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- tr.nhs.uk @DafyddSiencyns
Some unpleasant truths All exposure of bacteria to an>microbials An>microbial resistance Resistance is effec>vely irreversible New an>microbial development is stalled
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;34:1589-1596
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 24-48 hours at best. So use empirical broad- spectrum an>bacterials BUT. This increases resistance
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
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
Then Focus - this means: reviewing the clinical diagnosis and the con>nuing need for an>bio>cs at 48-72 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
Is Start Smart Then Focus SMART?
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)
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?
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
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?
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;69:842-846
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
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
What s happening in Leicester? DDD/1000 bed days Surviving sepsis campaign started
Are de- escala5on decisions made appropriately? Are appropriate microbiological samples collected prior to an>bacterial treatment? Do clinicians act on results?
Survey of carbapenem use in French hospitals in 2011 2338 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;46:707-712
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?
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 2013. Issue 3 Art No CD007934
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;40:1399-1408
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;59:4689-4694
What will happen if SSTF doesn t deliver?
The rise in carbapenem- resistant Klebsiella pneumoniae across Europe 2008 Source:EARS- Net
The rise in carbapenem- resistant Klebsiella pneumoniae across Europe 2010 Source:EARS- Net
The rise in carbapenem- resistant Klebsiella pneumoniae across Europe 2012 Source:EARS- Net
The rise in carbapenem- resistant Klebsiella pneumoniae across Europe 2014 Source:EARS- Net
What will happen to an5bacterial efficacy on the back of Surviving Sepsis?
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