Respiratory Viral Panel Research Articles

1793. Clinical Outcomes among Febrile Infants Before and After Implementation of BioFire® FilmArray® Panels

BackgroundThe clinical benefits of multiplex polymerase chain reaction panels are not well defined. We evaluated outcomes among infants before and after implementation of the BioFire® FilmArray® Respiratory Panel 2 (RP2) and Meningitis Encephalitis Panel (MEP).MethodsThis single-center study compared outcomes among infants ≤ 90 days presenting to the Emergency Department with fever (T ≥ 38.0°C) or hypothermia (T < 35.8°C) during 3 time periods. P1 (January 1, 2011–December 31, 2014) had batch testing using a Genmark Dx® respiratory viral panel (RVP) and no standardized clinical practice guideline (CPG); P2 (January 1, 2015–April 30, 2018) had the RVP and a CPG; and P3 (May 1, 2018–March 31, 2019) had on-demand RP2 and MEP testing and a CPG. Clinical data were collected from medical records. Statistical analyses were performed using Kruskal–Wallis and Pearson tests.ResultsThere were 5195 total patients: 2514 in P1, 2082 in P2, 599 in P3. Groups did not differ in pathogens or antimicrobials used. Testing was faster and performed more commonly in P3 than P1 or P2 (P1, 10%; P2, 6.9%; P3, 71%; Table 1). From P1 to P3 there were significant decreases in length of stay (LOS), % receiving antimicrobials, antibiotic durations, ancillary test use, lumbar punctures (LPs), and chest X-rays (Table 1). In P3 compared with P2, infants more commonly received no antimicrobials (43.1% vs. 32.4%, P < 0.001; Figure 1), had fewer median (IQR) number of ancillary tests (5 (5–8) vs. 7 (3–10); P < 0.001), and shorter median (IQR) days of antibiotics (2.0 (1.0–2.7) vs. 2.4 (1.1–3.4); P < 0.001; Table 1). Among P3 infants, those with positive RP2 and/or MEP results were less likely to receive antimicrobials, be hospitalized or readmitted, had fewer ancillary tests and LPs, and shorter LOS and antibiotic durations than those with negative tests (Table 2).ConclusionIn this large pre-post intervention study among infants ≤ 90 days with fever or hypothermia, a clinical guideline plus rapid testing with RP2 and MEP was associated with less antimicrobial use and ancillary testing than a clinical guideline alone. Infants with positive RP2 and/or MEP results had fewer admissions, shorter LOS, and less antimicrobial and ancillary test use than those with negative tests. Rapid pathogen testing has benefit for infants. DisclosuresRitu Banerjee, MD, PhD, Accelerate Diagnostics: Grant/Research Support; BioFire: Research Grant; Biomerieux: Research Grant; Roche: Research Grant.

2314. Burden of Respiratory Syncytial Virus (RSV) Infection Among Hospitalized Older Adults and Those with Underlying Chronic Obstructive Pulmonary Disease (COPD) or Congestive Heart Failure (CHF)

BackgroundData are limited about the burden of respiratory syncytial virus (RSV)-related hospitalizations in older adults and those with COPD or CHF.MethodsWe conducted prospective surveillance at two hospitals from October 2018 to March 2019 for adults ≥50 years of age admitted with acute respiratory infections (ARI) and adults of any age with COPD or CHF-related admissions. Adults were eligible if they were residents of an 8 county region in Atlanta, Georgia. Asymptomatic adults ≥50 years of age were enrolled as controls. Nasopharyngeal and oropharyngeal swabs were tested for RSV and influenza (Flu) using BioFire® FilmArray® Respiratory Viral Panel (RVP) and acute/convalescent serology was obtained for RSV antibodies detection by enzyme immunoassay against RSV lysate. Standard of care results were included for enrollees. We compare the number of RSV+, Flu+ and RSV−/Flu− cases along with demographic features and outcomes.ResultsWe screened 12,453 patients to identify 1,515 eligible adults of which 617 (41%) were enrolled. The most common reasons for failing to enroll were refusal (676, 75%) and inability to obtain informed consent (221, 25%). Of the 617, 36 (6%) were RSV+ and 41 (7%) were Flu+. RSV was detected in 1/126 (0.8%) and Flu in 0/126 healthy controls. RSV+ occurred earlier in surveillance and peaked at a higher frequency (figure). Clinical characteristics and outcomes are in the table. In a convenience sample, a four-fold rise in RSV antibody titer was detected among 8/15 RSV+, 0/42 RSV−/Flu−, and 0/42 healthy controls.ConclusionThe burden and outcomes for RSV are similar to Flu in adults admitted to the hospital with ARI, CHF, or COPD. A vaccine for RSV would be beneficial. DisclosuresNadine Rouphael, MD, Merck: I conduct as Emory PI the PNEUMO MERCK study at Emory, Research Grant; Pfizer: I conduct as co-PI the RSV PFIZER study at Emory, Research Grant; Sanofi-Pasteur: I conducted as Emory PI the CDIFFENSE trial at Emory, Research Grant.

1791. Novel Metabolomics Approach for the Diagnosis of Respiratory Viruses Directly from Nasopharyngeal Specimens

BackgroundRespiratory virus infections are important causes of morbidity and mortality among pediatric and adult patients. These viruses infect respiratory epithelial cells, where they may induce specific metabolite alterations. As a proof-of-concept, we investigate the novel use of liquid chromatography (LC) combined with quadrupole time-of-flight mass spectrometry (Q-TOF) for the study of host cell metabolite alterations to diagnose and differentiate respiratory viruses.MethodsWe studied nasopharyngeal swab samples positive for respiratory viruses by the eSensor Respiratory Viral Panel (GenMark Diagnostics, Carlsbad, CA). Banked, frozen samples (−80°C) stored in viral transport media were retrieved and thawed. Aliquots of 100 μL were centrifuged at 13.3 × g for 15 minutes, and the filtrate was analyzed by Agilent 6545 Quadrupole LC/Q-TOF (Agilent Technologies, Santa Clara, CA). Compounds were separated using a novel column arrangement based on hydrophobicity and charge using a quaternary solvent manager, followed by accurate mass analysis by LC/Q-TOF. Agilent Mass Profiler 3D principal component analysis was performed, and compound identification was completed using the METLIN metabolite database.ResultsA total of 235 specimens were tested by LC/Q-TOF, including 195 positive specimens [including adenovirus, coronavirus, influenza A H1N1 and H3N2, influenza B, human metapneumovirus, parainfluenza viruses 1, 2, 3, and 4, respiratory syncytial virus (RSV), and rhinovirus] as well as 40 negative clinical specimens. LC/Q-TOF primary component analysis (PCA) allowed preliminary identification of key metabolites that distinguished all virus-positive specimens compared with the negative group, and differentiated respiratory viruses from one another including between influenza A 2009 H1N1 and H3N2 subtypes (Figure 1).ConclusionPreliminary data from our LC/Q-TOF analysis show that respiratory viruses exhibit different host cell metabolomic profiles that allow viral differentiation to the species level, and for influenza A virus, the subtype level. This metabolomic approach has substantial potential for diagnostic applications in infectious diseases directly from patient samples, and may be eventually adapted for point-of-care testing. Disclosures All authors: No reported disclosures.

2627. Dynamics of Respiratory Viral Co-infections: Predisposition for and Clinical Impact of Viral Pairings in Children and Adults

BackgroundThe clinical relevance of respiratory viral co-infections is unclear. Few studies determine epidemiology and impact of specific co-infection pairings. Here we assess the dynamics of respiratory viral co-infections, determine any predisposition for specific pairings to occur and evaluate resulting clinical impact on hospitalization.MethodsWe reviewed respiratory viral panel results collected at The Cleveland Clinic between November 2013 to Jun 2018. Monthly prevalences, mono-infections and co-infections of 13 viral pathogens were tabulated. Employing a mathematical model which utilized each individual virus’ co-infection rate and prevalence patterns of concurrent circulating respiratory viruses, we calculated an expected number of occurrences for 132 viral pairing permutations. Expected vs observed co-infection occurrences were compared using binomial tests. For viral pairings occurring at significantly higher prevalence than expected, logistic regression models were used to compare hospitalization between patients with co-infection to ones with mono-infection.ResultsOf 30,535 respiratory samples, 9,843 (32.2%) samples were positive for at least 1 virus and 1,018 (10.82%) were co-infected. Co-infections occurred in 18% of pediatric samples and only 3% of adult samples (P < 0.001). Adenovirus C (ADVC had the highest co-infection rate (68.3%) while influenza B had the lowest (10.07%). Using our model, ADVC – rhinovirus (HRV), RSVA - HRV, and RSVB - HRV pairings occurred at significantly higher prevalence than expected (P < 0.05). In children, HRV-RSVB co-infection were significantly less likely to be hospitalized than patients with HRV mono-infections (ORmono/co = 2.3; 95% CI 1.1 to 4.7; P = 0.028). Additionally, HRV - ADVC co-infected children were less likely to be hospitalized than either HRV (ORmono/co = 3.3; 95% CI 1.6 to 6.8; P < 0.001) or ADVC (ORmono/co = 1.9; 95% CI 1.1 to 3.2; P = 0.024) mono-infected children. Regardless of the infecting virus, children were less likely to be hospitalized than similarly-infected adults.ConclusionRespiratory viral co-infections are largely a pediatric phenomenon. Select viral pairings occur more often than predicted by our model, many of which are associated with altered severity of resultant disease. Disclosures All authors: No reported disclosures.

2011. Reaction of Clinicians to Positive Respiratory Viral Panels in Non-critically Ill Patients Without Bacterial Infection

BackgroundRespiratory viral panels (RVPs) can detect multiple viral pathogens and give clinicians diagnostic confidence to discontinue antibiotics. However, relatively little is known about how these tests influence antibiotic prescribing in hospital settings.MethodsThis was a 26-month retrospective chart review of patients with positive RVPs. Hospitalized adults receiving antibiotics at the time of the RVP were included. Exclusion criteria were: ICU care, solid-organ transplantation (SOT), positive RVP for influenza, positive bacterial cultures, and antibiotic administration for bacterial infection (e.g., cellulitis). A multivariate linear regression model was created to investigate associations with longer antibiotic use after a positive RVP.Results1,346 patients were screened and 242 met inclusion criteria. Primary reasons for exclusion were SOT, ICU, and influenza diagnosis. Patients were a median age of 60.5 years [IQR 51,70] and 35.5% were men. The median length of stay (LOS) was 4 days [IQR 3.6]. 233 patients (6.3%) had chest radiology performed, of which 71 (30.4%) had possible pneumonia noted. 50 (20.7%) were immunocompromised (IC). 199 (82.2%) had a history of pulmonary disease, most commonly COPD. Rhinovirus was isolated in 156 patients (64.5%), followed by metapneumovirus (35, 14.9%) and RSV (32, 13.3%). Antibiotics were given for a median total of 3 days [IQR 3.6]; they were discontinued within 24 hours of the RVP result in 107 patients (44.2%).ConclusionIn this population of patients with viral infection and no discernable bacterial infection, 44.2% of patients had antibiotics discontinued within 24 hours of RVP results. On multivariate linear regression analysis, younger age, longer LOS, and IC status were associated with longer antibiotic duration after a positive RVP. A comparison with patients with negative RVP results could reveal if the test prompted discontinuation. Disclosures All authors: No reported disclosures.

1776. Step-Wise Algorithm for the Detection of Respiratory Viruses: Integrating a Rapid Influenza A/B and RSV PCR with a Multiplex Respiratory Virus Panel to Target High-Risk Patient Populations

BackgroundIn clinical settings, multiplex molecular panels are becoming increasingly common for the detection of respiratory pathogens. Little evidence is available to guide appropriate use of respiratory multiplex panels, particularly with respect to the patient populations most likely to benefit from such testing.MethodsDuring the 2018–2019 influenza season, all patients with a nasopharyngeal swab submitted for respiratory virus detection were initially tested on a commercial rapid PCR platform for influenza A/B and respiratory syncytial virus (RSV) (Cepheid GeneXpert, Sunnyvale, CA). Patients with negative swabs were reviewed by a laboratory physician based on pre-defined criteria (Table 1) for additional testing by a laboratory-developed multiplex assay for parainfluenza 1/2/3, adenovirus, and human metapneumovirus (hMPV).ResultsIn total, 1144 nasopharyngeal swabs were tested. 287 (25.1%) were positive on the GeneXpert: influenza A (234, 81.5%), influenza B (13, 4.5%), and RSV (40, 13.9%). Of the patients who tested negative, 234 (27.3%) met criteria for further respiratory virus testing. The most commonly detected viral pathogens on the multiplex assay were hMPV (20/30, 66.7%), parainfluenza 3 (7/30, 23.3%) and adenovirus (3/30, 10%). The yield of the multiplex assay was highest for patients selected for antimicrobial stewardship (AS) criteria (13/56, 23.2%), followed by transplant (2/16, 12.5%), HIV (7/64, 10.9%), cystic fibrosis (2/19, 10.5%), critical care (6/68, 8.8%), and other/upon physician request (0/11, 0%). Of the patients who received multiplex testing for AS criteria and tested positive for a viral pathogen, only 3/13 (23.1%) had antibiotics discontinued by the medical team within 48 hours of the report.ConclusionAdditional testing for respiratory viral pathogens had low overall diagnostic yield, and further refinement of the algorithm is needed to better target utilization of respiratory virus testing. The patient population with the highest yield (those who met AS criteria) failed to demonstrate consistent timely discontinuation of unnecessary antibiotics by the medical team. Implementation of respiratory multiplex panels would be strengthened by collaboration with AS teams. Disclosures All authors: No reported disclosures.

Molecular detection of respiratory pathogens among children aged younger than 5 years hospitalized with febrile acute respiratory infections: A prospective hospital-based observational study in Niamey, Niger.

Background and AimsIn Niger, acute respiratory infections (ARIs) are the second most common cause of death in children aged younger than 5 years. However, the etiology of ARI is poorly understood in the country. This study aims to describe viral and bacterial infections among children aged younger than 5 years hospitalized with febrile ARI at two hospitals in Niamey, Niger's capital city, and the reported clinical procedures.MethodsWe conducted a prospective study among children aged younger than 5 years hospitalized with febrile ARI at two national hospitals in Niamey between January and December 2015. Clinical presentation and procedures during admission were documented using a standardized case investigation form. Nasopharyngeal specimens collected from each patient were tested for a panel of respiratory viruses and bacteria using the Fast Track Diagnostic 21 Plus kit.ResultsWe enrolled and tested 638 children aged younger than 5 years, of whom 411 (64.4%) were aged younger than 1 year, and 15 (2.4%) died during the study period. Overall, 496/638 (77.7%) specimens tested positive for at least one respiratory virus or bacterium; of these, 195 (39.3%) tested positive for respiratory viruses, 126 (25.4%) tested positive for respiratory bacteria, and 175 (35.3%) tested positive for both respiratory viruses and bacteria. The predominant viruses detected were respiratory syncytial virus (RSV) (149/638; 23.3%), human parainfluenza virus (HPIV) types 1 to 4 (78/638; 12.2%), human rhinovirus (HRV) (62/638; 9.4%), human adenovirus (HAV) (60/638; 9.4%), and influenza virus (INF) (52/638; 8.1%). Streptococcus pneumoniae (249/638; 39.0%) was the most frequently detected bacterium, followed by Staphylococcus aureus (112/638; 12.2%) and Haemophilus influenzae type B (16/638; 2.5%). Chest X‐rays were performed at the discretion of the attending physician on 301 (47.2%) case patients. Of these patients, 231 (76.7%) had abnormal radiological findings. A total of 135/638 (21.2%) and 572/638 (89.7%) children received antibiotic treatment prior to admission and during admission, respectively.ConclusionA high proportion of respiratory viruses was detected among children aged younger than 5 years with febrile ARI, raising concerns about excessive use of antibiotics in Niger.

ACUTE FIBRINOUS AND ORGANIZING PNEUMONIA: A RARE CAUSE OF INTERSTITIAL LUNG DISEASE

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Acute fibrinous and organizing pneumonia (AFOP) is a rare cause of interstitial lung disease that is commonly misdiagnosed in patients presenting with diffuse alveolar opacities. Here we present a case of a 60-year-old previously healthy man who presented with fevers, shortness of breath and cough and was eventually diagnosed with steroid-responsive AFOP. CASE PRESENTATION: A 60-year-old otherwise healthy man presented to the hospital with shortness of breath, dry cough and recurrent fevers as high as 40C of two weeks duration. Physical exam was significant for a respiratory rate of 22, oxygen saturation on room air of 94% and bibasilar crackles. Lab work-up revealed elevated white blood cell count at 12K, erythrocyte sedimentation rate and C-reactive protein were highly elevated at >120mm and 190 mg/L, respectively. Respiratory viral panel and atypical respiratory bacterial culture were negative. Chest x-ray showed left basilar and right lower lobe opacities. After 4 days of broad-spectrum antibiotics, the patient failed to improve with paroxysmal high fevers and hypoxemia, requiring 3-5L of oxygen with nasal cannula. A high-resolution CT of the chest (Figure 1) showed worsening multi-focal parenchymal consolidation in the lower lobes and new patchy involvement in the upper lobes. Antibiotics were discontinued after bronchoscopy & bronchoalveolar lavage showed the absence of infectious organisms. Work-up for collagen vascular disease was negative. Biopsy of the lung parenchyma was done and showed prominent intra-alveolar fibrin, scattered inflammatory cells, and patchy intraluminal connective tissue consistent with AFOP. The patient was started on high dose oral prednisone of 80mg daily with a plan for a prolonged taper over 8 weeks. Over the next few days, his symptoms, oxygen requirements and chest X-ray findings all improved. The patient was discharged home with no oxygen supplementation. DISCUSSION: One of the rare histologic interstitial pneumonias, AFOP was first reported in 2002 (1). It is defined as a subgroup of idiopathic interstitial lung disease with acute lung injury characterized by intra-alveolar fibrin deposition and organization of loose connective tissue (2). Patients with AFOP tend to present with pulmonary as well as extra-pulmonary symptoms. Cough, both productive and non-productive, has been found to be the most common symptom, followed by dyspnea and fever. While AFOP can present as an idiopathic disease process, it has been found to be associated with other disease processes as well including autoimmune, infectious and connective tissue diseases.Treatment consists of systemic glucocorticoids and immunosuppression (3). CONCLUSIONS: AFOP is a rare histopathological diagnosis that requires a high degree of clinical suspicion for diagnosis. Increasing awareness of this entity might lead to earlier diagnosis and more prompt initiation of appropriate therapy. Reference #1: Beasley MB, Franks TJ, Galvin JR, et al. Acute fibrinous and organizing pneumonia: a histological pattern of lung injury and possible variant of diffuse alveolar damage. Arch Pathol Lab Med 2002;126:1064. Reference #2: Travis WD, Costabel U, Hansell DM, King TE Jr, Lynch DA, Nicholson AG, et al. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2013;188(6):733–48. Reference #3: Bhatti S, Hakeem A, Torrealba J, et al. Severe acute fibrinous and organizing pneumonia (AFOP) causing ventilatory failure: successful treatment with mycophenolate mofetil and corticosteroids. Respir Med 2009;103:1764. DISCLOSURES: No relevant relationships by Shameek Gayen, source=Web Response No relevant relationships by Xiang Liu, source=Web Response No relevant relationships by Mahmoud Madi, source=Web Response

RESPIRATORY SYNCYTIAL VIRUS MASQUERADING AS MICROSCOPIC POLYANGIITIS: DIAGNOSTIC CHALLENGES IN SMALL VESSEL VASCULITIS

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Small vessel vasculitis poses significant diagnostic challenges. For one, many conditions can mimic the presentation of systemic vasculitis, not limited to infection. Given the potential risks of immunosuppression in the setting of infection, correctly identifying vasculitis is of utmost importance before initiating therapy[1]. We describe the case of a patient with respiratory syncytial virus (RSV) who presented with a pattern of organ and tissue involvement consistent with microscopic polyangiitis (MPA). Empiric treatment unfortunately led to prolonged ventilation and unfavorable course. CASE PRESENTATION: A 55-year-old male with presumed ANCA-negative vasculitis presented with a 2-day history of purpuric rash, dyspnea, and intermittent hemoptysis. He was evaluated at an outside hospital one year prior for a rash over both legs, accompanied by myalgias, arthralgias, and weight loss. Skin biopsy showed leukocytoclastic vasculitis. Subsequent renal biopsy showed glomerulonephritis, without evidence of crescents or immune deposits. On presentation, labs were notable for leukocytosis and elevated creatinine. Further work-up revealed normal inflammatory markers, as well as negative antineutrophilic cytoplasmic antibodies (ANCA). Though no serological markers were found to support a definitive diagnosis, chest imaging revealed pulmonary opacities concerning for diffuse alveolar hemorrhage (DAH). He was thus treated empirically with high-dose corticosteroids for suspected flare of MPA. He subsequently developed rapidly worsening hypoxia necessitating intubation, with serial imaging showing progressive bilateral alveolar infiltrates concerning for acute respiratory distress syndrome (ARDS). Bronchoalveolar lavage later showed no evidence of hemosiderin-laden macrophages, ruling out DAH. Respiratory viral panel would ultimately come back positive for RSV, suggesting a primary viral process with a superimposed bacterial infection as the cause of his symptoms. He improved with antibiotics and supportive care. DISCUSSION: Illness caused by acute viral infections can imitate systemic vasculitis. Leukocytoclastic vasculitis can be triggered by a variety of causes, including infections. When accompanied by constitutional symptoms, it can be confused for systemic disease[2]. Though testing for ANCA can support clinical suspicion, the absence of antibodies does not exclude the diagnosis of ANCA-associated vasculitis, further obscuring a potential diagnosis[1]. High-dose steroids may worsen outcomes in patients with ARDS caused by infectious processes[3]. As such, it is important to distinguish mimics from true systemic vasculitis in order to avoid potentially harmful treatment. CONCLUSIONS: RSV and other viral infections can mimic the presentation of systemic vasculitis. Attempts must be made to differentiate between the two prior to initiation of treatment, in order to prevent unfavorable outcomes. Reference #1: Suresh E. Diagnostic approach to patients with suspected vasculitis. Postgrad Med J. 2006 Aug;82(970):483-8. Reference #2: Moreno Martínez MJ, Palma Sánchez D, Peñas Martínez E, et al. Leukocytoclastic vasculitis and infection. Report of a case. Reumatol Clin. 2017 Sep - Oct;13(5):297-298. https://doi.org/10.1016/j.reuma.2016.04.002. Reference #3: Takaki M, Ichikado K, Kawamura K, et al. The negative effect of initial high-dose methylprednisolone and tapering regimen for acute respiratory distress syndrome: a retrospective propensity matched cohort study. Crit Care. 2017 Jun 8;21(1):135. https://doi.org/10.1186/s13054-017-1723-0. DISCLOSURES: No relevant relationships by David Chetrit, source=Web Response No relevant relationships by Michelle Rumbaugh, source=Web Response No relevant relationships by Tanuja Yalamarti, source=Web Response

CASE SERIES OF ADENOVIRUS-ASSOCIATED ARDS

SESSION TITLE: Wednesday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM PURPOSE: Adenovirus has been emerging as a cause of fulminant ARDS with a high mortality rate, with no current consensus on management. The objective was to compare our practice patterns and outcomes with those reported in the other published case series. METHODS: We included all patients with confirmed adenovirus infection who were treated in our Medical Intensive Care Unit (MICU) for acute hypoxic respiratory failure requiring mechanical ventilation, between December 2015 and December 2016. Patients were considered to have an adenovirus infection if the adenovirus reverse transcription polymerase chain reaction, respiratory viral panel or viral culture from nasopharyngeal swabs, tracheal aspirates, or bronchoalveolar lavage (BAL) specimens was positive. We excluded patients who were less than 18 years old. Approval was obtained from the Institutional Review Board of our hospital. We also performed a systematic review of literature for all published case reports of ARDS secondary to adenoviral infection and compared the trends with our data. RESULTS: Of the 8 adults admitted with adenoviral infection, 5 developed ARDS. Of these, 5 patients met criteria for ARDS. Amongst the ARDS patients the median age was 28 years (IQR [22-55]), the median BMI was 28 Kg/m2 (IQR [26-31], median SOFA score was 9 (IQR [8-11]) and median APACHEIII score was 74 (IQR [73-107]). All patients were placed on a lung protective strategy (Vt), and required support with high PEEP (median PEEP of 16 cm of water, IQR [12-18]). The median plateau pressure in these patients was 26 cm of water (IQR [24-28]) and the median Oxygenation Index (OI) was 41 (IQR [25-41]). Due to ongoing refractory hypoxemia 2 patients underwent prone position ventilation and 1 had to be placed on extra-corporeal support. The median duration of mechanical ventilation was 24 days (IQR [15-31]), median ICU length of stay was 19 days (IQR [19-31]) and median hospital length of stay 27 days (IQR [24-39]). 1 patient died during the hospital stay. The mortality in the systematic review was 46% CONCLUSIONS: Adenovirus infection can rapidly progress to ARDS which tends to be severe with high morbidity and mortality. Because of the paucity of literature, there has been no consensus on management of severe adenovirus induced respiratory failure. These patients often require prolonged ICU care and may also need adjunctive and salvage therapies. We suggest testing for adenovirus as a part of routine respiratory viral panel testing and if tested positive, these patients should be transferred to tertiary or quaternary centers with specialized skill set and experience of managing complicated ARDS patients including resources for various rescue modalities. CLINICAL IMPLICATIONS: We recommend that adenovirus testing should be included in routine respiratory viral panel testing for patients in respiratory distress and rapid escalation of care to tertiary centers once positive. DISCLOSURES: No relevant relationships by Abhijit Duggal, source=Web Response No relevant relationships by Rishik Vashisht, source=Web Response

DIFFUSE ALVEOLAR HEMORRHAGE FOLLOWING DUAL CHECKPOINT INHIBITOR THERAPY

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Immune checkpoint inhibitors (ICIs) have emerged as new therapeutic agents with survival benefit for various cancers, but are associated with various complications (1,2). ICI related pulmonary toxicity usually manifests in the form of pneumonitis, but diffuse alveolar hemorrhage (DAH) caused by ICIs has not been previously described (3). CASE PRESENTATION: A 72-year-old man with history of Diabetes Mellitus, Asthma, Acute Myeloid Leukemia who failed three lines of chemotherapy and bone marrow transplant, was started on ICI therapy with ipilimumab and nivolumab. He was admitted to hospital for worsening night sweats, fatigue and recurrent falls. On day 2, he developed fever, dyspnea, minor hemoptysis (<5mL) and hypoxemia requiring supplemental oxygen (3L via nasal cannula). CT chest revealed bilateral ground-glass infiltrates. He was treated with diuresis and antimicrobials including meropenem and posaconazole. His course was complicated by increasing oxygen requirements (non-invasive ventilation). Extensive infectious workup was negative including blood, urine cultures, respiratory viral panel and fungal serologies. Bronchoalveolar lavage (BAL) performed on day 3 revealed grossly hemorrhagic fluid with no change on 3 sequential lavages. Hemosiderin laden macrophages were reported on the cytologic exam. Of note, he had thrombocytopenia from leukemia, and his platelet count was 13000/cu.mm on the day of bronchoscopy. Following BAL, he was started on IV methylprednisolone 1 mg/kg/day for suspected pneumonitis related to ICI therapy. Within 24 hours, he showed significant improvement in work of breathing and oxygen was weaned to 2L via nasal cannula. BAL culture grew Pseudomonas aeruginosa and vancomycin resistant Enterococcus faecium. He was transitioned to oral steroids was discharged in a stable condition on room air. DISCUSSION: Association of ICIs with pulmonary toxicity in the form of pneumonitis is well recognized. However, DAH has not been described in association with this therapy. We report a case of DAH that appeared after 3 months of ipilimumab and nivolumab treatment. DAH was confirmed through grossly hemorrhagic sequential lavages with the presence of hemosiderin-laden macrophages. Though BAL cultures in this patient showed growth, infection as a cause of DAH is extremely unlikely given progression of disease despite antibiotics and dramatic response to steroids. Further research is needed to elucidate the mechanism and association of DAH in setting of ICI therapy and prognostic and therapeutic implications of such presentation. CONCLUSIONS: Use of immunotherapy for cancer is rapidly expanding, and complications related to such therapy are being increasingly recognized. We describe a case of DAH manifesting with hemoptysis and hypoxic respiratory failure in a patient who was receiving ipilimumab and nivolumab. To our knowledge, this is the first description of such an association. Reference #1: Valadolid J, Amin A. Immune checkpoint inhibitors in clinical practice: update on management of immune-related toxicities. Trans Lung Cancer Res. 2015;4(5):560-75 Reference #2: Suresh, Karthik et al. Pneumonitis in Non–Small Cell Lung Cancer Patients Receiving Immune Checkpoint Immunotherapy: Incidence and Risk Factors Journal of Thoracic Oncology , Volume 13 , Issue 12 , 1930 – 1939 Reference #3: Naidoo J, Wang X, Woo KM, et al. Pneumonitis in Patients Treated With Anti-Programmed Death-1/Programmed Death Ligand 1 Therapy. J Clin Oncol. 2016;35(7):709-717. DISCLOSURES: No relevant relationships by Herbert Berger, source=Web Response No relevant relationships by Vikas Koppurapu, source=Web Response No relevant relationships by Roger Struble, source=Web Response

RESPIRATORY ALKALOSIS FROM HYPERVENTILATION SECONDARY TO MODAFINIL: WHEN STIMULANTS GO AWRY

SESSION TITLE: Wednesday Fellows Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Modafinil is a psychostimulant medication that is approved for shift work disorder, narcolepsy, and other sleep disorders. While studies have shown modafinil raises blood pressure and heart rate, little is known of its effects on the respiratory drive. Here we present a patient who had primary hyperventilation suspected to be secondary to modafinil use. CASE PRESENTATION: A 36 year-old female with a history of mild asthma (as needed albuterol inhaler), anxiety, and shift work sleep disorder presented to the emergency department in acute respiratory distress. One week prior to presentation she had a prodrome of cough and congestion while returning from a road trip. Her home medications include albuterol and modafinil as needed. She took modafinil prior to presentation for her long drive. On physical exam, she was tachypneic with a respiratory rate of 30-50 breaths/min and in obvious distress. She was sitting leaning forward in tripod position with accessory muscle use and inability to complete full sentences. Of note, she had bilateral breath sounds with good air entry and no wheezes, rales, or rhonchi. Laboratory values at time of examination included pH 7.52, pCO2 15, pO2 156 on 4L oxygen, chemistry bicarbonate is 9, potassium 2.9, lactic acid 7.2 with no other derangements. Chest radiograph and computed tomography angiogram of chest were unremarkable. She was placed on bilevel positive airway pressure (BIPAP) to assist her work of breathing but she remained tachypneic. Respiratory viral panel and echocardiogram were within normal limits. Dexmedetomidine was initiated with significant improvement in her work of breathing and resolution of tachypnea. A repeat arterial blood gas showed pH 7.37, pCO2 35, pO2 67% on 35%. She was weaned off BIPAP to room air. DISCUSSION: Modafinil acts upon the arousal state of the brain via the dopaminergic and sympathetic nervous system pathways. The theory of its effect, as seen in our patient, is through the brainstem respiratory system, resulting in its stimulation. The end pharmacologic result is increased wakefulness and increased respiratory drive. Taneja et al demonstrated that modafinil causes a strong central adrenergic response, resulting in increased catecholamines and an increase in respiratory drive. Dexmedetomidine is a centrally acting sympatholytic agent that was used in our patient for respiratory drive suppression with great success and resolution of symptoms. Modafinil use likely stimulated our patient’s sympathetic drive resulting in hyperventilation causing respiratory alkalosis and lactic acidosis. CONCLUSIONS: Early recognition and targeting treatment of central hyperventilation is crucial to treat secondary metabolic derangements. While there is a need for more research regarding modafinil’s effects on the ventilatory drive, It is prudent that clinicians are aware of the side effects of this medication as seen in our patient. Reference #1: Taneja I, Haman K, Shelton RC, Robertson D (2007). A randomized, double-blind, crossover trial of modafinil on mood. J Clin Psychopharmacol 27: 76–78. DISCLOSURES: No relevant relationships by Thomas Blair, source=Web Response No relevant relationships by Lakshmi Kallur, source=Web Response No relevant relationships by Poorvi King, source=Web Response No relevant relationships by JENNIFER Stahl, source=Web Response

EUGLYCEMIC DIABETIC KETOACIDOSIS SECONDARY TO EMPAGLIFLOZIN USE

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Physicians are facing Euglycemic Diabetic Ketoacidosis (euDKA) in patients at increasing rates. Diagnosis can be challenging as it lacks one of the criteria required to diagnose DKA: hyperglycemia. We present a case of a patient presenting with euDKA secondary to Empagliflozin use. CASE PRESENTATION: 57-year-old male with past medical history of coronary artery disease, diabetes mellitus type 2, hypertension, hyperlipidemia, COPD presented to the emergency room with complaints of fever, shortness of breath, myalgias, right sided pleuritic chest pain, mild epigastric abdominal pain, and nausea for the last 3 days. On physical exam patient was hypotensive, tachycardiac, tachypneic, hypoxic and had diminished breath sounds bilaterally with inspiratory and expiratory wheezes. ECG showed sinus tachycardia. Laboratory values were significant for acidosis with pH 7.25, WBC count of 13.2/L, anion gap of 17mmol/L and glucose 102 mg/dL. Chest X-ray was notable for increased interstitial markings. Respiratory viral panel was positive for Influenza A. Home medications included Metformin, Empagliflozin, Lantus, Lisinopril and Simvastatin. Patient was admitted on the medicine floor for the management of acute viral and suspected superimposed bacterial pneumonia. He was treated with intravenous Levofloxacin and oral Tamiflu. Acidosis was not improving despite adequate medical management and hydration. Given patients history of diabetes, serum acetone and osmolality were checked. He was found to have serum osmolality of 312 mosml/L and large level of acetone. Serum chemistry showed persistent anion gap. Urine studies revealed glucosuria and ketonuria. He was upgraded to the medical ICU for further management of euglycemic DKA likely secondary to Empagliflozin, which was held upon admission. Patient was started on intravenous insulin drip and fluids. After 24 hours the anion gap closed, and metabolic acidosis resolved. Patient was switched to subcutaneous insulin and educated to avoid further use of SGLT-2 inhibitors. DISCUSSION: Some reported causes of euDKA include fasting/starvation, pregnancy, pancreatitis, cocaine intoxication, protracted vomiting or diarrhea, use of insulin pumps, and use of SGLT2 inhibitors. SGLT2 inhibitors work by acting on the receptors in the proximal tubule of the kidney to decrease glucose reabsorption, thereby increasing glucose clearance in the kidney. This leads to glucosuria. Glucosuria contributes to the euglycemic state by causing patients to develop ketoacidosis secondary to SGLT2 inhibitor use. CONCLUSIONS: Reported cases of euDKA have included patients with Type 1 and Type DM. Even though SGLT2 inhibitors are not approved for type 1 diabetics, their off-label use is fairly common. This is an important factor to remember when diabetics present with symptoms of acidosis and dehydration, especially because a delayed diagnosis of euDKA can increase morbidity and mortality. Reference #1: Rawla P, Vellipuram AR, Bandaru SS, Raj JP. Euglycemic diabetic ketoacidosis: a diagnostic and therapeutic dilemma.Endocrinol Diabetes Metab Case Rep. 2017 Sep, EDM170081, https://doi.org/10.1530/EDM-17-0081 Reference #2: Rosenstock J, Ferrannini E. Euglycemic Diabetic Ketoacidosis: A Predictable, Detectable, and Preventable Safety Concern With SGLT2 Inhibitors. Diabetes Care. 2015 Sep;38(9):1638-42. https://doi.org/10.2337/dc15-1380. Reference #3: Bader N, Mirza L. Euglycemic Diabetic Ketoacidosis in a 27 year-old female patient with type-1-Diabetes treated with sodium-glucose cotransporter-2 (SGLT2) inhibitor Canagliflozin. Pak J Med Sci. 2016 May-Jun; 32(3): 786–788. https://doi.org/10.12669/pjms.323.9201 DISCLOSURES: No relevant relationships by Anna Abbasi, source=Web Response No relevant relationships by Sushilkumar Gupta, source=Web Response No relevant relationships by Tina Nguyen, source=Web Response No relevant relationships by Taek Sang Yoon, source=Web Response

DURVALUMAB-INDUCED PNEUMONITIS IN A PATIENT WITH RHEUMATOID ARTHRITIS-INTERSTITIAL LUNG DISEASE

SESSION TITLE: Wednesday Fellows Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Immune check point inhibitors (CPIs) are now widely used for different malignancies. Patients with autoimmune diseases, have been excluded from the CPIs clinical trials due to concerns of worsening of their autoimmune disease. Thus, the evidence regarding the toxicity of CPIs in this population is limited. Durvalumab, a CPI, is anti-programmed death ligand 1 (PD-L1) monoclonal antibody. We present a case of durvalumab induced pneumonitis in a patient with Rheumatoid arthritis related interstitial lung disease (RA-ILD). CASE PRESENTATION: A 63-year man with active seropositive RA with ILD treated with methotrexate 15 mg/week. He was recently diagnosed with stage IIIB lung adenocarcinoma. He was treated with platinum-based chemo-radiotherapy but developed severe fatigue and was given a treatment-free interval. Decision was made afterwards to administer durvalumab. Four days after infusion, patient had severe dyspnea, dry cough and chest pain requiring hospitalization. His oxygen requirements increased from room air oxygen to 8 L via nasal cannula. Patient was afebrile and labs were significant for normal WBC count, procalcitonin level, negative nasal swab for influenza antigen and respiratory viral panel. Blood and sputum cultures remained negative. A computerized tomography of the chest (CT) , compared to a previous CT, showed new diffuse upper-lobe predominant ground glass opacities with background ILD findings (figure 1). Durvalumab was held and patient was initially treated with empiric antibiotics that was stopped later with negative infectious work up. Patient was diagnosed with grade 4 immune pneumonitis and he was started on intravenous (IV) methylprednisolone (2 mg/kg) tapered down to 60 mg prednisone over 5 weeks with minimal clinical improvement. We decided to treat him again with IV methylprednisolone (250 mg) for 3 days and to add infliximab infusion (500 mg infusion). Over the next 10 days, patient improved clinically with decreasing oxygen requirements and plan was to discharge him to finish a slow steroids taper over 32 weeks with outpatient follow up. DISCUSSION: We describe a case of active RA who was treated with durvalumab for his lung cancer. In our case, patient was steroid-refractory initially but showed clinical improvement after giving another pulse dose steroids with infliximab infusion. Pneumonitis is uncommon immune related toxicity of CPIs but can be fatal. Incidence was reported to be 5% in one report. Our case is important as it describes severe pneumonitis in a patient with underlying RA-ILD who showed a promising response to steroid and infliximab. CONCLUSIONS: Immune mediated toxicities of CPIs, can be life threatening. More studies are needed to clarify whether a pre-existing autoimmune disease pose a higher risk of these adverse events. Clinicians should only start CPIs after having full discussion with their patients about the potential risks and benefits. Reference #1: 1. Review AS. R EVIEW Use of Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Autoimmune Disease. 2018. https://doi.org/10.7326/M17-2073 Reference #2: 2. Yamaguchi S, Ito S, Akaike K, et al. A case report of using nivolumab for a malignant melanoma patient with rheumatoid arthritis. Int Cancer Conf J. 2016;5(4):192-196. https://doi.org/10.1007/s13691-016-0256-8 Reference #3: 3. Leduc C, Menzies AM, Iyriboz T, et al. Pneumonitis in Patients Treated With Anti–Programmed Death-1/Programmed Death Ligand 1 Therapy. J Clin Oncol. 2016;35(7):709-717. https://doi.org/10.1200/jco.2016.68.2005 DISCLOSURES: No relevant relationships by bashar alzghoul, source=Web Response No relevant relationships by Runi Foster, source=Web Response No relevant relationships by Wissam Hanayneh, source=Web Response No relevant relationships by Saminder Kalra, source=Web Response

A RARE CAUSE OF CRAZY PAVING: POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE

SESSION TITLE: Tuesday Fellows Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Crazy paving on computed tomography (CT) is defined as interlobular septal thickening with areas of ground glass attenuation. It can be caused by a variety of pathologies. Here we describe an unusual cause of crazy paving in an immunosuppressed patient. CASE PRESENTATION: A 58-year old man presented for syncope. His past medical history included acute myelogenous leukemia in complete remission post stem cell transplant, and complicated by cytomegalovirus colitis. Upon arrival to the emergency department, he was found to be obtunded and was intubated. Home medications included tacrolimus, ganciclovir, sulfamethoxazole-trimethoprim, and voriconazole. Vital signs were significant for a blood pressure of 62/38mmHg and heart rate of 138/minute. Laboratory studies revealed a white blood cell count of 13.6K/mm3, with 15% lymphocytes, 5% atypical lymphocytes, 34% plasmacytes, and 44% neutrophils. Lactic acid was 10.8mmol/L, bicarbonate 15mmol/L, and creatinine 3mg/dL. Arterial blood gas was consistent with metabolic acidosis. Tacrolimus level was 6ng/mL (goal 5-10). Computed tomography (CT) of the chest (Images 1-3) revealed interlobular septal thickening with ground glass opacities, and prominent mediastinal, cervical, and axillary lymphadenopathy. The patient required vasopressor support and was started on broad spectrum antibiotics, antivirals, antifungals. Bronchoalveolar lavage showed 38% neutrophils, 52% monocytes, and 10% lymphocytes. Gram stain, cultures, stain for acid fast bacilli, cytology, galactomannan, fungal cultures, and viral respiratory panel were negative. Serum flow cytometry revealed plasmacytoid cells with positive Epstein-Barr virus (EBV) in situ hybridization. Serum EBV PCR showed >39,000,000 copies/mL. These findings were consistent with post-transplant lymphoproliferative disease (PTLD). DISCUSSION: PTLD is a category of lymphoid disorders that arise after solid organ or hematopoietic transplants in the setting of active immunosuppression, most commonly with active EBV infection. Severity is graded as early, polymorphic, or monomorphic. Treatment can involve decreasing immunosuppression, rituximab in CD20+ disease, chemotherapy (with surgery if localized disease), or EBV-targeted cytotoxic T-cell instillation. Prevention of PTLD in transplant patients has included rapid tapering of immunosuppression as appropriate, and close monitoring of EBV viral levels, with elevations prompting reduction in immunosuppression or initiation of rituximab. Given its in vitro inhibition of EBV replication, ganciclovir has been suggested prophylactically, but there is no consensus regarding antiviral prophylaxis. CONCLUSIONS: Our patient rapidly decompensated and went into multiorgan system failure; he was made comfort care and expired. This case demonstrates the need for a high index of suspicion for PTLD in all transplanted patients with crazy paving present on imaging. Reference #1: Al-Mansour Z, Nelson BP, Evens AM. Post-transplant lymphoproliferative disease: risk factors, diagnosis, and current treatment strategies. Curr Hematol Malig Rep. 2013 September; 8(3): 173-183. Reference #2: Rossi SE, Erasmus JJ, Volpacchio M, et al. "Crazy Paving” pattern at thin-section CT of the lungs: radiologic-pathologic overview. Radiographics 2003; 26 (6): 1509-1519. Reference #3: AlDabbagh, MR, Gitman MR, Kumar D et al. The Role of Antiviral Prophylaxis for the prevention of Epstein-Barr virus-associated posttransplant lymphoproliferative disease in solic organ transplant recipients: a systematic review. Am J Transplant. 2017; 17: 770-781. DISCLOSURES: No relevant relationships by Payam Nabizadeh, source=Web Response No relevant relationships by Paul Simpson, source=Web Response

A CASE OF EMPYEMA SECONDARY TO ACTINOMYCES NEUII

SESSION TITLE: Monday Fellow Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Actinomyces neuii is a gram-positive organism infrequently recognized and can cause a myriad of infections. To date, no infections have been described in the pleural space. We present a case of empyema secondary to A. neuii. CASE PRESENTATION: 74 year old woman presented with 2 months of dyspnea on exertion, 5 days of acute pleuritic chest pain, fever, and oxygen desaturation to 88% on room air as outpatient prompting hospitalization. She denied weight loss, had a history of hypothyroidism, remote history of removed left breast fibro-adenoma and quit smoking 40 years prior. She received antibiotics for an upper respiratory infection a month prior. She had a neutrophil predominant leukocytosis to 19.4 and elevated liver enzymes. Computed tomography of chest showed right hilar lymphadenopathy and loculated pleural effusion. She was admitted and started on broad spectrum antibiotics. A chest tube was placed yielding purulent drainage and fluid analysis revealed 85% neutrophils with lactate dehydrogenase of 1843 U/L indicating an exudate. She was treated according to the MIST II protocol for empyema. Further workup revealed negative respiratory viral, HIV, immunoglobulin and hepatitis panels. Blood culture grew gram positive rods 84 hours after admission in anaerobic media which speciated 2 weeks after as A. neuii. Pleural fluid cytopathology was negative for malignancy and culture, including acid fast bacilli. CT of her abdomen and pelvis was negative for intra-abdominal source of infection, but revealed fibroid uterus and an intrauterine device (IUD) without evidence of infection. She completed 4 weeks of Ceftriaxone followed by 4.5 months of Amoxicillin with resolution of leukocytosis, lymphadenopathy and complete resolution of pleural space on outpatient interval imaging. DISCUSSION: A. neuii is an aerobic and facultative anaerobic organism that does not produce sulfur granules or branching filaments. It can cause soft tissue abscesses especially surrounding foreign bodies, post intravitreal injection endopthalmitis, and 2 cases of neonatal sepsis that resulted in premature delivery. One mother had emergent placement of cervical cerclage while the other had prolonged use of IUD. A. neuii is susceptible to beta-lactam antibiotics, clindamycin and erythromycin. Fluoroquinolones and trimethoprim-sulfamethoxazole have less in-vitro activity against isolates. Surgical resection is usually indicated for soft tissue infections. Though inconclusive, the preceding respiratory infection or the prolonged use of IUD may have been sources for infection. We suspect A. neuii was the causative organism for the empyema despite the fact that it was only cultured from blood and not from the pleural space. CONCLUSIONS: To date, no cases of empyema due to A. neuii have been reported in literature. We describe a case with successful non-surgical management. Reference #1: 1. Zelyas N, Gee S, Nilsson B, Bennett T, Rennie R. Infections Caused by Actinomyces neuii: A Case Series and Review of an Unusual Bacterim. Can J Infect Dis Med Mircobiol. 2016;2016:6017605 Reference #2: 2. Olson JM, Vary JC Jr. Primary Cutaneous Actinomyces neuii Infection of the Breast Successfully Treated with Doxycycline. Cutis 2013;92(16)E3-4 Reference #3: 5. Alsohime F, Assiri RA, Al-Shahrani F, Bakeet H, Elhazmmi M, Somily AM. Premature labor and neonatal sepsis caused by Actinomyces neuii. J Infect Public Health 2018 S1876-0341(18)30037-6 DISCLOSURES: no disclosure on file for Stella Hahn; no disclosure on file for Gita Lisker; No relevant relationships by Etieno Umobong, source=Web Response

LENALIDOMIDE-INDUCED ACUTE EOSINOPHILIC PNEUMONIA

SESSION TITLE: Wednesday Fellows Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: MDS/MPD (Myelodysplastic Syndrome/Myeloproliferative disorder) overlap syndrome is characterized by dysplasia and cytopenias which prevalence is not known. Lenalidomide is an immunomodulatory drug analogous to thalidomide that is frequently used in myelodysplastic syndrome and also used in cases of Polycythemia Vera. Pulmonary side effects are rare. We present a case of lenalidomide induced acute eosinophilic pneumonia. CASE PRESENTATION: A 76-year-old male with a history of MDS/MPD overlap syndrome, primary and secondary hemochromatosis (transfusion dependent) who recently started lenalidomide was admitted for shortness of breath. He had 2 days of respiratory distress, desaturation (83% room air), new onset of cough and nasal congestion. No history of fever, chills, chest pain, palpitations, no sick contacts. He had chronic fatigue but not worse than baseline. The physical exam was positive for a respiratory distress, a flow systolic murmur and rales at the pulmonary bases. Work up included a negative procalcitonin, negative respiratory viral panel, negative blood cultures. Chest x-ray showed diffuse hazy interstitial and airspace opacity. Chest CT showed ground glass pulmonary infiltrates. His initial management included blood transfusions, diuretics, broad spectrum antibiotics and coverage for PCP and atypical pneumonia, oxygen by nasal canula with 2 Litters. Diuretics were given for suspected pulmonary edema. His Echo showed an ejection fraction of 60-65% and despite effective diuresis, symptoms did not improve. Patient underwent a bronchoalveolar lavage which showed 27% eosinophils, negative gram stain, negative bacterial and fungal cultures. Cytology was negative for malignancy. PCP DFA was negative. A new diagnosis of acute eosinophilic pneumonia was made and patient was treated with steroids and lenalidomide was stopped as well as antibiotics. DISCUSSION: Lenalidomide is becoming a frequently used medication in the last few years due to its new multiple uses approved by the FDA. Pulmonary side effects are rare and acute eosinophilic pneumonia is added to this list. The Naranjo Drug Adverse Drug Reaction Probability Scale was positive for 8 points in our case, making it a probable drug reaction. This is the first case to our knowledge ever reported in MDS/MPD treatment with Lenalidomide. CONCLUSIONS: Lenalidomide is a pharmacologic agent that is linked to multiple but rare pulmonary side effects. Providers should be aware that acute eosinophilic pneumonia can be one of this rare side effects. Reference #1: Toma, Andrew & P. Rapoport, Aaron & Burke, Allen & Sachdeva, Ashutosh. (2017). Lenalidomide-induced eosinophilic pneumonia: Lenalidomide and eosinophilic pneumonia. Respirology Case Reports. 5. e00233. 10.1002/rcr2.233 Reference #2: Mankikian J, Lioger B, Diot E, et al. 2014. Pulmonary toxicity associated with the use of lenalidomide: case report of late-onset acute respiratory distress syndrome and literature review. Heart Lung 43(2):120–123. Reference #3: Naranjo CA, Busto U, Sellers EM, et al. 1981. A method for estimating the probability of adverse drug reactions. Clin. Pharmacol. Ther. 30(2):239–245. DISCLOSURES: No relevant relationships by Mohamad Bitar, source=Web Response No relevant relationships by Fernando Fuentes, source=Web Response No relevant relationships by Shahla Mallick, source=Web Response

Choosing the Right Test (Influenza) Versus Respiratory Viral Panel With Faster Turnaround Time and Cost Savings

Abstract Introduction Respiratory infections are very common in hospital patients. Viral pathogens including influenza (Flu) and respiratory syncytial virus (RSV) are frequent causes. Respiratory viral panels (RVPs) have been routinely ordered in our institution with a turnaround time (TAT) of 48 hours at a cost of approximately $170/test. Meanwhile, Flu and RSV PCR are offered in house with a TAT of only 40 minutes and much lower cost ($40/test) than RVP. Here, we examined the optimization of use of these tests in our medical center. Methods Results of the specimens sent for RVP testing as well as their results from Flu/RSV PCR and the negative result rate were reviewed. The TAT and costs were compared between RVP and Flu/RSV PCR. Results We reviewed 69 specimens from MICU sent for RVP during 10/1/2018 to 1/31/2019. Total negative specimen rate was 74%. The specimens identified positive for Flu or RSV by RVP were also positive for in-house Flu/RSV PCR. Therefore, we have recommended clinicians to order in-house highly sensitive and specific Flu/RSV PCR first for faster TAT and cost saving. Since the recommendation, the number of RVP orders has dropped from 660 (January 2018) to 131 (January 2019), with savings of more than $80,000 in 1 month. Conclusion In-house Flu/RSV PCR test is highly sensitive and specific for identifying the common viral pathogens in patients with respiratory infection. It is fast and relatively low cost compared to RVP and should be considered as an effective first-line test.

Verification of a Novel Multiplex PCR Respiratory Virus Panel in a US Biocontainment Unit

Emerging infectious diseases carry unique logistical, financial, and clinical ramifications. Rapid diagnostic testing methods can alleviate some of these challenges by providing definitive diagnoses earlier in the clinical course, leading to appropriate targeted therapy, cost savings, and improved patient outcomes. The BioFire FilmArray Respiratory Panel 2 plus (RP2plus; bioMérieux, Marcy l’Etoile, France) is a multiplexed nucleic acid test for detection of Middle East respiratory syndrome coronavirus (MERS-CoV) and 14 common viral and 4 bacterial respiratory pathogens in nasopharyngeal swabs obtained from those meeting MERS-CoV epidemiological criteria. The aim of this study was to verify the FilmArray RP2plus for use in our biocontainment unit. Of note, the RP2plus is FDA approved but not currently available for sale in the United States. Eight patient samples were tested with known results (GenMark Respiratory Virus Panel [RVP] or Cepheid Xpert Flu/RSV). We had concordant results between the platforms for samples containing influenza A, respiratory syncytial virus (RSV), parainfluenza virus 2, rhinovirus, and a negative sample. We evaluated two influenza B samples from two different patients. The FilmArray RP2plus did not detect influenza B in one of the patient samples. The sample was exhausted and repeat testing could not be performed. A second rhinovirus sample was not detected by the RP2plus, but Coronavirus 229E was detected in this sample, a virus not detected by the RVP. The sample was repeated and again did not detect rhinovirus. Further investigation into this discrepancy revealed that rhinovirus was originally detected by RVP at a signal of 34.4 nA (repeat of 46.9 nA). The concordant rhinovirus sample had a signal of 226.7 nA by RVP, which was much higher than the discrepant sample. Because of the low signal by RVP in the discrepant sample, perhaps the viral load was below the limit of detection of the RP2plus. All other quality control sample pools passed verification testing, including day-to-day and operator variance. It is not uncommon for a person under investigation (PUI) for a highly communicable disease to be evaluated in our facility. The performance of the RP2plus test on clinical samples showed acceptable concordance with our current means of testing for respiratory pathogens. The RP2plus will eliminate challenges implicated in storing and transporting specimens to an off-site lab, facilitate quicker turnaround time, and streamline the often cumbersome, complex protocols and practices required to work up a serious communicable disease.

The effect of respiratory viral assay panel on antibiotic prescription patterns at discharge in adults admitted with mild to moderate acute exacerbation of COPD: a retrospective before- after study

BackgroundDespite well-defined criteria for use of antibiotics in patients presenting with mild to moderate Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD), their overuse is widespread. We hypothesized that following implementation of a molecular multiplex respiratory viral panel (RVP), AECOPD patients with viral infections would be more easily identified, limiting antibiotic use in this population. The primary objective of our study was to investigate if availability of the RVP decreased antibiotic prescription at discharge among patients with AECOPD.MethodsThis is a single center, retrospective, before (pre-RVP) - after (post-RVP) study of patients admitted to a tertiary medical center from January 2013 to March 2016. The primary outcome was antibiotic prescription at discharge. Groups were compared using univariable and multivariable logistic-regression.ResultsA total of 232 patient-episodes were identified, 133 following RVP introduction. Mean age was 68.1 (pre-RVP) and 68.3 (post-RVP) years respectively (p = 0.88). Patients in pre-RVP group were similar to the post-RVP group with respect to gender (p = 0.54), proportion of patients with BMI < 21(p = 0.23), positive smoking status (p = 0.19) and diagnoses of obstructive sleep apnea (OSA, p = 0.16). We found a significant reduction in antibiotic prescription rate at discharge in patients admitted with AECOPD after introduction of the respiratory viral assay (pre-RVP 77.8% vs. post-RVP 63.2%, p = 0.01). In adjusted analyses, patients in the pre-RVP group [OR 2.11 (CI: 1.13–3.96), p = 0.019] with positive gram stain in sputum [OR 4.02 (CI: 1.61–10.06), p = 0.003] had the highest odds of antibiotic prescription at discharge.ConclusionsIn patients presenting with mild to moderate Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD), utilization of a comprehensive respiratory viral panel can significantly decrease the rate of antibiotic prescription at discharge.