Improving Consultative Feel of the Laboratory: Adding Post-Analytical Comments to Your ReportsPaul C. Schreckenberger, Ph.D., D(ABMM), F(AAM)Professor of PathologyDirector, Clinical Microbiology LaboratoryLoyola University Medical CenterPschrecken@lumc.edu

Herbert M. Sommers, M.D.

2

Financial Disclosures

3

4

Objectives

• Develop strategies for optimal laboratory testing with the goal of eliminating unnecessary and inappropriate test methods

• Identify opportunities to improve physician understanding of laboratory results issued by their own laboratory

• List specific post-analytic comments used in microbiology to clarify relevance and significance of microbiology results

5

Evidence Based Medicine

•Using objective scientific data to make a clinical diagnosis or predict the success of a specific treatment

•Based on accurate reproducible test results and proven clinical outcomes

6

Evidence Based Medicine

•Does a Physician have the right to expect that the laboratory results are accurate, significant and clinically relevant?

• If the answer is YES, then where should we begin?

7

Evidence Based Medicine

•Should begin by acting as consultants, not just someone who provides a service– We are physicians, doctoral scientists,

microbiologists, technologist…… not just laboratory people

8

Phases of Diagnostic TestingPreanalytical Analytical Postanalytical

Patient Assessment Testing Result Reporting

Test Request Quality Control Result Interpretation

Specimen Collection Verification Post-test Specimen

Specimen Transport Management

Specimen Receipt

Specimen Processing

Evidence Based MedicineThe Clinical Laboratory

9

Specimen Selection

Sputum (based on stain)

Endotracheal (based on stain)

Routine Throat cultures

Routine Vaginal cultures

Urine (based on UA)

Wounds (based on stain)

Sterile Fluids, AFB sent on swabs

Stool (>3 days)

Stool for fungus

C. difficile on formed stool

C. diff as test of cure

CSF for fungi and TB

Direct Agn tests on CSF

>3 blood cultures in 24h

Things we can say “no” to:

10

• Key to accurate laboratory diagnosis

• Affects patient care and patient outcomes

• Influences therapeutic decisions

• Impacts hospital infection control

• Impacts patient length of stay, hospital costs and laboratory costs

• Influences laboratory efficiency

Impact of Specimen Management

11

Impact of Specimen Management

•Not just trying to get out of doing things, we are trying to help physicians help their patients– Rules for acceptance and work up of

specimens are good for the patient

12

Pre-Analytical Assessment

Specimen Collection•Recovery of microorganisms is directly related to

specimen quantity•Collect as much specimen as possible•DON’T USE SWABS! (exceptions:

throat; nasopharyngeal; cervical/vaginal)•Use syringes to aspirate fluid and scalpels for

tissue

13

• Test Requested: AFB Culture

• Specimen: Swab

• Result: “Test cancelled: swab specimens are inappropriate for AFB culture. Appropriate specimens include; body fluids (min. vol. 3-10 ml), respiratory secretions (min. vol. 3-10 ml), and tissue.”

Pre-Analytical Comment Patient Report

14

• Tissue, needle aspirates, and …. swabs

• We perform culture if specimen acceptable and another specimen not easily obtainable

• Add disclaimer to final report: “Specimen received on swab. Results may not be reliable. For maximum sensitivity submit, tissue, fluid, or needle aspirate.”

• Good idea for a QA monitor

Post Analytical Comment Patient Report

15

CSF Cultures for AFB/Fungus• RULE: Screen all CSF requests from adults

Fungus and AFB testing not performed if:- Clear CSF- WBC less than 5 x 106 cells/L- Glucose >3.3 mmol/L (60 mg/dL)

• Unused fluid frozen in original sterile vial. Stored 30 days. Laboratory performs testing if physician then requests testing– Albright RE et al: AJCP 95:418-423, 1991– Bromberg K: Lancet 1:1023, 1980– Crowson TW et al: JAMA 251:70-72, 1984

16

• “Test Cancelled: CSF Fungus and AFB cultures are only performed if cellular or chemical abnormalities are present in the CSF. Specific test was not performed because analysis of this sample revealed glucose >55 mg/dL and WBC <5 cells/uL. If consultation is required, page the microbiology laboratory director (12504).”

Pre-Analytical Assessment

Patient Report - LUMC

17

Screening Criteria for HSV PCR• RULE: Screen all CSF HSV PCR requests

Test performed only if:

- Patient with HIV- Patient with history of transplant- An age of <2 years- CSF WBC count >5 cells/mm3

- CSF protein >50 mg/dl

18

Screening Criteria for HSV PCR• Unused fluid frozen in original sterile vial.

Stored 30 days. Laboratory performs testing if physician then requests testing.– Hanson KE et al. Validation of laboratory screening

criteria for herpes simplex virus testing of cerebrospinal fluid.J Clin Microbiol. 2007 Mar;45(3):721-4.

– Ihekwaba UK et al. Clinical features of viral meningitis in adults: significant differences in CSF among HSV, VZV and EV infections. Clin Infect Dis. 2008 Sep 15;47(6):783-9

19

Screening Sputum

• RULE: perform Gram stain and evaluate under LPF (10 x). Reject if >10 SEC/LPF, unless also see a predominant field of WBCs assoc. with single morphotype of bacteria

• Ref:– Murray PR, Washington II JA: Mayo Clinic Proc.

50:339-344, 1975– Wong LK et al: JCM 16:627-631, 1982

20

21

Pre-Analytical Comment

Screening Sputum

• Cancel Culture, Charge for Gram Stain only

• DON’T REQUEST REPEAT CULTURE: Add Comment: “specimen contaminated with epithelial cells represents oropharyngeal contamination further processing would yield potentially misleading results.”

22

Screening Endotrachs

• RULE: specimens with >10 SEC/LPF,or no organisms seen on Gram stain(or yeast only) are not cultured

• References:– Morris AJ et al: JCM 31:1027, 1993

– Zaidi AK, Reller LB : JCM 34:352, 1996

– Rand KH: Diagn Micro Infect Dis 27:55, 1997

– Gilligan PH: Clin Micro Newsl 21:44, 1999

23

• RULE: Restrict culture and O & P exam to outpatients and inpatients admitted <3 days

• RULE: Reject fungal culture on stools. Add statement: “Fungal cultures of stool have not been shown to be clinically useful.”

• Reference:– Hines J, et al: Clin Infect Dis 23:1292, 1996

Stool Cultures

24

Post-Analytical Comment Comment for E. coli 0157:H7

25

Post Analytical Comment Comment for E. coli 0157:H7

26

• “Antimicrobial agents should not routinely be used to treat gastroenteritis due to E. coli 0157:H7 because they may increase the risk of hemolytic uremic syndrome.”– Wong CS et al: The risk of the hemolytic-uremic syndrome

after antibiotic treatment of Escherichia coli O157:H7 infections. N Engl J Med. 2000 Jun 29;342(26):1930-6.

– Cieslak PR, Swerdlow DL: Escherichia coli O157:H7: What the Clinician Needs to Know. Infect Dis Clin Pract 4(2):123-127, March/April 1995

Post Analytical Comment Comment for E. coli 0157:H7

27

Guidelines for Submitting C. difficile• Test only when following criteria are met:

1. Antibiotic within 2 mos. prior to diarrhea2. Diarrhea water/profuse: 6 episodes in 36h3. Absence of other diagnosis for diarrhea

• Test only fresh diarrheal stools, no swabs

• Do not test asymptomatic patients and young children

*Shea Position Paper

–Cohen SH, et al. Infect Control Hosp Epidemiol. 2010 May;31(5):431-55.

28

Guidelines for Submitting C. difficile• Infants and children

– Neonates (< 6 weeks) and infants < 2 yrs may have toxin-producing strains in stool but are asymptomatic

– Colonization of neonates occurs within a few days of birth usually from environmental sources rather than maternal

– Prevalence of C. difficile carrier state in healthy, asymptomatic infants < 18 mos. as high as 70%

– Children > 2 yrs. epidemiology similar to adults

McGowan KL: Clin Micro Newsl 21:49-53, 1999

Cerquetti M et al: Pediatr Infect Dis J 14:598-603, 1995

29

Clinical Practice Guidelines for CDI in Adults: 2010 Update by SHEA/IDSA

• First update of guidelines originally published in ICHE in 1995

• Literature reviewed from 1994 through April 2009

• Panel of experts met face-to-face and via conference calls

• Strength of evidence and quality of recommendations were based on Canadian Task Force (CMAJ 1979)

• Document underwent external & internal review with final approval by SHEA and IDSA Boards of Directors

Cohen SH et al. Infect Cont Hosp Epidemiol 2010;31:431-55

30

Diagnosis Recommendations

• .. the sensitivity and specificity of a stool culture and identification of a toxigenic isolate (i.e. toxigenic culture) .. provides the standard against which other clinical test results should be compared (B-III)

• EIA testing for toxin A and B is rapid but is less sensitive than the cell cytotoxin assay and is thus .. sub-optimal .. (B-II)

• .. One potential strategy is a two-step method using EIA or GDH as an initial screen and the cell cytotoxicity assay or toxigenic culture as the confirmatory test on GDH positive stools .. (B-II)Cohen SH et al. Infect Cont Hosp Epidemiol 2010;31:431-55

31

2-Step Testing Caveats

• Rationale for 2-step strategy predicated on GDH as a sensitive screening test

• Sensitivity range: 71% to 89%

Ribes J et al. ICAAC-IDSA. 2008; Washington, DC. Abstract D-2277 (84 to 87%)

Broeck JV et al. ECCMID. 2009; Helsinki, Finland. Abstract P-1169 (71 to 89%)

32

Diagnosis Recommendations, cont.

• PCR testing appears to be rapid, sensitive and specific and may ultimately address testing concerns. More data needed .. (B-II)

• Repeat testing during the same episode of diarrhea is of limited value and should be discouraged (B-II)

 

Cohen SH et al. Infect Cont Hosp Epidemiol 2010;31:431-55

33

Results of Xpert C. difficile Clinical Trial Data

• A total of 2296 patient samples from seven sites tested by Xpert C. difficile assay, enriched anaerobic culture and toxin testing, and the sites’ standard of care

Tenover FC et al. J Clin Microbiol. 2010 Oct;48(10):3719-24

34

Sensitivity of Xpert C. difficile and other methods compared to enriched toxigenic culture

Sensitivity Specificity PPVa NPVa

Site N Site Assay Xpert Site Xpert Site Xpert Site Xpert Site

1 1023 Toxin A/B EIA 94.1% 67.5% 93.7% 92.0% 74.6% 62.6% 98.8% 93.5%

2 268 GDH-EIA 91.4% 74.3% 93.6% 94.8% 68.1% 68.4% 98.6% 96.1%

3 293 Toxin A/B EIA 92.3% 53.8% 94.5% 97.6% 72.0% 77.8% 98.8% 93.2%

4 312 Toxin A/B EIA 91.4% 54.3% 94.2% 95.7% 66.7% 61.3% 98.9% 94.3%

5 114 GDH-EIA-PCR 92.3% 69.2% 96.0% 97.0% 75.0% 75.0% 99.0% 96.1%

6 173 Toxin A/B EIA 97.0% 33.3% 93.6% 93.6% 78.0% 55.0% 99.2% 85.6%

7 110 Cytotoxin 90.9% 54.5% 94.9% 98.0% 66.7% 75.0% 98.9% 95.1%

Tenover FC et al. J Clin Microbiol. 2010 Oct;48(10):3719-24

35

Ability of Xpert C. difficile versus EIA to Identify Specific Ribotypes

Xpert C. difficile Enzyme Immunoassay

Ribotype

n Positive

Negative

Sensitivity (%)

Positive

Negative

Sensitivity (%)

P value

001 8 8 0 100 6 2 75.0 0.46

002 13 13 0 100 2 11 15.4 <0.0001

017 11 10 1 90.9 7 4 63.6 0.311

027 74 74 0 100 58 16 78.4 <0.0001

053 12 12 0 100 8 4 66.7 0.093

078 11 9 2 81.8 7 4 63.6 0.635

104 6 5 1 83.3 3 3 50.0 0.545

106 16 12 4 75.0 3 13 18.8 0.004

Tenover FC et al. J Clin Microbiol. 2010 Oct;48(10):3719-24

36

37

Post-Analytical Comment

Clostridium difficile

• Hard stool: “Testing for Clostridium difficile toxin is not performed on this stool sample because it is solid (not diarrheal). Treatment for Clostridium difficile toxin is not recommended for asymptomatic carriers (i.e. patients without diarrhea). If this patient was previously positive, 10% of patients will remain positive for weeks to months in spite of resolution of symptoms. Test-of-cure is not recommended.”

–Cohen SH, et al. Infect Control Hosp Epidemiol. 2010 May;31(5):431-55.

38

Post-Analytical Comment

Clostridium difficile

• Children < 2 years old: “Clostridium difficile toxin testing not performed on children under 2 years of age.”– Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo

VG, McDonald LC, Pepin J, Wilcox MH. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp Epidemiol. 2010 May;31(5):431-55.

39

Wound Culture-Work up

• Priority List-Potential Pathogens– Staphylococcus aureus– Beta Streptococcus– Pseudomonas aeruginosa

• Predominant morphyotype associated with PMNs

• Specific organisms based on patient condition or type wound eg. Bite

• Apply Rule of three

40

Culture work-up

“The number of species found in a clinical specimen is in some way indirectly proportional to the patient care value of the report”

- Ray Bartlett, M.D.

41

Culture work-up: Rule of Three• RULE: Do not work up culture when 3

or more pathogens are present with no single pathogen present as the predominant organism

• REPORT AS: “mixed flora consisting of (enter no.) Gram-positive and (enter no.) Gram-negative organisms.”

42

Diabetic Foot Ulcers

• Plantar ulcers associated with diabetes mellitus

• Inability of PMNs to kill organisms• Foot infection diagnosed primarily on clinical

grounds• Most important pathogens

– S. aureus– beta streptococci, – P. aeruginosa

43

• Always look for and report S. aureus, Beta Strep, P. aeruginosa, pure culture GNB otherwise report as:“mixed flora consisting of (enter no.) Gram-positive and (enter no.) Gram-negative organisms. Culture negative for Staphylococcus aureus, Beta Streptococcus and Pseudomonas aeruginosa”

Post-Analytical Comment Patient Report - Wound

44

Post-Analytical Comment

Blood Cultures

•Only 1 culture obtained:“In order to evaluate possible skin contamination and to ensure adequate volume of blood sampled, 2 separate venipunctures are recommended for blood culture.”

45

•Less than 5 ml of blood in bottle: “Less than 5 ml of blood received in one or both blood culture bottles. Optimal recovery of pathogens requires 8-10 ml per bottle.”

Post-Analytical Comment

Blood Cultures

46

• Greater than 3 blood cultures ordered/24 hour period: “Test cancelled: Nearly all positives detected by 3 sets”

• Nearly all episodes of bacteremia and fungemia in adult patients are detected with 2-3 blood cultures. – Wilson, M. L. Clinically Relevant, Cost-Effective Clinical

Microbiology. Am J Clin Pathol. 1997 Feb;107(2):154-67. Review.

– Principles and Procedures for Blood Cultures; Approved Guideline. CLSI document M47-A. Wayne, PA: Clinical and Laboratory Standards Institute; 2007.

Post-Analytical Comment

Blood Cultures

47

• Contamination Comment: Added for following organism types: Coag Neg Staph, Viridans Strep, Corynebacterium, Bacillus spp., Micrococcus, Lactobacillus, Rothia mucilaginosa, Propionibacterium whenever isolated from single blood culture set or when isolated from multiple sets from different days that are separated by negative blood culture sets. “Coagulase negative Staph isolated from a single set of blood cultures. This suggests probable skin contamination. No further work up.” or

Post-Analytical Comment

Blood Cultures

48

•“Susceptibility will not be performed because clinical significance of coagulase negative Staphylococci isolated from a single blood culture is undetermined. Please consult Microbiology if further work-up is needed.”

Post-Analytical Comment

Blood Cultures

49

Catheter Tip Cultures•“No clinical significance has been established for the use of catheter tip cultures in the absence of concomitant positive blood cultures.”– O’Grady NP et. al. 2002. Clin Infect Dis 35:1281-307– Mermel L.A. et al. Clinical practice guidelines for the diagnosis

and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2009 Jul 1;49(1):1-45.

– Widmer, A.F., M. Nettleman, K. Flint, and R.P. Wenzel. 1992. Clinical impact of culturing central venous catheters. Arch Intern Med. 152:1299-1302.

50

Catheter Tip Cultures

• Perform quantitative cultures only. Qualitative catheter tip cultures, have minimal value as predictors of bacteremia

• Do not work up if concurrent blood culture not submitted within 24 h. Report: “Catheter tip culture in the absence of concurrent blood culture has no clinical relevance”

51

Catheter Tip Cultures

• Do not work up unless companion blood culture is positive, then give descriptive ID only, perform ID/AST from significant blood culture isolates

• References:Nahass RG, Weinstein MP: DMID 13:223, 1990Widmer AF, et al. Arch Int Med 152:1299, 1992Peacock SJ, et al. J Hosp Infect 40:35, 1998

"Insanity is doing the same thing over and over

again and expecting a different result”

Albert Einstein