Luminex xTAG Gastrointestinal Pathogen Panel Research Articles

QIAstat-Dx gastrointestinal panel and Luminex xTAG gastrointestinal pathogen panel comparative evaluation.

The diagnosis of acute gastroenteritis is an ongoing clinical challenge in terms of identification of the etiologic agent, time to results, and appropriate treatment. Rapid detection of gastrointestinal pathogens is needed to improve patient care. This study evaluates the performance of the QIAstat-Dx gastrointestinal panel (Q-GP; Investigational Use Only) compared to the Luminex xTAG gastrointestinal pathogen panel (L-GPP; US-IVD). Using 245 stool specimens, we evaluated 10 different targets including rotavirus, norovirus, Salmonella, Shigella, Campylobacter, Giardia, Cryptosporidium, Escherichia coli O157, enterotoxigenic E. coli (ETEC), and Shiga toxin-producing E. coli (STEC). For the viral targets, the percent positive agreement (PPA) for rotavirus was 100% (n = 19) and that for norovirus was 91% (20/22). For the parasitic targets, the PPA was 100% for Giardia and Cryptosporidium (n = 18 and n = 23, respectively). The PPA was 96% for Salmonella (22/23) and Campylobacter (22/23), and the PPA for Shigella was 100% (n = 23). For the E. coli targets, a PPA of 94% was achieved for STEC (32/34) and 96% for ETEC (24/25). We did not assess PPA for the E. coli O157 target as the Q-GP O157 call is stx dependent. The negative percent agreement across all targets was 99.1%. Our study suggests that QIAstat-Dx GP provides comparable results to Luminex GPP based on the analysis of targets found on both panels.

Accuracy and comparison of two rapid multiplex PCR tests for gastroenteritis pathogens: a systematic review and meta-analysis

ObjectivesThe primary aim is to provide a summary of evidence for the diagnostic accuracies of multiplex PCR gastrointestinal (GI) panels—BioFire FilmArray and Luminex xTAG on the detection of gastroenteritis pathogens....

Comparison of BioFire FilmArray gastrointestinal panel versus Luminex xTAG Gastrointestinal Pathogen Panel (xTAG GPP) for diarrheal pathogen detection in China

ObjectivesTo compare the performance of two syndromic panels: Luminex xTAG Gastrointestinal Pathogen Panel (GPP) and FilmArray Gastrointestinal (GI) panel. MethodsA total of 243 diarrhea specimens were detected by two panels in parallel, and the inconsistent results were analyzed by real-time PCR or reverse transcription PCR (RT-PCR). The target concentration in specimens was examined by comparing the crossing point values of FilmArray, the median fluorescence intensity of xTAG and the cycle threshold values in any discrepancies. ResultsFor pathogens detected by both panels, the positive rates of FilmArray GI and xTAG GPP were 65.0% and 48.6%, respectively. The two panels showed high consistency (kappa ≥0.74) in detecting norovirus, rotavirus and Campylobacter, while there was low consistency (kappa ≤0.40) in detecting Cryptosporidium, Salmonella, Shiga toxin-producing Escherichia coli (STEC) and enterotoxigenic Escherichia coli (ETEC). Samples with low concentration targets were more often detected by FilmArray than with xTAG GPP. The xTAG GPP was more likely to be affected by amplification inhibitors. Several defects of xTAG GPP were found in detecting ETEC. ConclusionsFilmArray was more sensitive. For specimens with low target concentrations or containing ETEC heat stable enterotoxin, the false negatives of xTAG GPP need to be considered.

Comparative Evaluation of Enteric Bacterial Culture and a Molecular Multiplex Syndromic Panel in Children with Acute Gastroenteritis.

Although enteric multianalyte syndromic panels are increasingly employed, direct comparisons with traditional methods and the inclusion of host phenotype correlations are limited. Luminex xTAG gastrointestinal pathogen panel (GPP) and culture results are highly concordant. However, phenotypic and microbiological confirmatory testing raises concerns regarding the accuracy of the GPP, especially for Salmonella spp. A total of 3,089 children with gastroenteritis submitted stool specimens, rectal swab specimens, and clinical data. The primary outcome was bacterial pathogen detection agreement for shared targets between culture and the Luminex xTAG GPP. Secondary analyses included phenotype assessment, additional testing of GPP-negative/culture-positive isolate suspensions with the GPP, and in-house and commercial confirmatory nucleic acid testing of GPP-positive/culture-negative extracts. The overall percent agreement between technologies was >99% for each pathogen. Salmonella spp. were detected in specimens from 64 participants: 12 (19%) by culture only, 9 (14%) by GPP only, and 43 (67%) by both techniques. Positive percent agreement for Salmonella spp. was 78.2% (95% confidence interval [CI], 64.6%, 87.8%). Isolate suspensions from the 12 participants with specimens GPP negative/culture positive for Salmonella tested positive by GPP. Specimens GPP positive/culture negative for Salmonella originated in younger children with less diarrhea and more vomiting. GPP-positive/culture-negative specimen extracts tested positive using additional assays for 0/2 Campylobacter-positive specimens, 0/4 Escherichia coli O157-positive specimens, 0/9 Salmonella-positive specimens, and 2/3 Shigella-positive specimens. For both rectal swab and stool samples, the median cycle threshold (CT ) values, determined using quantitative PCR, were higher for GPP-negative/culture-positive samples than for GPP-positive/culture-positive samples (for rectal swabs, 36.9 [interquartile range {IQR}, 33.7, 37.1] versus 30.0 [IQR, 26.2, 33.2], respectively [P = 0.002]; for stool samples, 36.9 [IQR, 33.7, 37.1] versus 29.0 [IQR, 24.8, 30.8], respectively [P = 0.001]). GPP and culture have excellent overall agreement; however, for specific pathogens, GPP is less sensitive than culture and, notably, identifies samples false positive for Salmonella spp.

1106. Infectious Etiologies of Acute Gastroenteritis in Children during the First 100 Days Post-Allogeneic Hematopoietic Cell Transplant

BackgroundAcute gastroenteritis (AGE) is a frequent sequela in children undergoing hematopoietic cell transplant (HCT). Although rotavirus and norovirus have been implicated as important causes of AGE, the frequency of other pathogens is unknown. Little data exist on longitudinal prevalence of infectious AGE in HCT.MethodsFrom February 2015 to May 2016, subjects <18 years undergoing allogeneic HCT were enrolled at four CDC-NVSN sites: Oakland, Kansas City, Seattle, and Nashville. Stool samples were collected at enrollment, weekly until discharge or day 100 (whichever occurred earliest), during re-admissions within the first 100 days, and day 100. AGE was defined as unexplained ≥3 episodes diarrhea and/or ≥1 episode vomiting/24 hours. Specimens were tested using Luminex xTAG Gastrointestinal Pathogen Panel (Austin, TX) and real-time PCR for adenovirus, astrovirus, norovirus, and sapovirus.ResultsThirty-one patients were enrolled at four sites (Seattle: 13, Kansas City: 8, Oakland: 6, Nashville: (4) with median age 5 (IQR 3–10) years. Two hundred sixteen samples were obtained with median 7 samples/subject. During the first 100 days, 29 (94%) subjects met the AGE definition. Thirty-six single pathogen detections occurred in 16 (52%) subjects. Clostridium difficile was the most frequent pathogen (Figure 1), with 14 detections in nine patients, all ≥3 years; 50% of detections were asymptomatic. Seven (50%) detections occurred at HCT onset and none received targeted C. difficile therapy. Sapovirus was detected nine times in four patients, with seven (78%) detections associated with AGE symptoms. Rotavirus was detected nine times, during five symptomatic episodes, in three patients. Adenovirus was detected four times in three patients and all were symptomatic.ConclusionWe longitudinally characterized the etiology of infectious AGE in children undergoing HCT. Despite the majority of patients meeting the definition for AGE, only half had a pathogen detected, suggesting that differentiating infectious vs. noninfectious AGE (e.g., medication induced) in this population is difficult. Although all subjects with adenovirus and most with sapovirus were symptomatic, asymptomatic C. difficile detection was common. Interestingly, norovirus was not detected. Further investigation of AGE is warranted in this population.Figure 1.Pathogens detected during the first 100 days post-HCT.Disclosures All authors: No reported disclosures.

Quantitative Thresholds Enable Accurate Identification of Clostridium difficile Infection by the Luminex xTAG Gastrointestinal Pathogen Panel.

Clostridium difficile colonizes the gastrointestinal (GI) tract, resulting in either asymptomatic carriage or a spectrum of diarrheal illness. If clinical suspicion for C. difficile is low, stool samples are often submitted for analysis by multiplex molecular assays capable of detecting multiple GI pathogens, and some institutions do not report this organism due to concerns for high false-positive rates. Since clinical disease correlates with organism burden and molecular assays yield quantitative data, we hypothesized that numerical cutoffs could be utilized to improve the specificity of the Luminex xTAG GI pathogen panel (GPP) for C. difficile infection. Analysis of cotested liquid stool samples (n = 1,105) identified a GPP median fluorescence intensity (MFI) value cutoff of ≥1,200 to be predictive of two-step algorithm (2-SA; 96.4% concordance) and toxin enzyme immunoassay (EIA) positivity. Application of this cutoff to a second cotested data set (n = 1,428) yielded 96.5% concordance. To determine test performance characteristics, concordant results were deemed positive or negative, and discordant results were adjudicated via chart review. Test performance characteristics for the MFI cutoff of ≥150 (standard), MFI cutoff of ≥1,200, and 2-SA were as follows (respectively): concordance, 95, 96, and 97%; sensitivity, 93, 78, and 90%; specificity, 95, 98, and 98%; positive predictive value, 67, 82, and 81%;, and negative predictive value, 99, 98, and 99%. To capture the high sensitivity for organism detection (MFI of ≥150) and high specificity for active infection (MFI of ≥1,200), we developed and applied a reporting algorithm to interpret GPP data from patients (n = 563) with clinician orders only for syndromic panel testing, thus enabling accurate reporting of C. difficile for 95% of samples (514 negative and 5 true positives) irrespective of initial clinical suspicion and without the need for additional testing.

Enterovirus detection in patients with acute gastroenteritis in Switzerland.

Acute gastroenteritis (GE) has a major impact on morbidity and mortality worldwide, yet comprehensive data regarding infectious agents including enteroviruses are scarce. We hypothesized that enteroviruses constitute a significant cause of acute GE. We analyzed 677 stool samples from 504 patients, which had been submitted for suspected infectious GE. 0.2 mL of stool suspension was extracted using the Abbott m2000sp robot and analysed by multiplex nucleic acid testing (NAT) using the Luminex xTAG gastrointestinal pathogen panel (GPP) as well as by specific NATs detecting enteroviruses and polioviruses. Median age of the patients was 6.6 years (IQR 1.1-50.6; pediatric <18 years). 292 of 677 (43%) samples were positive for at least one pathogen. Enterovirus was detected in 5.3% (36/677) as sole pathogen (67%), and more frequently in children (P = 0.0054). Only rotavirus (18.6%) and norovirus (12.1%) were more frequent. Clostridium difficile and Campylobacter jejuni were detected in 5.5% and 2.2% of stools, respectively. Adenovirus, E. coli O157, Salmonella, Shiga toxin-producing E. coli (STEC), Shigella, Giardia lamblia, Cryptosporidium, and Entamoeba histolytica were rare (<1% of samples). Vibrio cholerae, Yersinia enterocolitica, enterotoxigenic E. coli (ETEC) and poliovirus were not detected. Thus, non-polio enteroviruses are the third most frequent pathogen in acute GE suggesting that enteroviruses may play an important role in GE even in developed, industrial health care settings.

Quantitative thresholds enable accurate identification of clostridium difficile infection by the luminex xTAG gastrointestinal pathogen panel

Quantitative thresholds enable accurate identification of clostridium difficile infection by the luminex xTAG gastrointestinal pathogen panel

Enteropathogen detection in children with diarrhoea, or vomiting, or both, comparing rectal flocked swabs with stool specimens: an outpatient cohort study

Enteropathogen detection traditionally relies on diarrhoeal stool samples, but these are inconvenient to collect if they are not immediately available, leading to suboptimum return rates of samples and delayed or missed diagnostic opportunities. We sought to compare the enteropathogen yields of rectal swabs and stool specimens in children with diarrhoea or vomiting, or both. The Alberta Provincial Pediatric EnTeric Infection TEam (APPETITE) did a study in three outpatient cohorts in Calgary and Edmonton (AB, Canada)-children enrolled in the Pediatric Emergency Research Canada emergency departments, children receiving routine vaccinations at a Calgary health clinic, and symptomatic children who met criteria for treatment at home. Eligible participants were children younger than 18 years, with at least three episodes of vomiting or diarrhoea in the preceding 24 h and fewer than 7 days of symptoms. After excluding those enrolled within the previous fortnight, unable to follow-up, or having psychiatric illness, neutropenia, or requiring emergent care, we attempted to collect rectal swabs and stool from all participants. Specimens were tested with the multianalyte assay Luminex xTAG Gastrointestinal Pathogen Panel, an in-house five-virus panel and bacterial culture. Primary outcomes were comparative yield (calculated as the proportion of submitted paired specimens only in which at least one pathogen was identified) and overall yield (which calculated the proportion of study participants in whom at least one pathogen was identified in all specimens, where unsubmitted specimens were analysed as negative). We used McNemar's test to do pathogen-specific analyses, and generalised estimating equations (GEE) for the global (ie, any) pathogen analyses, with adjustments made for the presence of diarrhoea, location, and their interactions with specimen type. Between Dec 12, 2014, and Aug 31, 2016, we studied 1519 eligible participants, 1147 (76%) of whom provided stool specimens and 1514 (>99%) provided swab specimens. 871 (76%) of 1147 stool specimens and 1024 (68%) of 1514 swabs were positive for any pathogen (p<0·0001). Comparative yield adjusted odds ratios (ORs) for stool specimens relative to swabs were 1·24 (95% CI 1·11-1·38) in children with diarrhoea at presentation and 1·76 (1·47-2·11) in children without diarrhoea. GEE analysis identified an interaction between the presence of diarrhoea and specimen type (p=0·0011) and collection location (p=0·0078). In an overall yield analysis, pathogen yield was 57% (871 of 1519 children) for stool specimens and 67% (1024 of 1519 children) for rectal swabs, with an unadjusted OR of 0·65 (95% CI 0·59-0·72) for stool relative to swab. Rectal swabs should be done when enteropathogen identification and rapid detection are needed, appropriate molecular diagnostic technology is available, and a stool specimen is not immediately available. In view of their high yield, we urge that the recommendation against the use of rectal swabs as diagnostic specimens be reconsidered. Alberta Innovates-Health Solutions Team Collaborative Research Innovation Opportunity.

Enteropathogen Detection in Children with Diarrhea and/or Vomiting: A Cohort Study Comparing Rectal Flocked Swabs and Stool Specimens

BackgroundDiarrheal stool samples are currently preferred for enteropathogen detection, but they are inconvenient to collect if they are not immediately available, leading to suboptimal return rates and delayed or missed diagnostic opportunities. We sought to compare the enteropathogen yields of rectal swabs and stool specimens in an outpatient cohort of children with diarrhea and/or vomiting.MethodsEligible children were < 18 years of age, with ≥3 episodes of vomiting or diarrhea in 24 hours and <7 days of symptoms. After excluding those enrolled within the prior fortnight, unable to follow-up, having psychiatric illness, neutropenia, or requiring emergent care, we attempted to collect rectal swabs and stool from all participants. Specimens were subjected to testing with the Luminex xTAG Gastrointestinal Pathogen Panel, an in-house 5-virus panel and bacterial culture. Primary outcomes were comparative (submitted paired specimens only) and overall (all specimens, unsubmitted specimens analyzed as negative) yields. We used McNemar’s test to conduct pathogen-specific analyses, and generalized estimating equations to perform global (i.e., any) pathogen analyses with adjustments made for the presence of diarrhea, location, and their interactions with specimen type.ResultsOf the 1,519 subjects enrolled, 1,147 (75·5%) and 1,514 (99·7%) provided stool and swab specimens, respectively. The proportions of specimens positive for any pathogen were 75.9% (871/1,147) and 67.6% (1,024/1,514); P < 0.0001. Comparative yield adjusted OR in stool relative to swabs were 1.24 (95% CI: 1.11, 1.38) and 1.76 (95% CI: 1.47, 2.11) in children with and without diarrhea at presentation, respectively. Overall concordance analysis yielded a kappa of 0.76 (95% CI: 0.71, 0.80). Paired positive viral specimens had lower median cycle threshold values (i.e., higher viral loads; P < 0·0001) in SSs compared with swabs for all viruses. In overall yield analysis, the proportions positive for a pathogen were 57.3% and 67.4 for stool and rectal swabs, respectively; unadjusted OR: 0.65 (95% CI: 0.59, 0.72) for stool relative to swab.ConclusionRectal swabs should be performed when enteropathogen identification, and/or rapid detection, is needed, molecular diagnostic technology available, and stool not immediately available.Disclosures All authors: No reported disclosures.

Relationship Between Enteropathogen and Acute Gastroenteritis Disease Severity: A Prospective Cohort Study

BackgroundLittle is known about the association between specific enteropathogens and disease severity in outpatient children with acute gastroenteritis. Recent advances in diagnostics enabling the rapid and simultaneous detection of common enteropathogens have become readily available. While such knowledge can be used to optimize therapy it also has the potential to predict disease severity. Such knowledge can aid clinical decision making, can clarify guidance and expectations provided to families, and can guide public health policy.MethodsWe conducted a prospective cohort study of children with acute gastroenteritis who were brought for emergency department care. The primary outcome measure was the 20-point Modified Vesikari Scale (MVS) score calculated from symptom onset until day14 of follow-up (total MVS score). Stool and/or rectal swab specimens were collected and analyzed for 18 unique pathogens by molecular diagnostic assays (in-house 5 virus panel, Luminex xTAG Gastrointestinal Pathogen Panel) and/or bacterial culture. An enteropathogen was deemed to be present if a candidate pathogen was identified in the rectal swab or stool specimens by any testing method. Binary logistic regression was performed to assess the association between pathogens (including all pathogens as present or not) and disease severity with the dependent variable being the total MVS score categorized as severe (11–20 points) vs.. non-severe (0–10 points).ResultsThe mean total MVS score (SD) was 12.8 (3.2) and 73.0% (807/1102) of participants experienced severe disease. A pathogen was identified in 72.8% (802/1102) of study participants. Rotavirus, norovirus GII and adenovirus were identified in 26.6% (293/1102), 23.0% (253/1102) and 16.0% (176/1102) of participants respectively. After adjusting for other pathogens significant predictors of severe disease were: rotavirus (OR=8.0; 95% CI: 4.8, 13.2), Salmonella (OR=5.4; 95% CI: 1.2, 24.4), adenovirus (OR=2.1; 95% CI: 1.3, 3.3), and norovirus GII (OR=1.8; 95% CI: 1.3, 2.6). Clostridium difficile (OR=1.6; 95% CI: 0.96, 2.6) and Aeromonas (OR=0.97; 95% CI: 0.2, 4.7) were not significantly associated with severe disease.ConclusionIn children with acute gastroenteritis, the enteropathogens associated with severe disease included rotavirus, Salmonella, adenovirus and norovirus GII.Disclosures All authors: No reported disclosures.

Evaluation of the xTAG Gastrointestinal Pathogen Panel Assay for the Detection of Enteric Pathogens in Kuwait

Objective: To evaluate the utility of the Luminex xTAG gastrointestinal pathogen panel (GPP) assay in the detection of enteric pathogens from diarrheal stool samples in Kuwait. Materials and Methods: The Luminex xTAG GPP assay was used according to the manufacturer's instructions to evaluate single diarrheal stool samples from 109 hospitalized patients at Mubarak Al-Kabeer Hospital, Kuwait, from March 2014 to June 2015. The assay procedure involved nucleic acid extraction from stool samples, amplification of the target by reverse transcriptase polymerase chain reaction, hybridization of the amplified target by probe, detection of the target by the Luminex instrument and computerized data analysis. Conventional microbiological assays were used as the gold standard for comparison. Results: From the 109 diarrheal stool samples, 20 (18.4%) pathogens were detected by the xTAG GPP assay compared to 10 (9.2%) pathogens using conventional assays. Both methods detected 3 Salmonella spp., 3 Clostridium difficile, 2 rotavirus and 2 norovirus. In addition, the xTAG GPP assay detected 1 Shigella sp., 6 Campylobacter spp., 1 Cryptosporidium sp. and 2 Giardia lamblia which were missed by conventional assays. Conclusions: In this study, xTAG GPP detected twice as many pathogens as the conventional assays. We recommend the introduction of this assay in routine diagnostic laboratories for a rapid and better diagnosis and treatment of diarrheal disease.

The value of a multiplexed gastrointestinal pathogen panel in 2 distinct patient populations

We assess the value of the Luminex xTAG Gastrointestinal Pathogen Panel (GPP) in 2 different patient populations: an uninsured, indigent population seeking primary care, and a tertiary care hospital specializing in surgical, transplant, and oncology care. Stool specimens collected April to August 2013 for infectious workup were tested on the GPP, and discordant results were further analyzed by alternative methods. Compared to the tertiary care setting, stool pathogen detection was nearly twice as frequent in the primary care setting (25% versus 14%; P<0.05) with a broader array of pathogens detected (15 versus 4). Overall, the greatest value of the GPP was in detection of viral causes of gastroenteritis that were not routinely sought and in detection of Campylobacter spp. when patients presented late in the disease course. Application of a GPP should consider the characteristics of the patient population to maximize its clinical utility in different healthcare settings.

Risk of Rotavirus Vaccination for Children with SCID

To the Editors: Quinn et al.1 demonstrated reduced morbidity and mortality from acute gastroenteritis by rotavirus vaccination in young children in Australia. We agree with the consensus statement highlighting these benefits in both developed and developing settings, which clearly outweigh the small increased risk of intussusception.2 Nevertheless, we think that the additional risk rotavirus vaccination poses for children with severe combined immunodeficiency (SCID) needs comment. Recently, we saw a 21-month-old boy from a country in the Middle-East who was in reduced general condition for further diagnosis and management at our center. Although his older brother died at 20 months of age suffering from postvaccinational BCGitis and severe cytomegalovirus infection, our patient had received rotavirus vaccine (Rotarix, GlaxoSmithKline Biologicals, Rixensart, Belgium) twice at 3 and 4 months of age. Ever since, he suffered from chronic gastroenteritis, which resulted in severe stunting and wasting. The patient had a x-linked hemizygous mutation in Exon 2 of the IL2RG gene (c.252C>A, p.Asn84Lys; MIM# 300400) and curative therapy with stem cell transplantation was initiated at our specialized medical center.3 We identified rotavirus vaccine strain in stool samples by sequencing of 8 different gene segments (VP1, VP2, VP4, VP6, VP7, NSP2, NSP4 and NSP5). In all segments vaccine-associated sequences harboring few new mutations were found, leading to the conclusion that the child’s chronic gastroenteritis was caused by persisting infection with the vaccine rotavirus strain (see Table, Supplemental Digital Content 1, https://links.lww.com/INF/B978). No other pathogen could be identified in multiple stool samples, including uncommon parasites, coccidia and helminths. Notably, all stool, blood and respiratory specimens were also tested by Luminex xTAG respiratory and xTAG gastrointestinal pathogen panel (Abbott Molecular, Wiesbaden, Germany). In samples from the respiratory tract, we detected high copy numbers of human bocavirus (HBoV) and rhinovirus, which most likely subsequently caused respiratory failure in our patient. Despite all intensive supportive care and treatment, the boy’s condition deteriorated and he died on day 1 after stem cell transplantation. In addition to the association with intussusception, shedding of rotavirus for a period of time after oral vaccination and vaccine-induced severe gastroenteritis including infection of healthy siblings have been reported.4 The observation of acute and chronic infections by vaccine strain rotavirus in immunocompromised children led to the addition of SCID as contraindication for administration of rotavirus vaccine.5–7 Our SCID patient presented already with advanced disease and severely reduced general condition. We believe that viral shedding of rotavirus for such a prolonged period of time has not been previously reported and might be explained by the lack of timely adequate medical management. We cannot completely exclude that other gastrointestinal infections and other comorbidities might have been involved, but we propose that vaccine-acquired rotavirus-infection had probably contributed significantly to the fatal outcome. The clinical manifestation and diagnosis of SCID patients might be delayed well into the life period after the recommended vaccination schedule. Therefore, we emphasize the negative effect that rotavirus vaccination might have in these endangered patients and we strongly support efforts of mandatory newborn screening for SCID.8TABLE 1: Comparison of Rotavirus Sequences From Patient Sample and Vaccine StrainDennis Klinkenberg, MD Martin Blohm, MD Department of Paediatrics University Medical Center Hamburg-Eppendorf Hamburg, Germany Marina Hoehne, PhD Andreas Mas Marques, PhD Robert-Koch-Institute Berlin, Germany Monika Malecki, PhD Kliniken der Stadt Köln gGmbH Institut für Hygiene Köln-Merheim, Germany Verena Schildgen, PhD Klinken der Stadt Köln gGmbH Institut für Pathologie Furth, Germany Reinhard Schneppenheim, MD, PhD Ingo Müller, MD, MSc Department for Paediatric Haematolog and Oncology University Medical Center Hamburg-Eppendorf Bone Marrow Transplantation Unit Hamburg, Germany Oliver Schildgen, PhD Klinken der Stadt Köln gGmbH Institut für Pathologie Furth, Germany Robin Kobbe, MD Department of Paediatrics University Medical Center Hamburg-Eppendorf Hamburg, Germany

A cost benefit analysis of the Luminex xTAG Gastrointestinal Pathogen Panel for detection of infectious gastroenteritis in hospitalised patients

Recent advances in the laboratory detection of infectious diarrhoea allow more rapid and sensitive identification of infected patients. Several commercial multiplex molecular panels are now available and may have significant advantages over culture based techniques. Faster and more sensitive testing of hospitalised patients with suspected infectious gastroenteritis could result in significant efficiencies in the utilisation of isolation facilities, however few studies have examined this potential benefit. We studied the potential clinical and cost benefits of a commercially available molecular panel. An eight-month parallel diagnostic study was conducted to measure potential economic benefits of testing hospitalised patients with the Luminex xTAG Gastrointestinal Pathogen Panel (GPP) compared with conventional laboratory testing (based on a combination of culture, microscopy and enzyme immunoassay). Laboratory testing costs and patient isolation costs were measured or estimated for 800 patients. Although costing an additional £22,283, use of GPP could enable a reduction in isolation time from 2202 to 1447 days, a saving of £66,765, which more than offsets the additional laboratory testing costs. Syndromic testing of patients against a broad panel of organisms using a multiplex molecular panel can both improve detection rates and allow better laboratory workflow practices. Removing patients testing negative using this panel could result in significant patient isolation savings.

Evaluation of the Luminex xTAG Gastrointestinal Pathogen Panel and the Savyon Diagnostics Gastrointestinal Infection Panel for the detection of enteric pathogens in clinical samples.

Infectious gastrointestinal disease is caused by a diverse array of pathogens, and is a challenging syndrome to correctly diagnose and manage. Conventional laboratory diagnostic methods are often time-consuming and frequently suffer from low detection rates. Two commercial multiplex nucleic acid amplification tests [Luminex xTAG Gastrointestinal Pathogen Panel (GPP) and Savyon Diagnostics Gastrointestinal Infection Panel (GIP)] were applied to 1000 stored diarrhoeal clinical stool samples. The Luminex xTAG GPP and Savyon GIP detected Campylobacter in 42/44 and 44/44 culture-positive samples, Salmonella in 4/4 and 3/4 culture-positive samples, Shigella in 1/1 culture-positive sample, Clostridium difficile toxin in 32/35 ELISA-positive samples, and Giardia in 6/6 wet-preparation-microscopy-positive samples, respectively. When the Luminex GPP assay was used concurrently with conventional methods for 472 clinical samples, it detected Campylobacter in 22/22 culture-positive samples, Salmonella in 1/1 culture-positive sample, Clostridium difficile toxin in 14/14 ELISA-positive samples and Giardia in 4/4 wet-preparation-microscopy-positive samples. The pathogen/toxin detection rate for conventional methods in both sample sets was <10%. The Luminex xTAG GPP detection rate was 24.8% in the stored samples and 32.6% in the concurrently tested samples. The Savyon GIP detection rate was 22.5%. From stored samples, 2.4% of Luminex xTAG GPP detections and 3.1% of Savyon GIP detections could not be confirmed using alternative nucleic acid amplification tests. Enhanced detection rates resulted from increased detection of pathogens routinely sought using conventional methods and were also due to ascertainment of micro-organisms that current testing strategies do not diagnose. Use of multiplex nucleic acid amplification tests will allow clinical laboratories to diagnose infectious gastroenteritis in more patients with diarrhoeal disease by increasing the sensitivity of pathogen detection and by reducing the selective bias of current strategies. The clinical and economic impact of these results warrants further investigation.