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Antibiotics use and overuse
- 1. Antibiotics : Use and overuse KM Murali MD (Med), DM (Neph), DNB (Neph), F Neph (Canada) Consultant Nephrologist MIMS, Kozhikode
- 4. Cold war
- 6. Spread of “jewish poison”
- 9. Anton V Leeuwenhock : “animalcules” 1674 AD
- 10. Louis Pasteur: “germ theory of disease” 1857 1822 - 1895
- 11. Gram Staining Gram Positive Staphylococci Coagulase + ve Coagulase - ve Streptococci Enterococci Gram +ve bacilli Gram +ve anaerobes
- 12. 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
- 14. The “antibiotic surge” • Penicillin 1941 • Streptomycin 1944 • Tetracycline 1948 • Erythromycin 1952 • Vancomycin 1958 • Methicillin 1959 • Gentamicin 1962
- 15. “...... 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
- 16. Antibacterial weaponry Penicillins Fluoroquinolones Cephalosporins Macrolides Monobactams Sulfonamides Carbopenams Streptogramins Aminoglycosides Oxazolidinediones Glycopeptides Others
- 17. + DNA DNA-RNA polymerase Cell wall Cell membrane Protein synthesis Folate synthesis PABA DHFA THFA
- 18. Penicillin and beta-lactam ring
- 19. • 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
- 21. Penicillin vs Cephalosporin vs Carbapenams
- 28. “Excessive use of penicillin can lead to its resistance” - Sir Alexander Fleming (1941)
- 29. 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
- 30. Staphylococcus aureus PCN resistance
- 31. 0 5 10 15 20 25 30 1990 1992 1994 1996 1998 2000 Year Non ICU ICU Enterococcus Vancomycin resistance
- 32. 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
- 33. RESISTANCE : Survival of the fittest Revertant Resistant Compensatory mutations Passages
- 35. Categories of resistance Acquired Staphylococci Streptococci Gram –ve cocci Enterobacteriaceae Intrinsic Pseudomonas Enterococci
- 36. Categories of acquired resistance • Mutational • Single drug • Low level resistance • Surpassable Transferable Often multiple drugs High level resistance Unsurpassable
- 37. • Enzymatic inactivation of drug Biochemical basis of drug resistance
- 38. Beta – lactamase opens penicillin ring Beta - lactamase
- 40. Beta – lactamase inhibitors • Flucloxacillin • Clavulanate • Sulbactam • Tazobactam
- 41. • Enzymatic inactivation of drug • Alteration of drug target Biochemical basis of drug resistance
- 42. • 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
- 43. Vancomycin resistance in enterococcus
- 44. • Enzymatic inactivation of drug • Alteration of drug target • Changes in drug uptake or efflux Biochemical basis of drug resistance
- 45. The toughest enemy: Pseudomonas
- 47. Conspiracy: Sharing of intelligence Pseudomonas Enterobacteriacea Campylobacter Staphylococci Enterococci Streptococci
- 48. Man vs Microbe : Are we lost ?? • We are not winning • But let us not lose • Let us not overuse antibiotics
- 49. Physician practices in antibiotic use • 2/3 of outpatient antibiotic use is avoidable • 40% inpatient antibiotic selection incorrect • Costly antibiotics being overused
- 50. 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
- 51. 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
- 52. 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 !!
- 53. Practical solutions • Prevention of infection • Give only essential treatment • Monitoring policies
- 54. Preventing infections • Universal precautions • Hand washing • Avoid non-essential lines and tubes • Isolation of patients infected with muti- drug resistant pathogens
- 55. Essential treatment • Use the right antibiotic • Avoid broad spectrum antibiotic • Use the right dose • Use for the right time
- 56. Monitoring policies • Infection control surveillance • Bacteriological surveillance • Prescription surveillance
- 57. Thank you