La resistencia bacteriana, necesidad de innovación. dr. ian m. gould

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  • The final point I want to briefly mention is that we have looked at the relationships between prevalence of the ALERT organisms and antibiotic use.
  • La resistencia bacteriana, necesidad de innovación. dr. ian m. gould

    1. 1. Dr. Ian M. Gould Medical Microbiology Aberdeen Royal Infirmary Empirical Antibiotic Therapy; a Need for Innovation “ At least the waiting lists are improving - I only had to wait one week to get MRSA”
    2. 2. IF YOU DON’T LOOK PROPERLY , YOU WON’T SEE IT
    3. 3. How well do you know your enemy: How long have bacteria existed on our planet? <ul><ul><li>3.5 billion years </li></ul></ul><ul><ul><li>1 billion years </li></ul></ul><ul><ul><li>500 million years </li></ul></ul><ul><ul><li>200 million years </li></ul></ul><ul><ul><li>50 million years </li></ul></ul>
    4. 4. The Enemy <ul><li>Microbes </li></ul><ul><li>Very old </li></ul><ul><li>Highly adaptable </li></ul><ul><li>Unparalleled ability to survive: virulence factors, antigenic changes </li></ul><ul><li>Generation time of 20 minutes vs 30 years in man </li></ul><ul><li>Only 10% of cells in/on our bodies are human, the rest are bacteria </li></ul>Stromatolites are the fossalized remains of a colony or mat of Cyanobacteria that normally exhibits either a domed or a column-like shape. The oldest known stromatolites occur in rocks in Warrawoona Group of Western Australia and are some 3.4 to 3.5 billion years old. Homo sapiens lived from 250,000 years ago.
    5. 8. <ul><li>It is time to close the book on infectious diseases, and declare the war against pestilence won </li></ul><ul><li>Spellberg B: Dr William H, Stewart: mistaken or maligned? </li></ul><ul><li>Clin Infect Dis 2008, 47:294. </li></ul>
    6. 9. Paradox 1 <ul><li>Antibiotics initially led to poorer hospital hygiene </li></ul>
    7. 10. “ Haven’t you heard – we’ve got MRSA sweeping the hospital”
    8. 11. MRSA Infection Control Just the hands Frickerson!
    9. 12. Environmental contamination 20-50 % antibiotic use in humans not necessary 40-80% antibiotics used for animals questionable value
    10. 16. Integron MULTIPLE ANTIBIOTIC RESISTANT DETERMINANT GENE CASSETTES conserved DNA 4FQ integrase tet macrolide  -lactam promoter Amino- glycoside conserved DNA
    11. 18. Paradox 3 <ul><li>Antibiotics increase infections </li></ul>
    12. 19. Deaths from HAI, USA <ul><li>1992………..13,300 </li></ul><ul><li>2008……… 100,000 </li></ul><ul><li>Antibiotics and Resistance,(IDSA website/Researchandmarket.com) </li></ul>
    13. 20. Jan 96 Jan 97 Jan 98 Jan 99 Jan 00 % MRSA Sum of lagged antimicrobial series % MRSA Total ab. Consumption: DDD/1000 bed days Relationship between % MRSA and antibiotic use. (3 rd GC, FQ, MAC) Emerg. Inf. Dis 2004, 1432 3 rd GC lags = 4 – 7 months FQ lags = 4 & 5 months MAC lags = 1 – 3 months
    14. 22. CID 2008:46 (Suppl 1) S25 MA of Risk of C diff v Antibiotic Exposure
    15. 23. HPS Reported bacteraemia
    16. 24. The Antibiotic Resistance Spiral Adapted from: J. Carlet. resistance RESISTANCE CONCERN SELECTION BROAD-SPECTRUM EMPIRIC THERAPY cross- transmission dosage duration new antibiotics (promotion from pharmaceutical industry)
    17. 26. Current MDR Concerns <ul><li>ESBLS </li></ul><ul><li>16S rRNA Methylase +/- ESBL/MBL. HL res to all aminoGs, transposon/plasmid born </li></ul><ul><li>PMQR +/- ESBL. (Gyr/Topo,efflux and hydrolysis) </li></ul><ul><li>Carbapenemases </li></ul><ul><li>Acinetobacter </li></ul><ul><li>Burkholderia </li></ul><ul><li>Stenotrophomonas </li></ul>
    18. 29. ESBLs <ul><li>TEM(Temoneira)/SHV(sulhydril) (over 100 in Enterobacteriaceae) </li></ul><ul><li>CTX-M (from Kluyvera spp) </li></ul><ul><li>VEB/PER etc (uncommon in UK) </li></ul><ul><li>OXA(Class D,Turkey) </li></ul><ul><li>IRTs </li></ul>
    19. 32. Courtesy of D Livermore, HPA
    20. 33. Carbapenemases <ul><li>Class A inhib by clavulanate eg KPC (plasmid), SME IMI/NMC-A, GES </li></ul><ul><li>Class B metalloenzymes eg IMP(SE Asia), VIM (Europe) aztreonam susc, plasmid/integron located </li></ul><ul><li>Class C, CMY-10 in an E. aerogenes </li></ul><ul><li>Class D in A. baumannii </li></ul>
    21. 34. Pseudomonas aeruginosa: proportion of invasive isolates resistant to carbapenems in 2006
    22. 35. McGowan & Tenover ‘04 Nature Reviews Microbiology 2 251
    23. 36. SPAIN – EARSS data 2007
    24. 38. Incidence of inadequate antibiotic therapy in hospitals N=147 N =1255 N = 34 n = 146 N = 27 Bloodstream infection Nosocomial/Ventialor-associated pneumonia Ibrahim et al Chest 2000; 118:146-155 Leibovici et al J Intern Med 1998; 244:379-386 Luna et al Chest 1997; 111:676-685. Alvarez-Lerma Inten Care Med 1996; 22:387-394 Rello et al Am J Respir Crit Care 1997; 156:196-200
    25. 39. Bloodstream infections Nosocomial/Ventilator-associated pneumonia Influence of inadequate antibiotic therapy on mortality Ibrahim et al Chest 2000; 118:146-155 Leibovici et al J Intern Med 1998; 244:379-386 Luna et al Chest 1997; 111:676-685. Alvarez-Lerma Inten Care Med 1996; 22:387-394 Rello et al Am J Respir Crit Care 1997; 156:196-200
    26. 40. For Septic shock: Each hour delay in antibiotic initiation over the first 6 hours has been shown to be associated with an average decrease in survival of 7.6% Adapted from Kumar A, Critical Care medicine 2006 Vol.34, No 6.
    27. 43. ViResiST
    28. 44. Conclusions <ul><li>Antibiotic resistance is increasing at an unprecedented rate. </li></ul><ul><li>The correct empiric therapy saves lives (not too little) and prevents resistance (not too much) </li></ul><ul><li>Local data is essential to inform local empiric therapy protocols. </li></ul>
    29. 45. Thanks

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