Surviving Sepsis and Stewardship

Transcription

1 Surviving Sepsis and Stewardship Start Smart Then Focus Are these hopelessly compe5ng objec5ves? Dr David R Jenkins, Consultant Medical Microbiologist and Infec>on Control Doctor, University Hospitals of Leicester NHS Trust & Honorary Reader, University of Leicester Medical School david.jenkins@uhl-

2 Some unpleasant truths All exposure of bacteria to an>microbials An>microbial resistance Resistance is effec>vely irreversible New an>microbial development is stalled

3 Delayed effec5ve an5bacterial treatment in sep5c shock is lethal Kumar A et al. Dura5on of hypotension before ini5a5on of effec5ve an5microbial therapy is the cr5cal determinant of survival in human sep5c shock. Crit Care Med 2006;34:

4 The sepsis challenge Sepsis is lethal Delays in effec>ve an>bio>c treatment increase risk of dying Microbiological diagnosis and suscep>bility tes>ng of causa>ve organisms takes hours at best. So use empirical broad- spectrum an>bacterials BUT. This increases resistance

5 The de- escala5on compromise 1. Start with broad- spectrum empirical an>bacterial treatment (single agent or combina>on) 2. Use culture results to: Switch to narrow spectrum single agent, or Drop redundant component of combina>on 3. Hope you haven t done too much ecological damage

6 Start Smart - this means: do not start an>microbial therapy unless there is clear evidence of infec>on take a thorough drug allergy history ini>ate prompt effec>ve an>bio>c treatment within one hour of diagnosis (or as soon as possible) in pa>ents with severe sepsis or life threatening infec>ons. Avoid inappropriate use of broad spectrum an>bio>cs comply with local an>microbial prescribing guidance document clinical indica>on (and disease severity if appropriate), drug name, dose and route on drug chart and in clinical notes include review/stop date or dura>on obtain cultures prior to commencing therapy where possible (but do not delay therapy) prescribe single dose an>bio>cs for surgical prophylaxis where an>bio>cs have been shown to be effec>ve document the exact indica>on on the drug chart (rather than sta>ng long term prophylaxis) for clinical prophylaxis ESPAUR SSTF Implementa5on subgroup. Start Smart- Then Focus. An5microbial Stewardship Toolkit for English Hospitals. (2015) Public Health England

7 Then Focus - this means: reviewing the clinical diagnosis and the con>nuing need for an>bio>cs at hours and documen>ng a clear plan of ac>on - the an>microbial prescribing decision the five an>microbial prescribing decision op>ons are: 1. Stop an>bio>cs if there is no evidence of infec>on 2. Switch an>bio>cs from intravenous to oral 3. Change an>bio>cs - ideally to a narrower spectrum or broader if required 4.Con>nue and document next review date or stop date 5.Outpa>ent Parenteral An>bio>c Therapy (OPAT) it is essen>al that the review and subsequent decision is clearly documented in the clinical notes and on the drug chart where possible eg stop an>bio>c ESPAUR SSTF Implementa5on subgroup. Start Smart- Then Focus. An5microbial Stewardship Toolkit for English Hospitals. (2015) Public Health England

8 Is Start Smart Then Focus SMART?

9 What does smart mean? Smart vi To feel or be the loca-on of a prolonged s-nging pain; to be punished (for) vt To cause to smart n A smar-ng pain; smart money; a dandy adj Sharp and s-nging; brisk; acute, wi?y; clever, brainy; pert, vivacious; trim, spruce, fine; fashionable; keen, quick and efficient in business; technologically advanced and able to respond to changing condi-ons; computer- guided or electronically controlled as in smart house, smart bomb, smart weapon. The Chambers Dic5onary 10 th edi5on (2006)

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13 Ques5ons 1. Does SSTF lead to accurate use of empirical broad spectrum an>bacterials? 2. Are de- escala>on decisions made appropriately? 3. Does de- escala>on lead to non- inferior outcomes compared with con>nued broad spectrum treatment? 4. What will happen if SSTF doesn t deliver?

14 Does SSTF lead to accurate use of empirical broad spectrum an5bacterial therapy? SSTF depends on ability of clinicians to: Accurately diagnose sepsis Iden>fy infec>on focus Iden>fy clinical features linked to raised risk of resistant causa>ve organism/s OR give everyone a carbapenem

15 UK Sepsis Trust Inpa5ent Sepsis Screening and Ac5on Tool (2016) Begs the ques>on, is the pa>ent infected? Are front line junior doctors competent to decide?

16 European medical students a`tudes and percep5ons Online survey of the knowledge and perspec>ves of medical students in seven European medical schools (Dundee, Geneva, Linkoping, Ljubljana, Madrid, Nice, Oxford) The majority of students at six of the seven medical schools wanted more an>bio>c educa>on. However, only a minority of Oxford students wanted more. Dyar OJ et al. European medical students: a first mul5centre study of knowledge, a`tudes and percep5ons of an5bio5c prescribing and an5bio5c resistance. J An5microb Chemother 2014;69:

17 Empiric choices for sepsis treatment and associated outcomes - Spanish experience DCCT = different- class combina>on therapy Mortality rate significantly lower in pa>ents given DCCTs than those given non- DCCTs (34% versus 40%, P=0.042) Diaz- Mar>n A et al. An>bio>c prescrip>on pakerns in the empiric therapy of severe sepsis: combina>on of an>microbials with different mechanisms of ac>on reduces mortality. Cri>cal Care 2012;16:R223

18 What we say to junior doctors: Don t jump straight to meropenem. Assess the pa>ent, take appropriate cultures, treat according to the an>microbial guidance, only use meropenem for severe sepsis if appropriate What they hear: Blah blah blah blah blah meropenem blah blah blah blah blah blah meropenem blah blah blah blah blah Gary Larson

19 What s happening in Leicester? DDD/1000 bed days Surviving sepsis campaign started

20 Are de- escala5on decisions made appropriately? Are appropriate microbiological samples collected prior to an>bacterial treatment? Do clinicians act on results?

21 Survey of carbapenem use in French hospitals in pa>ents received carbapenems 52.6% of use was empirical, mainly because of severe sepsis. Median dura>on of empiric treatment was 6 days, 25% received empiric treatment for > 10 days. De- escala>on occurred in only 23% of pa>ents treated empirically, unless an an>bio>c consultant intervened when the de- escala>on rate was 35%. Nearly half of pa>ents were without posi>ve microbiological results to guide de- escala>on Gauzit R et al. Carbapenem use in French hospitals: A na5onwide survey at the pa5ent level. Int J An5microb Agents 2015;46:

22 Does de- escala5on lead to non- inferior outcomes compared with con5nued broad spectrum treatment? Is there good evidence that de- escala>on doesn t cause pa>ent harm or increased resource use?

23 De- escala5on of an5microbial treatment for adults with sepsis, severe sepsis or sep5c shock Cochrane Collabora>on systema>c review of effec>veness and safety of de- escala>on an>microbial treatment for adult pa>ents diagnosed with sepsis, severe sepsis or sep>c shock Search strategy retrieved 493 studies. No published RCTs tes>ng de- escala>on were iden>fied. One ongoing RCT was found No adequate direct evidence of effec>veness or safety of de- escala>on. Silva BNG et al. De- escala5on of an5microbial treatment for adults with sepsis, severe sepsis or sep5c shock. Cochrane Database of Systema5c Reviews Issue 3 Art No CD007934

24 RCT of de- escala5on versus con5nua5on of empirical treatment in severe sepsis Interven>on Randomised controlled trial of de- escala>on versus con>nua>on of empirical an>bio>c treatment in pa>ents with severe sepsis in 9 French ICUs Results De- escala>on pa>ents had longer ICU stays (14.9 versus 12.1 days) De- escala>on pa>ents had more super- infec>ons (27% versus 11%) De- escala>on pa>ents had more an>bio>c treatment days (14.1 versus 9.9 days) All above P<0.05 Leone M et al. De- escala5on versus con5nua5on of empirical an5microbial treatment in severe sepsis: a mul5center non- blinded randomized noninferiority trial. Intensive Care Med 2014;40:

25 De- escala5on linked to possible under- treatment Simula>on study of pharmacokine>cs of β- lactam an>bio>cs in pa>ents with severe sepsis Time for which an>bio>c concentra>on exceeds MIC calculated (ft >MIC ) Broad- spectrum β- lactams: Meropenem Piperacillin- tazobactam ft >MIC >89% for all simula>ons Narrower- spectrum β- lactams: E coli Co- amoxiclav ft >MIC 85% Cefuroxime ft >MIC 65% Staph aureus Flucloxacillin ft >MIC 74% Cefepime ft >MIC 88% Cefazolin ft >MIC 90% Carlier M et al. A simula5on study reveals lack of pharmacokine5c/pharmacodynamic target akainment in de- escalated an5bio5c therapy in cri5cally ill pa5ents. An5microb Agents Chemother 2015;59:

26 What will happen if SSTF doesn t deliver?

27 The rise in carbapenem- resistant Klebsiella pneumoniae across Europe 2008 Source:EARS- Net

28 The rise in carbapenem- resistant Klebsiella pneumoniae across Europe 2010 Source:EARS- Net

29 The rise in carbapenem- resistant Klebsiella pneumoniae across Europe 2012 Source:EARS- Net

30 The rise in carbapenem- resistant Klebsiella pneumoniae across Europe 2014 Source:EARS- Net

31 What will happen to an5bacterial efficacy on the back of Surviving Sepsis?

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33 What should we do? Insist on sufficient curriculum >me for medical student an>microbial prescribing Is a medical degree sufficient licence to prescribe an>microbials? Increase presence of an>microbial prescribing exper>se on wards Make inappropriate an>microbial prescribing an odious offence