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Dr Andrew Dodgson Consultant Microbiologist and Infection Control Doctor

Carbapenemases in practice - lessons learnt from spread in our patch, prophylaxis and first/second line treatments. Dr Andrew Dodgson Consultant Microbiologist and Infection Control Doctor Health Protection Agency & Central Manchester University Hospitals NHS Foundation Trust. Carbapenemases.

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Dr Andrew Dodgson Consultant Microbiologist and Infection Control Doctor

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  1. Carbapenemases in practice - lessons learnt from spread in our patch, prophylaxis andfirst/second line treatments Dr Andrew Dodgson Consultant Microbiologist and Infection Control Doctor Health Protection Agency & Central Manchester University Hospitals NHS Foundation Trust

  2. Carbapenemases • Phenotypically similar enzymes • Genotypically diverse • Epidemiologically Diverse

  3. Classification • Class A (serine based) • KPC, GES, SME, NMC, IMI • Class B (metallo-enzymes) • NDM, IMP, VIM, GIM, SIM, SMP, L1, BCII, Ccra • Class D (serine) • OXA From Queenan and Bush, CMR 2007

  4. Chromosomal Class A SME, NMC, IMI Class B BCII, L1, Ccra Plasmid Class A KPC, GES Class B NDM, IMP Class D OXA Classification From Queenan and Bush, CMR 2007

  5. “Transmission” of Resistance • Clonal spread (particularly ST258 K. pneumofor KPC) • Transmission of plasmid • Other enterobacteriaceae implicated, e.g. Enterobacter, E.coli

  6. Therapy • Need to know local epidemiology • i.e. clonal spread • all isolates have the same antibiogram • or polyclonal, transmission of plasmid • sensitivities vary depending on the background of the strain carrying the plasmid

  7. Local situation? • Many different strains • Same plasmid E. coli Enterobacter KPC producer from a nearby hospital Courtesy N. Woodford

  8. Carbapenems? • Some carbapenemase producers will have MIC’s below the breakpoint for resistance Carmeli et al. CMI 2010

  9. Miriagou et al. CMI 2010.

  10. Carbapenems? • Somecarbapenemase producers will have MIC’s below the breakpoint for resistance • Carbapenems show some activity in animal models against these strains • Strong inoculum effect noted in in-vitro models • MIC ≤8 Mortality 29%, MIC>8 75% Carmeliet al. CMI 2010; Daikoset al, AAC 2009

  11. Other options • Again, depends on susceptibility results. • Many strains multi (or almost pan-) resistant

  12. Other options • Quinolones • Aminoglycosides • Tigecycline • Colistin • Trimethoprim • Fosfomycin • Temocillin • Combinations (which ones?)

  13. What should we do? • Review of 298 published cases (244 BSI) Tzouvelekiset al, CMR 2011

  14. Sensitivities • Data from 30 Blood cultures

  15. What do we do? • Plasmid mediated resistance • Necessitates individual patient approach • Usually based on sensitivities of previous screening or clinical isolates • Some broad principles: • 2 agents • B-lactam (if poss) • Aminoglycoside if possible • Colistin never alone

  16. Prophylaxis • Difficult to generalise due to variable susceptibilities • GI Surgery • Tigecycline • Urology • Aminoglycoside or Cipro

  17. Empiric Rx • Paedsneutropenic sepsis: • Pip/Taz and Amikacin 1st line • Close scrutiny of sens of all BC’s • And sens of CPC screening isolates • No Amik resistance (yet)

  18. Empiric Rx • GNR in blood culture, pt known to be colonised • Depends on sens and site of primary infection • Toxicity often less of a concern (due to lack of options) • Almost always add suitable aminoglycoside • Tige/Colistin not used alone

  19. Empiric Rx • What have we done? • 30 bacteraemic adult pt’s • 18 different regimes used • 11 received monotherapy (cip 4, gent 4, tige, col, mero) • 15 had 2 Abx, 1 had 3 and 1 4. • 16 of 19 with 2 or more abx had an aminoglycoside

  20. Summary • Carbapenemase producing enterobacteriaceaeare heterogenous • Know your local epidemiology • Take MIC’s into account (esp. Carb’s) • Be prepared to think laterally

  21. Acknowledgements • Dr Louise Sweeney • Dr Barry Neish • All the Micro staff at CMFT • Prof Neil Woodford

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