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 Phenotypically similar enzymes Genotypically diverse Epidemiologically Diverse 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 Classification Chromosomal Class A SME, NMC, IMI Class B BCII, L1, Ccra Plasmid Class A KPC, GES Class B NDM, IMP Class D OXA From Queenan and Bush, CMR 2007 Transmission of Resistance Clonal spread (particularly ST258 K. pneumo for KPC) Transmission of plasmid Other enterobacteriaceae implicated, e.g. Enterobacter, E.coli 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 Local situation? Many different strains Same plasmid Enterobacter E. coli KPC producer from a nearby hospital Courtesy N. Woodford Carbapenems? Some carbapenemase producers will have MICs below the breakpoint for resistance Carmeli et al. CMI 2010 SIR Erta0.51>1 0.5->64 Imi24-8>8 0.5->64 Mero24-8> Miriagou et al. CMI 2010. Carbapenems? Some carbapenemase producers will have MICs 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% Carmeli et al. CMI 2010; Daikos et al, AAC 2009 Other options Again, depends on susceptibility results. Many strains multi (or almost pan-) resistant Other options Quinolones Aminoglycosides Tigecycline Colistin Trimethoprim Fosfomycin Temocillin Combinations (which ones?) What should we do? Review of 298 published cases (244 BSI) Tzouvelekis et al, CMR 2011 TreatmentFailure rate 2 drugs, inc carbapenem (MIC