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American Society for MicrobiologyDistinguished Lecturer Program

Advancing Scientific Excellence � on the Local Level More than 50 years … More than 500 lectures

Provided by ASM for ASM Branches

Funded by ASM and the Waksman Foundation for Microbiology

asmscience.org/join1

The American Society for Microbiology

• Largest Single Life Science Society• 50,000 + members (scientists and health professionals)

• National and International• Mission: promote and advance the microbial sciences

• Membership benefits: Career/job resources, eligibility for Listserv chats, discounts, travel grants, volunteering, a vote in ASM elections,

and more!

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• ASM Membership Helps Advance Your…> Science > Career > Network > Society

asm.org/join

Nancy S. Miller, M.D.Medical Director, Clinical Microbiology & Molecular Diagnostics

Boston Medical Center

Associate Professor, Department of Pathology and Laboratory MedicineBoston University School of Medicine, Boston, MA

nancy.miller@bmc.org

Views expressed are those of the speaker and not BMC, BU, or BUSM

Disclosures: Grant support, Roche Molecular; Speaker fee, BioFire Diagnostics

Products mentioned are for illustration only and no endorsement is intended

Any products that are non-FDA cleared or non-approved will be identified as such

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The culture of blood culturesAt the crossroads of perception, practice, and promise

NCASM March 20184

Objectives

1. Define the clinical and prognostic significance of blood cultures and name key elements that contribute to optimal blood culture practices

2. Discuss current standards and evidence-based blood culture practices and distinguish these from common misperceptions

3. Recognize new and promising methods for detection and profiling bloodstream pathogens and challenges to integration with existing BC workflow

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Perception and Practice

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Bloodstream infections (BSI)

• Detecting microbial pathogens in the blood is one of the most important functions in the clinical microbiology laboratory

• Inappropriate, inadequate or delayed initial empirical therapy is associated with increased mortality, morbidity, length of hospital stay

• Currently blood culture diagnosis is still the gold standard for microbiological diagnosis of bacteremia, fungemia and sepsis

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Annual burden of BSI in the U.S.

Overall estimates from three population-based studies:

• 536K – 628K episodes of BSI

• 72K – 85K deaths (13.5% mortality)

Nosocomial estimates:

• 102.3K –120K (19%) of all BSI episodes are nosocomial

• 15.3K–36K deaths (15–30 % case fatality rate)

• Nosocomial infection surveillance data may substantially underestimate estimates of nosocomial BSI compared to population-based data

8M. Goto and M. N. Al-Hasan. Clin Microbiol Infect 2013; 19: 501–509

Estimated BSI mortality contribution vs. other causes of death

9Xu et al. NCHS Data Brief No. 267 Dec 2016; M. Goto and M. N. Al-Hasan. 2013

BSI mortality rate, 23.5–27.5

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Annual burden of BSI: Global perspective

• Estimated 2 million episodes and one-quarter of a million deaths from BSI annually in North America and Europe combined

• Burden of BSI will probably increase over the next decade due to increase in life expectancies

• Conceivable that annual deaths from BSI globally may be comparable to number of deaths caused by top 3 infectious diseases:

HIV (1.8 million deaths in 2010), tuberculosis (1.4 million deaths in 2011), and malaria (660 000 deaths in 2010)

10M. Goto and M. N. Al-Hasan. Clin Microbiol Infect 2013; 19: 501–509

Sepsis in the U.S.

• Sepsis = Life-threatening organ dysfunction due to a dysregulated host response to infection

• >1.5 million cases of per year (CDC)

• Mortality: ~250,000 (16.6%)– 1 in 3 hospital deaths

– 15% non-acute care settings (long term care, rehab, dialysis)

• CDC data set 1999-2014:– 6% of all U.S. deaths documented as “sepsis-related”

– Sepsis was the “underlying cause” in 22% of this 6%

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https://www.cdc.gov/sepsis/; Epstein L. et al. MMWR April 8, 2016;

MMWR / March 4, 2011; Shankar-Hari et al. JAMA 2016

12Weinstein M. et al. 1997; Novosad SA et al. MMWR 2016; Mayr and Angus. 2014; CDC.gov/sepsis; M. Kollef. 2008

Most frequently cited etiologies: S. aureus, E. coli, coagulase-negative staph,

Enterococcus spp, K. pneumoniae, Candida spp, other enterics, P. aeruginosa,

Acinetobacter spp, β-streps, viridans streps

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BSI pathogen recovery = impact on patient care

• Guides early management decisions– Adequate antibiotic therapy within first 24-48 hours: decreased mortality,

earlier recovery, shorter length of hospital stay, reduced adverse effects

• Establishes etiology of infection and facilitates prognostication

• Enables susceptibility profiling to optimize directed therapy

• Enables Infection Control precautions

• Detection of break-through BSI can highlight issues of inadequate therapy, loss of source control, failing host defenses

• And yet up to 1/3 septic patients never have positive blood cultures!

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Blood Cultures: Key considerations

• Operational: Lab hours and BC coverage

• Administrative: Practice standards and policies

• Pre-analytical– Clinical indications for BC– Skin antisepsis and collection technique– Timing, volume, number of cultures– Special populations and special collections– Transport and instrument on-boarding

• Analytical– Characteristics of automated systems– Duration of incubation– Rapid direct detection of pathogens and resistance markers

• Post-analytical– Reporting and Interpretation– Integration of BC with other technology– Quality assurance monitors

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Operational shortfalls have a significant negative impact

• Delayed onboarding of BC bottles onto the instrument = delayed time-to-positivity and/or inaccurate results

• Limited hours of lab operation = delayed onboarding and reporting

• Timely bottle removal and Gram stain reporting is critical– Rapid BC reporting associated with broadly improved outcomes and

efficiencies in patient management

– Significantly increased mortality rate when Gram stain performed >/= 1 hour after signal positive BC

• Studies support need for 24/7 coverage of blood culture instruments

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Eskira et al. 2006; Hall and Lyman 2006; Beekmann et al 2003;

Munson et al 2003; Barenfanger et al 2008

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Blood culture systems

1. How many of you think most of your clinical and administrative stakeholders know the basic theory and performance aspects of your automated blood culture system?

2. How many of you have engaged these stakeholders before making changes to your automated blood culture instrument or blood culture media?

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Continuous Monitoring Blood Culture Systems (CMBCS)

• Becton Dickinson: BACTEC FX

• bioMerieux: Virtuo (L) and BacT/Alert (R)

• ThermoScientific: VersaTREK

17FDA CLEARED

CMBCS – features shared by all systems

• Modular, scalable

• Proprietary broth media bottles

• Temperature stable incubation

• Programmable incubation protocols

• Continuous (q10-12 min) monitoring

• Computer-assisted interpretation

• Microbial growth alarm signal

• On-board electronics for bottle tracking

• Interface capability – LIS, middleware data management

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CMBCS Differences: Incubation and detection

• Bottle agitation for aerobic cultures– Rocking bottles

– Magnetic stir bar

• Detection of microbial growth by CO2 production– pH change alters a gas-permeable sensor in the BC bottle

– Optical reader: Fluorescent or colorimetric detection of pH change

• Detection of microbial growth by head gas pressure changes– O2consumption, H2 ,N2, CO2 production produces pressure changes

– Manometric detection of changes in the BC bottle

• Ability to monitor BC bottle fill volumes - CAP MIC.22640 compliance

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CMBCS Differences: BC bottles and volumes

• Glass versus plastic bottles

• Bottle inoculation adapters– Multi-draw– Vacutainer compatible

• Broth volumes– 10 to 80 mL

• Minimum and maximum draw volumes– 0.1 to 10 mL

• Proprietary blood-broth inoculation ratios– 1:4 to 1:9 (adult)

• Delayed bottle-to-instrument tolerances

• Additional indications: sterile body fluids, platelets, AFB susceptibility

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CMBCS Differences: Media options

• Aerobic and anaerobic

• Adult and pediatric proprietary formulations

• AFB, fungi

• Antimicrobial neutralization– Dilutional approach (1:9 blood:broth ratio)

– Activated charcoal

– Resin

– Adsorbent Polymeric Beads (APB)

• Anticoagulant additives (e.g. SPS)

• Other: platelet sterility testing media

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A true story…

At an inter-departmental meeting to revise the hospital venipuncture BC policy, several colleagues bemoan the fact that there are no practice standards for blood cultures. What do YOU say?

a. Fear not! We will create some!

b. Fear not! Of course there are and I will share them with you!

c. @%^&**WTF**@&^%!!!

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What your colleagues may not know

• Cumitech: Blood Cultures, American Society for Microbiology (ASM Press)

• CLSI M47: Principles and Procedures for Blood Cultures, Approved Guideline

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Pre-analytical collection shortfalls have a significant negative impact

Sub-optimal BC collection practices increase risk for:

• Low diagnostic yield

• Unnecessary costs due to blood culture contamination (BCC)– BCC: Up to 50% of positive blood cultures

– Unnecessary therapy, prolonged stay, increased costs

– Estimated $4000 USD per BC episode

• High quality BC collection requires standardized, guideline-based protocols, proper technique, and continuous staff education

24Eskira et al. 2006. Clin Microbiol Infect 2006; 12: 818–821; Hall and Lyman 2006

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Proper skin antisepsis = proper technique and time-to-dry

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Mechanism of

Action

Rapidity of

Action

Residual

antimicrobial

Effect

Affected by

Organic Matter

2% chlorhexidine

gluconate/70%

isopropyl alcohol

Denature

protein &

disrupt cell

membrane

Rapid

30 sec.

Excellent Efficacy not

affected by

organic matter

Iodophors

Povidone-iodine

(e.g. Betadine)

Substitution

by free iodine

Intermediate

1.5-2 min.

Minimal Diminished

efficacy by

organic matter

Alcohol

70% isopropyl

Denature

proteins

Rapid None No data

Tincture of Iodine

(2%)

Denature

proteins &

substitution

by free iodine

Rapid

30 sec.

Minimal

Note toxicity

concerns

No data

Skin antisepsis: The punch line

• Chlorexhidine-gluconate and tincture of iodine are probably equivalent to each other and both are superior to povidone-iodine

• Chlorhexidine gluconate is recommended for patients >2 months old– Single-use preps

– Does not obscure venipuncture site

– Non-staining, no post-venipuncture skin cleaning

• Patients <2 months old: Use 70% isopropyl alcohol

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New tools to reduce BC contamination: Initial specimen diversion devices

• Steripath: Vein-to-bottle closed collection: initial blood diversion 1.5-2 mL and secondary sterile flow path; peripheral and IV line draws

• Kurin: Initial blood diversion 0.15 mL; but further studies warranted to validate performance and equivalency

27https://magnolia-medical.com/steripath/; clpmag.com; http://www.kurin.com/; FDA-cleared

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Adults: Optimal collection

Practice standards

• One culture = one set = all blood obtained from one venipuncture site

• Adults: 2-3 cultures per febrile episode if no contraindication

• Blood:broth ratio per BC system

• Ideal volume per venipuncture episode = 35-60 mL

In Practice

• BC x 2 or x 3 per febrile episode– 1 BC set = 1 aerobic + 1 anaerobic

– BC x 2 = 4 bottles (2 + 2)

– BC x 3 = 6 bottles (3 + 3)

• One venipuncture site per set

• Collect simultaneously

• Fill volume: 7-10 mL per bottle

28CLSI M47-A. Clinical and Laboratory Standards Institute (CLSI); 2007

What to avoid

• Single set collections

• Initial collection after antimicrobial administration

• Repeating BC before 2 to 5 days after starting antimicrobial therapy

• Daily and test of cure cultures– Exceptions: infective endocarditis, S. aureus bacteremia and candidemia

• Surveillance cultures

• Line draws (venous and arterial)

• Improperly labeled specimens re: site, source

29CLSI M47-A 2007

Adults: Volume per BC set is the most important variable for optimal pathogen recovery

• Adult BSI = <1 to 10 CFU/mL

• The sensitivity of a single blood culture set is further limited by– Transient bacteremia or fungemia

– Antimicrobial administration

– Some cases of endovascular infection, endocarditis

• Some studies suggest as many as 4 BC sets may be needed to achieve a cumulative detection rate of >99% for bloodstream infections

• Median proportion solitary BC sets:– 10-33% adult, as high as 89-100% pediatrics

30Baron, E.J., et al. Cumitech 1C Blood Culture IV 2005; Lee et al. 2007, 2008;

Hall and Lyman 2006

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Adults: Cumulative sensitivity of BC sets within 24 hours

Percentage yields, consecutive BC:

• First BC: 106 (65.1%)

• Two BC: 131 (80.4%)

• Three BC: 156 (95.7%)

• For each mL the yield of microorganism increases in direct proportion up to 30 mL after the first 10mL

• Lee et al (2007): 4 BC sets may be needed to ensure >99% detection

31Cockerill, et al, 2004, Clin Infect Dis 38:1742-1730 – n=163 cases without endocarditis

Pediatrics: Optimal BC volume

• Direct relationship between volume and pathogen recovery

• Bacteremia 100 to 1000 CFU/mL , but may be </= 10 CFU/mL

• Use aerobic bottle unless an anaerobic infection is suspected

• Pediatric BC media formulations are available for some BC systems, may improve microbial recovery

• Recommended volume of blood is weight-based for infants, children:– No more than 1% of total blood volume (CLSI M-47A)

– Suggested volumes 1.8 to 4% (Cumitech 1C) with caveats

32CLSI M47A 2007; Baron EJ et al. 2005 Cumitech 1C; Kellogg et al 2000

Hanging chads: Timed collections

• Should blood collections be timed to specific fever spikes?– Diagnostic yield is not enhanced by timing collection to a specific fever spike

or shaking chill after the onset of clinical symptoms

– Collect all BC sets at the same time soon after onset of clinical symptoms

– Collect blood from multiple venipuncture sites

• Should blood be collected at specific intervals? – Interval collections (e.g. every 1-2 hours) are unnecessary unless to document

a continuous bacteremia or fungemia associated with infective endocarditis or an endovascular catheter-associated infection

33Li et. al. 1994; Riedel S. et al. 2008; CLSI M47-A; 2007; Baron EJ et al. 2005 Cumitech 1C

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Hanging chads: Bottle inoculation

• Order of draw: BC first, vacutainers last

• Which bottle should be inoculated first?– Needle and syringe: Inoculate the anaerobic bottle first

– Butterfly device: Inoculate the aerobic bottle first

• What is the optimal fill volume (blood: broth ratio) per bottle?– Is vendor-defined for proprietary media formulations

– Routinely for adults = 10 mL; pediatrics varies, 4 to 10 mL

• What if there is not enough blood to optimally fill both/all bottles?– Inoculate the aerobic (s) bottle with optimal volume first, then put residual volume

into anaerobic bottle

– The majority of BSI are caused by bacteria and yeast that can be recovered in the aerobic bottle

34CLSI M47-A. Clinical and Laboratory Standards Institute (CLSI); 2007

Hanging chads: Anaerobic bottles

• Is it necessary to use an anaerobic BC bottle?– 25% of BC episodes included anaerobes (1970s)

– Decrease in anaerobic BSI raised interest in selective use (1980-1990s)

– Increase in anaerobic BSI, 12-year study at Mayo Clinic (2007)

– Anaerobic BSI: An independent variable for in-hospital mortality

– Increased recovery shown for aerobic-anaerobic paired bottles (2003)

• Routine BC should include paired aerobic and anaerobic bottles– Data otherwise is conflicting, inconclusive, unvalidated

• If an anaerobic bottle is not used, substitute an additional aerobic bottle to ensure sufficient collection volume

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CLSI M47-A. 2007; Riley, et al 2003; Lassman et al. 2007; Diekema et al. 2000

Robert R et al. 2008; Rohner P et al. 1997

Hanging chads: Antimicrobial inhibition

• Ideally, collect blood cultures before therapy is started

• If patient is already on therapy consider:– Collecting blood immediately before the next therapeutic dose

– Using BC media formulated for antimicrobial neutralization

• Compared to standard media within a single BC system, media with an antimicrobial neutralization device can improve microbial recovery and time to detection

– Benefits should be weighed against increased contaminant recovery and cost

– Comparative studies between systems: very heterogenous

36CLSI M47-A; 2007; Baron EJ et al. 2005 Cumitech 1C

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Length of BC incubation

• Five day protocols adequate for most pathogens on current systems– One study: 3 day incubation may suffice to recover 95- 98% of pathogens but

this needs further investigation and verification

• Terminal subcultures are not routinely required

• Routinely extending incubation is NOT necessary for recovery of fastidious organisms associated with endocarditis

– Brucella, Capnocytophaga and Campylobacter spp

– Abiotrophia and Granulicatella spp

– HACEK group: Haemophilus spp (except H. influenzae), Aggregatibacter spp(previously Actinobacillus), Cardiobacterium hominis, Eikenella corrodens, Kingella spp

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Hardy DJ, et. al. 1992; Bourbeau et al 2005; Cockerill et al 2004;EJ Baron 2005; Petti et al 2006

Fastidious etiologies of IE (e.g. HACEKs) are rare and usually detected within 5 days of incubation on CMBCS

• Cockerill, et al. 2004 Clin Infect Dis: 99.5% non-endocarditis BSI and 100% endocarditis episodes detected within 5 days of incubation

• Baron EJ. 2005. Clin Infect Dis 41:1677-80: 3BC x 21 days, blind subs– 3/215 (1.4%) isolates recovered from extended BC, $33,550/positive

– 24 HACEKs etc recovered in routine BC incubation

• Petti CA et al. 2006 J Clin Microbiol 44:257: Multi-site, retrospective– 407 extended cultures – no growth

– 16/15,826 (0.1%) HACEK recovered from positive BC, at average 3.4 days

– 12 year analysis Duke Univ: < 0.1% HACEKs in 49K positive BC, avg 2.6 days

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Hardy DJ, et. al. 1992; Bourbeau et al 2005; Cockerill et al 2004;EJ Baron 2005; Petti et al 2006

What if BC are negative and clinical concern persists?

• Communication is imperative to decide alternative options

• Review clinical history and antimicrobial administration

• If initial BC negative at 24-48 hours, collect 2-3 additional BC sets

• Consider:– Extended incubation

– Terminal subculture to chocolate

– Therapeutic management change

– Uncultivable etiologies

– Non-infectious etiologies

– Isolator lysis collection – blood and bone marrow• Blood collected in special tube media that lyses cells and releases microorganisms

• Enables concentration of sediment and selective media plating

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Isolator lysis BC – superior to routine BC?

• Dogma: Enhances recovery of Bartonella, Brucella, Francisella, Nocardia, AFB, pathogenic fungi, moulds, non-Candida yeast

• Most superiority studies done in 1980s-1990s before modern CMBCS

• Antigen, serology, or PCR testing has supplanted culture for dx of rare BC pathogens like Blastomyces and Histoplasma yeast, or Bartonella

spp

• Current thinking: Isolator BC are unnecessary with few exceptions– Proven utility: recovery of disseminated mycobacterial infection

– Possible utility: rare pathogens (e.g., Malassezia spp yeast), rare cases of culture-negative endocarditis, endovascular (line) infections

40https://blogs.jwatch.org/hiv-id-observations/index.php/id-learning-unit-isolator-blood-cultures/2013/05/21/

BC reporting and interpretation: Major considerations

• BC contamination and uncertain clinical significance of positive BC– BC contaminants are typically skin commensals: CoNS, viridans strep,

Corynebacterium spp, Bacillus spp, C. acnes, Micrococcus spp

– That said, CoNS are the primary cause of catheter- and prosthetic device-associated infections; may be clinically significant in up to 20% of cases

• Multiple serial BC – referral policy for ID and susceptibility

• Critical action values and provider notification policy

• Use of new technologies concurrent with routine BC

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Skin flora: True or pseudo bacteremia?

Unreliable correlation

• Number of positive bottles in a single BC set – do not report

• Identity of the organism

• Uni- vs polymicrobial culture

Potentially useful

• Number of positive sets, PPV

• Antibiotic susceptibility profiles

• Speciation (CoNS)

Not yet standardized:

• Time-to-positivity

• Clinical prediction rules, mulitvariate algorithms

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Hall K and J Lyman, 2006;

CLSI M47-A 2007; Shapiro et al 2008

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True or pseudo? Practice and policy

• CoNS: Do not routinely perform or report susceptibilities for– Single BC or 2 non-contiguous sets, adults

– 2 contiguous sets with different species

– Add comment to report re: possible contaminant, clinical correlation

• Potential pseudo pathogens: Engage clinical stakeholders regarding policy– Adult versus NICU and pediatrics single sets

– Viridans strep, IE concerns even if single set; not the same as CoNS

• Maintain low threshold for possible true BSI, clinical correlation:– High risk patient – injection drug use, immunocompromised

– Locations: Dialysis, NICU, Heme-onc, etc.

– Less common organism or multiple sets: Micrococcus spp.

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The opioid crisis, injection drug use, and BSI

• Bacillus spp. and Paenibacillus spp.

• Aerotolerant Actinomyces spp.

• Aerotolerant lactobacilli

• S. aureus

• Rothia spp.

• Streptococci and strep-like variants

• Streptobacillus moniliformis

• Sphingomonas paucimobilis

• Candida spp.

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Serial positive BC – when and what to refer?

A patient has multiple serial positive BC sets from 4 collection dates. The first BC set is MRSA. BC from the 2nd , 3rd , and 4th days look like S. aureus. Your lab only does phenotypic testing (no PCR, no MALDI-TOF). Do you:

a. Perform full identification and susceptibilities on all BC sets, no matter how many?

b. Identify and profile the first isolate and refer all others to the first?

c. Refer the BC ID and susceptibility to a concurrent MRSA wound isolate?

d. Establish a policy for interval ID and susceptibility BC referrals?

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Practice and promise

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Positive antemortem blood culture, deceased adult

• Multiplex PCR BC assay: Neisseria meningitidis

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New technologies supplement traditional BC but

challenge integration with traditional BC workflow

• Highly-multiplexed PCR BC panels – from positive BC aliquot

• MALDI-TOF MS proteomic identification from pure culture– On label: Pure cultures from agar (FDA-cleared)

– Off-label: From positive BC aliquot (not FDA-cleared)

• Novel systems: ID and susceptibility MICs from positive BC aliquot

• T2NMR direct detection of Candida yeast from whole blood

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MALDI-TOF MS = Matrix Assisted Laser Desorption Ionized Time Of Flight Mass Spectrometry

NMR = Nuclear Magnetic Resonance

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Highly multiplexed sample-to-answer target-based PCR

from positive BC aliquots

49http://www.biomerieux-diagnostics.com/filmarray; http://www.luminexcorp.com/; Verigene assay, BOTH FDA cleared

• BioFire platform: • Gram negative and Gram positive on one panel

• Includes 3 resistance markers (mecA, vanA/B, KPC)

• Microfluidic pouch with nested PCR

• 2 minutes hands-on time, ~1 hour run time

• Luminex Verigene: – Separate Gram positive and Gram negative cartridges

– Three GP resistance markers, Six GN markers

– ~5 min hands on time

– 2.5 hours run time

Novel direct BC pathogen detection and next-gen synergistic systems

• Direct pathogen detection without blood culture incubation

– Results in 5-6 hours

– T2 Magnetic Resonance biosensor technology

– Nanoparticles bind target analyte and change T2MR signal

• Next-gen ID and susceptibility from positive BC aliquot

– 48 channel cassette

– 90 minutes to ID

– 7 hours to MIC results

T2 BIOSYSTEMS: FDA cleared Candida assay. Others in development. ACCELERATE DX : PhenoTest BC Kit, FDA cleared

PCR BC panels and result reporting

• How many of you have revised your critical action call policy to include results from new technology in addition to the BC Gram stain?

• How do you report PCR ID and resistance marker results?a. In the EMR as a molecular test separate from the culture?b. Within the BC module on lines used for ORG ID?

• How do you account for BC PCR results that are or might be discrepant with culture and/or susceptibility profiles?

a. Append comments such as “detected by PCR only?”b. Caveats to resistance marker detection: “pending confirmation”?c. Report mecA detection only for S. aureus or for all staphylococci?

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BC pathogen detection (or not!): PCR versus culture

Your BC PCR assay detects streptococcus species and Candida krusei. Culture recovers 2 morphotypes of alpha-hemolytic strep but no yeast.Repeat testing of the BC bottles by PCR are negative for yeast. What do you do?

a. Call the provider and discuss clinical correlation and impact on Rx

b. Re-subculture the BC bottles on BAP and SAB with antibiotic

c. Correct the BC report to indicate the C. krusei was a false positive

d. Create BC protocols to account for repeat PCR testing and forPCR positive / culture negative reports

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Serial positive BC and mecA, B, C, or D?

A patient has multiple serial positive BC sets over several days. The first BC set is MRSA. Three subsequent BC are referred to this one. A BC from the 5th day is reported as MSSA and a subsequent BC is referred to this. The ID fellow calls and requests culture review.

Your lab performs phenotypic testing, MALDI-TOF MS ID, and also has a multiplex PCR panel for BC with mecA gene detection.

The original MRSA confirms as MRSA. Repeat testing of the MSSA BC by PCR detects a mecA gene, S. aureus, and staphylococcus species. In this assay, the mecA gene is not co-localized to S. aureus. Now what?

a. This result could indicate MRSA, MRSE, or MSSA and MRSE

b. Revise BC protocols to eliminate any BC referrals

c. Create BC protocols to account for mecA gene detection, culture confirmation or discrepancies

d. Create BC protocols to ensure confirmation of MRSA <=> MSSA in real time

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Blood cultures: Quality management considerations

• Operational coverage

• Institutional policy and procedures

• Staff competencies

• Critical action value policy

• Integration of molecular and phenotypic methods

• Educational outreach

• Quality assurance monitors– Critical action value calls– Blood culture collection volumes– Pathogen recovery and positivity rate– Single set blood culture collections– Contamination rate

54Baron et al. Cumitech 1C 2005, Hall ad Lyman 2006

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The future?

• One day we may completely surrender the traditional culture of blood in favor of culture-independent methods that may be capable of simultaneous detection of pathogens and immunological determinants of infection

• Or there may never be a single, stand-alone diagnostic for bloodstream infection, and the future will bring new clever tools that supplement but not replace blood cultures

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Summary

• BC remain a critically important tool for diagnosing BSI and sepsis

• Adherence to optimal BC practices can have a significant impact on detection of bloodstream pathogens and improved clinical outcomes

• New technologies improve time-to-detection and accurate pathogen profiling BUT may present new challenges regarding integration into BC workflow and result reporting

• LIS-IT systems require improvements to integrate new BC technologies, and to improve data management and result reporting

• Communication between clinical providers and the laboratory remains key to maintain optimal practices, procedures and patient care

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References 1• Gill VJ, Fedorko DP, Witebsky FG in Mandell,Douglas and Bennett’s Principles and Practice

of Infectious Diseases, ed 5. Philadelphia, Churchill Livingstone, 2000, pp 184–221

• Magadia and Weinstein. 2001; Infect Dis Clinics N Amer 15:1009

• Diekema D, et al. 2003; J Clin Microbiol 41:3655

• M. Kollef. 2008; Clin Infect Dis 47 (Suppl 1)

• Edmond et al. 1999; Clin Infect Dis 29; 239-244

• Weinstein, et al, 1997; Clin Infect Dis 24:584-602

• https://www.cdc.gov/sepsis/

• Epstein L. et al. MMWR April 8, 2016 / 65(13);342–345

• MMWR / March 4, 2011 / Vol. 60 / No. 8

• Novosad SA et al. MMWR / August 26, 2016 / Vol. 65 / No. 33

• Mayr and Angus. Jan 1, 2014; Virulence 5:1, 4–11

• M. Goto and M. N. Al-Hasan. Clin Microbiol Infect 2013; 19: 501–509

• Xu et al. NCHS Data Brief No. 267 December 2016

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References 2• Palmer HR, Palavecino EL, Johnson JW, Ohl CA, Williamson JC. 2013. Clinical and microbiological

implications of time-to-positivity of blood cultures in patients with Gram-negative bacilli bacteremia. Eur J Clin Microbiol Infect Dis 32:955–959. http://dx.doi.org/10.1007/s10096-013 -1833-9. 5.

• Ferrer R, Martin-Loeches I, Phillips G, Osborn TM, Townsend S, Dellinger RP, Artigas A, Schorr C, Levy MM. 2014. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med 42:1749 –1755. http://dx.doi.org/10 .1097/CCM.0000000000000330.

• Goto M, Al-Hasan MN. 2013. Overall burden of bloodstream infection and nosocomial bloodstream infection in North America and Europe. Clin Microbiol Infect 19:501–509. http://dx.doi.org/10.1111/1469-0691 .12195.

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