2.  Antimicrobial agents share certain common properties.  We can learn much about how these agents work and why they sometimes do not work by considering such properties as: o selective toxicity, o spectrum of activity, o mode of action, o side effects, o resistance of microorganisms to them.

3. 1.Selective Toxicity:  Some chemical substances with antimicrobial properties are too toxic to be taken internally and are used only for topical application—application to the skin’s surface.  For internal use, an antimicrobial drug must have selective toxicity—that is, it must harm the microbes without causing significant damage to the host.

4. 2.The Spectrum of Activity : The range of different microbes against which an antimicrobial agent acts is called its spectrum of activity. The spectrum of activity is divided to: a)Broad spectrum of activity b)Narrow spectrum of activity

5. Broad spectrum of activity : Those agents that are effective against a great number of microorganisms from a wide range of taxonomic groups, including both Gram-positive and Gram-negative bacteria. Narrow spectrum of activity : That are effective against only a small number of microorganisms

6.  A broad-spectrum drug is especially useful when a patient is seriously ill with an infection caused by an unidentified organism. Using such a drug increases the chance that the organism will be susceptible to it.  However, if the identity of the organism is known, a narrow spectrum drug should be used.

7. Mode of action: It is always desirable to know the mode of action of an agent. Five different modes of action of antimicrobials are discussed here: 1. inhibition of cell wall synthesis, 2. Disruption of cell membrane function, 3. inhibition of protein synthesis, 4. inhibition of nucleic acid synthesis,

9. 1.Inhibition of cell wall synthesis:  Many bacterial and fungal cells have rigid external cell walls.  inhibiting cell wall synthesis selectively damages bacterial and fungal cells.

10. Example: Antibiotics such as penicillin and cephalosporin contain a chemical structure called a b-lactam ring, which attaches to the enzymes that cross-link peptidoglycans. By interfering with the cross-linking of tetrapeptides, these antibiotics prevent cell wall synthesis

11. 2-Inhibition of protein synthesis:  In all cells, protein synthesis requires not only the information stored in DNA, plus several kinds of RNA, but also ribosomes.  Differences between bacterial (70S) and animal (80S) ribosomes allow antimicrobial agents to attack bacterial cells without significantly damaging animal cells—that is, with selective toxicity.

12. Example:  Aminoglycoside antibiotics, such as streptomycin.  Chloramphenicol and erythromycin

13. 3-Inhibition of nucleic acid synthesis: Differences between the enzymes used by bacterial and animal cells to synthesize nucleic acids provide a means for selective action of antimicrobial agents. Example: Antibiotics of the rifamycin family bind to a bacterial RNA polymerase and inhibit RNA synthesis.

14. The side effects of antimicrobial agents on infected persons (hosts) fall into three general categories:  toxicity,  allergy,  disruption of normal microflora.

15. Toxicity: By their selective toxicity and modes of action, antimicrobial agents kill microbes without seriously harming host cells. However, some antimicrobials do exert toxic effects on the patients receiving them.

16. Allergy: An allergy is a condition in which the body’s immune system responds to a foreign substance, usually a protein. For example, breakdown products of penicillins combine with proteins in body fluids to form a molecule that the body treats as a foreign substance. Allergic reactions can be limited to mild skin rashes and itching, or they can be life-threatening.

17. Disruption of normal microflora: Antimicrobial agents, especially broad-spectrum antibiotics, may exert their adverse effects not only on pathogens but also on indigenous microflora—the microorganisms that normally inhabit the skin and the digestive, respiratory, and urogenital tracts.

18. Resistance of a microorganism to an antibiotic means that a microorganism formerly susceptible to the action of the antibiotic is no longer affected by it.

19. Mechanisms of resistance: Five mechanisms of resistance have been identified, each of which involves the alteration of a different microbial structure: 1.Alteration of Targets. 2.Alteration of Membrane Permeability 3.Alteration of Enzymes. 4.Development of Enzymes. 5.Alteration of a Metabolic Pathway

20. Microorganisms vary in their susceptibility to different chemotherapeutic agents, and susceptibilities can change over time. Ideally, the appropriate antibiotic to treat any particular infection should be determined before any antibiotics are given. Sometimes an appropriate agent can be prescribed as soon as the causative organism is identified from a laboratory culture.

21. Methods used for Determining microbial sensitivities to Anti-microbial agents: 1.disk diffusion (Kirby-Bauer method) 2.automated methods

23. The characteristics of an ideal antimicrobial agent: 1.Solubility in Body Fluids 2. Selective Toxicity 3.Toxicity not Easily Altered

24. The characteristics of an ideal antimicrobial agent: 4.Nonallergenic 5.Stability 6.Resistance by Microorganisms not Easily Acquired 7.Reasonable Cost

25. Antibiotic: Is a chemical substance produced by microorganisms which has the capacity to inhibit the growth of bacteria and even destroy bacteria and other microorganisms in dilute solution. In contrast, agents synthesized in the laboratory are called synthetic drugs. Some antimicrobial agents are synthesized by chemically modifying a substance from a microorganism.