ANTIBIOTIC RESISTANCE

PRESENTATION BY:R.MADHURIROLL NO:5PHARM-D III YEAR

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

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

• 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.

INTRODUCTION

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

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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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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 increased mortality rates in patients with bloodstream infections due to resistant species.• 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.

• Resistant bacteria may also spread and become broader infection-control problems, not only within healthcare institutions, but in communities as well.

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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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FACTORS CONTRIBUTING TO RESISTANCE

Antibiotic use Antibiotic resistance

Travel of peopleand foodstuffs

Patient movement within andbetween medical institutions

Socioeconomicfactors

Appropriateness of use

poor adherence

Dose/duration of treatment

over-prescribing Gene

transfer

Non-antibioticselection

Infection controlmeasures

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ACTION OF ANTIBIOTICS ON BACTERIAL CELL

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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

RESISTANCE TO ANTIBIOTICS

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MECHANISMS FOR ACQUIRING RESISTANCE

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DEVELOPMENT OF RESISTANCEBacterial 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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•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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EVOLUTION OF.. ANTIBIOTIC RESISTANCE

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Managing the Drug Resistance ProblemLimiting 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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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.

Development of New Antibiotics

Phage TherapyPhage 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 MechanismsThis 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 FloraOne could also potentially use normal bacterial flora to suppress some pathogens.

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E coli: Development of Resistance to Third-Generation CephalosporinsE 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 ResistanceMRSA 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 ResistanceP aeruginosa is a major cause of opportunistic infections among immunocompromised individuals. The spread of this organism in healthcare settings is often difficult to controldue to the presence of multiple intrinsic and acquired mechanisms of antimicrobial resistance.

EXAMPLES OF FEW SPECIES THAT HAVE DEVELOPED RESISTANCE…

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.

CONCLUSION

1983-87 1988-92 1993-97 1998-2002 2002-2008

Antibacterial Drugs Approved By FDA

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REFERENCE

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

• 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 WorldYing ZHANG ,Baltimore, USA

• Mechanisms of Antimicrobial Resistance in BacteriaFred 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://biomed.emory.edu/PROGRAM_SITES/PBEE/pdf/tenover1.pdf

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THANK YOU…..