THIS PRESENTATION IS ABOUT THE MISUSE OF DRUGS WHICH CAUSE RESISTANCE AND ITS IMPACT ON HEALTH AND ENVIRONMENT AND HOW PHARMACISTS COMBAT IT

1.  ROLE OF PHARMACISTS IN COMBATING DRUG RESISTANCE.
 BY Neel Ratnam

3.  What is antimicrobial resistance
 Why antibacterial resistance is a concern To
Pharmacists
 How antibacterials work
 Mechanisms of resistance to antibacterials
 Strategies to contain resistance

4. Microbiologist
Physician
Bacterial
sensitivity
test and find
out the
possible
causes of
development Treat Infection

5. Microbiologist
Physician
Pharmacologist
Advise the
proper and
adequate
antibiotics with
balancing the
economy of
hospital

6.  Throughout history there has been a
continual battle between human beings and
multitude of micro-organisms that cause
infection and disease.
 The pharmacist's role in combating and
preventing infectious diseases is essential as
antibiotic and vaccine regimens become
more complex due to the continuously
evolving epidemiology of infections.

7.  The decrease in drug development makes the
preservation of currently available
antibiotics paramount.
 Pharmacists as Custodian and experts in
Medicines Must Play a Pivotal Role In
combating Drug Resistance and Must
understand How drug resistance happens at
molecular level.

8. In his 1945 Nobel Prize lecture, Fleming
himself warned of the danger of resistance –
“It is not difficult to make microbes
resistant to penicillin in the laboratory by
exposing them to concentrations not
sufficient to kill them”
History
Nobel Lecture, December 11, 1945
Sir Alexander Fleming
The Nobel Prize in Physiology or Medicine
1945

9. Environmental
Factors
Drug
Related
Factors
Patient
Related
Factors
Prescriber
Related
Factors
Antibiotic
Resistance

10.  Huge populations and overcrowding
 Poor sanitation
 Ineffective infection control programs
 Widespread use of antibiotics in animal husbandry and
agriculture and as medicated cleansing products

12.  Over the counter availability of antimicrobials
 Counterfeit and substandard drug causing sub-
optimal blood concentration
 Irrational fixed dose combination of
antimicrobials
 Soaring use of antibiotics
Policy
Decision at
Higher
level

13.  Poor adherence of dosage Regimens
 Poverty
 Lack of sanitation concept
 Lack of education
 Self-medication
 Misconception
Patient
Counseling,
Awareness
Program

14.  Inappropriate use of available drugs
 Increased empiric poly-antimicrobial use
 Poor clinical practice
 Inadequate dosing
 Lack of current knowledge and training

16.  Resistant organisms lead to treatment failure
 Increased mortality
 Resistant bacteria may spread in Community
 Add burden on healthcare costs
 Threat to return to pre-antibiotic era
 Selection pressure

17. • The concentration of drug at the site of
infection must inhibit the organism and
also remain below the level that is toxic to
human cells.
•Principles Of Chemotherapy must be
applied when selecting which antibiotic to
use
Antibiotic Resistance

18.  Selection of the most appropriate antimicrobial agent
requires knowing
1) The organism’s identity : gram +/-
2) The organism’s susceptibility to a particular agent
3) The site of the infection- blood-brain barrier effects,
protein binding, lipid solubility and MW of the drug
4) Patient’s factor- Renal/Hepatic nature,age, gender,
pregnancy, lactation and immune system
5) The cost of therapy

19. 1. Inhibition of cell wall synthesis
2. Inhibition of function of cell membrane
3. Inhibition of protein synthesis
4. Inhibition of nucleic acid synthesis
5. Inhibition of folic acid synthesis

21. Defined as micro-organisms that are not
inhibited by usually achievable systemic
concentration of an antimicrobial agent with
normal dosage schedule and / or fall in the
minimum inhibitory concentration (MIC)
range.

23. Understanding Mechanism of Antibiotic
Resistance at Molecular Level
Intrinsic (Natural) Acquired
Genetic Methods
Chromosomal Methods
Mutations
Extra chromosomal Methods
Plasmids

24.  It occurs naturally
1. Lack target :
• No cell wall; innately resistant to
penicillin
2. Innate efflux pumps:
• Drug blocked from entering cell or
↑ export of drug (does not achieve
adequate internal concentration).
Eg. E. coli, P. aeruginosa
3. Drug inactivation: Cephalosporinase
in Klebsiella

25. Acquired Resistance
Mutations
• It refers to the change in DNA structure
of the gene.
• Occurs at a frequency of one per ten
million cells.
• Eg. Mycobacterium tuberculosis,
Mycobacterium lepra.
• Often mutants have reduced
susceptibility

26. Plasmids
• Extra chromosomal genetic elements can replicate
independently and freely in cytoplasm.
• Plasmids which carry genes resistant ( r-genes) are
called R-plasmids.
• These r-genes can be readily transferred from one
R-plasmid to another plasmid or to chromosome.
• Much of the drug resistance encountered in clinical
practice is plasmid mediated

27. Mechanism of Resistance by
Gene Transfer
• Transfer of r-genes from one
bacterium to another
 Conjugation
 Transduction
 Transformation
• Transfer of r-genes between
plasmids within the bacterium
 By transposons
 By Integrons

28. Transfer of r-genes from one
Bacterium to Another
 Conjugation : Main mechanism for spread of
resistance
The conjugative plasmids make a connecting
tube between the 2 bacteria through which
plasmid itself can pass.

29. Transfer of r-genes from one
Bacterium to Another
 Transduction : Less common method
The plasmid DNA enclosed in a
bacteriophage is transferred to another
bacterium of same species. Seen in
Staphylococci , Streptococci
 Transformation : least clinical problem.
Free DNA is picked up from the environment
(i.e.. From a cell belonging to closely related or
same strain.

30.  Transposons are sequences of DNA that can
move around different positions within the
genome of single cell.
 The donor plasmid containing the
Transposons, co-integrate with acceptor
plasmid. They can replicate during co-
integration
 Both plasmids then separate and each
contains the r-gene carrying the transposon.

32.  Integron is a large mobile DNA that can
spread Multidrug resistance
 Each Integron is packed with multiple
gene casettes, each consisting of a
resistance gene attached to a small
recognition site.
 These genes encode several bacterial
functions including resistance and
virulence.

33. • Prevention of drug accumulation in the bacterium
• Modification/protection of the target site
• Use of alternative pathways for metabolic / growth
requirements
• By producing an enzyme that inactivates the antibiotic

34. Decreased permeability: Porin Loss
Interior of organism
Cell wall
Porin channel
into organism
Antibiotic
Antibiotics normally enter bacterial cells via porin channels
in the cell wall

35. Interior of organism
Cell wall
Modified target site
Antibiotic
Changed site: blocked binding
Antibiotics are no longer able to bind to modified binding proteins
on the bacterial cell surface

36. • Bacteria are capable of flushing out
antibiotics before they reach their target
site.

37. Environment
Cytoplasm
Porin
Efflux System Pump
Efflux System
Exit Portal
Linker
Lipoprotein

39. Modification/Protection of the Target site
Resistance resulting from altered target sites:
Target sites Resistant Antibiotics
Ribosomal point mutation Tetracyclines,Macrolid
es, Clindamycin
Altered DNA gyrase Fluoroquinolones
Modified penicillin binding
proteins (Strepto.pneumonia)
Penicillins
Mutation in DNA dependant
RNA polymerase
(M.tuberculosis)
Rifampicin

40. Drug Mechanism of resistance
Pencillins &
Cephalosporiins
B Lactamase cleavage of the Blactam
ring
Aminoglycosides Modification by phosphorylating,
adenylating and acetylating enzymes
Chloramphenicol Modification by acetylytion
Erythromycin Change in receptor by methylation of r
RNA
Tetracycline Reduced uptake / increased export
Sulfonamides
Active export out of the cell & reduced
affinity of enzymes

41.  Developing new antibiotics
 Judicious use of the existing antibiotics
 Community Pharmacists as Gateway
Practitioners-Prevent Antibiotic Misuse.
 Vaccination-by preventing primary
infection and indirectly by preventing
bacterial super infection

42.  Education:-
-Patient and clinician education
 infection-control practices such as
general hygiene, hand hygiene, cough
etiquette, immunizations, and staying
home when sick

43.  Prudent antimicrobial prescribing
 UK hospitals have appointed microbiologists or
infectious diseases physicians with antibiotic
management , Pharmacists as Drug Experts Must
undertake such roles as Lead Antibiotics
Pharmacists
 Establishment of Hospital Antibiotic Policy

44.  A dedicated pharmacist has the time and skills to
monitor antibiotic prescribing and manage it
appropriately
 Key roles for pharmacists include:-
• Education of medical,
• Pharmaceutical and
• Nursing staff,
• Audit of local practices,
• Monitoring of antibiotic consumption,
• Participation in infection control,
• Formulary development and
• Appraisal of new antimicrobials

45.  Many physicians, medical microbiologists and
infectious diseases physicians might feel
threatened by such proposals but
Pharmacists are inseparable to drugs

46.  Linezolid: targets 50S ribosome
 Tigecycline: targets 30S ribosome
 Daptomycin: depolarization of bacterial cell membrane
 Dalbavacin: inhibits cell wall synthesis
 Telavacin: inhibition of cell wall synthesis and disruption of
membrane barrier function
 Ceftobiprole: 5th generation cephalosporins
 Ceftaroline: Advanced generation cephalosporin
 Iclaprim: Inhibits Dihydrofolate reductase

47.  Target definitive therapy to known pathogen
 Treat infection, not contamination
 Treat infection, not colonization
 Isolate Pathogen, utilise microbiology lab
 Break the chain of contagion – Keep our hands clean.

48. Thank You
!!!!!!!!!!!!
Hope is not exhausted….yet