: Was described by immunochemist Paul Ehrlich.

8 Selective toxicity Ideally the antimicrobial agent should act at a target side Present in the infecting organism But absent from host cell

9 Selective toxicity:proposed by Paul Ehrlich( )

10 Selective toxicity is more likely achievable in microorganisms which are procaryotes (bacteria) than those that are eucaryotes(fungi) because procaryotes are structurally more distinct from host cells which is eucaryotic

11 Classification of antibacterials According to whether they are bactericidal or bacteriostatic By target site(mechanisms of action) By chemical structure

12 Bactericidal antibacterials kill bacteria irreversible more effective in immunocompromised patienst

13 Bacterostatic antibacterials They only inhibit the growth of bacteria It is reversable They prevent the bacterial population from increasing Host defense mechanism can consequently cope with the static population

14 Some agents are capable of killing some bacteria And only bacteriostatic for others

15 1935:chemotherapy of systemic bacterial infections. Although antiseptics had been applied topically to prevent the growth of microorganisms, the existing antiseptics were ineffective against systemic bacterial infections. In 1935, the dye prontosil was shown to protect mice against systemic streptococcal infection and to be curative in patients suffering from such infections. It was soon found that prontosil was cleaved in the body to release p-aminobenzene sulfonamide (sulfanilamide), which was shown to have antibacterial activity. This first "sulfa" drug ushered in a new era in medicine.

16 Compounds produced by microorganisms (antibiotics) were eventually discovered to inhibit the growth of other microorganisms. For example, Alexander Fleming was the first to realize the mold Penicillium prevented the multiplication of staphylococci. A concentrate from a culture of this mold was prepared, and the remarkable antibacterial activity and lack of toxicity of the first antibiotic, penicillin, were demonstrated. Streptomycin and the tetracyclines were developed in the 1940s and 1950s, followed rapidly by the development of additional aminoglycosides, semisynthetic penicillins, cephalosporins, quinolones, and other antimicrobials. All these antibacterial agents greatly increased the range of infectious diseases that could be prevented or cured.

17 Although the development of new antibacterial antibiotics has lagged in recent years, some new classes of agents have been introduced, including the ketolides (e.g., telithromycin), glycylcyclines (tigecycline), lipopeptides (daptomycin), streptogramins (quinupristin-dalfopristin), and oxazolidinones (linezolid).

18 Unfortunately, with the introduction of new chemotherapeutic agents, bacteria have shown a remarkable ability to develop resistance. Thus antibiotic therapy will not be the magical cure for all infections, as predicted; rather, it is only one weapon, albeit an important one, against infectious diseases. It is also important to recognize that because resistance to antibiotics is often not predictable, physicians must rely on their clinical experience for the initial selection of empirical therapy. Guidelines for the management of infections caused by specific organisms are discussed.

19 Antibacterial Agents Mechanisms of action Antibacterial spectrum Common mechanisms of resistance

20 The five main target sites for antibacterial action are: Cell wall synthesis Protein synthesis Nucleic acid synthesis Methabolic pathways Cell membrane function

21 Classification according to mechanisms of action Inhibitors of cell wall synthesis Inhibitors of protein synthesis Inhibitors of nucleic acid synthesis Antimetabolites Inhibitors of cytoplasmic membrane function

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24 Antibacterial spectrum Range of activity of an antimicrobial against bacteria Broad spectrum: inhibits a wide variety of gram-positive and gram-negative bacteria Narrow spectrum: active against a limited variety of bacteria : Vancomycin

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26 Antibiotic combinations To broaden the spectrum for empirical therapy or treatment of polymicrobial infections To prevent the emergence of resistant microorganisms To achieve a synergistic killing effect

27 Antibiotic combinations A good example is the treatment of tuberculosis

28 Antibiotic synergism: Antibiotic antagonism:

29 A)Synergism B)Antagonism

30 Antibacterial agents Sulfonamide Penicillin (Flemming) Streptomycin Tetracyclin...and many others

31 Despite the rapidity of the introduction of new chemotherapeutics Development of resistance!!!

32 In vitro antimicrobial susceptibility testing Selects the active chemotherapeutic agent

33 Susceptibility tests Disc diffusion Dilution tests

34 Disc diffusion

35 Disc diffusion test result

36 Dilution test

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38 Resistance 1-Genetic bases of resistance 2-Biochemical mechanism of resistance

39 1-Genetic basis of resistance Mutation of cellular genes Acquisition of resistance genes Mutation of acquired genes

40 Biochemical mechanism of resistance Modification of the antibiotic: such as betalactamases Modification of the target molecule Restricted access to the target Efflux pumps

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