1. Antibiotics : Use and overuse
KM Murali
MD (Med), DM (Neph), DNB (Neph), F Neph (Canada)
Consultant Nephrologist
MIMS, Kozhikode

2. First world war

3. Second world war

4. Cold war

5. Man
vs
Microbe
Timeless 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

20. Penicillin vs Cephalosporin

21. Penicillin vs Cephalosporin vs Carbapenams

22. Penicillin vs Aztreonam

23. Penicillin vs Vancomycin

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

39. Penicillinase
Oxacilinase
Cephalosporinase
Carbenicilinase
Carbapenamase
ESBL

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

46. Pseudomonas: Efflux pump

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