Evolution of Testing Algorithms at a University Hospital for Detection of Clostridium difficile Infections

Culbreath, Karissa; Ager, Edward; Nemeyer, Ronald J.; Kerr, A. G.; Gilligan, Peter H.

doi:10.1128/jcm.00992-12

Cited by 52 publications

(31 citation statements)

References 27 publications

(63 reference statements)

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“…The diagnostic accuracy measures for lateral-flow GDH and lateral-flow GDH-Tox were lower in our model than those of many published estimates (12,(19)(20)(21)(37)(38)(39)(40). Several studies con- Table 3 can be seen on the x axis, where the minimal cost lines intersect ($1,600 and $6,900).…”

Section: Discussioncontrasting

confidence: 41%

Economic Evaluation of Laboratory Testing Strategies for Hospital-Associated Clostridium difficile Infection

et al. 2014

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dClostridium difficile infection (CDI) is the most common cause of infectious diarrhea in health care settings, and for patients presumed to have CDI, their isolation while awaiting laboratory results is costly. Newer rapid tests for CDI may reduce this burden, but the economic consequences of different testing algorithms remain unexplored. We used decision analysis from the hospital perspective to compare multiple CDI testing algorithms for adult inpatients with suspected CDI, assuming patient management according to laboratory results. CDI testing strategies included combinations of on-demand PCR (odPCR), batch PCR, lateral-flow diagnostics, plate-reader enzyme immunoassay, and direct tissue culture cytotoxicity. In the reference scenario, algorithms incorporating rapid testing were cost-effective relative to nonrapid algorithms. For every 10,000 symptomatic adults, relative to a strategy of treating nobody, lateral-flow glutamate dehydrogenase (GDH)/odPCR generated 831 true-positive results and cost $1,600 per additional true-positive case treated. Stand-alone odPCR was more effective and more expensive, identifying 174 additional true-positive cases at $6,900 per additional case treated. All other testing strategies were dominated by (i.e., more costly and less effective than) stand-alone odPCR or odPCR preceded by lateral-flow screening. A cost-benefit analysis (including estimated costs of missed cases) favored stand-alone odPCR in most settings but favored odPCR preceded by lateral-flow testing if a missed CDI case resulted in less than $5,000 of extended hospital stay costs and <2 transmissions, if lateral-flow GDH diagnostic sensitivity was >93%, or if the symptomatic carrier proportion among the toxigenic culture-positive cases was >80%. These results can aid guideline developers and laboratory directors who are considering rapid testing algorithms for diagnosing CDI.

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Section: Discussioncontrasting

confidence: 41%

Economic Evaluation of Laboratory Testing Strategies for Hospital-Associated Clostridium difficile Infection

et al. 2014

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Section: Discussionmentioning

confidence: 99%

“…In recently published studies in which such calculations were performed, the full benefits of molecular assays or IA tests/ EIAs used alone or in two-step algorithms were not comprehensively assessed (15,16,24). In the studies by Walkty et al and Culbreath et al, a GDH/EIA two-step algorithm was found to be the most economical approach to screening for CDI, but only the costs of reagents and consumables were taken into account (15,16). In contrast, in the study by Chapin et al, greater savings were actually attained with direct molecular screening, compared with a Two of the three specimens with positive GenomEra C. difficile assay results but negative toxigenic culture results were confirmed as positive with the GeneXpert C. difficile PCR assay (Cepheid).…”

Section: Discussionmentioning

confidence: 99%

“…These are sensitive but have several drawbacks, including long turnaround times and labor-intensive sample preparation and analysis, which limit their clinical utility (9)(10)(11)(12)(13). An alternative approach is the detection of C. difficile toxins or glutamate dehydrogenase (GDH) in stool samples by immunochromatographic antigen (IA) tests or enzyme immunoassays (EIAs) (14)(15)(16). These assays are rapid but are less sensitive and less specific than toxigenic cultures.…”

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Evaluation of a New Automated Homogeneous PCR Assay, GenomEra C. difficile, for Rapid Detection of Toxigenic Clostridium difficile in Fecal Specimens

2013

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bWe evaluated a new automated homogeneous PCR assay to detect toxigenic Clostridium difficile, the GenomEra C. difficile assay (Abacus Diagnostica, Finland), with 310 diarrheal stool specimens and with a collection of 33 known clostridial and nonclostridial isolates. Results were compared with toxigenic culture results, with discrepancies being resolved by the GeneXpert C. difficile PCR assay (Cepheid). Among the 80 toxigenic culture-positive or GeneXpert C. difficile assay-positive fecal specimens, 79 were also positive with the GenomEra C. difficile assay. Additionally, one specimen was positive with the GenomEra assay but negative with the confirmatory methods. Thus, the sensitivity and specificity were 98.8% and 99.6%, respectively. With the culture collection, no false-positive or -negative results were observed. The analytical sensitivity of the GenomEra C. difficile assay was approximately 5 CFU per PCR test. The short hands-on (<5 min for 1 to 4 samples) and total turnaround (<1 h) times, together with the high positive and negative predictive values (98.8% and 99.6%, respectively), make the GenomEra C. difficile assay an excellent option for toxigenic C. difficile detection in fecal specimens.T oxin-producing Clostridium difficile is the most common cause of hospital-acquired and antibiotic-associated diarrhea (1, 2). The main virulence factors of C. difficile are C. difficile toxin A (TcdA) and C. difficile toxin B (TcdB), which are encoded by the genes tcdA and tcdB, respectively (3, 4). In addition, a separate binary toxin is produced by a small group of isolates with or without TcdA and/or TcdB (5, 6), and it has been suggested that the binary toxin may play a part in the recurrence of C. difficile infection (CDI) (7). As the role of the binary toxin in CDI currently is not well understood, it has not become a common target for diagnostic assays.CDI is prevalent in many hospitals and health care facilities throughout the world. It is associated with increases in hospitalization times and mortality rates, leading to augmented health care costs (2,6,8). In order to limit the transmission of C. difficile and to decrease the burden of CDI, rapid reliable detection of toxigenic C. difficile isolates and good infection prevention practices are required.Cytotoxigenic cultures and cytotoxin assays are considered standard diagnostic methods. These are sensitive but have several drawbacks, including long turnaround times and labor-intensive sample preparation and analysis, which limit their clinical utility (9-13). An alternative approach is the detection of C. difficile toxins or glutamate dehydrogenase (GDH) in stool samples by immunochromatographic antigen (IA) tests or enzyme immunoassays (EIAs) (14-16). These assays are rapid but are less sensitive and less specific than toxigenic cultures. Moreover, relying only on GDH detection reveals nothing about the toxigenic nature of the possible C. difficile isolates. To improve the detection of CDI using IA tests or EIAs, a two-step diagnostic algorithm has bee...

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“…The intervention also reduces laboratory workload and hospital costs and empowers clinicians to accept negative results and avoid unnecessary antibiotic treatment and patient isolation without having to wait for the results of a repeat test. Although a formal cost analysis was not done, if the cost of each test is assumed to be approximately $40 based on values reported in the literature, the 91% reduction in repeat testing equates to a savings of 1,353 tests, or $54,120, in the postintervention period, not including the additional savings in labor, vancomycin usage, hospital isolation days, and other hospital-wide costs (15,16). As institutions put limits on repeat testing for C. difficile PCR, ordering multiple tests to diagnose CDI may soon be relegated to the past.…”

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confidence: 99%

Alerting Physicians during Electronic Order Entry Effectively Reduces Unnecessary Repeat PCR Testing for Clostridium difficile

2013

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cHospital information systems (HIS) alerts restricting repeat Clostridium difficile PCR ordering by physicians in patients with a prior result within 7 days eliminated 91% of repeat tests, from 14.5% (282/1,949) repeats preintervention to 1.3% (135/10,285) postintervention. HIS alerting is an effective, targeted, patient-specific tool for improving the quality and utilization of C. difficile results.C lostridium difficile is a major cause of diarrhea in hospitalized patients, particularly after antibiotic treatment, and can lead to colitis, toxic megacolon, and even death (1, 2). Although a variety of tests are used for the diagnosis of C. difficile infection (CDI), including enzyme immunoassays (EIAs) and lateral flow tests, PCR testing is growing in popularity (3-5). The high sensitivity of PCR has eliminated the need for multiple repeat tests, which was commonly done with EIAs, despite evidence suggesting that even repeating EIAs is of no value (3-6). Several studies, including one at our own institution, have demonstrated that repeat PCR testing, especially within the first 7 days of an initial negative test, does not change the test result for 97 to 99% of patients and leads to increased hospital costs and consequential false-positive results (6-10).Based on these findings, our institution developed a policy for rejecting repeat PCR testing for CDI within 7 days of an initial test, except with the approval of the microbiology laboratory director, typically in cases where the initial diarrhea had resolved and was followed by a new bout of diarrhea and when there was high clinical suspicion for CDI. Tests with indeterminate results were automatically repeated. The rejection policy was enforced electronically through the hospital information systems (HIS), Epic Systems' HIS (Verona, WI) and Cerner HIS (Kansas City, MO), at the level of physician order entry. When electronic orders were placed for C. difficile PCR, an HIS algorithm was triggered to search the patient's orders and results to determine if the test had been collected (day 0) and/or resulted in the past 7 days. For repeat orders, a pop-up alert stated, "Order placed for the procedure in last 7 days." The alert also displayed the date, time, and result of the last order. This provided the physician with the information needed to understand the current status of C. difficile testing when given the choice to cancel or continue placing the duplicate order. If the physician decided to continue with the order, a second alert stated, "C. diff toxin B PCR is a highly sensitive test and should not be repeated within 7 days of a previous order. Consult to GI is recommended." The alert also indicated that a message would be sent to the microbiology laboratory for review if the duplicate test was still ordered, which alerted the laboratory accessioning supervisor to intercept and manually reject duplicate C. difficile PCR orders that were not approved for repeat testing. The objective of the current study was to evaluate the impact of this HIS intervention on ...

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Evolution of Testing Algorithms at a University Hospital for Detection of Clostridium difficile Infections

Cited by 52 publications

References 27 publications

Economic Evaluation of Laboratory Testing Strategies for Hospital-Associated Clostridium difficile Infection

Economic Evaluation of Laboratory Testing Strategies for Hospital-Associated Clostridium difficile Infection

Evaluation of a New Automated Homogeneous PCR Assay, GenomEra C. difficile, for Rapid Detection of Toxigenic Clostridium difficile in Fecal Specimens

Alerting Physicians during Electronic Order Entry Effectively Reduces Unnecessary Repeat PCR Testing for Clostridium difficile

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