06/08/2020 Session Outcomes • Discuss the origins of bacteria, antibiotics and the development of antimicrobial resistance (AMR) ANTIMICROBIAL STEWARDSHIP • Introduce the concept of antimicrobial stewardship (AMS) in AN INTRODUCTION TO MICROBIOLOGY response to AMR • What is your role in AMS? July 2020 • How can we improve patient outcomes? 1 2 Bacteria: friend or foe? 3 4 5 6 1
06/08/2020 7 8 Fighting back Antibiotics in response to bacteria The origins of antibiotics 9 10 Streptomyces Penicillium Other bacteria Man-made “Synthetic” 11 12 2
06/08/2020 What is Antibiotic Resistance (AMR)? Antibiotic resistance is the ability of microbes to resist the effects of life-saving drugs (e.g. penicillin) - simple infections require hospitalisation for treatment - severe infections result in higher mortality rate - developing microbes with no treatments available 13 14 Multi-drug resistant bacteria: a rough overview Staph aureus Clostridium difficile Pneumococci Corynebactera Enterococci E. Coli Klebsiella Salmonella Pseudomonas Acinetobacter Gonococci Stenotrophomonas Helicobacter …plus many others 15 16 Multi-drug resistant bacteria: a rough overview Multi-drug resistant bacteria: a rough overview Staph aureus Staph aureus Clostridium Clostridium difficile difficile (MRSA) (MRSA) Corynebactera Corynebactera Pneumococci Pneumococci Enterococci Enterococci (VRE) (VRE) E. Coli E. Coli Klebsiella Klebsiella Salmonella Salmonella Pseudomonas Pseudomonas Acinetobacter Acinetobacter Gonococci Gonococci Stenotrophomonas Stenotrophomonas Helicobacter Helicobacter …plus many others …plus many others Resistance to ESBL producing Enterobacterales Penicillins, Cephalosporins Carbapenem resistant Enterobacterales Penicillins, Cephalosporins (CRE) Carbapenems (VIM,NDM-1, KPC-2,oxa-48) + others 17 18 3
06/08/2020 19 20 https://www.cdc.gov/vitalsigns/protect-patients/images/graphic-a_920px.jpg 21 22 30-day mortality Sensitive 6% ESBL 6 – 18% CRE >38% 23 24 4
06/08/2020 Costs associated with CRE • Approx £15K additional treatment costs • Reduced activity at acute trusts (closure of infected units across UK in last 24 months) • Additional screen costs incurred for hospitals (£7.5 million / year at CMFT, Manchester) 25 26 Resistance Defining antimicrobial resistance in the lab 27 28 Klebsiella pneumoniae ESBL present Pseudomonas aeruginosa Porin loss High dose ABX needed 29 30 5
06/08/2020 Empiric Guidelines – Septic shock Case Presentation: • An 81 year-old woman was admitted to the A&E with nausea, vomiting and hypotension. She had a history of hypertension, Type II AMR in Practice Diabetes, renal insufficiency and dementia • Pyrexia – 38.7 • Hypotensive (95/62) unresponsive to fluid challenge • U/O – (Less than 30ml/hr) • Rx: – ? 31 32 Empiric Guidelines – Septic shock Empiric Guidelines – Septic shock Case Presentation: Consequences of under-Rx: Case Presentation: Consequences of under-Rx: • • An 81 year-old woman was An 81 year-old woman was admitted to the A&E with nausea, admitted to the A&E with nausea, vomiting and hypotension. She had vomiting and hypotension. She had a history of hypertension, Type II a history of hypertension, Type II Diabetes, renal insufficiency and Diabetes, renal insufficiency and dementia dementia • • Pyrexia – 38.7 Pyrexia – 38.7 • • Hypotensive (95/62) unresponsive Hypotensive (95/62) unresponsive to fluid challenge to fluid challenge • • U/O – (Less than 30ml/hr) U/O – (Less than 30ml/hr) • • Rx: Rx: – – Broad-spectrum beta-lactam Broad-spectrum beta-lactam – – Add aminoglycoside (likely AKI) Add aminoglycoside (likely AKI) N Engl J Med 2017; 376:2235-2244 N Engl J Med 2017; 376:2235-2244 33 34 Time Line: Time Line: KPC: Negative OXA 48: Positive Day 0: Blood Culture Day 0: Blood Culture NDM: Negative + 24 hours: Culture stain (Gram –ve rod) + 24 hours: Culture stain (Gram –ve rod) --------------------------------------- + 48-72 hours: ABX sensitivities + 48-72 hours: ABX sensitivities ORGANISM: Enterobacter cloacae ++ isolated METHOD: DISC SENSITIVITY Gentamicin: Resistant Ciprofloxacin: Resistant Cefuroxime: Resistant Tazocin: Resistant Amoxycillin: Resistant Temocillin: Resistant Cefotaxime: Resistant Meropenem: Resistant Trimethoprim: Resistant Ceftazidime: Resistant Augmentin: Resistant Amikacin: Sensitive 35 36 6
06/08/2020 Minimise the ecological impact of Antimicrobial Resistance: • Infection Prevention & Control Avoidance of infection and exposure to resistant organisms is key We expose our most vulnerable patients to our highest-risk practice • Antimicrobial Stewardship Any reduction in antimicrobial usage will reduce risk of resistance The ‘easy win’ is inappropriate usage - reduce broad spectrum ABX (traditional AMS role) - reduce durations (greatest impact?) - reduce ABX when no infection is present (pt education) 37 38 Antimicrobial Stewardship in response to AMR Defining Antimicrobial Stewardship: (evolving terminology that rapidly changes in response to new antimicrobial related challenges) “Antibiotic stewardship refers to a set of coordinated strategies to improve the use of antimicrobial medications with the goal of enhancing patient health outcomes , reducing antimicrobial resistance , and decreasing unnecessary costs ” Relatively new concept, created in response to the C.difficile related infections of 10-15 years previously, that was linked to excessive and inappropriate antimicrobial usage AMS services embedded into secondary care and has evolved across boundaries of healthcare for a more holistic approach in light of rising AMR O.J. Dyar et al. / Clinical Microbiology and Infection 23 (2017) 793e798 40 39 40 The function of Antimicrobial Stewardship service Individual Patient focus Population level focus Optimise the outcome of infected Minimising ecological impact of patients antimicrobial usage - Timely recognition and treatment - Appropriate antimicrobial choice Reduce selective pressure of - Adequate drug dosing based on antimicrobial usage - patient characteristics Working in collaboration across - Adjusting therapy based on all boundaries of healthcare - clinical response Educating our clinical colleagues - Minimising harm to patient on precious resource of antimicrobials - Promoting evidence base guidelines that balance population risk vs individual risk 42 41 42 7
06/08/2020 Reducing ABX in self-limiting infections Low risk invasive Low risk of Severe / invasive infection invasive infection infection Risk of Mortality % ABX Diagnostic Code Broad prescription Targeted respiratory tract (including ENT) 46.0 spectrum cough 22.7 Lower RTI 17.9 Sore throat 16.7 Upper RTI 14.5 Ear-related diagnosis / other 28 urogenital tract 22.7 Scale of Infection skin and wounds 16.3 other body systems 10.3 multiple body systems 4.7 43 44 45 46 A confusing time for prescribers • Sepsis More aggressive management of septic patients Changing Net widening to identify sub-acute presentations (specificity reducing) NICE Sepsis 2016 / NCEPOD Behaviours vs AMS (reduce ABX) / ESPAUR Resistance How to improve AMS performance • Antimicrobial Stewardship Targeted reduction in overall ABX usage National target to: - reduce total ABX usage (1-2% / year) - reduce broad-spectrum ABX usage - reduce all carbapenem usage 47 48 8
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