Performance of PCR/Electrospray Ionization-Mass Spectrometry on Whole Blood for Detection of Bloodstream Microorganisms in Patients with Suspected Sepsis.

Blood culture (BC) often fails to detect bloodstream microorganisms in sepsis. However, molecular diagnostics hold great potential. The molecular method PCR/electrospray ionization-mass spectrometry (PCR/ESI-MS) can detect DNA from hundreds of different microorganisms in whole blood. The aim of the present study was to evaluate the performance of this method in a multicenter study including 16 teaching hospitals in the United States (n = 13) and Europe (n = 3). First, on testing of 2,754 contrived whole blood samples, with or without spiked microorganisms, PCR/ESI-MS produced 99.1% true-positive and 97.2% true-negative results. Second, among 1,460 patients with suspected sepsis (sepsis-2 definition), BC and PCR/ESI-MS on whole blood were positive in 14.6% and 25.6% of cases, respectively, with the following result combinations: BC positive and PCR/ESI-MS negative, 4.3%; BC positive and PCR/ESI-MS positive, 10.3%; BC negative and PCR/ESI-MS positive, 15.3%; and BC negative and PCR/ESI-MS negative, 70.1%. Compared with BC, PCR/ESI-MS showed the following sensitivities (coagulase-negative staphylococci not included): Gram-positive bacteria, 58%; Gram-negative bacteria, 78%; and Candida species, 83%. The specificities were >94% for all individual species. Patients who had received prior antimicrobial medications (n = 603) had significantly higher PCR/ESI-MS positivity rates than patients without prior antimicrobial treatment-31% versus 22% (P < 0.0001)-with pronounced differences for Gram-negative bacteria and Candida species. In conclusion, PCR/ESI-MS showed excellent performance on contrived samples. On clinical samples, it showed high specificities, moderately high sensitivities for Gram-negative bacteria and Candida species, and elevated positivity rates during antimicrobial treatment. These promising results encourage further development of molecular diagnostics to be used with whole blood for detection of bloodstream microorganisms in sepsis.

Multicenter Clinical Evaluation of the Novel Alere i Strep A Isothermal Nucleic Acid Amplification Test.

Rapid detection of group A beta-hemolytic streptococcus (GAS) is used routinely to help diagnose and treat pharyngitis. However, available rapid antigen detection tests for GAS have relatively low sensitivity, and backup testing is recommended in children. Newer assays are more sensitive yet require excessive time for practical point-of-care use as well as laboratory personnel. The Alere i strep A test is an isothermal nucleic acid amplification test designed to offer highly sensitive results at the point of care within 8 min when performed by nonlaboratory personnel. The performance of the Alere i strep A test was evaluated in a multicenter prospective trial in a Clinical Laboratory Improvement Amendments (CLIA)-waived setting in comparison to bacterial culture in 481 children and adults. Compared to culture, the Aleri i strep A test had 96.0% sensitivity and 94.6% specificity. Discrepant results were adjudicated by PCR and found the Alere i strep A test to have 98.7% sensitivity and 98.5% specificity. Overall, the Alere i strep A test could provide a one-step, rapid, point-of-care testing method for GAS pharyngitis and obviate backup testing on negative results.

Improving patient flow in acute coronary syndromes in the face of hospital crowding.

BACKGROUND: The current paradigm for the evaluation of patients with suspected acute coronary syndromes (ACS) in the emergency department (ED) is focused on the identification of patients with active underlying coronary disease. The majority of patients evaluated in the ED setting do not have active underlying cardiac disease. OBJECTIVE: To measure the effect of bedside point-of-care (POC) cardiac biomarker testing on telemetry unit admissions from the ED. Furthermore, to evaluate the effect telemetry admissions have on ED length of stay (LOS) and overall hospital LOS. METHODS: Primary data were collected over two 6-month periods in an urban teaching hospital ED. This was an observational cohort study conducted pre- and post-availability of a POC testing platform for cardiac biomarkers. Major measures included number of overall telemetry admissions, ED LOS, hospital LOS, and disposition. Patients were followed at 30 days for significant cardiac events, repeat ED visit or admission, and death. RESULTS: In the post-implementation period there was a 30% (95% confidence interval [CI] 36-44%) reduction in admissions to telemetry with a 33% (95% CI 26-39%) reduction in ED LOS and a 20% (95% CI 7-34%) reduction in hospital LOS. There was a 62% reduction in overall mortality between the pre-implementation period and the post-implementation period (p=0.001). CONCLUSION: The focused use of a rapid cardiac disposition protocol can dramatically impact resource utilization, expedite patient flow, and improve short-term outcomes for patients with suspected ACS.

The Impact of a Concierge Medicine Model on Door to Doctor Time and Patient Flow in an Urban Emergency Department.

INTRODUCTION: Emergency Department (ED) crowding negatively impacts patient outcomes, patient satisfaction, and patient safety. One solution involves introducing a Concierge Physician (CP) whose sole purpose is to provide a brief initial assessment (BIA) and aid patient navigation through the ED. The goal of this study was to quantify the impact of a CP on patient flow dynamics in an urban ED setting. METHODS: We performed a retrospective observational cohort study in an urban academic ED over a 6-month period. Initially, the CP was present in the treatment area during weekdays; during the last half of the observation period, an additional CP was added to the waiting room on weekends. We identified four major milestones in the ED visit with regards to patient throughput. Adult patients presenting to the ED with a triage level of Urgent (ESI 3) were analyzed for this study. Data were stratified based on the patient's ultimate disposition (admitted or discharged) and presented as means with predictive analysis. RESULTS: Between August 2016 and January 2017, the ED evaluated 42,397 adult patients. Of those, 26,976 (64%) were triage level Urgent (3). Of the level 3 patients, 10,279 (38%) received a BIA from a CP. Patients evaluated by a CP were seen approximately 30 mins faster (40% reduction in Door to Doctor time), but stayed 30 mins longer in the ED on average, because the medical decision-making process took >1 hr longer when the patient was initially evaluated by a CP. CONCLUSION: Adapting a concierge medicine model to rapidly evaluate patients resulted in a dramatically reduced Door to Doctor time, but an increase in overall time spent in the ED. This discrepancy was a direct result of the delay in physician disposition.

A prospective, multi-centre US clinical trial to determine accuracy of FebriDx point-of-care testing for acute upper respiratory infections with and without a confirmed fever.

BACKGROUND: FebriDx is a 10-minute disposable point-of-care test designed to identify clinically significant systemic host immune responses and aid in the differentiation of bacterial and viral respiratory infection by simultaneously detecting C-reactive protein (CRP) and myxovirus resistance protein A (MxA) from a fingerstick blood sample. FebriDx diagnostic accuracy was evaluated in the emergency room and urgent care setting. METHODS: A prospective, multicentre, observational cohort study of acute upper respiratory tract infections (URIs), with and without a confirmed fever at the time of enrolment, was performed to evaluate the diagnostic accuracy of FebriDx to identify clinically significant bacterial infection with host response and acute pathogenic viral infection. The reference method consisted of an algorithm with physician override that included bacterial cell culture, respiratory PCR panels for viral and atypical pathogens, procalcitonin, and white blood cell count. RESULTS: Among 220 patients enrolled, 100% reported fever 100.5°F within the last 72 hours while 55% had a measured hyperthermia (T > 100.4) at the time of enrolment. FebriDx demonstrated a sensitivity of 95% (95% CI: 77-100%), specificity of 94% (88-98%), PPV of 76% (59-87%), and a NPV of 99% (93-100%). CONCLUSION: FebriDx may identify clinically significant bacterial URI's and supports outpatient antibiotic decisions. Key messages FebriDx is an outpatient POC test designed to identify a clinically significant systemic host immune response and aid in the differentiation of viral and bacterial infection through rapid measurement of MxA and CRP from a fingerstick blood sample. FebriDx test was determined to be an accurate test, with a 85% sensitivity, 93% specificity and 97% NPV to rule out bacterial infection for any patient presenting with symptoms and reported fever within the prior 3 days, and when confirming fever (hyperthermia) at the time of testing, the test was even more sensitive (95%) and specific (94%) with a 99% NPV. FebriDx may support antibiotic stewardship by rapidly identifying clinically significant bacterial URIs.

Diagnostic Accuracy of FebriDx: A Rapid Test to Detect Immune Responses to Viral and Bacterial Upper Respiratory Infections.

C-reactive protein (CRP) and myxovirus resistance protein A (MxA) are associated with bacterial and viral infections, respectively. We conducted a prospective, multicenter, cross-sectional study of adults and children with febrile upper respiratory tract infections (URIs) to evaluate the diagnostic accuracy of a rapid CRP/MxA immunoassay to identify clinically significant bacterial infection with host response and acute pathogenic viral infection. The reference standard for classifying URI etiology was an algorithm that included throat bacterial culture, upper respiratory PCR for viral and atypical pathogens, procalcitonin, white blood cell count, and bandemia. The algorithm also allowed for physician override. Among 205 patients, 25 (12.2%) were classified as bacterial, 53 (25.9%) as viral, and 127 (62.0%) negative by the reference standard. For bacterial detection, agreement between FebriDx and the reference standard was 91.7%, with FebriDx having a sensitivity of 80% (95% CI: 59-93%), specificity of 93% (89-97%), positive predictive value (PPV) of 63% (45-79%), and a negative predictive value (NPV) of 97% (94-99%). For viral detection, agreement was 84%, with a sensitivity of 87% (75-95%), specificity of 83% (76-89%), PPV of 64% (63-75%), and NPV of 95% (90-98%). FebriDx may help to identify clinically significant immune responses associated with bacterial and viral URIs that are more likely to require clinical management or therapeutic intervention, and has potential to assist with antibiotic stewardship.

Comparing an Unstructured Risk Stratification to Published Guidelines in Acute Coronary Syndromes.

INTRODUCTION: Guidelines are designed to encompass the needs of the majority of patients with a particular condition. The American Heart Association (AHA) in conjunction with the American College of Cardiology (ACC) and the American College of Emergency Physicians (ACEP) developed risk stratification guidelines to aid physicians with accurate and efficient diagnosis and management of patients with acute coronary syndrome (ACS). While useful in a primary care setting, in the unique environment of an emergency department (ED), the feasibility of incorporating guidelines into clinical workflow remains in question. We aim to compare emergency physicians' (EP) clinical risk stratification ability to AHA/ACC/ACEP guidelines for ACS, and assessed each for accuracy in predicting ACS. METHODS: We conducted a prospective observational cohort study in an urban teaching hospital ED. All patients presenting to the ED with chest pain who were evaluated for ACS had two risk stratification scores assigned: one by the treating physician based on clinical evaluation and the other by the AHA/ACC/ACEP guideline aforementioned. The patient's ACS risk stratification classified by the EP was compared to AHA/ACC/ACEP guidelines. Patients were contacted at 30 days following the index ED visit to determine all cause mortality, unscheduled hospital/ED revisits, and objective cardiac testing performed. RESULTS: We enrolled 641 patients presenting for evaluation by 21 different EPs. There was a difference between the physician's clinical assessment used in the ED, and the AHA/ACC/ACEP task force guidelines. EPs were more likely to assess patients as low risk (40%), while AHA/ACC/ACEP guidelines were more likely to classify patients as intermediate (45%) or high (45%) risk. Of the 119 (19%) patients deemed high risk by EP evaluation, 38 (32%) were diagnosed with ACS. AHA/ACC/ACEP guidelines classified only 57 (9%) patients low risk with 56 (98%) of those patients diagnosed with no ACS. CONCLUSION: In the ED, physicians are more efficient at correctly placing patients with underlying ACS into a high-risk category. A small percentage of patients were considered low risk when applying AHA/ACC/ACEP guidelines, which demonstrates how clinical insight is often required to make an efficient assessment of cardiac risk and established criteria may be overly conservative when applied to an acute care population.