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
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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.
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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.
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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
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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
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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
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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.
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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.
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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
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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.
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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.
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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
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