bioMérieux (United States)

Multiplex molecular diagnostic panels have greatly enhanced detection of gastrointestinal pathogens. However, data on the impact of these tests on clinical and patient-centered outcomes are limited. We conducted a prospective, multicenter, stepped-wedge trial to determine the impact of multiplex molecular testing at 5 academic children's hospitals on children presenting to the emergency department with acute gastroenteritis. Caregivers were interviewed on enrollment and 7-10 days after enrollment to determine symptoms, risk factors, subsequent medical visits, and impact on family members. During the pre-intervention period, diagnostic testing was performed at the clinician's discretion . During the intervention period, multiplex molecular testing was performed on all children, with results available to clinicians. The primary outcome was return visits to a healthcare provider within 10 days of enrollment. Potential pathogens were identified by clinician-ordered tests in 19 of 571 (3.3%) in the pre-intervention period compared with 434 of 586 (74%) in the intervention period; clinically relevant pathogens were detected in 2.1% and 15%, respectively. In the multivariate model, the intervention was associated with a 21% reduction in the odds of any return visit (odds ratio, 0.79; 95% confidence interval, .70-.90) after adjusting for potential confounders. Appropriate treatment was prescribed in 11.3% compared with 19.6% during the intervention period (P = .22). Routine molecular multiplex testing for all children who presented to the ED with acute gastroenteritis detected more clinically relevant pathogens and led to a 21% decrease in return visits. Additional research is needed to define patients most likely to benefit from testing. Clinical Trials Registration. NCT02248285.

Our study addresses a significant issue in the medical and scientific community-the delayed administration of appropriate antimicrobial treatments due to the time-consuming process of phenotypic susceptibility data collection in gram-negative bloodstream infections. Our research indicates that a multiplex PCR rapid diagnostic test (RDT) significantly outperformed two clinical scoring tools in predicting ceftriaxone susceptibility. Multiplex PCR also led to reduced instances of undertreatment with ceftriaxone and minimized overtreatment with carbapenems. Furthermore, multiplex PCR demonstrated high sensitivity and specificity in predicting ceftriaxone susceptibility. The results of our study underscore the potential RDTs to reduce the time to appropriate antimicrobial therapy, leading to improved patient outcomes and reduced healthcare costs.

Abstract Background Advancements in nucleic acid testing has enabled point of care testing solutions to provide clinicians with greatly improved time to diagnosis and patient care. However, complex technologies and regulatory requirements demand close monitoring of assay performance to accurately identify shifts, trends, and random errors to ensure accurate patient reporting. To support these requirements, MMQCI has developed a synthetic, easy-to-use, external control that simultaneously monitors the accurate identification of 15 respiratory pathogens (11 viral, 4 bacterial targets) detected with the BIOFIRE® SPOTFIRE® Respiratory (R) Panel. Methods The multiplex control contains genome segments of all pathogens detected by the SPOTFIRE R Panel. Sequences were designed in silico, ligated into MMQCI vectors, and transformed to create stable frozen clone stocks. In vitro RNA transcripts were generated, quantified, and formulated in a proprietary matrix to stabilize and carry the RNA through the entire test process. Validation studies were conducted to demonstrate precision across multiple reagents, operators and sites. Failure-mode, shipping and stability studies were conducted to confirm robustness and reliability. Three unique lots of the SPOTFIRE RSP Positive and Negative controls were manufactured to include variability in key components and tested across 6 different sites, incorporating multiple reagent lots, operators and instruments. A total of 361 runs were performed across the positive and negative controls using the SPOTFIRE R Panel. Results Of the 361 total runs across the 6 sites, 351 were valid and used for analysis. A total of 171/172 positive controls resulted in correct calls (99.3%), and all 179 negative controls were called correctly (100%). A regression analysis was performed to confirm real-time stability for 12 months when stored at temperatures ranging from 2oC to 25oC.Table 1.Summary of Reproducibility Test Results: External and Internal Site Conclusion Validation studies demonstrated reproducibility, and overall precision and robustness of SPOTFIRE RSP Positive and Negative Controls. The SPOTFIRE RSP Positive and Negative Controls provide a stable, ease to use solution for training, verification and routine monitoring of the performance of the BIOFIRE® SPOTFIRE® Respiratory Solution. Disclosures Nithya Sivaji, MS, Maine Molecular Quality Controls Inc.: employer Emma Farrell, n/a, Maine Molecular Quality Controls Inc.: employer Tania R. Spenlinhauer, PhD, Maine Molecular Quality Controls Inc.: employer Joan Gordon, n/a, Maine Molecular Quality Controls, Inc: President|Maine Molecular Quality Controls, Inc: Ownership Interest Monica Cronin, n/a, bioMerieux: Stocks/Bonds Brad Graham, n/a, bioMerieiuux: Employee Jeffrey Bastar, n/a, bioMerieux: Employee|bioMerieux: Stocks/Bonds

OBJECTIVES:To determine the feasibility, safety, and efficacy of a biomarker-guided implementation of a kidney-sparing sepsis bundle (KSSB) of care in comparison with standard of care (SOC) on clinical outcomes in patients with sepsis.DESIGN:Adaptive, multicenter, randomized clinical trial.SETTING:Five University Hospitals in Europe and North America.PATIENTS:Adult patients, admitted to the ICU with an indwelling urinary catheter and diagnosis of sepsis or septic shock, without acute kidney injury (acute kidney injury) stage 2 or 3 or chronic kidney disease.INTERVENTIONS:A three-level KSSB based on Kidney Disease: Improving Global Outcomes (KDIGOs) recommendations guided by serial measurements of urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 used as a combined biomarker [TIMP2]•[IGFBP7].MEASUREMENTS AND MAIN RESULTS:The trial was stopped for low enrollment related to the COVID-19 pandemic. Nineteen patients enrolled in five sites over 12 months were randomized to the SOC (n = 8, 42.0%) or intervention (n = 11, 58.0%). The primary outcome was feasibility, and key secondary outcomes were safety and efficacy. Adherence to protocol in patients assigned to the first two levels of KSSB was 15 of 19 (81.8%) and 19 of 19 (100%) but was 1 of 4 (25%) for level 3 KSSB. Serious adverse events were more frequent in the intervention arm (4/11, 36.4%) than in the control arm (1/8, 12.5%), but none were related to study interventions. The secondary efficacy outcome was a composite of death, dialysis, or progression of greater than or equal to 2 stages of acute kidney injury within 72 hours after enrollment and was reached by 3 of 8 (37.5%) patients in the control arm, and 0 of 11 (0%) patients in the intervention arm. In the control arm, two patients experienced progression of acute kidney injury, and one patient died.CONCLUSIONS:Although the COVID-19 pandemic impeded recruitment, the actual implementation of a therapeutic strategy that deploys a KDIGO-based KSSB of care guided by risk stratification using urinary [TIMP2]•[IGFBP7] seems feasible and appears to be safe in patients with sepsis.

1 U.S. Medical Affairs, bioMérieux, Salt Lake City, UT. 2 Division of Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, PA. 3 Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. *See also p. 681. Dr. Prinzi disclosed that she is an employee of bioMérieux. Dr. Chiotos has disclosed that she does not have any potential conflicts of interest.

Rapid pathogen identification is key to the proper management of patients with bloodstream infections (BSIs), especially in the intensive care setting. This multicentre study compared the time to pathogen identification results in 185 patients admitted to intensive care with a confirmed BSI, using conventional methods (n = 99 patients) and upon implementation of the BIOFIRE® Blood Culture Identification 2 (BCID2) Panel, a rapid molecular test allowing for the simultaneous identification of 43 BSI-related nucleic acids targets (n = 86 patients). The median time to result informing optimal antibiotic therapy was significantly shorter following the implementation of the BCID2 Panel (92 vs. 28 h pre vs. post BCID2 implementation; p < 0.0001). BCID2 usage in addition to conventional methods led to the identification of at least one pathogen in 98.8% patients vs. 87.9% using conventional methods alone (p = 0.003) and was associated with a lower 30-day mortality (17.3% vs. 31.6%, respectively; p = 0.019). This study at three intensive care units in the United Arab Emirates therefore demonstrates that, in addition to conventional microbiological methods and an effective antimicrobial stewardship program, the BCID2 Panel could improve the clinical outcome of patients admitted to the intensive care unit with a confirmed BSI.

Abstract A standardized inoculum of bacteria is swabbed onto the surface of a low‐thymine‐thymidine‐concentration, cation‐adjusted Mueller‐Hinton agar plate, in accordance with the ISO 16782 standard. Gradient diffusion test strips, i.e., strips containing a continuous gradient of antimicrobial concentrations, are placed on the agar surface. After overnight incubation, an elliptical zone of inhibition forms as the antimicrobial agent inhibits growth. The MIC is read where growth intersects the gradient test strip. MICs can be interpreted in categories based on the breakpoints established by breakpoint‐establishing agencies such as the Food and Drug Administration (FDA), the CLSI, or the European Committee on Antimicrobial Susceptibility Testing (EUCAST). The gradient test strips are commercial antimicrobial gradient products and are not specifically addressed in CLSI or EUCAST standards. The CLSI does acknowledge FDA‐cleared antimicrobial gradient tests that perform comparably to CLSI reference methods as acceptable for use in clinical laboratories.

The BACT/ALERT® MP Reagent System is a broth culture medium for optimal detection and recovery of mycobacteria from clinical samples. The MP formulation was recently modified to improve detection and recovery times. A multicenter prospective matched pair study design was conducted to validate the performance of improved MP (MP-I) versus current MP (MP-C) bottles utilizing nonsterile and normally sterile samples, except blood, from patients suspected of having mycobacterial infections. A total of 1488 clinical samples were collected to obtain 212 mycobacteria samples by either or both MP culture bottles. MP-I and MP-C sensitivities were 86.6% and 81.4%, respectively, but the difference was not significant (P = 0.163) while specificities were 96.8% and 93.8%, respectively, and that difference was significant (P = 0.002). Overall recovery was 94.34% for MP-I and 88.68% for MP-C (recovery was 100% for both bottles with 52 seeded samples). Overall performance of MP-I was better than MP-C for sensitivity, specificity, and recovery.

ABSTRACTA retrospective observational study was performed to assess the relationship between diagnostic method (traditional work-up [TW], multiplex PCR panel with < 12 target pathogens [PCR < 12], or multiplex PCR panel with ≥ 12 target pathogens [PCR12]), and diagnostic yield, health care resource use (HRU), and cost in adult outpatients visiting U.S. hospitals for acute infectious gastroenteritis (AGE). Using data from PINC AI Healthcare Database during January 1, 2016–June 30, 2021, we analyzed adult patients with an AGE diagnosis and stool testing performed during an outpatient visit. Detection rates for different pathogens were analyzed for those with microbiology data available. Among 36,787 patients, TW was most often performed (57.0%). PCR12 testing was more frequent in patients from large, urban, and teaching hospitals, compared to TW (all P < 0.01). PCR12 was associated with a higher mean index visit cost (by $97) but lower mean 30-day AGE-related follow-up cost (by $117) than TW. Patients with PCR12 had a lower 30-day AGE-related hospitalization risk than TW (1.7% versus 2.7% P < 0.01). Among the 8,451 patients with microbiology data, PCR12 was associated with fewer stool tests per patient (mean 1.61 versus 1.26), faster turnaround time (mean 6.3 versus 25.7 h) and lower likelihood of receiving in-hospital antibiotics (39.4% versus 47.1%, all P < 0.01) than TW. A higher percentage of patients with PCR12 had a target pathogen detected (73.1%) compared to PCR < 12 (63.6%) or TW (45.4%, P < 0.01). Thus, we found that large multiplex PCR panels were associated with lower 30-day AGE-related follow-up cost and risk of AGE-related hospitalization, and increased diagnostic yield compared to TW.