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pathway presentation.pptx

  1. 1. Bacterial Antibiotic Resistance Old genes, new problems Presented By: Anila Sajjad
  2. 2. Throughout history there has been a continual battle between human beings and multitude of micro- organisms that cause infection and disease.
  3. 3. Microbial Pathogenesis Entry into the Host Must access and adhere to host tissues, penetrate or evade host defenses, and damage tissue to cause disease. Portals of Entry The three main portals of entry are: • Mucous membranes • Skin • Parenteral
  4. 4. Mechanisms of Bacterial Resistance : how DO they do it ??
  5. 5. • Resistant organisms lead to treatment failure • Increased mortality • Resistant bacteria may spread in Community • Low level resistance can go undetected • Added burden on healthcare costs • Threatens to return to pre-antibiotic era • Selection pressure Why is a concern resistance?
  6. 6. Antibiotic Resistance • 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. • 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. Silver L. L, 2011
  7. 7. Antibiotic Resistant Bacteria Are: • Bacteria that mutate and are able to resist the antibiotics that are meant to kill them. • This is a normal process speeded up by the overuse and misuse of antibiotics. Bacteria that mutate and are able to resist the antibiotics that are meant to kill them. • Antibiotic that are meant to kill them. • This is a normal process speeded up by the overuse and misuse of antibiotics. Silver L. L, 2011
  8. 8. Cassir, N; (2014)
  9. 9. Bacteria: Mechanism of Resistance Levy et al. 2004
  10. 10. There are four major mechanisms that mediate bacterial resistance to drugs (1)Bacteria produce enzymes that inactivate the drug; eg, lactamases can inactivate penicillins and cephalosporins by cleaving the lactam ring of the drug. (2) Bacteria synthesize modified targets against which the drug has no effect; eg, a mutant protein in the 30S ribosomal subunit can result in resistance to streptomycin, and a methylated 23S rRNA can result in resistance to erythromycin.
  11. 11. Silver L. L, 2011
  12. 12. (3) Bacteria decrease their permeability such that an effective intracellular concentration of the drug is not achieved; eg., changes in porins [membrane transport proteins] can reduce the amount of penicillin entering the bacterium. (4) Bacteria actively export drugs using a "multidrug resistance pump" (MDR pump, or "efflux" pump). The MDR pump imports protons and, in an exchange-type reaction, exports a variety of foreign molecules including certain antibiotics, such as quinolones. • Alekshun M N, 2007
  13. 13. Efflux mediated antibiotic resistance in Gram-negative bacteria Li X-Z, 2015
  14. 14. Wright G.D 2011
  15. 15. Alekshun M N, 2007
  16. 16. Cassir, N., 2014
  17. 17. Podschun R ,1998
  18. 18. Pseudomonas aeruginosa •Pseudomonas aeruginosa is a Gram-negative rod shaped bacteria. It is common inhabitant of soil, water and vegetation. •It is opportunistic pathogen: the disease process begins with some alteration or circumvention of normal host defense •Nearly 70% of people with Cystic Fibrosis are chronically infected with Pseudomonas aeruginosa. •It causes a wide range of diseases, which include septicemia, urinary tract infection, pneumonia, chronic lung infections, endocarditic, and osteochondritis
  19. 19. Resistance Mechanism In Pseudomonas aeruginosa Li X-Z , 2015
  20. 20. Antibiotic resistance and MSRA • Some strains of Staphylococcus aureus evolved because resistant to one or more of the commonly used antibiotic including methicillin. These are termed methicillin- resistant staphylococcus aureus (MRSA) • MSRA is especially prevalent in hospitals: --Here patients tend to be more vulnerable to the infection i.e. older, sicker and weaker --People live together and are examined by doctors and nurses that have touched other patients. --Many antibiotic strains are used, any resistant strains therefore have an advantage. Lowy FD, 2003
  21. 21. Lowy FD, 2003
  22. 22. Silver, L. L. , 2011
  23. 23. Alekshun M N, 2007
  24. 24. Alekshun M N, 2007
  25. 25. Modification/Protection of the Target site Resistance resulting from altered target sites : Target sites Resistant Antibiotics Ribosomal point mutation Tetracyclines, Macrolides, Clindamycin Altered DNA gyrase Fluoroquinolones Modified penicillin binding proteins (Strepto.pneumonia) Penicillines Mutation in DNA dependent RNA polymerase (M. tuberculosis) Rifampicin Wright G.D 2011
  26. 26. SELECTION OF RESISTANT BACTERIA BY OVERUSE & MISUSE OF ANTIBIOTICS • Prescribe unnecessarily long courses of antibiotic therapy • Sold over the counter to the general public • Antibiotics are used in animal feed to prevent infections and promote growth
  27. 27. References: 1. AlekshunMN, et al., (2007) Molecular mechanisms of antimicrobial multi drug resistance , cell, 128(6), 1037-50 2. Cassir, N; Rolain, JM; Brouqui, P (2014). “A new strategy to fight antimicrobial resistance: the revival of old antibiotic”. Frontiers in Microbiology. 5: 55 3. Kruse, et al., (1994) Transfer of multi drug resistant plasmids between bacteria of diverse origins in natural microenvironments, Applied and Environmental Microbiology, p. 4015-4021 4. Li X-Z, Plésiat P, Nikaido H. 18 March 2015. The challenge of effluxmediated antibiotic resistance in Gram-negative bacteria. Clin Microbiol Rev doi:10.1128/CMR.00117-14 5. Lowy FD (2003), Antimicrobial resistance: the example of Staphylococcus aureus, J clin invest, 111(9) : 1265-1273 6. Podschun R, et al., klebsiella spp. as nosocomial pathogen, clin microbiology rev, 11(4) :589-603 7. Silver, L. L. (2011). Challenges of Antibacterial Discovery. Clinical Microbiology Reviews, 24(1), 71–109. doi:10.1128/CMR.00030-10 8. Wright G.D ,(2011), Molecular mechanisms of antibiotic resistance, chem. Commun, 47, 4055-4061

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