IMBS second day by Barbara Ghiglione https://padlet.com/barbaraghiglione/vnmady22wggmb2qn Made with joy en-us 2020-10-13 20:51:27 UTC 2020-10-14 14:01:24 UTC hello@padlet.com Kpn ST258 barbaraghiglione https://padlet.com/barbaraghiglione/vnmady22wggmb2qn/wish/826650743 1. Worldwide dissemination
  • Kpn ST 258 high-risk clone
  • Plasmid IncFII Tn4401
  • KPC-2 and KPC-3 (KPC-2 + H272Y)
2. R: To all Beta-lactams, including CARBAPENEMS
3. Co-R: AG, COL, FQ, impermeability
4. Virulence (More?)
pilV on ICEKp258.2 (transmissibility and survival)
5. Virulence (Less?)
ST258 lacks 
  •  K1, K2, and K5 capsular antigen genes
  • aerobactin genes
  •  regulator of mucoid
    phenotype gene, rmpA
  •  (is nonvirulent in animal models, is highly susceptible to
    serum killing, and can rapidly undergo phagocytosis)
]]> 2020-10-13 20:57:02 UTC https://padlet.com/barbaraghiglione/vnmady22wggmb2qn/wish/826650743 Kpn ST307 barbaraghiglione https://padlet.com/barbaraghiglione/vnmady22wggmb2qn/wish/826722400 1. Worldwide dissemination
  • KPC, NDM, OXA-48, VIM
  • Usually associated to CTX-M-15
2. Virulence (More or less?)
Several virulence factors, different from ST258.
Evidence for increased virulence and fitness of ST307 when compared to other K.
pneumoniae clones or isolates, is currently lacking

]]> 2020-10-13 21:34:37 UTC https://padlet.com/barbaraghiglione/vnmady22wggmb2qn/wish/826722400 Changing epidemiology in Argentina (and the world?) barbaraghiglione https://padlet.com/barbaraghiglione/vnmady22wggmb2qn/wish/826771273 1. In Argentina, ST258 is not prevalent any more
2. Dissemination of more virulent lineages: 
  • hypermucoviscous ST25 
  •  high-risk clone ST307 and occurrence of blaKPC-3 
  • blaKPC-3 can conduce to variants with significantly reduced ceftazidime-avibactam susceptibility.
  • low virulent ST258/capsulated ST307  (higher R to complement-mediated killing).
  • ST307 clone harbours a cluster for glycogen synthesis, long-term survival and growth in environments outside the host

]]> 2020-10-13 22:03:48 UTC https://padlet.com/barbaraghiglione/vnmady22wggmb2qn/wish/826771273 Kpn ST258 KPC-3 producers CAZ/AVI R intratreatment barbaraghiglione https://padlet.com/barbaraghiglione/vnmady22wggmb2qn/wish/826798157 1. KPC-3
  • 9-30 > kcat/Km than KPC-2 CAZ
  • omega loop 165-179
2. CAZ/AVI R mutants
D179Y/T243M > D179Y > V240G
  • omega-loop substitutions  enhance ceftazidime affinity, which may prevent binding of AVI (CAZ IMPACT, NOT AVI)
  • CARBAPENEM S
3. KPC-3 predisposition factor?
4. Combination therapy with carbapenems?
]]> 2020-10-13 22:21:30 UTC https://padlet.com/barbaraghiglione/vnmady22wggmb2qn/wish/826798157 More CAZ/AVI R KPC-3 mutants barbaraghiglione https://padlet.com/barbaraghiglione/vnmady22wggmb2qn/wish/826823499 D179Y, T243M, D179Y/T243M, and EL165-166
>MICs CAZ/AVI
<MICS CARBAPENEMS (other beta-lactams)
OMEGA LOOP HIGHER IMPACT
Combination therapy with carbapenems?]]> 2020-10-13 22:39:10 UTC https://padlet.com/barbaraghiglione/vnmady22wggmb2qn/wish/826823499 KPC-41 (PNK269270) barbaraghiglione https://padlet.com/barbaraghiglione/vnmady22wggmb2qn/wish/826831056 NOT OMEGA LOOP IMPLICATION
> CAZ affinity
< Susceptibility to AVI
< Carbapenemase activity

Circulating strains! Not intratreatment selection!
Still detectable by phenotypic tests (ertapenem hydrolisis)]]> 2020-10-13 22:44:48 UTC https://padlet.com/barbaraghiglione/vnmady22wggmb2qn/wish/826831056