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Blood Culture Dilemmas Dr Peter Cowling Chair Bacteriology SMI Committee Blood Culture Dilemmas Dr Peter Cowling Chair Bacteriology SMI Committee

UK Standards for Microbiological Investigations (SMIs) Steering Committee Syndromic Algorithm Committee Virology/ Serology SMI UK Standards for Microbiological Investigations (SMIs) Steering Committee Syndromic Algorithm Committee Virology/ Serology SMI Committee Bacteriology SMI Committee

Our responsibility. . does not start at the laboratory door Starts at the point Our responsibility. . does not start at the laboratory door Starts at the point the clinician considers the differential diagnosis

Our involvement in specimen pathway From start To finish Our involvement in specimen pathway From start To finish

Partnership Working Equal partners Nominated representatives Regular two way reporting Optimal consultation processes Increased Partnership Working Equal partners Nominated representatives Regular two way reporting Optimal consultation processes Increased joint ownership Increased authority

NICE Accreditation NHS Evidence accredited processes for SMIs Follows AGREE protocol Sets the UK NICE Accreditation NHS Evidence accredited processes for SMIs Follows AGREE protocol Sets the UK standard for diagnostic microbiology Covers whole specimen pathway Also certified to ISO 9001: 2008

SMI B 37 Investigation of Blood Cultures Issued 27 March 2013 Issue number 7 SMI B 37 Investigation of Blood Cultures Issued 27 March 2013 Issue number 7

Acknowledgements 1 Dr Shabnam Iyer Dr Mike Weinbren Mr Ian Sturgess Acknowledgements 1 Dr Shabnam Iyer Dr Mike Weinbren Mr Ian Sturgess

Consultation through usual process Additional parallel consultation through BIA Total responses Accepted Partially accepted Consultation through usual process Additional parallel consultation through BIA Total responses Accepted Partially accepted Rejected No action 59 23 6 7 23

B 37 Amendments Standards for Ta. Ts Inclusion of SIRS and neonatal sepsis Removal B 37 Amendments Standards for Ta. Ts Inclusion of SIRS and neonatal sepsis Removal of differential quantitative culture Direct sensitivity testing Inclusion of molecular methodologies Contamination target <3% Pre-incubation advice Lab management of transportation

Dilemmas Ta. Ts and Transforming Pathology agenda Meeting the needs and expectations of users Dilemmas Ta. Ts and Transforming Pathology agenda Meeting the needs and expectations of users (e. g paediatricians) Pre-loading handling of bottles (requesting/ transportation/ off site incubators/ off site culture) Empirical blind antimicrobial treatment Existing plate-based methodologies

Turnaround times (Ta. Ts) Turnaround times (Ta. Ts)

Proposals for improvement Mike Weinbren, Shabnam Iyer, Ian Sturgess Set standards for Ta. Ts Proposals for improvement Mike Weinbren, Shabnam Iyer, Ian Sturgess Set standards for Ta. Ts Collection to loading Initial positive reports and sens testing Endorse rapid tests on positive bottles Set standards for satellite/peripheral labs Request CPA to formally include b. c audits Request BSAC to recommend direct sens testing

Mike Weinbren’s audits Load delay average 7 h (max 20 h) Unload delay average Mike Weinbren’s audits Load delay average 7 h (max 20 h) Unload delay average 5 h (max 14 h) On site laboratory Worst out of hours and weekends 2 nd audit of transport delays showed little delay on site 60% loaded within 2 h of receipt but long tail on graph (n=191). Bottles rec’d 24 h but loaded only 08. 00 -19. 00 Potential for saving up to 2 days of Ta. T if loading/unloading delays are reduced + rapid testing

Kavi, Weinbren & Sturgess survey Telephone survey of blood culture methods in UK 43 Kavi, Weinbren & Sturgess survey Telephone survey of blood culture methods in UK 43 respondents across UK 4/16 off site blood cultures stored in incubator 0/43 load during night 21/43 pre-incubate overnight, 22/43 at RT 31/43 have 24 h on site shift systems (blood sciences) 1/43 rapid sens on GNBs, 41/43 do direct sens discs

User expectations User expectations

Neonatal blood cultures NICE guideline CG 149 Aug 2012 Requirement for 36 h reporting Neonatal blood cultures NICE guideline CG 149 Aug 2012 Requirement for 36 h reporting of a negative culture Allows cessation of antimicrobials, 2 nd gentamicin dose Allows timely discharge Is cost effective

Duration of antibiotic treatment: early-onset neonatal infection without meningitis Positive blood culture or strong Duration of antibiotic treatment: early-onset neonatal infection without meningitis Positive blood culture or strong suspicion of infection Usual antibiotic duration should be 7 days. Consider longer if baby has not recovered or if advised. Negative blood culture Consider stopping antibiotics at 36 hours. If continuing beyond 36 hours, review the baby at least once every 24 hours to consider whether antibiotics can be stopped. NICE (CG 149) Aug 2012

Duration of antibiotics treatment: decisions 36 hours after starting antibiotic treatment To fully implement Duration of antibiotics treatment: decisions 36 hours after starting antibiotic treatment To fully implement the guideline, hospital systems to provide real time blood culture results at 36 hours are needed. Consider stopping antibiotics at 36 hours: if • • blood culture is negative and initial suspicion of infection was not strong and baby’s clinical condition reassuring (no clinical indicators) and levels and trends of C-reactive protein are reassuring. NICE (CG 149) Aug 2012

Rationale for 36 h decision “Since the health economic analysis conducted for the guideline Rationale for 36 h decision “Since the health economic analysis conducted for the guideline showed that stopping antibiotic treatment at 36 hours in the babies listed above will be cost saving, and one of the criteria for stopping treatment depends on the result of blood culture, the cost savings can be realised only if the blood culture results are available within 36 hours. ” NICE (CG 149) Aug 2012

Antibiotics for suspected infection in the baby Use intravenous benzylpenicillin with gentamicin as first- Antibiotics for suspected infection in the baby Use intravenous benzylpenicillin with gentamicin as first- choice. Benzylpenicillin 25 mg/kg every 12 hours. Gentamicin, starting dosage of 5 mg/kg. If a second gentamicin dose is required, give 36 hours after the first (interval may be shortened based on clinical judgment). (My emphasis) NICE (CG 149) Aug 2012

Therapeutic monitoring for gentamicin Trough concentrations Measure trough immediately before second dose. Concentrations should Therapeutic monitoring for gentamicin Trough concentrations Measure trough immediately before second dose. Concentrations should be available in time to inform the next dose (If not, do not withhold dose unless renal dysfunction is evident). Consider repeating measurement of trough concentrations at least before every third dose. NICE (CG 149) Aug 2012

Neonatal blood cultures 36 h rule: UK experience 4/31 significant isolates >36 h incl. Neonatal blood cultures 36 h rule: UK experience 4/31 significant isolates >36 h incl. 1 baby discharged home 11/119 +ve cultures >36 h post loading (9 contaminants, 2 CNS infections already on treatment). 23/119 >36 h post collection (4 significant but on antibiotics pre b. c. and clinically septic) 92% 4410 cultures +ve <36 h (100% of paediatric) 18/76 +ve cultures post collection (16 contaminants, 2 significant, 1 on treatment) “nearly all signalled within 18 h, never mind 36!”

Acknowledgments 2 Dr Tom Lewis Dr Sarah Abu Hassan Dr John Cheesbrough Dr Alaric Acknowledgments 2 Dr Tom Lewis Dr Sarah Abu Hassan Dr John Cheesbrough Dr Alaric Colville Dr J Kavi Dr Martin Sheppard

Future dilemmas Emergence of multi-resistance Less effective & more toxic blind treatment Need for Future dilemmas Emergence of multi-resistance Less effective & more toxic blind treatment Need for replacement of 19 th Century Microbiology Rapid, molecular methodology for whole specimen pathway (“Star Trek” vision) Near patient testing

The Embarrassing Truth? Blood Sciences Microbiology The Embarrassing Truth? Blood Sciences Microbiology

Laissez faire Long Ta. Ts generally accepted as the norm by laboratories, users and Laissez faire Long Ta. Ts generally accepted as the norm by laboratories, users and patients Technology available to revolutionise Microbiology Insufficient challenge to status quo

Wrong focus Laboratory accreditation-focussed Not patient-focussed ISO standards are an improvement Wrong focus Laboratory accreditation-focussed Not patient-focussed ISO standards are an improvement

Purchaser Provider Model Purchaser Provider Model

Voice of the Customer Purchaser - Provider (adversarial) Customer involvement and joint ownership (partnership) Voice of the Customer Purchaser - Provider (adversarial) Customer involvement and joint ownership (partnership)

Acknowledgements 3 The Standards Unit, PHE Ruhi Siddiqui, Head of Unit Clare Harris, Standards Acknowledgements 3 The Standards Unit, PHE Ruhi Siddiqui, Head of Unit Clare Harris, Standards Microbiologist Ayuen Lual, Standards Microbiologist Ijeoma Ezeajughi, Research Scientist Nicola Day, Technical Support Officer Caroline Lawson, Information Office Shirley Boland, Administrative Assistant and………. Val Bevan and Brian Duerden

Thank you Thank you