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PRESENTATION BY:
    R.MADHURI
    ROLL NO:5
    PHARM-D III YEAR
1
INTRODUCTION
• First discovered in 1929 by A. Fleming. Brought
  into widespread use in the 1940s.

• Antibiotic: Of biological origin. Produced by a
microbe, inhibits other microbes.

•Bacteria are rapidly growing organisms. A typical
infection that causes symptoms will contain many
bacteria.

•Based on normal genetic variability, this population of bacteria will have a
wide variability of response to an individual antibiotic.

•The treatment of bacterial infections is increasingly complicated by the ability of
bacteria to develop resistance to antibiotics


   2
When antibiotics are used, six events may occur
with only one being beneficial:


•Antibiotic aids the host defenses to gain control and eliminate the infection.


On the other hand…..
•The antibiotic may cause toxicity or allergy.
•Initiate a super infection with resistant bacteria.
•Promote microbial chromosomal mutations to resistance.
•Encourage resistance gene transfer to susceptible species.
•Promote the expression of dormant resistance genes.




    3
There are a number of reasons why
bacterial resistance should be a concern
for physicians….
• First, resistant bacteria, particularly staphylococci, enterococci, Klebsiella pneumoniae,
and Pseudomonas are becoming commonplace in healthcare institutions.

• Bacterial resistance often results in treatment failure, which can have serious
consequences, especially in critically ill patients.

• Inadequate empiric antibacterial therapy, defined as the initial use of an antibacterial
agent to which the causative pathogen was not susceptible, has been associated with
• Resistant bacteria may also spread and become broader infection-control species.
increased mortality rates in patients with bloodstream infections due to resistant
problems, not only within healthcare institutions, but in communities as well.

• The spread of resistant bacteria within the community poses obvious additional
problems for infection control.

• Prolonged therapy with antimicrobial agents, such as vancomycin or linezolid,
may also lead to the development of low-level resistance that compromises therapy.
    4
WHAT IS ANTIBIOTIC MISUSE…..?
   Taking antibiotics when they are not
    needed:
     for viral infections
   When needed, taking antibiotics
    incorrectly:
     Stopping the medicine when you
       feel better - not finishing the
       prescription
     Saving antibiotics for a future
       illness
     Sharing or using other’s medicine




     5
FACTORS CONTRIBUTING TO
             Patient
RESISTANCE movement within
   Travel of        and
   people           between medical     Appropriate
   and              institutions        ness of use
   foodstuffs

 Socioecono                                   Infection
 mic                                          control
 factors                                      measures


Antibiotic use                        Antibiotic
                                      resistance
                                           Dose/durati
  poor                                        on of
  adherence                                   treatment

                                      Non-
      over-                           antibiotic
      prescribing       Gene          selection
                        transfer
                                                          6
ACTION OF ANTIBIOTICS ON BACTERIAL
CELL




                                     7
RESISTANCE TO ANTIBIOTICS
   Denied access: membrane becomes impermeable for antibiotic: e.g. Imipenem
   Antibiotic modification: some bacteria have enzymes that cleave or modify
    antibiotics: e.g. beta lactamase inactivates penicillin
   Altered target site: antibiotic cannot bind to its intended target because the
    target itself has been modified
   Pumping out the antibiotic faster than it gets in: e.g. tetracyclines
   Alternative target (typically enzyme): e.g. Alternative penicillin binding protein
    (PBP2a) in MRSA




                                                                                     8
MECHANISMS FOR ACQUIRING
RESISTANCE




                           9
DEVELOPMENT OF
RESISTANCE   Bacterial cells that have
                       developed resistance are not
                       killed off.


                       They continue to divide
                       resulting in a completely
                       resistant population.



                       Mutation and evolutionary
                       pressure cause a rapid increase
                       in resistance to antibiotics.
                                                   10
•The use of broad-spectrum antibiotics rather than narrow-spectrum drugs is
known to favor the emergence of resistance by broadly eliminating competing
susceptible flora, leading to the rise in resistance.
• It permits the SUPER INFECTION effect.




                                                                         11
EVOLUTION OF..
ANTIBIOTIC
RESISTANCE




                 12
Managing the Drug Resistance Problem
Limiting the Spread of Drug Resistant Bacteria
• Use better treatment strategies….Give the optimal antibiotic
 Is it necessary ?
 Is the pathogen sensitive ?
 Will the drug get to the site of infection ?
 Are therapeutic concentrations achieved at the site of infection ?
 Is toxicity acceptable (risk vs. benefit)
 Is the therapy cost effective ?
 Better immunization programmes
 Improved hygiene and nutrition

•Better education of health care professionals to prevent the prescription of
unnecessary antibiotics

• A second strategy is to ensure that they are used for the appropriate time
Patient compliance is a key problem in that respect

• A third strategy for limiting drug resistance is to use antibiotic combinations
   13
Phage Therapy
Phage can be applied on the wounds of a patient to kill the bacteria, and has
proven to be quite effective. Of course, it cannot be used for internal
infections, and the bacteria might also develop phage resistance.

Mobilization of Host Defense Mechanisms
This can be achieved through the mobilization of innate immunity such as
defensins, or through the development of vaccines, which make antibiotics
less necessary. The idea is to boost the immune response capability to control
the bacterial infection. Of course, that approach is not always successful.

The Use of Normal Bacterial Flora
One could also potentially use normal bacterial flora to suppress some pathogens.

Development of New Antibiotics
Although the idea is appealing, in reality, it is extremely difficult since 99% of the
drug candidates fail, and antibiotics are not as profitable as other, more
Commonly used, drugs.
   14
EXAMPLES OF FEW SPECIES THAT HAVE
DEVELOPED RESISTANCE…
E coli: Development of Resistance to Third-Generation
Cephalosporins
E coli is a common cause of urinary tract infections and bacteremia in humans, and is
frequently resistant to aminopenicillins, such as amoxicillin or ampicillin, and narrow
spectrum cephalosporins

S Aureus: Development of High-Level Vancomycin Resistance
MRSA is a common cause of infection among hospitalized patients. Vancomycin is the
typical treatment for these infections, but over the last decade there has been increasing
concern about the development of MRSA strains with reduced susceptibility to
vancomycin.

P aeruginosa: Development of Multidrug Resistance
P aeruginosa is a major cause of opportunistic infections among immunocompromised
individuals. The spread of this organism in healthcare settings is often difficult to control
due to the presence of multiple intrinsic and acquired mechanisms of antimicrobial
resistance.

    15
CONCLUSION
 Through billions of years of evolution, microbes have developed myriad defense
mechanisms designed to ensure their survival. This protection is readily transferred to
their fellow life forms via transposable elements.


 Despite very early warnings, humans have chosen to abuse the gift of antibiotics and
have created a situation where all microorganisms are resistant to some antibiotics and
some microorganisms are resistant to all antibiotics.

 Finally, antibiotics are ‘‘societal drugs’’ that affect microbial resistance not only in the
person taking the drug but also everyone else, because resistance genes are easily passed…

 Improving hygiene in hospitals, Screening of hospital visitors and isolating patients
can control the spread of resistance to some extent.


          1983-87            1988-92           1993-97           1998-2002          2002-
        2008
                       Antibacterial Drugs Approved By FDA
REFERENCE
• The impact of antibiotic use on resistance development and persistence
 eresa M. Barbosa,1 Stuart B. Levy 1,2

• Mechanisms of Antibiotic Resistance in the Microbial World
Ying ZHANG ,Baltimore, USA

• Mechanisms of Antimicrobial Resistance in Bacteria
Fred C. Tenover, PhD

•Division of Healthcare Quality Promotion, Centers for Disease Control and
Prevention, Atlanta, Georgia, USA

•http://www.who.int/drugresistance/amr_q&a.pdf


•http://www.accesspharmacy.com/content.

•http://biomed.emory.edu/PROGRAM_SITES/PBEE/pdf/tenover1.pdf


   17
18

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R.Madhuri's Presentation on Antibiotic Resistance

  • 1. PRESENTATION BY: R.MADHURI ROLL NO:5 PHARM-D III YEAR 1
  • 2. INTRODUCTION • First discovered in 1929 by A. Fleming. Brought into widespread use in the 1940s. • Antibiotic: Of biological origin. Produced by a microbe, inhibits other microbes. •Bacteria are rapidly growing organisms. A typical infection that causes symptoms will contain many bacteria. •Based on normal genetic variability, this population of bacteria will have a wide variability of response to an individual antibiotic. •The treatment of bacterial infections is increasingly complicated by the ability of bacteria to develop resistance to antibiotics 2
  • 3. When antibiotics are used, six events may occur with only one being beneficial: •Antibiotic aids the host defenses to gain control and eliminate the infection. On the other hand….. •The antibiotic may cause toxicity or allergy. •Initiate a super infection with resistant bacteria. •Promote microbial chromosomal mutations to resistance. •Encourage resistance gene transfer to susceptible species. •Promote the expression of dormant resistance genes. 3
  • 4. There are a number of reasons why bacterial resistance should be a concern for physicians…. • First, resistant bacteria, particularly staphylococci, enterococci, Klebsiella pneumoniae, and Pseudomonas are becoming commonplace in healthcare institutions. • Bacterial resistance often results in treatment failure, which can have serious consequences, especially in critically ill patients. • Inadequate empiric antibacterial therapy, defined as the initial use of an antibacterial agent to which the causative pathogen was not susceptible, has been associated with • Resistant bacteria may also spread and become broader infection-control species. increased mortality rates in patients with bloodstream infections due to resistant problems, not only within healthcare institutions, but in communities as well. • The spread of resistant bacteria within the community poses obvious additional problems for infection control. • Prolonged therapy with antimicrobial agents, such as vancomycin or linezolid, may also lead to the development of low-level resistance that compromises therapy. 4
  • 5. WHAT IS ANTIBIOTIC MISUSE…..?  Taking antibiotics when they are not needed:  for viral infections  When needed, taking antibiotics incorrectly:  Stopping the medicine when you feel better - not finishing the prescription  Saving antibiotics for a future illness  Sharing or using other’s medicine 5
  • 6. FACTORS CONTRIBUTING TO Patient RESISTANCE movement within Travel of and people between medical Appropriate and institutions ness of use foodstuffs Socioecono Infection mic control factors measures Antibiotic use Antibiotic resistance Dose/durati poor on of adherence treatment Non- over- antibiotic prescribing Gene selection transfer 6
  • 7. ACTION OF ANTIBIOTICS ON BACTERIAL CELL 7
  • 8. RESISTANCE TO ANTIBIOTICS  Denied access: membrane becomes impermeable for antibiotic: e.g. Imipenem  Antibiotic modification: some bacteria have enzymes that cleave or modify antibiotics: e.g. beta lactamase inactivates penicillin  Altered target site: antibiotic cannot bind to its intended target because the target itself has been modified  Pumping out the antibiotic faster than it gets in: e.g. tetracyclines  Alternative target (typically enzyme): e.g. Alternative penicillin binding protein (PBP2a) in MRSA 8
  • 10. DEVELOPMENT OF RESISTANCE Bacterial cells that have developed resistance are not killed off. They continue to divide resulting in a completely resistant population. Mutation and evolutionary pressure cause a rapid increase in resistance to antibiotics. 10
  • 11. •The use of broad-spectrum antibiotics rather than narrow-spectrum drugs is known to favor the emergence of resistance by broadly eliminating competing susceptible flora, leading to the rise in resistance. • It permits the SUPER INFECTION effect. 11
  • 13. Managing the Drug Resistance Problem Limiting the Spread of Drug Resistant Bacteria • Use better treatment strategies….Give the optimal antibiotic  Is it necessary ?  Is the pathogen sensitive ?  Will the drug get to the site of infection ?  Are therapeutic concentrations achieved at the site of infection ?  Is toxicity acceptable (risk vs. benefit)  Is the therapy cost effective ?  Better immunization programmes  Improved hygiene and nutrition •Better education of health care professionals to prevent the prescription of unnecessary antibiotics • A second strategy is to ensure that they are used for the appropriate time Patient compliance is a key problem in that respect • A third strategy for limiting drug resistance is to use antibiotic combinations 13
  • 14. Phage Therapy Phage can be applied on the wounds of a patient to kill the bacteria, and has proven to be quite effective. Of course, it cannot be used for internal infections, and the bacteria might also develop phage resistance. Mobilization of Host Defense Mechanisms This can be achieved through the mobilization of innate immunity such as defensins, or through the development of vaccines, which make antibiotics less necessary. The idea is to boost the immune response capability to control the bacterial infection. Of course, that approach is not always successful. The Use of Normal Bacterial Flora One could also potentially use normal bacterial flora to suppress some pathogens. Development of New Antibiotics Although the idea is appealing, in reality, it is extremely difficult since 99% of the drug candidates fail, and antibiotics are not as profitable as other, more Commonly used, drugs. 14
  • 15. EXAMPLES OF FEW SPECIES THAT HAVE DEVELOPED RESISTANCE… E coli: Development of Resistance to Third-Generation Cephalosporins E coli is a common cause of urinary tract infections and bacteremia in humans, and is frequently resistant to aminopenicillins, such as amoxicillin or ampicillin, and narrow spectrum cephalosporins S Aureus: Development of High-Level Vancomycin Resistance MRSA is a common cause of infection among hospitalized patients. Vancomycin is the typical treatment for these infections, but over the last decade there has been increasing concern about the development of MRSA strains with reduced susceptibility to vancomycin. P aeruginosa: Development of Multidrug Resistance P aeruginosa is a major cause of opportunistic infections among immunocompromised individuals. The spread of this organism in healthcare settings is often difficult to control due to the presence of multiple intrinsic and acquired mechanisms of antimicrobial resistance. 15
  • 16. CONCLUSION  Through billions of years of evolution, microbes have developed myriad defense mechanisms designed to ensure their survival. This protection is readily transferred to their fellow life forms via transposable elements.  Despite very early warnings, humans have chosen to abuse the gift of antibiotics and have created a situation where all microorganisms are resistant to some antibiotics and some microorganisms are resistant to all antibiotics.  Finally, antibiotics are ‘‘societal drugs’’ that affect microbial resistance not only in the person taking the drug but also everyone else, because resistance genes are easily passed…  Improving hygiene in hospitals, Screening of hospital visitors and isolating patients can control the spread of resistance to some extent. 1983-87 1988-92 1993-97 1998-2002 2002- 2008 Antibacterial Drugs Approved By FDA
  • 17. REFERENCE • The impact of antibiotic use on resistance development and persistence eresa M. Barbosa,1 Stuart B. Levy 1,2 • Mechanisms of Antibiotic Resistance in the Microbial World Ying ZHANG ,Baltimore, USA • Mechanisms of Antimicrobial Resistance in Bacteria Fred C. Tenover, PhD •Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA •http://www.who.int/drugresistance/amr_q&a.pdf •http://www.accesspharmacy.com/content. •http://biomed.emory.edu/PROGRAM_SITES/PBEE/pdf/tenover1.pdf 17
  • 18. 18