Antimicrobial agent


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Antimicrobial agent

  2. 2. Antimicrobials Agents <ul><li>Definition Antibiotic is : </li></ul><ul><ul><li>A chemical substance produce by microorganism (natural products) which has the capacity to inhibit the growth of bacteria, fungi, viruses or protozoa. It has a high chemotherapeutical index to reduce the active process in organism in a diluted solution. </li></ul></ul><ul><li>Antibiotics = anti microorganisms = anti microbes </li></ul>FK UNISBA
  3. 3. Classification of antibiotics <ul><li>1. Based on chemical structures </li></ul><ul><li>2. Based on the sources </li></ul><ul><li>3. Based on mechanism of action </li></ul><ul><li>4. Based on spectrum of action / activity </li></ul><ul><li>5. Based on modes of action </li></ul>FK UNISBA
  4. 4. 1. Based on chemical structures <ul><li>1. Groups of sulfonamides  Sulfamethoxazole, sulfadiazine </li></ul><ul><li>2. Groups of Penicillin  Penicillin G (Benzylpenicillin), Penicillin V, Ampicillin, amoxicillin, nafcillin </li></ul><ul><li>3. Groups of cephalosporins  cefalotin, cefazolin, cefamandole, cefuroxime, cefotaxime, ceftriaxone. </li></ul><ul><li>4. Groups of aminoglycosides  streptomycin, neomycin, kanamycin, gentamycin, tobramycin </li></ul><ul><li>5. Groups of chloramphenicol  chloramphenicol, tiamphenicol </li></ul>FK UNISBA
  5. 5. 1. Based on chemical structures <ul><li>6. Groups of tetracyclines  chlortetracycline, oxytetracycline, doxycycline, minocycline HCl </li></ul><ul><li>7. Groups of macrolides  erythromycin, roxithromycin, spiramycin, azithromycin </li></ul><ul><li>8. Groups of polyenes  amphotericin B, nystatin </li></ul><ul><li>9. Groups of Lincomycins  lincomycin, clindamycin </li></ul><ul><li>10. Groups of polymixins  Polymyxin B, Polymyxin E </li></ul><ul><li>11. Groups of sulfon  dafsone </li></ul>FK UNISBA
  6. 6. 1. Based on chemical structures <ul><li>12. Other groups  vancomycin, cycloxerine, bacitracin, metronidazole </li></ul><ul><li>13. Groups of quinolones  nalidixic acid, norfloxacin, ciprofloxacin, offloxa cin </li></ul>FK UNISBA
  7. 7. II. Based on the sources <ul><li>Antibiotic from microbes </li></ul><ul><ul><li>A.B. from fungi  Penicillin from P. notatum </li></ul></ul><ul><ul><li>A.B. from bacteria </li></ul></ul><ul><ul><ul><li>A.B. from eubacteria  polymyxin from bacillus polymyxa </li></ul></ul></ul><ul><ul><ul><li>A.B. from micromonosporaceae  gentamyicin from micromonospora purpurea </li></ul></ul></ul><ul><li>b. Antibiotics from algae  Usnat Acid </li></ul><ul><li>c. Antibiotics from higher plants  Garlisina from Allium sativum </li></ul><ul><li>d. Antibiotics from animals  Eritrina from hemoglobin of cow </li></ul>FK UNISBA
  8. 8. III. Based on mechanism of action <ul><li>A. Inhibition of cell wall synthesis leads to the death of the bacteria lysis (bactericidal effect)  penicillin, cycloserine, vancomycin, bacitracin, cefottaxime, ceftriaxone. </li></ul><ul><li>B. Disruption of cell membrane function  polymyxin (polymyxin B, polymyxin E), polyenes, nystatin </li></ul><ul><li>C. Inhibition of protein synthesis: </li></ul><ul><li>This antibiotics inhibit one of the reactions in the process of transcription </li></ul><ul><ul><li>Inhibition of translation process of microbes </li></ul></ul>FK UNISBA
  9. 9. III. Based on mechanism of action <ul><ul><ul><li>Inhibit ribosome on the 30 S subunit  streptomycin, tetracylines, netilmicin, kanamycin </li></ul></ul></ul><ul><ul><ul><li>Inhibit ribosom on the 50 S subunit  chloramphenicol, clyndamycin, lincomycin </li></ul></ul></ul><ul><ul><li>Inhibits the transcription process of microbes  Rifampin, actinomycin </li></ul></ul><ul><li>D. Inhibits spesific metabolic reaction </li></ul><ul><ul><li>Inhibits the enzymatic reactions  sulfonamides, INH, PAS, trimethoprim </li></ul></ul>FK UNISBA
  10. 10. IV. Based on spectrum of action <ul><li>Broad spectrum: Effective to Gram +, Gram - bacteria, mycoplasmas, chlamydiae, rickettsiae, sometimes protozoa  chloramphenicol, tetracyclines </li></ul><ul><li>Narrow spectrum: Effective to Gram + / Gram - bacteria only  penicillins, cephalosporins, erythromycins, polymyxins </li></ul>FK UNISBA
  11. 11. V. Based on modes of action <ul><li>1938 : N. gonorrhoeae are sensitive to sulfa </li></ul><ul><li>1948 : N. gonorrhoeae became resistant, sulfa was no longer used </li></ul><ul><li>N. gonorrhoeae that resistant to penicillin ----- penicillinase producer - strains. </li></ul><ul><li>Staphylococcus that resistant to penicillin beta-lactamase enzymes. </li></ul><ul><li>Paul Ehrlich (1902 – 1909) mice infected with trypanosoma and treated with azo dyes, organic arsenyl and triphenyl methone trypanosoma became resistant after contacted with the drugs. </li></ul>FK UNISBA
  12. 12. Mechanisms of resistance <ul><li>Bacteria produce enzymes that destroy the active drugs such as beta-lactamases which will destroy beta-lactams antibiotics. </li></ul><ul><li>Natural resistance : </li></ul><ul><ul><li>genetic  chromosomal resistance and extrachromosomal resistance </li></ul></ul><ul><ul><li>non genetic </li></ul></ul><ul><li>Genetic resistance happen because of genetic changes </li></ul><ul><li>Non genetic resistance happen because of antibiotics come into contact with bacteria which have active metabolism. </li></ul>FK UNISBA
  13. 13. Mechanisms of resistance <ul><li>Example : M. tbc can persist in the tissues for a long time. The bacteria persist for years after infection without replication, due to the good immune system of the patient. </li></ul><ul><li>In this condition M .tuberculosis can not be killed by antibiotics </li></ul><ul><li>Acquired resistance  Sensitive bacteria will get this resistance properties through plasmid which contains resistance factors (R factors) from resistance bacteria. </li></ul>FK UNISBA
  14. 14. Mechanisms of resistance (Weinstein, 1984) <ul><li>1. Alteration of cell membrane permeability, such alteration inhibit penetration of antibiotics to bacterial cell  Staphylococcus against tetracyclines </li></ul><ul><li>2. Alteration in bacterial cell, so that a big ammount of antibiotic destroy enzymes are produced </li></ul><ul><ul><li> -lactamase against penicillins and cephalosporins </li></ul></ul><ul><ul><li>Acetyltransferase against chloramfenicol </li></ul></ul><ul><ul><li>Phosphorilase, acetylase and adenylase against aminoglycosides </li></ul></ul>FK UNISBA
  15. 15. Mechanisms of resistance (Weinstein, 1984) <ul><li>3. Alteration of receptors usually affects bacterial ribosomes. The mutation alters the DNA that produces a ribosomal protein receptor so the a antibiotics cannot bind to it  erythromycin receptor in staphylococcus </li></ul><ul><li>4. Alteration of a metabolic pathway in bacterial cell, to bypass a reaction inhibited by an antimicrobial agent  dehidrofolate by trimethoprim, sulfanomide, INH and PAS </li></ul>FK UNISBA
  16. 16. Some approaches to solve resistance problems <ul><li>Administration of antibiotics prescription only if the clinical signs and tests indicated that certain bacteria are the most probable caused of infection </li></ul><ul><li>Bacteriologic diagnosis must be sought and susceptibility tests must be determined </li></ul><ul><li>Avoid the usage of antibiotics which have been known resistance in one population </li></ul><ul><li>Reduce the usage of topical antibiotics, use antiseptics instead. </li></ul><ul><li>Limit the period of consuming antibiotics </li></ul>FK UNISBA
  17. 17. Some approaches to solve resistance problems <ul><li>Reduce the usage of prophylactic antibiotics </li></ul><ul><li>Use narrow spectrum antibiotics </li></ul><ul><li>Always follow directions for use of antibiotics </li></ul><ul><li>Prescrible antibiotics based on clinical situation and not on patient’s will or pharmaceutical advertisements. </li></ul><ul><li>Rational drug: drugs given after accurate diagnosis. It will be effective with minimal side effects. </li></ul>FK UNISBA
  18. 18. Factors involve in the usage of AB rationally, effectively and safely. <ul><li>Accurate diagnosis </li></ul><ul><li>Accurate choices of antibiotics </li></ul><ul><li>Deliver accurate dose </li></ul><ul><li>Accurate dosing interval </li></ul><ul><li>Accurate examinations of patophysiologic conditions of the patient </li></ul><ul><li>Factors involve in choosing antibiotics </li></ul><ul><ul><li>Disease factors </li></ul></ul><ul><ul><li>Drug factors </li></ul></ul><ul><ul><li>Recipient factors </li></ul></ul>FK UNISBA
  19. 19. Factors involve in choosing antibiotics <ul><li>Disease factors </li></ul><ul><ul><li>Selective for etiologic bacteria susceptibility test </li></ul></ul><ul><ul><li>Types and doses depend on location of infection </li></ul></ul><ul><ul><li>Enough penetrating potentials to cross : </li></ul></ul><ul><ul><ul><li>blood-brain barrier in </li></ul></ul></ul><ul><ul><ul><li>abscess walls </li></ul></ul></ul><ul><li>Drugs factors  Ideal antibiotics : </li></ul><ul><li>Have a narrow spectrum, affect only to etiologic bacteria </li></ul><ul><li>Have a bactericidal effect, unless none is sensitive, bacteriostatic drugs can be delivered </li></ul>FK UNISBA
  20. 20. Ideal antibiotics : <ul><li>Effective even in the presence of body fluids exudate, protein or enzymes. </li></ul><ul><li>Ability to reach the infected tissue, enough drug concentration during the span of a dosing interval in blood / infected area. </li></ul><ul><li>Do not caused resistance </li></ul><ul><li>Have a minimal toxic effects for the patient </li></ul><ul><li>Safe for pregnancy and pediatric patients </li></ul><ul><li>Low costs </li></ul>FK UNISBA
  21. 21. Factors involve in choosing antibiotics <ul><li>3. Patient factors : </li></ul><ul><ul><li>Age </li></ul></ul><ul><ul><li>Genetics </li></ul></ul><ul><ul><li>Pregnancy </li></ul></ul><ul><ul><li>Accompanying diseases </li></ul></ul><ul><li>Antibiotic prophylaxis: An antibiotic is used to anticipate infection from certain bacteria which are sensitive to the drug. </li></ul><ul><li>Goal : To minimize the surgical wound infection, by treating with antibiotic in lethal concentration for microorganisms at the beginning of surgery until it finished (done). </li></ul>FK UNISBA
  22. 22. Sensitivity tests / resistance tests <ul><li>Qualitative : </li></ul><ul><ul><li>Stokes method </li></ul></ul><ul><ul><li>Ericcson method </li></ul></ul><ul><ul><li>Kirby-Bauer method </li></ul></ul><ul><ul><li>Comparison method </li></ul></ul><ul><li>Quantitative : </li></ul><ul><ul><li>MIC </li></ul></ul><ul><ul><li>MIC plate </li></ul></ul>FK UNISBA
  23. 23. Qualitative <ul><li>The Kirby-Bauer Method: Commonly in microbiology use the Kirby-Bauer Method . It use medium of Mueller-Hinton Agar on the susceptibility test </li></ul><ul><li>Mueller-Hinton Agar </li></ul><ul><ul><li>Sensitive : clear area (zones of inhibition) </li></ul></ul><ul><ul><li>Resistance : No zones of inhibition </li></ul></ul>FK UNISBA
  24. 24. Side effects of antibiotics <ul><li>Allergic reaction : Is a respond in sensitive individual due to the abnormality in his immune system  Penicillin, Sulfonamides, Streptomycin </li></ul><ul><ul><li>Mild symptoms are skin rashes and itching. </li></ul></ul><ul><ul><li>Severe symptoms are anaphylactic shock. </li></ul></ul><ul><li>Toxic reaction : Can happen in individual depend on the doses of drugs in the body  Hearing disorder because of gentamycin </li></ul><ul><li>Manifestation can occur : </li></ul><ul><ul><li>Temporary and permanently </li></ul></ul><ul><ul><li>After a prolonged used / acute respond </li></ul></ul>FK UNISBA
  25. 25. Antiviral Agents <ul><li>Inhibit viruses coverage </li></ul><ul><li>Inhibit DNA and RNA synthesis in the viruses </li></ul><ul><li>Inhibit protein synthesis in the viruses </li></ul><ul><li>Inhibit specific enzymes activities in the viruses </li></ul><ul><li>Inhibit the growth of viruses </li></ul><ul><li>Promote immunity system of the body </li></ul><ul><li>Prevent virus infection to the body </li></ul>FK UNISBA
  26. 26. The Drugs that use : <ul><li>To inhibit viruses coverage: Amantadine, Rimantidine </li></ul><ul><li>To inhibit DNA and RNA synthesis: Acyclovir, Ganciclovir, Foscarnet, Ribavirin, Valacyclovir, vidarabine, cidofovir </li></ul><ul><li>To inhibit return transcription from nucleocid: Zidovudine, Didanosine, Zalcitabine </li></ul><ul><li>Inhibit protease enzyme Other antiviral drugs: Idoxuridine, Trifluridine, Fluorouracil, Interferons, Immunoglobulins </li></ul><ul><li>Notes : Antiviral drugs only inhibit the early stage of replication </li></ul>FK UNISBA
  27. 27. Antifungal Agents <ul><li>Fungal infection occur less frequently than bacterial or viral infections. </li></ul><ul><li>Three major groups of antifungal agents : </li></ul><ul><ul><li>Groups of polyenes : </li></ul></ul><ul><ul><ul><li>Amphotericin B </li></ul></ul></ul><ul><ul><ul><li>Nystatin </li></ul></ul></ul><ul><ul><li>Groups of Azole Imidazoles : </li></ul></ul><ul><ul><ul><li>Ketoconazole </li></ul></ul></ul><ul><ul><ul><li>Miconazole </li></ul></ul></ul><ul><ul><ul><li>Clotrimazole </li></ul></ul></ul><ul><ul><ul><li>Fluconazole </li></ul></ul></ul><ul><ul><ul><li>Itraconazole </li></ul></ul></ul>FK UNISBA
  28. 28. Antifungal Agents <ul><ul><li>Groups of Alilamin: </li></ul></ul><ul><ul><ul><li>Terbinafin </li></ul></ul></ul><ul><ul><ul><li>Naftitin </li></ul></ul></ul><ul><li>Other antifungal agents : </li></ul><ul><ul><li>Griseofulvin </li></ul></ul><ul><ul><li>Flucytosine </li></ul></ul>FK UNISBA
  29. 29. ALHAMDULILLAH Thank You !