BSAC Bacteraemia Resistance Surveillance Update 2013 Rosy Reynolds, Shazad Mushtaq, David Livermore on behalf of The BSAC Standing Committee on Resistance Surveillance FIS, Harrogate, 24-26th Nov 2014 rosy.reynolds@nbt.nhs.uk

BSAC Resistance Surveillance Project Bacteraemia 2012 Yearly targets (since 2010)*: 560 S. aureus, E. coli 280 CoNS, enterococci, S. pneumoniae, other α/non-haemolytic streptococci, β- streptococci; Klebsiella, Enterobacter, Serratia, Proteeae, Pseudomonas. Central laboratory testing BSAC agar dilution MICs & BSAC/EUCAST breakpoints. (All 250 from 2001; E.coli & S. aureus 500 in 2008, 2009.) Brief outline of the methods of the BSAC Resistance Surveillance Project. Full protocols on website. We always use the current breakpoints (applied retrospectively to all isolates) for susceptible/intermediate/resistance categorisation, so changes in breakpoints do not create artefacts in the trends over time. UK & Ireland 40 laboratories (25 up to 2009) www.bsacsurv.org PHE, London 2

BSAC Bacteraemia Resistance Surveillance Programme ACKNOWLEDGEMENTS BSAC Bacteraemia Resistance Surveillance Programme Central Laboratory PHE Colindale Shazad Mushtaq David Livermore ... and many others Collecting Laboratories 40, UK & Ireland – see website Sponsors 2009-2013 Astellas AstraZeneca Basilea Cempra Cerexa / Forest Cubist J&J / Janssen-Cilag Melinta (associate) Novartis Pfizer 3

Gram-positives

Familiar story of fall in MRSA since around 2006. Methicillin resistance rate in coagulase-negative staph remains around 70%. 5

Focussing on last 5 years - fall in MRSA has levelled out over the last 3 years at around 12% of S. aureus in bacteraemia. Methicillin resistance rate in coagulase-negative staph remains around 70%. 6

As before, MRSA have high rates of resistance to ciprofloxacin and erythromycin while MSSA are generally susceptible to these agents. There is a similar pattern among coagulase-negative staph. 7

However, there are many agents that are effective against MRSA However, there are many agents that are effective against MRSA. Graph shows: vancomycin teicoplanin linezolid tigecycline ceftobiprole (recently-licensed MRSA-active cephalosporin) There is some resistance to teicoplanin, tigecycline and ceftobiprole among CoNS, but - in terms of MICs - it is not particularly high-level resistance. 8

There has been a gradual increase in the proportion of E There has been a gradual increase in the proportion of E. faecium among bacteraemias caused by enterococci over the surveillance period. 9

Like MRSA among S. aureus, E Like MRSA among S. aureus, E. faecium are much more likely than other enterococci to be resistant. Graph shows: ampicillin imipenem gentamicin vancomycin teicoplanin linezolid tigecycline 10

The change in resistance for invasive S The change in resistance for invasive S. pneumoniae looks complicated, and has been influenced by vaccination schedules. (7-valent conjugate vaccine was introduced xxxxxdate and replaced by 10-valent xxxxxxdate.) The obvious trend is reduction in prevalence of erythromycin resistance. Graph shows: penicillin non-susceptibility (MIC>0.12 mg/L); almost all are intermediate (<=2 mg/L) erythromycin resistance (MIC>0.5 mg/L) tetracycline resistance (MIC>2 mg/L) fluoroquinolone resistance (ciprofloxacin MIC>8 mg/L, previously shown to predict moxifloxacin resistance) multi-resistance (3 or more of above) 11

Gram-negatives

The rapid increase in prevalence of ESBL production and non-susceptibility to ciprofloxacin and gentamicin from 2001 to 2006 is well known. Rates dipped after that but are now rebounding and ESBL % in 2013 just exceeded its previous peak in 2006. (GEN-NS tracks ESBL so closely that you might guess all GEN-NS are ESBL and vice versa, but that’s not the case although they have strong statistical association - GEN-NS 6% vs 37% in ESBL-neg vs pos. CIP-NS is clearly more prevalent than ESBL but tracks a similar course because it too is strongly associated with ESBL (12 vs 85% in ESBL-neg vs pos). 13

Focussing on last 5 years: ESBL production and resistance to ciprofloxacin and gentamicin is on a rising trend. 14

Each panel shows non-susceptibility to: cefotaxime piperacillin-tazobactam imipenem ciprofloxacin gentamicin colistin Carbapenem resistance is still rare, but worrying. We saw on KPC-producing Klebsiella and one OXA-48-producing Enterobacter in 2013. There is colistin resistance in Enterobacter (and more so in respiratory Enterobacter). It is not clinically problematic because the isolates are generally susceptible to more favoured antibiotics, but it is of interest and we are investigating it further. N/A marks not applicable - inherent resistance or no breakpoint. 15

Note scale - only up to 20%, and all non-susceptibilities for Pseudomonas aeruginosa in 2013 were below 10%. Graph shows: ceftazidime piperacillin-tazobactam imipenem ciprofloxacin gentamicin colistin and 2 new agents that do not yet have breakpoints: ceftolozane-tazobactam ceftobiprole 16

SUMMARY

MRSA prevalence has levelled out at 12% after earlier falls. Resistance in E. coli is on an upward trend. These are numerically by far the most important causative organisms of bacteraemia. 18

More data at… www.bsacsurv.org

(This slide prepared for but not shown at FIS 2014.) Prevalence of non-susceptibility to cefotaxime and ciprofloxacin has fallen gradually over the surveillance period. Note that the cefotaxime-NS is not due to ESBLs. 20

(This slide prepared for but not shown at FIS 2014.) The proportion of Proteus mirabilis among bacteraemias caused by Proteeae has increased gradually over the course of the surveillance and Morganella morganii has declined correspondingly. We do not know a reason for this, but it is possibly interesting that both E. coli (which has caused increasing numbers of bacteraemias over recent years) and P. mirabilis bacteraemias are commonly and increasingly of community onset (E. coli 44% hospital-onset over whole study, 37% over last 5 years; P. mirabilis 42% whole study, 36% last 5 years). M. morganii is more commonly hospital-onset (55%). 21