Antibiotics use and overuse

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Antibiotics use and overuse

  1. 1. Antibiotics : Use and overuse KM Murali MD (Med), DM (Neph), DNB (Neph), F Neph (Canada) Consultant Nephrologist MIMS, Kozhikode
  2. 2. First world war
  3. 3. Second world war
  4. 4. Cold war
  5. 5. Man vs Microbe Timeless war
  6. 6. Spread of “jewish poison”
  7. 7. Anton V Leeuwenhock : “animalcules” 1674 AD
  8. 8. Louis Pasteur: “germ theory of disease” 1857 1822 - 1895
  9. 9. Gram Staining Gram Positive Staphylococci Coagulase + ve Coagulase - ve Streptococci Enterococci Gram +ve bacilli Gram +ve anaerobes
  10. 10. Gram Positive Gram Negative Enterobacteriaceae Eschericiae Klebsiellae Proteaceae Pseudomonas Vibrio Hemophilus Others Gram Staining Staphylococci Coagulase + ve Coagulase - ve Streptococci Enterococci Gram +ve bacilli Gram +ve anaerobes
  11. 11. The “antibiotic surge” • Penicillin 1941 • Streptomycin 1944 • Tetracycline 1948 • Erythromycin 1952 • Vancomycin 1958 • Methicillin 1959 • Gentamicin 1962
  12. 12. “...... It’s time to close the book on infectious diseases, the war against pestilence is over” William Stewart, Surgeon General Message to US Congress, 1969
  13. 13. Antibacterial weaponry Penicillins Fluoroquinolones Cephalosporins Macrolides Monobactams Sulfonamides Carbopenams Streptogramins Aminoglycosides Oxazolidinediones Glycopeptides Others
  14. 14. + DNA DNA-RNA polymerase Cell wall Cell membrane Protein synthesis Folate synthesis PABA DHFA THFA
  15. 15. Penicillin and beta-lactam ring
  16. 16. • The prototype Penicillin G • Acid resistant Penicillin V • Penicillinase resistant Methicillin, Oxacillin • “Broad Spectrum” Amoxicillin, Ampicillin • “Antipseudomonas” Azlocillin, piperacillin • Combinations Augmentin, Timentin • (+ β-lactamase inhibitor) The big penicillin family
  17. 17. Penicillin vs Cephalosporin
  18. 18. Penicillin vs Cephalosporin vs Carbapenams
  19. 19. Penicillin vs Aztreonam
  20. 20. Penicillin vs Vancomycin
  21. 21. “Excessive use of penicillin can lead to its resistance” - Sir Alexander Fleming (1941)
  22. 22. Preliminary reports of resistance • Penicillin 1941  1942 • Streptomycin 1944  1946 • Tetracycline 1948  1952 • Erythromycin 1952  1955 • Vancomycin 1958  1990 • Methicillin 1959  1968 • Gentamicin 1962  1975 • Ciprofloxacin 1988  1989
  23. 23. Staphylococcus aureus PCN resistance
  24. 24. 0 5 10 15 20 25 30 1990 1992 1994 1996 1998 2000 Year Non ICU ICU Enterococcus Vancomycin resistance
  25. 25. 0 5 10 15 20 25 30 35 40 OverallPercentResistance PCN ERY CLINDA TET TMP-SMX 1994-1995 1997-1998 1999-2000 Streptococcus antibiotic resistance
  26. 26. RESISTANCE : Survival of the fittest Revertant Resistant Compensatory mutations Passages
  27. 27. Categories of resistance Acquired Staphylococci Streptococci Gram –ve cocci Enterobacteriaceae Intrinsic Pseudomonas Enterococci
  28. 28. Categories of acquired resistance • Mutational • Single drug • Low level resistance • Surpassable Transferable Often multiple drugs High level resistance Unsurpassable
  29. 29. • Enzymatic inactivation of drug Biochemical basis of drug resistance
  30. 30. Beta – lactamase opens penicillin ring Beta - lactamase
  31. 31. Penicillinase Oxacilinase Cephalosporinase Carbenicilinase Carbapenamase ESBL
  32. 32. Beta – lactamase inhibitors • Flucloxacillin • Clavulanate • Sulbactam • Tazobactam
  33. 33. • Enzymatic inactivation of drug • Alteration of drug target Biochemical basis of drug resistance
  34. 34. • Penicillin binding proteins (PBPs) – Streptococcus pneumoniae (penicillin) – Staphylococcus aureus (MRSA, nafcillin; mecA gene) • Ribosomal binding site (23S rRNA) – Streptococcus pneumoniae, Helicobacter pylori (macrolides) • DNA gyrase – Gram negative bacteria (quinolones) • Cell wall precursor targets – Vancomycin resistant enterococci (VRE) Alteration of Drug Target
  35. 35. Vancomycin resistance in enterococcus
  36. 36. • Enzymatic inactivation of drug • Alteration of drug target • Changes in drug uptake or efflux Biochemical basis of drug resistance
  37. 37. The toughest enemy: Pseudomonas
  38. 38. Pseudomonas: Efflux pump
  39. 39. Conspiracy: Sharing of intelligence Pseudomonas Enterobacteriacea Campylobacter Staphylococci Enterococci Streptococci
  40. 40. Man vs Microbe : Are we lost ?? • We are not winning • But let us not lose • Let us not overuse antibiotics
  41. 41. Physician practices in antibiotic use • 2/3 of outpatient antibiotic use is avoidable • 40% inpatient antibiotic selection incorrect • Costly antibiotics being overused
  42. 42. Ground realities in Indian scenario • Poor awareness about sample collection • Poor microbiological infrastructure • Low yield of blood culture • Low yield of anaerobic bacteriae • Lack of faith in laboratory reports
  43. 43. EMPIRICAL ANTIBIOTIC THERAPY IS DIRECTED AGAINST THE MOST PROBABLE PATHOGEN…………….. NOT AGAINST ALL PATHOGENS !!! BUT THEN CULTURES SHOULD FOLLOW Empirical initiation of therapy Empirical completion of therapy
  44. 44. ICU Antibiotic cocktail • One for gram positive • One for gram negative • One for anaerobe • One for ‘atypical’ • One for the master and one for the dame !!
  45. 45. Practical solutions • Prevention of infection • Give only essential treatment • Monitoring policies
  46. 46. Preventing infections • Universal precautions • Hand washing • Avoid non-essential lines and tubes • Isolation of patients infected with muti- drug resistant pathogens
  47. 47. Essential treatment • Use the right antibiotic • Avoid broad spectrum antibiotic • Use the right dose • Use for the right time
  48. 48. Monitoring policies • Infection control surveillance • Bacteriological surveillance • Prescription surveillance
  49. 49. Thank you

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