Implications of C. difficile diagnostic testing

Not seeing the wood for the trees

Warren LowmanPathlink/ Vermaak & Partners Pathologists

Wits Donald Gordon Medical CentreClinical Microbiology & Infectious Diseases, University of the

Witwatersrand

Pubmed & C. difficile

1. 9298 hits2. + Clinical trials = 3303. + Diagnosis = 1694. + Testing = 20

Clinical relevance…

2 key issues that are largely ignored:–Pre-test probability–PPV

ICU HC Surgical Medical Oncology0

20

40

60

80

100

120

C. diff pos+C. diff requestsN

o.

Are we selecting accurately?

67.1 tests/ 10 000 pt bed days (range, 29 – 153)

C. difficile diagnostics…

1. We are floundering- survey of UK labs indicate >25 different algorithms

2. Multitude of different assays3. Impacts on our understanding of the

epidemiology of CDI.

Jan Feb Mar AprMay Jun Jul AugSeptOct Nov Dec0

2

4

6

8

10

12

C. diff Rate/ 10 000 patient days

Rate (/10 000 pt days)2013 Cumulative rate

The “best” study

Lancet Infect Dis 2013

1.Diagnostic assays2.Study design3.Clinical data

Salient points

1. Tested all faecal samples irrespective of request

2. Wide scope of practice3. Detection of 3 targets: bacterium; toxin; gene4. Predefined groups: diagnostic; severity5. Statistically very “sound”6. Diagnostic performance assessed in training

phase

Clinical relevance by assay

1. Data for 6522 inpatient episodes

Variable Grp1 vs Grp2 Grp1 vs Grp3

Mean WCC 0.0004 <0.0001

Died 0.022 <0.0001

Death rate 0.0195 0.0033

…clinical relevance by assay1. Same comparison using PCR as surrogate for

cytotoxigenic culture

Variable Grp1 vs Grp2 Grp1 vs Grp3

Mean WCC <0.0001 <0.0001

Died 0.004 <0.0001

Death rate 0.0317 0.0018

The point…clinically

So what do we do about diagnosis?

What’s best?

Performance GDH + EIA NAAT + EIA

Sensitivity 81.8% 82.9%

Specificity 99.5% 99.6%

PPV 91.6% 92.1%

NPV 98.9% 98.9%

The implications

TOXIN POSITIVITY

DIAGNOSTIC ASSAY

CLINICAL OUTCOME

MANAGEMENT

C. difficile excretors…an issue?

Overtreatment…excessive antibiotic use!Cost…this all adds up

GDH EIA Toxin PCR

POSITIVE 14 7 14

NEGATIVE 11 18 11

3-stage algorithmGDH

EIA Toxin

Not CDAD

CDAD

NAAT

C. difficile excretor

Not CDAD8%

Thank you!