1 / 25

VRE - treatment options for severe infections

VRE - treatment options for severe infections. Dr Nick Brown Addenbrooke’s Hospital, Cambridge 14 March 2013. Conflict of interest: None. Evidence biased medicine. Class 0 Things I believe Class 0a Things I believe despite the available data

fallon
Télécharger la présentation

VRE - treatment options for severe infections

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. VRE - treatment options for severe infections Dr Nick Brown Addenbrooke’s Hospital, Cambridge 14 March 2013 Conflict of interest: None

  2. Evidence biased medicine Class 0 Things I believe Class 0a Things I believe despite the available data Class 1 Randomized controlled clinical trials that agree with what I believe Class 2 Other prospectively collected data Class 3 Expert opinion Class 4 Randomized controlled clinical trials that don’t agree with what I believe Class 5 What you believe that I don’t Bleck TP. BMJ 2000; 321: 239

  3. VRE - treatment options for severe infections • Context • Confounding factors • Treatment options • Studies of efficacy • Combination therapy

  4. Characteristics of infection with enterococci • Rarely occur in the healthy host • Majority of infections are nosocomial • Bacteraemia is often polymicrobial • In-hospital crude mortality is high Moellering R. J Antimicrob Chemother 1991; 28: 1-12 Hoge CW et al. Rev Infect Dis 1991; 13: 600-5.

  5. ‘Enterococcal bacteraemia – to treat or not to treat?’ 81 enterococcal bacteraemias in US 50% considered clinically significant Treatment assessed for appropriateness Even non-significant bacteraemia mortality ~50% • Appropriateness of treatment made no difference Overall 51% mortality if significant • Treated appropriately = 38% • Treated inappropriately = 83% Hoge CW et al. Rev Infect Dis 1991; 13: 600-5.

  6. Identification of 222 enterococci submitted to ARMRL as part of the BSAC bacteraemia resistance surveillance programme. National Glycopeptide-Resistant Enterococcal Bacteraemia Surveillance Working Group report to the Department of Health August 2004. J Hosp Infect. 2006; 62 Suppl 1: S1-27

  7. Mandatory surveillance of glycopeptide-resistant enterococcus bacteraemia, England 2003-2011 http://www.hpa.org.uk

  8. Mandatory surveillance of glycopeptide-resistant enterococcus bacteraemia, England 2003-2011 http://www.hpa.org.uk

  9. ~20% Vanc-R ~2% Vanc-R Voluntary surveillance of enterococcal bacteraemia, England, Wales & NI 2003-2010 http://www.hpa.org.uk

  10. Enterococcus faecium: percentage (%) of invasive isolates resistant to vancomycin, by EU/EEA country, 2011 Antimicrobial resistance surveillance in EuropeAnnual report of the European Antimicrobial Resistance Surveillance Network (EARS-Net) 2011

  11. Trends in vancomycin-resistant enterococcal bacteraemiarates in the SENTRY Antimicrobial Surveillance ProgramUS Hospitals 2000–2010 Arias CA et al. Clin Infect Dis 2012; 54(S3): S233–8

  12. The main contenders Penicillin/amoxicillin +/- aminoglycoside Linezolid Daptomycin (Quinupristin-dalfopristin) Tigecycline Have been used at some point (usually as part of combination) Teicoplanin Chloramphenicol Tetracycline Rifampicin Fosfomycin Quinolones Treatment options for invasive infection due to VRE • Not quite here yet • Oritavancin • Dalbavancin • (new oxazolidonones) • (Cephalosporins with enhanced Gram positive activity) No specific recommendations in AHA, ESCMID or BSAC endocarditis guidelines

  13. Combination therapy reported in the literature(note - data on efficacy are extremely limited and conflicting evidence of synergy or antagonism have been reported for some combinations) • ampicillin + quinupristin-dalfopristin • ampicillin + quinolone • quinupristin-dalfopristin + doxycycline + rifampicin • quinupristin-dalfopristin + minocycline • minocycline + chloramphenicol • daptomycin + ampicillin +/- gentamicin • daptomycin + gentamicin + rifampicin • daptomycin + tigecycline • ampicillin + ciprofloxacin + tetracycline • ciprofloxacin + gentamicin + rifampicin • ceftriaxone + vancomycin + gentamicin • fosfomycin + ceftriaxone …and more…

  14. Comparative data on treatment outcome • Retrospective review 113 VRE bacteraemia Nebraska, USA 1993-2005 • 112 E. faecium, 1 E. faecalis • All isolates ampicillin-resistant and HLGR • Overall mortality 37.2% • Univariate analysis significant advantage to linezolid • Advantage disappeared when underlying factors taken into account Erlandson KM et al. Clin Infect Dis 2008; 46: 30-6.

  15. Comparative data on treatment outcome • Retrospective review 201 VRE bacteraemia treated with daptomycin or linezolid in larger cohort of 361 patients, US hospital 2004-2009 • All E. faecium • 63 daptomycin vs. 138 linezolid treatment • Daptomycin group more likely to have haematological malignancy (33% v 14%) or liver transplant (13% v 4%) Twilla JD et al. J Hosp Med. 2012; 7: 243-8

  16. Comparative data on treatment outcome • Retrospective review 96 VRE bacteraemia 2 US hospitals 2003-2007 • 92 E. faecium, 4 E. faecalis • 30 daptomycin vs. 68 linezolid treatment • No significance difference in baseline demographics or clinical characteristics, although daptomycin group more often on ICU Mave V et al. J Antimicrob Chemother 2009; 64: 175–180

  17. Comparative data on treatment outcome • Retrospective review of 116 VRE in cohort of 724 enterococcal bacteraemias in Australia 2002-2010 • All VRE were vanB genotype • 107 E. faecium, 9 E. faecalis • 54 teicoplanin 800mg once daily • 22 linezolid 600 mg twice daily • 14 no antibiotic treatment Cheah ALY et al. Clin Microbiol Infect. 2013 Epub ahead of print

  18. Review of VRE endocarditis treatment • Retrospective review of 50 VRE endocarditis cases 2000-2008 • 26 E. faecium, 24 E. faecalis Forrest GN et al. J Infect 2011; 63: 420-8

  19. Dose of daptomycin • Evaluation of 31 patients receiving daptomycin for VRE bacteraemia • Many had factors contra-indicating use of linezolid • 2 cases of endocarditis Factors associated with good outcome: • Older age • Disease other than haematological malignancy • Dose of daptomycin >6 mg/kg/day Grim SA et al. J Antimicrob Chemother 2009; 63: 414-6

  20. VRE in an in vitro model with simulated endocarditis vegetations E. faecalis Daptomycin MIC = 0.5 mg/L Hall AD et al. Antimicrob Agents Chemother 2012; 56: 3174-80

  21. VRE in an in vitro model with simulated endocarditis vegetations E. faecium Daptomycin MIC = 4 mg/L Hall AD et al. Antimicrob Agents Chemother 2012; 56: 3174-80

  22. Ampicillin plus daptomycin in VRE endocarditis E. faecium Amp-R, Vanc-R Daptomycin MIC = 1 mg/L Sakoulas G et al. Antimicrob Agents Chemother 2012; 56: 838-44

  23. Summary • No good evidence to show which treatment option should be used for bacteraemia due to VRE • Beta-lactam plus aminoglycoside combinations are still considered optimal where susceptibility allows • Some evidence of efficacy of both linezolid and daptomycin as single agents • Higher doses of daptomycin may have better efficacy • Combination therapy may be better for severe infection, such as endocarditis, but further data needed

More Related