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Anti Biotics

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Anti Biotics

  1. 2. <ul><li>Antibiotics are drugs derived wholly or partially from certain microorganisms and are used to treat bacterial or fungal infections. </li></ul><ul><li>Antibiotics either kill microorganisms ( bactericidal ) or stop them from reproducing ( bacteriostatic ). </li></ul><ul><li>Antibiotics are among the most frequently prescribed medications in modern medicine. </li></ul><ul><li>Today, over 100 different antibiotics are available to doctors to cure minor discomforts as well as life-threatening infections. </li></ul>
  2. 3. <ul><li>Up to 80% of antibiotics are prescribed in the outpatient setting: </li></ul><ul><ul><li>URTI's </li></ul></ul><ul><ul><li>UTI's </li></ul></ul><ul><li>50% of office visits colds and upper RTI’s </li></ul><ul><li>80% of visits for acute bronchitis </li></ul><ul><li>… are treated with antibiotics. </li></ul>
  3. 4. <ul><li>B-LACTAMS. </li></ul><ul><li>Aminoglycosides. </li></ul><ul><li>Quinolones. </li></ul><ul><li>Sulphonamides. </li></ul><ul><li>Macrolides. </li></ul>
  4. 5. <ul><li>1.Inhibit synthesis of bacterial cell wall. </li></ul><ul><li>2.Act directly on the cell membrane of the bacteria, causing it to break open. </li></ul><ul><li>3.Inhibit bacterial protein synthesis. </li></ul><ul><li>(nucleic acid synthesis , interferes with ribosomal functions) </li></ul><ul><li>4.Affect bacterial metabolism and growth. </li></ul>
  5. 6.
  6. 7. <ul><li>Their biological source: </li></ul><ul><ul><li>Plant, mold, soil microorganisms </li></ul></ul><ul><li>Their spectrum of action or coverage: </li></ul><ul><ul><li>Broad/wide spectrum - effective against a wide range of bacteria </li></ul></ul><ul><ul><li>Narrow spectrum - effective mainly against specific categories of bacteria </li></ul></ul><ul><ul><ul><li>e.g. Gram-positive or Gram-negative bacteria but not both </li></ul></ul></ul><ul><ul><li>Limited spectrum - effective against a single organism or disease </li></ul></ul><ul><li>Their mode of action: </li></ul><ul><ul><li>How they fight bacteria </li></ul></ul>
  7. 8.
  8. 9. <ul><li>Specific agents </li></ul><ul><ul><li>Penicillin G (IV), Penicillin V (oral) </li></ul></ul><ul><ul><li>Antistaphylococcal </li></ul></ul><ul><ul><ul><li>nafcillin, oxacillin, dicloxacillin </li></ul></ul></ul><ul><ul><li>Extended spectrum </li></ul></ul><ul><ul><ul><li>ampicillin, amoxicillin </li></ul></ul></ul><ul><ul><ul><li>ticarcillin, piperacillin </li></ul></ul></ul><ul><li>Clinical uses </li></ul><ul><ul><li>Streptococcal phayngitis (PCN) </li></ul></ul><ul><ul><li>MSSA (nafcillin) </li></ul></ul><ul><ul><li>E.coli, Proteus (ampicilin) </li></ul></ul><ul><ul><li>Pseudomonas (piperacillin) </li></ul></ul>
  9. 10. <ul><li>Mechanism of action </li></ul><ul><ul><li>Inhibits bacterial cell wall synthesis </li></ul></ul><ul><ul><li>Bind to Penicillin binding proteins </li></ul></ul><ul><ul><li>Bactericidal </li></ul></ul><ul><li>Mechanisms of resistance </li></ul><ul><ul><li>Altered penicillin binding proteins (PBPs) </li></ul></ul><ul><ul><ul><li>mecA/MRSA, Strep. Pneumo resistance </li></ul></ul></ul><ul><ul><li>Production of Beta-lactamases (penicillinases) </li></ul></ul><ul><ul><li>Decreased penetration/increased efflux (pseudomonas) </li></ul></ul>
  10. 11. <ul><li>Enzymes produced by bacteria which destroy beta-lactam antibiotics </li></ul><ul><li>Many different types </li></ul><ul><ul><li>Penicillinases, cephalosporinases, carbapenemases </li></ul></ul><ul><li>Narrow spectrum vs. extended spectrum </li></ul><ul><li>Most are plasmid mediated </li></ul>
  11. 12. <ul><li>Clavulanate </li></ul><ul><ul><li>With amoxicillin (Augmentin) </li></ul></ul><ul><ul><li>With ticarcillin (Timentin) </li></ul></ul><ul><li>Sulbactam </li></ul><ul><ul><li>With ampicillin (Unasyn) </li></ul></ul><ul><li>Tazobactam </li></ul><ul><ul><li>With piperacillin (Zosyn) </li></ul></ul>
  12. 13. <ul><li>Adverse effects </li></ul><ul><ul><li>Allergy (Anaphylaxis, rash, fever, interstitial nephritis) </li></ul></ul><ul><ul><li>Diarrhea –amoxicillin/clavulanate (augmentin) </li></ul></ul><ul><ul><li>Rash - ampicillin </li></ul></ul><ul><ul><li>Sodium overload- ticarcillin </li></ul></ul><ul><ul><li>Seizure especially with high doses and renal dysfunction </li></ul></ul>
  13. 14.
  14. 15. <ul><li>1 st generation – cefazolin </li></ul><ul><li>2 nd generation - cefuroxime </li></ul><ul><li>3 rd generation - ceftriaxone </li></ul><ul><li>4 th generation - cefepime </li></ul><ul><li>5 th generation - ceftobiprole </li></ul><ul><li>Differ in spectrum, resistance to beta lactamases, penetration into CNS </li></ul><ul><li>IV, IM: oral forms for 1 st , 2 nd ,3 rd gen. </li></ul>
  15. 16. <ul><li>Clinical uses </li></ul><ul><ul><li>Cellulitis – (cephalexin) </li></ul></ul><ul><ul><li>Prophylactic prior to surgery (cefotetan) </li></ul></ul><ul><ul><li>Meningitis – (ceftriaxone) </li></ul></ul><ul><li>Mechanism of action </li></ul><ul><ul><li>Inhibition of cell wall synthesis </li></ul></ul><ul><ul><li>Bactericidal </li></ul></ul>
  16. 17. <ul><li>Resistance mechanisms </li></ul><ul><ul><li>Destruction by beta-lactamases (cephalosporinases) </li></ul></ul><ul><ul><li>Alteration in the affinity of penicillin binding proteins (PBPs) for cephalosporins </li></ul></ul><ul><ul><li>Efflux of cephalosporins from microbe </li></ul></ul>
  17. 18. <ul><li>Adverse Effects </li></ul><ul><li>Allergic reactions – 10% cross reactivity with penicillins </li></ul><ul><li>GIT disturbances. </li></ul><ul><li>Pain & inflammation at site of injection. </li></ul><ul><li>Bleeding disorders and disulfiram-like effect. </li></ul>
  18. 19.
  19. 20. <ul><li>Specific agents </li></ul><ul><ul><li>Imipenem </li></ul></ul><ul><ul><ul><li>With cilastin (Primaxin) </li></ul></ul></ul><ul><ul><li>Meropenem (Merrem) </li></ul></ul><ul><ul><li>Ertapenem (Invanz) </li></ul></ul><ul><ul><li>Doripenem (Doribax) </li></ul></ul><ul><ul><li>IV only </li></ul></ul><ul><ul><li>Broad spectrum </li></ul></ul><ul><ul><ul><li>Gram positives </li></ul></ul></ul><ul><ul><ul><li>Gram negatives </li></ul></ul></ul><ul><ul><ul><li>Pseudomonas (except ertapenem </li></ul></ul></ul>
  20. 21. <ul><li>Clinical uses </li></ul><ul><ul><li>Intraabdominal infections </li></ul></ul><ul><ul><li>Polymicrobial infections </li></ul></ul><ul><ul><li>Pseudomonas aeruginosa </li></ul></ul><ul><ul><li>Neutropenic fever </li></ul></ul><ul><li>Mechanism of action </li></ul><ul><ul><li>Inhibit bacterial cell wall synthesis </li></ul></ul><ul><ul><li>Bactericidal </li></ul></ul><ul><li>Adverse effects </li></ul><ul><ul><li>Nausea/vomiting </li></ul></ul><ul><ul><li>Allergy – Significant cross reaction with pencillin allergy </li></ul></ul><ul><ul><li>Seizure </li></ul></ul>
  21. 22. <ul><li>Aztreonam (Azactam) </li></ul><ul><li>IV only </li></ul><ul><li>Antimicrobial spectrum </li></ul><ul><ul><li>Gram negative aerobic bacteria only </li></ul></ul><ul><ul><li>Including Pseudomonas </li></ul></ul><ul><li>Inhibits cell wall synthesis </li></ul><ul><li>Bactericidal </li></ul><ul><li>Adverse effects </li></ul><ul><ul><li>Allergy (<1% cross-reactive with penicillin) </li></ul></ul>
  22. 23. <ul><li>Specific agents </li></ul><ul><ul><li>Gentamicin </li></ul></ul><ul><ul><li>Tobramycin </li></ul></ul><ul><ul><li>Amikacin </li></ul></ul><ul><li>IV/IM/inhaled </li></ul><ul><li>Spectrum of action </li></ul><ul><ul><li>Aerobic Gram negative bacteria </li></ul></ul><ul><ul><li>Pseudomonas spp ., E.coli , others </li></ul></ul>
  23. 24. <ul><li>Mechanism of action </li></ul><ul><ul><li>Inhibit bacterial protein synthesis </li></ul></ul><ul><ul><li>Bactericidal </li></ul></ul><ul><li>Mechanisms of resistance </li></ul><ul><ul><li>Bacterial production of enzyme that inactivates aminoglycosides </li></ul></ul><ul><ul><li>Alteration of drug target site </li></ul></ul><ul><ul><li>Altered drug transport </li></ul></ul>
  24. 25. <ul><li>Adverse effects </li></ul><ul><ul><li>Nephrotoxicity </li></ul></ul><ul><ul><li>Ototoxicity </li></ul></ul><ul><ul><li>Vestibular toxicity </li></ul></ul><ul><ul><li>Neuromuscular (myasthenia gravis) </li></ul></ul>
  25. 26.
  26. 27.
  27. 28. <ul><li>Specific agents </li></ul><ul><ul><li>Norfloxacin </li></ul></ul><ul><ul><li>Ciprofloxacin </li></ul></ul><ul><ul><li>Levofloxacin (Levaquin) </li></ul></ul><ul><ul><li>Gatifloxacin (Tequin) </li></ul></ul><ul><ul><li>Moxifloxacin (Avelox) </li></ul></ul><ul><ul><li>Nalidixic acid </li></ul></ul>
  28. 29. <ul><li>Spectrum of action </li></ul><ul><li>Broad spectrum (varies by agent) </li></ul><ul><li>Inhibit DNA synthesis </li></ul><ul><li>Bactericidal </li></ul><ul><li>Mechanisms of resistance </li></ul><ul><ul><li>Change in target enzyme </li></ul></ul><ul><ul><li>Change in permeability of organism </li></ul></ul>
  29. 30.
  30. 31. <ul><li>Adverse Effects </li></ul><ul><ul><li>Nausea/vomiting </li></ul></ul><ul><ul><li>CNS – headache, confusion (in elderly), panic attack, anxiety, nightmares </li></ul></ul><ul><ul><li>Tendonitis or tendon rupture </li></ul></ul><ul><ul><li>Kidney stones due to loss of Oxalobacter formigenes. </li></ul></ul><ul><ul><li>Drug-Drug interactions with NSAID, Theophylline. </li></ul></ul>
  31. 32. <ul><li>Spectrum of activity </li></ul><ul><ul><li>Gram positives and some gram negatives </li></ul></ul><ul><ul><ul><li>Beta-hemolytic streptococci, staphylococci and enterococci Some pneumococcal </li></ul></ul></ul><ul><ul><li>Mycoplasma and legionella </li></ul></ul><ul><ul><li>Chlamydia </li></ul></ul><ul><li>Specific agents </li></ul><ul><ul><li>Erythromycin </li></ul></ul><ul><ul><li>Azithromycin (Unizithrin) </li></ul></ul><ul><ul><li>Clarithromycin (Klacid) </li></ul></ul>
  32. 33. <ul><li>Mechanism of action </li></ul><ul><ul><li>Inhibit bacterial protein synthesis </li></ul></ul><ul><ul><li>Bacteriostatic in small concentration & Bactericidal in high concentration </li></ul></ul><ul><li>Mechanism of resistance </li></ul><ul><ul><li>Decreased permeability of drug into the microbe </li></ul></ul><ul><ul><li>Modification of target sites </li></ul></ul><ul><ul><li>Hydrolysis of macrolide by bacterial enzymes </li></ul></ul><ul><li>Adverse effects </li></ul><ul><ul><li>Gastrointestinal </li></ul></ul><ul><ul><li>Arrhythmias </li></ul></ul><ul><ul><li>Liver toxicity </li></ul></ul>
  33. 34. <ul><li>Antimicrobial spectrum </li></ul><ul><ul><li>Anaerobes </li></ul></ul><ul><ul><li>Some gram positives </li></ul></ul><ul><li>Inhibits bacterial protein synthesis </li></ul><ul><li>Bacteriostatic </li></ul><ul><li>Adverse effects </li></ul><ul><ul><li>Nausea, diarrhea </li></ul></ul><ul><ul><li>Clostridium difficile </li></ul></ul>
  34. 35. <ul><li>Clinical use </li></ul><ul><ul><li>Broad spectrum </li></ul></ul><ul><ul><li>Also Mycoplasma pneumonia , Chlamydia, Rickettsia, Lyme disease </li></ul></ul><ul><li>Specific agents </li></ul><ul><ul><li>Tetracycline </li></ul></ul><ul><ul><li>Doxycycline (Vibramycin) </li></ul></ul><ul><ul><li>Minocycline (Minocin) </li></ul></ul>
  35. 36. <ul><li>Inhibit bacterial protein synthesis </li></ul><ul><li>Bacteriostatic </li></ul><ul><li>Adverse effects </li></ul><ul><ul><li>Food drug interaction (food and dairy interfere with absorption) </li></ul></ul><ul><ul><li>Also occurs with some antacids </li></ul></ul><ul><ul><li>GI irritation </li></ul></ul><ul><ul><li>Hepatic toxicity </li></ul></ul><ul><ul><li>Renal toxicity </li></ul></ul><ul><ul><li>Photosensitivity </li></ul></ul><ul><ul><li>Discoloration of teeth </li></ul></ul><ul><ul><li>Vertigo (Minocycline) </li></ul></ul>
  36. 37. <ul><li>Specific agents </li></ul><ul><ul><li>Sulfisoxazole </li></ul></ul><ul><ul><li>Sulfamethoxazole/trimethoprim (Bactrim) </li></ul></ul><ul><ul><li>Trimethoprim </li></ul></ul><ul><li>Clinical uses </li></ul><ul><ul><li>Broad spectrum (gram + and gram -) </li></ul></ul><ul><ul><li>Oral – UTIs </li></ul></ul><ul><ul><li>Topical – burn wounds, opthalmic preps </li></ul></ul><ul><ul><li>Pneumocystis, Nocardia </li></ul></ul>
  37. 38. <ul><li>Mechanism of action </li></ul><ul><ul><li>Inhibit folic acid synthesis </li></ul></ul><ul><ul><li>Bacteriostatic </li></ul></ul><ul><li>Mechanism of resistance </li></ul><ul><ul><li>Alternate mechanisms for folate synthesis </li></ul></ul><ul><ul><li>Sulfa not usually used alone due to resistance </li></ul></ul><ul><li>Adverse Effects </li></ul><ul><ul><li>Hypersensitivity </li></ul></ul><ul><ul><li>Hematologic toxicity </li></ul></ul><ul><ul><li>Renal toxicity </li></ul></ul><ul><ul><li>CNS </li></ul></ul><ul><ul><li>Photosensitivity </li></ul></ul><ul><ul><li>Hematopoetic </li></ul></ul><ul><ul><li>Drug interactions </li></ul></ul>
  38. 39. <ul><li>Mechanism of action </li></ul><ul><ul><li>Inhibits bacterial cell wall synthesis </li></ul></ul><ul><li>Bactericidal? </li></ul><ul><li>Spectrum </li></ul><ul><ul><li>Gram positive bacteria </li></ul></ul><ul><ul><li>Methicillin resistant Staphylococcus aureus </li></ul></ul><ul><ul><li>Clostridium difficile (oral) </li></ul></ul>
  39. 40. <ul><li>Mechanisms of resistance </li></ul><ul><ul><li>Production of a new cell wall component that vancomycin doesn’t inhibit </li></ul></ul><ul><li>Adverse Effects </li></ul><ul><ul><li>Red Man’s syndrome </li></ul></ul><ul><ul><li>Rash </li></ul></ul><ul><ul><li>Renal toxicity </li></ul></ul><ul><ul><li>Ototoxicity </li></ul></ul><ul><ul><li>Leukopenia </li></ul></ul>
  40. 41. <ul><li>Linezolid (Zyvox) </li></ul><ul><li>Mechanism of action </li></ul><ul><ul><li>Inhibit bacterial protein synthesis </li></ul></ul><ul><li>Bacteriostatic or bactericidal </li></ul><ul><li>IV/oral </li></ul>
  41. 42. <ul><li>Antimicrobial spectrum </li></ul><ul><ul><li>Anaerobes ( Clostridium difficile , Bacteroides) </li></ul></ul><ul><ul><li>Protozoa (Trichomonas, Entamoeba histolytica) </li></ul></ul>
  42. 43. <ul><li>Mechanism of action </li></ul><ul><ul><li>Not completely understood </li></ul></ul><ul><ul><li>Metronidazole is a prodrug </li></ul></ul><ul><ul><li>Metabolism of the drug produces toxic metabolites </li></ul></ul><ul><ul><li>Bactericidal </li></ul></ul><ul><li>Adverse effects </li></ul><ul><ul><li>Metallic taste </li></ul></ul><ul><ul><li>Peripheral neuropathy </li></ul></ul><ul><ul><li>Disulfuram effect – interaction with ethanol </li></ul></ul>
  43. 44.
  44. 45. <ul><li>Microbiological activity. </li></ul><ul><li>Concentration at site of infection. </li></ul><ul><li>How long it will remain at the site of action. </li></ul><ul><li>MIC. </li></ul>
  45. 46.
  46. 47.
  47. 48. <ul><li>Using AB only when absolutely needed and indicated: </li></ul><ul><li>AB often abused for viral infections (diarrhea, flu-symptoms, etc.) </li></ul><ul><li>– Starting with narrow-spectrum drugs </li></ul><ul><li>– Limiting use of newer drugs </li></ul><ul><li>– Identifying the infecting organism </li></ul><ul><li>– Defining the drug sensitivity of the infecting organism </li></ul><ul><li>– Considering all host factors: </li></ul><ul><li>site of infection, inability of drug of choice to penetrate the site of infection, etc. </li></ul><ul><li>– Using AB combinations only when indicated: </li></ul><ul><li>Severe or mixed infections, prevention of resistance (tuberculosis) </li></ul><ul><li>Worldwide more than 500 metric tons antibiotics are used anually !!! </li></ul>

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