Dr Peter CowlingChair Bacteriology SMI Committee
UK Standards for Microbiological Investigations (SMIs)
Steering CommitteeSyndromic Algorithm CommitteeVirology/ Serology SMI CommitteeBacteriology SMI Committee
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
Partnership WorkingEqual partnersNominated representativesRegular two way reportingOptimal consultation processesIncreased joint ownershipIncreased authority
NICE AccreditationNHS Evidence accredited processes for SMIsFollows AGREE protocolSets the UK standard for diagnostic
microbiologyCovers whole specimen pathwayAlso certified to ISO 9001:2008
SMI B 37Investigation of Blood Cultures
Issued 27 March 2013
Issue number 7
Acknowledgements 1
Dr Shabnam Iyer
Dr Mike Weinbren
Mr Ian Sturgess
Consultation
Consultation through usual process
Additional parallel consultation through BIA
Total responses 59Accepted 23Partially accepted 6Rejected 7No action 23
B37 Amendments
Standards for TaTsInclusion of SIRS and neonatal sepsisRemoval of differential quantitative cultureDirect sensitivity testingInclusion of molecular methodologiesContamination target <3%Pre-incubation adviceLab management of transportation
Dilemmas
TaTs and Transforming Pathology agendaMeeting 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 treatmentExisting plate-based methodologies
Proposals for improvement
Mike Weinbren, Shabnam Iyer, Ian SturgessSet standards for TaTs Collection to loadingInitial positive reports and sens testingEndorse rapid tests on positive bottlesSet standards for satellite/peripheral labsRequest CPA to formally include b.c auditsRequest BSAC to recommend direct sens
testing
Mike Weinbren’s auditsLoad delay average 7h (max 20h)Unload delay average 5h (max 14h)On site laboratoryWorst out of hours and weekends2nd audit of transport delays showed little delay on
site60% loaded within 2h of receipt but long tail on
graph (n=191). Bottles rec’d 24h but loaded only 08.00-19.00
Potential for saving up to 2 days of TaT if loading/unloading delays are reduced + rapid testing
Kavi, Weinbren & Sturgess surveyTelephone survey of blood culture methods in UK43 respondents across UK4/16 off site blood cultures stored in incubator0/43 load during night21/43 pre-incubate overnight, 22/43 at RT31/43 have 24h on site shift systems (blood
sciences)1/43 rapid sens on GNBs, 41/43 do direct sens
discs
Blood Culture Flags Positive
Removal and Initial Work
Receipt in Laboratory
Loading on Blood Culture
Machine
Time from Collection to LoadingTime from
Placement to Detection
Time from Flagging Positive to Identification and Susceptibility Results
Time from Receipt to Loading
Transport Time to Laboratory (TT)
Time from FlaggingPositive to Removal
Time from Removal to Results of Gram Stain,
Identification and Sensitivities
Variable Time – Opportunity to
Improve
Time Variable – NO Opportunity to
Improve
KEYTurnaround Time (TAT)
Laboratory Turnaround Time (LTAT)
Time to Detection(TTD)
Reporting of Results
Identification and
Sensitivities
Time to Reporting
Blood Culture Collection
Time from Results Availability to
Reporting Results
Time to Positivity(TTP)
Time
Treatment ends
Patient seeks medical advice,
treatment initiated
Patient dependent time variable.
No opportunity to improve.
Appropriate Treatment
Symptoms Start
Therapeutic Window
Patient Survives
Symptoms Start
Time
Treatment ends
Patient seeks medical advice,
treatment initiated
Patient dependent time variable.
No opportunity to improve.
Therapeutic Window
Patient Dies
Inappropriate Treatment
Symptoms Start
Time
Treatment ends
Patient seeks medical advice,
treatment initiated
Patient dependent time variable.
No opportunity to improve.
Therapeutic Window
Patient Dies
Appropriate Treatment
Delayed Blood Culture Result
Critical Time
Inappropriate Treatment
Symptoms Start
Time
Treatment ends
Patient seeks medical advice,
treatment initiated
Patient dependent time variable.
No opportunity to improve.
Inappropriate Treatment
Therapeutic Window
Patient Survives
Rapid Blood Culture Result
Critical Time
Appropriate Treatment
Summary Table 1: Pre-Analytical StandardsInoculated bottles should be incubated as soon as possible, and within a maximum of four hours.
Investigative Stage: Standard:
Pre-Analytical Time Period
Collection to Incubation ≤4hr
The four hour turnaround time from collection to incubation for blood culture samples reflects their clinical significance.
Summary Table 2: Analytical StandardsResults of the following identification and sensitivity tests (if performed) should be completed within the following time frames from flagging positive:
Investigative Stage: Criteria: Standard:Analytical
Flagging Positive to Microscopy, Identification and Sensitivities
Test (if test performed) Time Period to ResultGram Stain ≤2hrRapid Antigen Testing ≤2hrMolecular Assays same dayIsolate Identification (Direct/Automated) ≤24hrIsolate Identification(Conventional Methods)
24-48hr
Isolate Sensitivities (Direct/Automated) ≤24hrIsolate Sensitivities(Conventional Methods)
24-48hr
Summary Table 3: Post-Analytical StandardsStandards have also been set for the laboratory turnaround time (the time between receipt in the laboratory and reporting):Investigative Stage: Criteria: Standard:Post-Analytical
Negative Report
(from receipt in laboratory to negative reporting)
Report Type Turnaround time
Preliminary Negative Report48hr *
(dependant on local policy)
Final Negative Report
≤5 days
(or greater if extended incubation required)
Positive Report
(from receipt in laboratory to positive reporting)
Preliminary Positive Report
(Telephone/Fax/Email)
Immediately, within 2hr of identity/sensitivity availability.
(see Summary Table 2 above)
Final Positive Report
≤5 days
(or greater if extended incubation required, or if isolates are sent to a reference laboratory for confirmation)
*Refer to neonatal sepsis section of the introduction for further information regarding negative reporting of neonatal blood culture.
Neonatal blood cultures
NICE guideline CG 149 Aug 2012Requirement for 36h reporting of a negative
cultureAllows cessation of antimicrobials, 2nd
gentamicin doseAllows timely dischargeIs cost effective
Duration of antibiotic treatment: early-onset neonatal infection without meningitis
Positive blood culture or strong suspicion of infectionUsual antibiotic duration should be 7 days. Consider
longer if baby has not recovered or if advised.
Negative blood cultureConsider 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 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 36h 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
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
Antibiotics for suspected infection in the baby
Therapeutic monitoring for gentamicin
Trough concentrationsMeasure 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 36h rule:UK experience 4/31 significant isolates >36h incl. 1 baby
discharged home11/119 +ve cultures >36h post loading (9
contaminants, 2 CNS infections already on treatment). 23/119 >36h post collection (4 significant but on antibiotics pre b.c. and clinically septic)
92% 4410 cultures +ve <36h (100% of paediatric)18/76 +ve cultures post collection (16
contaminants, 2 significant, 1 on treatment)“nearly all signalled within 18h, never mind 36!”
Acknowledgments 2
Dr Tom LewisDr Sarah Abu HassanDr John CheesbroughDr Alaric ColvilleDr J KaviDr Martin Sheppard
Future dilemmasEmergence of multi-resistance
Less effective & more toxic blind treatment
Need for replacement of 19th Century Microbiology
Rapid, molecular methodology for whole specimen pathway (“Star Trek” vision)
Near patient testing
The Embarrassing Truth?
Blood Sciences
Microbiology
Laissez faire
Long TaTs 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
Purchaser Provider Model
Voice of the Customer
Purchaser - Provider (adversarial)
Customer involvement and joint ownership
(partnership)
Acknowledgements 3The Standards Unit, PHERuhi Siddiqui, Head of UnitClare Harris, Standards MicrobiologistAyuen Lual, Standards MicrobiologistIjeoma Ezeajughi, Research ScientistNicola Day, Technical Support OfficerCaroline Lawson, Information OfficeShirley Boland, Administrative Assistantand……….Val Bevan and Brian Duerden
Thank you