1. Evolution in the Type of Diagnostic Tests Used in Quebec, Canada,
for the Diagnosis of C. difficile Infection,
ECCMD
C. Bogaty MD1, S. Lévesque2, C. Garenc3,4, C. Frenette MD1, J. Longtin MD4, Y. Longtin MD1
(1) McGill University, Montreal, Canada (2) Laboratoire de Santé Publique du Québec, Canada (3) Institut National de Santé Publique du Québec, Canada (4) Laval University, Quebec, Canada
Brands of Commercial Assays
Among NAAT: 1 homebrew, 4 commercial assays; BD GeneOhm PCR was the most used
Among EIA: 8 commercial assays; Quik Chek Complete from TechLab was used by 53.9% and 63.1% of hospitals in 2010 and 2014 respectively (p=0.36)
Results
Introduction
Conclusions
Hospital Demographics
22 (40.7%) are academic institutions
54 (62.1%) have ≥100 hospital beds
73 (83.9%) have ≥35% of patients aged ≥65
Location of Testing
80 (84.2%) perform part of or the entire algorithm within their institution
Of these, 20 (25.0%) refer part of their algorithm to an outside facility
16 reference laboratories, 8 within Montreal
Evolution of Diagnostic Algorithms in Use
35 institutions (36.8%) changed algorithm between 2010 and 2014
NAAT increased 2.8-fold (p<0.001): non-academic (2 to 14 institutions, p=0.001), ≥100 beds (6 to 22 hospitals, p=0.001), ≥35% of patients aged ≥65 (9 to 25 hospitals, p=0.003)
EIA algorithms significantly decreased (p=0.05)
CCA-based algorithms have had a sizeable decrease from 40 to 33 institutions (p=0.37)
C. difficile accounts for 20%–30% of cases of antibiotic-associated diarrhea and is the most commonly recognized cause of infectious diarrhea in healthcare settings1
Quebec Surveillance System
Implemented in 2004 (population of 8 million)
95 acute care facilities admitting >1000 patients/year are required to participate in the surveillance program
Incidence rates are adjusted for academic mission, hospital size (≥100 beds), and patient mix (≥35% of patients aged ≥65 years)
No official recommendations have been made regarding which diagnostic tests to used across the province
The decision has been left to the discretion of each individual hospital
Incidence rates are not adjusted for the varying sensitivities of different diagnostic assays and algorithms
Goals of this Study
Evaluate the temporal evolution in testing strategies used to diagnose C. difficile infection (CDI) across Quebec
Investigate the association between incidence rates and the type of assays used to determine whether incidence rates should be stratified by type of assay to improve inter-hospital comparison
Table 1: Algorithms used between 2010 and 2014
Table 2: Assays used between 2010 and 2014
Temporal Evolution in Testing Strategies
A wide range of assays, diagnostic algorithms and brands are used to diagnose CDI across Quebec
Many hospitals changed diagnostic algorithm between 2010 and 2014, with an increase in the use of NAAT assays and an overall decrease in EIA assays
NAAT has become the third most utilized assay across the province, and the single-step NAAT is now the most commonly used algorithm
The significant decrease in EIA-based algorithms likely demonstrates a declining reliance on low-sensitivity assays2,3
CCA as a confirmatory test following GDH screening has remained relatively constant, but NAAT as a confirmatory test has increased significantly
This demonstrates a change in laboratory practice towards utilizing more rapid and sensitive screening tests before progressing to a specific but expensive and labour-intensive assay3,4
Association Between Incidence Rate and Type of Assay
Institutions that rely on a single-step NAAT or a GDH followed by CCA have significantly higher CDI incidence rates then their counterparts
The paradoxical increase in CDI incidence with the addition of a GDH-step to CCA is suspected to be due to other confounding variables impacting the surveillance data
Attempting to adjust for the diagnostic algorithm would not fully account for the variation in incidence rates between institutions
At this point in time the surveillance data cannot be retrospectively adjusted to compensate for the type of diagnostic algorithm used
Diagnostic Algorithm
2010
2014
p-value
Nucleic-acid amplification tests (NAAT)
Single-step NAAT test 8 20
Total
0.02
Cell cytotoxin analysis (CCA)-based tests
Single-step CCA 12 5
Tox AB + CCA 3 1
NAAT + CCA 15 7 NS
GDH-based with NAAT
GDH + NAAT 2
GDH + Tox AB + NAAT 4 13
GDH-based with CCA
GDH + CCA 6
GDH + Tox AB + CCA 19
GDH + CCA + TC 25 26
EIA-based tests
Single-step Tox A EIA
Single-step Tox AB EIA 17
GDH + Tox AB EIA
Single-step GDH 43 29
0.05 95
Assay Name (Company)
2010
2014
p-value
NAAT
BD GeneOhm (Beckton Dickinson) 8 15 NS
Xpect C. difficile (Cepheid) 2 7
Illumigene C. difficile (Meridian) 1 9
Unknown
Simplexa C. difficile Universal Direct (Focus Diagnostics)
Laboratory-developed test
Total 12 34
<0.01 
EIA-based tests
Quik Chek Complete (TechLab) 40 43
ImmunoCard Toxin A&B (Meridian) 11
C. Diff Quik Chek (TechLab)
Xpect C. difficile Toxin A/B (Remel) 3
Premier Toxins A&B (Meridian) 5 4
VIDAS C. difficile Toxin A&B (BioMérieux)
C. Diff Chek-60 (TechLab)
C. difficile Tox A/B II (TechLab)
Quik Chek (TechLab) + ImmunoCard 75 69
Table 3: Association between diagnostic algorithms and CDI incidence rates in 2014
Diagnostic Algorithm
No. hospitals
CDI incidence rate
95% CI
Incidence rate ratio (IRR)
p-value
Adjusted incidence rate ratio (aIRR)
NAAT 20
8.6
1.85
<0.001
1.62
CCA-based tests 7
5.1
1.09 NS
1.13
GDH-based with NAAT 13
4.6
1 [reference]
GDH-based with CCA or TC 26
8.7
1.88
1.69
EIA-based tests 29
1.15
Materials & Methods
Study Design and Data Acquisition
Cross-sectional study evaluating all 95 hospitals
Survey conducted between March 2013 and March 2014:
a) Type of test(s) used for hospitalized patients
b) Year of implementation of the current diagnostic test
A 2011 study by the Surveillance provinciale des diarrhées associées au C. difficile (SPIN-CD) was used as a comparator
Statistical Analysis
Standard descriptive statistics were used to describe the hospitals under study
Chi-square and Fisher’s Exact Test were used to calculate the difference in the proportion of hospitals using each type of assay
The algorithms in 2014 were clustered into 5 categories according to the generally accepted sensitivity of the first and final steps. They were compared with CDI incidence rates via Poisson regression. GDH + NAAT was used as the reference test as it was associated with the lowest incidence
Association Between Diagnostic Assay and CDI Incidence Rate
Incidence density was highest with the multi-step GDH-based with CCA algorithm and with the single-step NAAT assay
All other algorithm sets were statistically similar
After adjusting for academic mission, hospital size, and patient mix, the single-step NAAT assay and the multi-step GDH-based with CCA had significantly higher CDI incidence rates (aIRR 1.62 and 1.69 respectively, p<0.001)
CDI incidence rate ratios were not statistically different between CCA-based tests, GDH-based with NAAT algorithms, and EIA-based tests (p>0.05)
References
Cohen, S.H., et al., 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, (5): p
Ferguson, J.K., et al., Clostridium difficile laboratory testing in Australia and New Zealand: national survey results and Australasian Society for Infectious Diseases recommendations for best practice. Pathology, (5): p
Wilcox, M.H., et al., What is the current role of algorithmic approaches for diagnosis of Clostridium difficile infection? J Clin Microbiol, (12): p
Goldenberg, S.D., et al., Mandatory reporting and improvements in diagnosing Clostridium difficile infection: an incompatible dichotomy? J Infect, (5): p
Figure 1: Adjusted and non-adjusted incidence rate ratio of C. difficile infection between hospitals using different diagnostic algorithms in 2014
Contact Information
Yves Longtin MD,