Antibiotic resistance-MADHURI RUDRARAJU


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Antibiotic resistance-MADHURI RUDRARAJU

  2. 2. INTRODUCTION• First discovered in 1929 by A. Fleming. Brought into widespread use in the 1940s.• Antibiotic: Of biological origin. Produced by amicrobe, inhibits other microbes.•Bacteria are rapidly growing organisms. A typicalinfection that causes symptoms will contain manybacteria.•Based on normal genetic variability, this population of bacteria will have awide variability of response to an individual antibiotic.•The treatment of bacterial infections is increasingly complicated by the ability ofbacteria to develop resistance to antibiotics 2
  3. 3. When antibiotics are used, six events may occurwith 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. 4. There are a number of reasons whybacterial resistance should be a concernfor 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 seriousconsequences, especially in critically ill patients.• Inadequate empiric antibacterial therapy, defined as the initial use of an antibacterialagent 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 resistantproblems, not only within healthcare institutions, but in communities as well.• The spread of resistant bacteria within the community poses obvious additionalproblems 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. 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. 6. FACTORS CONTRIBUTING TO PatientRESISTANCE movement within Travel of and people between medical Appropriate and institutions ness of use foodstuffs Socioecono Infection mic control factors measuresAntibiotic use Antibiotic resistance Dose/durati poor on of adherence treatment Non- over- antibiotic prescribing Gene selection transfer 6
  8. 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. 10. DEVELOPMENT OFRESISTANCE 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. 11. •The use of broad-spectrum antibiotics rather than narrow-spectrum drugs isknown to favor the emergence of resistance by broadly eliminating competingsusceptible flora, leading to the rise in resistance.• It permits the SUPER INFECTION effect. 11
  13. 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 ofunnecessary antibiotics• A second strategy is to ensure that they are used for the appropriate timePatient compliance is a key problem in that respect• A third strategy for limiting drug resistance is to use antibiotic combinations 13
  14. 14. Phage TherapyPhage can be applied on the wounds of a patient to kill the bacteria, and hasproven to be quite effective. Of course, it cannot be used for internalinfections, and the bacteria might also develop phage resistance.Mobilization of Host Defense MechanismsThis can be achieved through the mobilization of innate immunity such asdefensins, or through the development of vaccines, which make antibioticsless necessary. The idea is to boost the immune response capability to controlthe 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.Development of New AntibioticsAlthough the idea is appealing, in reality, it is extremely difficult since 99% of thedrug candidates fail, and antibiotics are not as profitable as other, moreCommonly used, drugs. 14
  15. 15. EXAMPLES OF FEW SPECIES THAT HAVEDEVELOPED RESISTANCE…E coli: Development of Resistance to Third-GenerationCephalosporinsE coli is a common cause of urinary tract infections and bacteremia in humans, and isfrequently resistant to aminopenicillins, such as amoxicillin or ampicillin, and narrowspectrum cephalosporinsS Aureus: Development of High-Level Vancomycin ResistanceMRSA is a common cause of infection among hospitalized patients. Vancomycin is thetypical treatment for these infections, but over the last decade there has been increasingconcern about the development of MRSA strains with reduced susceptibility tovancomycin.P aeruginosa: Development of Multidrug ResistanceP aeruginosa is a major cause of opportunistic infections among immunocompromisedindividuals. The spread of this organism in healthcare settings is often difficult to controldue to the presence of multiple intrinsic and acquired mechanisms of antimicrobialresistance. 15
  16. 16. CONCLUSION Through billions of years of evolution, microbes have developed myriad defensemechanisms designed to ensure their survival. This protection is readily transferred totheir fellow life forms via transposable elements. Despite very early warnings, humans have chosen to abuse the gift of antibiotics andhave created a situation where all microorganisms are resistant to some antibiotics andsome microorganisms are resistant to all antibiotics. Finally, antibiotics are ‘‘societal drugs’’ that affect microbial resistance not only in theperson taking the drug but also everyone else, because resistance genes are easily passed… Improving hygiene in hospitals, Screening of hospital visitors and isolating patientscan control the spread of resistance to some extent. 1983-87 1988-92 1993-97 1998-2002 2002- 2008 Antibacterial Drugs Approved By FDA
  17. 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 WorldYing ZHANG ,Baltimore, USA• Mechanisms of Antimicrobial Resistance in BacteriaFred C. Tenover, PhD•Division of Healthcare Quality Promotion, Centers for Disease Control andPrevention, Atlanta, Georgia, USA••• 17
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