As a result of its being inexpensive, easy to perform, fast and accurate, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToF MS) is quickly becoming the standard means of bacterial identification from cultures in clinical microbiology laboratories. Its adoption for routine identification of yeasts and even dimorphic and filamentous fungi in cultures, while slower, is now being realized, with many of the same benefits as have been recognized on the bacterial side. In this review, the use of MALDI-ToF MS for identification of yeasts, and dimorphic and filamentous fungi grown in culture will be reviewed, with strengths and limitations addressed.
ClarIDHy: A phase 3 multicenter randomized double-blind study of AG-120 versus placebo in patients with non-resectable or metastatic cholangiocarcinoma with an IDH1 mutation.
TPS545 Background: Advanced cholangiocarcinoma (CC) is a life-threatening disease with limited effective chemotherapy options. Mutations in isocitrate dehydrogenase 1 (mIDH1) occur in 13–15% of CC cases, and up to 25% of intrahepatic CC cases, leading to epigenetic and genetic changes that promote oncogenesis via production of the oncometabolite 2-hydroxyglutarate (2-HG). AG-120 (ivosidenib), a first-in-class oral mIDH1 inhibitor, displayed a favorable safety profile and clinical activity in a phase 1 study enrolling 73 mIDH1 CC patients who had received ≥1 prior systemic regimen. As of 10 Mar 2017, 4/73 (5%) had a partial response and 41/73 (56%) stable disease. Progression free survival (PFS) rates at 6 months and 12 months were 38.5% and 20.7%, respectively. The 500 mg once daily dose level of AG-120 was selected for further development in mIDH1 CC. Methods: ClarIDHy is a global, phase 3, multicenter, double-blind, randomized (2:1) study of AG-120 (500 mg once daily) vs. matched placebo in 186 mIDH1 CC patients (ClinicalTrials.gov NCT02989857). Key eligibility criteria: non-resectable or metastatic CC, documented mIDH1 by central laboratory testing, ECOG performance status 0–1, measurable disease (RECIST v1.1), documented disease progression after ≤2 prior systemic therapies in the advanced setting including at least 1 gemcitabine- or 5-fluorouracil-containing regimen, and no prior mIDH inhibitor therapy. Crossover from placebo to AG-120 will be allowed at time of radiographic disease progression. Primary endpoint: PFS assessed by independent radiologists. Secondary endpoints: safety, tolerability, overall response rate (RECIST 1.1), overall survival, pharmacokinetic/pharmacodynamic analyses, and quality of life (EORTC QLQ-C30 and QLQ-BIL21 scales). An independent data monitoring committee will monitor the data during study conduct. The ClarIDHy study is currently activated at participating sites in the US, UK, EU, and S. Korea. R eused with permission from the American Society of Clinical Oncology (ASCO). This abstract was accepted and previously presented at the 2017 ASCO Annual Meeting. All rights reserved. Clinical trial information: NCT02989857.
Particles versus photons for the treatment of chordoma
Diagnosis of persistent infection at the time of reimplantation for staged revision of infected arthroplasties is challenging. Implant sonication culture for the diagnosis of prosthetic joint infection (PJI) has improved sensitivity compared to standard periprosthetic tissue culture.
2289. Accuracy of a Rapid Multiplex PCR Plus a Chromogenic Phenotypic Test Algorithm for the Detection of ESBL and Carbapenemase-Producing Gram Negatives Directly From Blood Cultures
2029. Comparison of Primers Amplifying Two Different Regions of the 16S Ribosomal RNA Gene for Microbiologic Diagnosis of Cardiovascular Implantable Electronic Device Infection
Abstract Background The BioFire FilmArray Gastrointestinal Panel (BioFire Diagnostics) (GIP) is a multiplex stool PCR test that detects 22 organisms. Studies in adults suggest that the diagnostic yield of the GIP in hospitalized patients is low. The utility of the GIP among hospitalized pediatric patients and indications for diagnostic stewardship of this test are not well described. Methods We conducted a retrospective chart review of hospitalized pediatric patients who had a GIP ordered between October 2015 and October 2017. Demographic, clinical, and laboratory information was extracted from the medical record. Statistical analysis was completed using JMP Pro 13.0.0 (SAS Institute Inc.). Results Over the 2-year study period, 193 GIPs were obtained on 155 individual pediatric patients. The mean patient age was 8 years and 59% were male. Forty-four percent of patients were immunocompromised and 21% had inflammatory bowel disease. The pediatric infectious disease (PID) team was consulted in 15% of patients at the time the test was ordered. The overall positivity rate of the GIP for one or more pathogens was 42% (Figure 1), with 76% of GIPs positive for one, 23% for two, and 1% for three pathogens. No parasitic infections were diagnosed. The GIP was more likely to be positive if GI symptom onset was prior to admission (48% vs. 24%, P = 0.004), if GI symptoms had been present for < 2 weeks vs. ≥2 weeks (52% vs. 20%, P = 0.0001), and if GI symptoms were the primary reason for the hospital admission (50% vs. 32%, P = 0.012). Only Clostridioides difficile or viral pathogens were detected in patients whose symptoms began in the hospital (Figure 2). Among patients with a positive test, 40% received treatment targeted at one or more of the detected pathogens (Figure 1). Enteropathogenic E.coli (EPEC) and Enteroaggregative E.coli (EAEC) were never treated (Figure 3). Conclusion The GIP was positive for one or more pathogens in 42% of hospitalized children for whom the test was ordered, and led to specific therapy in 40% of those with a positive test. EPEC and EAEC were not treated. The diagnostic yield of the GIP was higher if GI symptoms were present for <2 weeks, began before hospitalization, and were the primary reason for admission. The GIP was frequently obtained without guidance from the PID team. Disclosures R. Patel, CD Diagnostics, BioFire, Curetis, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, Allergan, and The Medicines Company: Grant Investigator, Research grant – monies paid to Mayo Clinic. Curetis, Specific Technologies, Selux Dx, GenMark Diagnostics, PathoQuest and Genentech: Consultant and Scientific Advisor, Consulting fee – monies paid to Mayo Clinic. ASM and IDSA: Travel reimbursement and editor’s stipends, Travel reimbursement and editor’s stipends. NBME, Up-to-Date and the Infectious Diseases Board Review Course: Varies, Honoraria. Mayo Clinic: Employee, Salary.