PCR For Respiratory Viruses Research Articles

Polio will go, AFM will stay – A case report

Background: Poliovirus related acute flaccid myelitis (AFM) was one of the most feared diseases. Due to effective vaccines, poliovirus is at the verge of global eradication. However, recent world-wide outbreaks of AFM cases associated with Enterovirus-D68 (EV-D68) are stimulating concerns about a new ‘polio-like’ epidemic, challenging mankind with the devastating outcomes, primarily in children. Case: A previously healthy, 5-year-old boy presented in paediatric ICU with sudden onset upper limbs weakness and breathing difficulty. Two days earlier, he had an upper respiratory illness with mild fever. On examination, he had hypotonia of truncal and limb muscles, with predominant loss of proximal power in the upper limbs. Intubation and mechanical ventilation were required for respiratory failure. MRI spine revealed myelitic changes. Respiratory viral PCR on nasopharyngeal swab was positive for Enterovirus. CSF had mildly raised WCC and proteins but was negative for viruses. EV-D68 was identified from faecal specimens by VP1 region sequencing at the National Enterovirus Reference Laboratory. Despite immunomodulatory therapy and intensive inpatient physiotherapy, the patient had ventilator dependence and a significant residual weakness in his upper limbs. Conclusion: EV-D68 is a neurotropic virus. Increasing awareness amongst clinicians, proper diagnostics and integrating EV-D68 into accessible surveillance systems will be essential to reveal the burden of disease.

The Discontinuation of Antibiotics in Patients with Chronic Obstructive Pulmonary Disease Exacerbation and a Positive Respiratory Viral Assay: A Single-center Retrospective Analysis

BackgroundThe use of antibiotics in chronic obstructive pulmonary disorder (COPD) exacerbations attributed to viral infections is observed in this study. The aim of this analysis is to describe the rate of discontinuation of antibiotics in patients who have an acute exacerbation of COPD (AECOPD) caused by viral infections, in turn encouraging the use of the respiratory viral panel in an effort to improve antibiotic stewardship at our facility.MethodsA retrospective chart review was performed. A total of 92 patients were analyzed who had a positive respiratory viral polymerase chain reaction (PCR) (RVP) admitted for COPD exacerbations, of which 20 patients had a bacterial co-infection by a sputum analysis. Patients with a positive infiltrate on chest X-ray (CXR) were excluded. The rate of discontinuation of antibiotics, excluding azithromycin and doxycycline, in patients with a positive RVP with and without a bacterial co-infection were analyzed.ResultsOf these 92 patients, we found that a bacterial co-infection was detected by sputum culture in 20 patients. The average number of days until discontinuation for patients with no bacterial coinfection was 1.67 days while for those with a bacterial co-infection was 3.20 days. The difference in the number of days was statistically significant (p<0.001).ConclusionIn conclusion, patients with an identified viral etiology of COPD exacerbations had antibiotics discontinued significantly sooner than those patients with bacterial coinfections.

Viral Pneumonia Requiring Differentiation from Acute and Progressive Diffuse Interstitial Lung Diseases.

Objective The clinical characteristics and chest imaging findings of viral pneumonia and several interstitial lung diseases (ILDs) overlap, and viral pneumonia may be underrecognized and misdiagnosed as certain ILDs. To clarify the frequency of viral pneumonia among patients with acute progressive clinical courses that required a differential diagnosis between ILDs and pneumonia, and to determine the most frequent ILDs misdiagnosed in cases of viral pneumonia. Patients and Methods We retrospectively analyzed patients hospitalized from 2010 to 2017 with an acute clinical course (≤30 days) who underwent bronchoalveolar lavage (BAL) for the differential diagnosis of infection and ILDs. We performed a multiplex PCR for respiratory viruses using the patients' preserved BAL fluid. The final diagnosis was made by a multidisciplinary approach and after considering the PCR results. The diagnosis at discharge was compared to the final diagnosis. Results Among the 109 patients, 53 were diagnosed with viral pneumonia. Viral pneumonia and other diseases showed some differences in symptoms and laboratory data; however, the differences were small or overlapped. Viral pneumonia was misdiagnosed on discharge as acute fibrinous organizing pneumonia, cryptogenic organizing pneumonia, or chronic eosinophilic pneumonia (AFOP/COP/CEP) (n=22), acute interstitial pneumonia (n=5), connective tissue disease-related ILDs (n=3), unclassifiable interstitial pneumonia (n=2), drug-induced ILD (n=1), and pneumonia (n=20). Conclusion Approximately half of the patients who underwent BAL had viral pneumonia. The most common ILD-related misdiagnoses were AFOP/COP/CEP. Differences in symptoms and laboratory findings between viral pneumonia and other diseases were small, and viral pneumonia should be included in the differential diagnosis when physicians encounter cases in which the abovementioned ILDs are suspected.

2135. Streptococcus pneumoniae DNA (lytA) Detection in Clinical Samples Sent for a Respiratory Viral Polymerase Chain Reaction: Is There Bacterial-Viral Association?

BackgroundStreptococcus pneumoniae (SPNEU) is a major cause of community-acquired pneumonia and frequently complicates respiratory viral infections. Clinical differentiation of viral and bacterial respiratory tract infection can be difficult, as can predicting which patients with respiratory viral infection will develop bacterial infection. A SPNEU polymerase chain reaction (PCR) to specific DNA region lytA may be able to determine which patients with viral infections may develop bacterial infection.MethodsStored nucleic acid extracts from clinical samples collected and tested for respiratory viral PCR (RVP) in 2015 and 2016 were tested for SPNEU lytA DNA using standard laboratory procedure. Analyses of demographic data, RVP and SPNEU PCR result were performed to determine relevant associations.Results1581 stored clinical RVP samples were tested for SPNEU DNA with PCR to lytA, 1550 of these had complete RVP panel results available for analysis. RVP samples from patients 0–5 years old were more likely to have a viral or bacterial pathogen detected than > 5 years old (78% vs. 45%, P < 0.001). Of 1,550 samples analyzed with SPNEU PCR, 19% were positive for SPNEU, this was more likely in those 0–5 years old than > 5 years old (50% vs. 10%, P < 0.0001). In 0–5 years old, SPNEU was more frequently detected when multiple pathogens were detected on RVP vs. those with no pathogen (63% vs. 43%, P = 0.031). In > 5 years old, compared with no pathogen samples, the presence of multiple pathogens, any single pathogen, influenza, rhinovirus and Bordetella pertussis were significantly associated with higher SPNEU positivity rates. Median SPNEU PCR DNA load was higher in multiple pathogen and single pathogen samples than in no pathogen RVP samples.ConclusionWe have demonstrated an association between common respiratory pathogens and detection of SPNEU DNA via PCR. This association is strongest in samples with multiple RVP pathogens, suggesting additional nasopharyngeal inflammation may contribute to SPNEU presence in the nasopharynx. Previous data have focused on those 0–5 years old, we have demonstrated an SPNEU-viral association in those > 5 years old. This tool may be clinically useful to determine which individuals with viral respiratory tract infection will progress to bacterial pneumonia and warrants further investigation.Disclosures All authors: No reported disclosures.

IMPACT OF RESPIRATORY SYNCYTIAL VIRUS INFECTIONS ON LUNG FUNCTIONS AMONG PATIENTS WITH LUNG TRANSPLANTATION

SESSION TITLE: Wednesday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM PURPOSE: Adverse effects of community acquired respiratory virus (CARV) infections among patients with lung transplantation (LT) are often due to progressive allograft dysfunction triggered via activation of alloimmune responses which can lead to acute rejection or progression to chronic lung allograft dysfunction (CLAD). Respiratory syncytial virus (RSV) infections have been noted to have a consistent association with poor outcomes. We sought to evaluate the impact of RSV infection on lung functions for up to one year after the episode in a large cohort of LT patients. We also report the risk of new or progressive CLAD among this cohort where this infection was managed aggressively using a multimodality pharmacotherapy protocol. METHODS: We queried the electronic medical records for the diagnosis of RSV infection among LT patients during 2013-2017. The diagnosis of RSV was based upon positive respiratory viral polymerase chain reaction assay. We reviewed the lung functions of each patients including best baseline, highest pre-RSV, highest and lowest in the subsequent year post-RSV, and new post-RSV baseline (at one year after the infection). We compared the slope of lung functions before and after the RSV infections. Definition of obstructive or restrictive CLAD were based upon standard guidelines. RESULTS: There were 90 episodes of RSV infection among 87 patients (mean age 56.3±13.1 years, M:F 52: 35).Most had a history of bilateral LT (82.8%). Complete data was available for 77 episodes among 75 patients (86.2% with seven deaths related to progressive CLAD). Established CLAD preceded 28 episodes of RSV (31.1%). The serial FVC and FEV1 levels (median with range) at different time points are presented in the Figure. Prior to RSV, the average rate of FVC decline for the group was 39 cc or 1.35% per month whereas the rate of FEV1 decline was 26 cc or 1.17% or per month. After RSV the rate of FVC and FEV1 decline tended to slow although there was no statistically significant change in the rate of decline of FVC or FEV1. As regards the individual episodes, the rate of decline appeared to accelerate for FVC after 35.1% of the episodes (n=27),FEV1 after 33.8% (n=26) and for both FVC and FEV1 after a quarter of the episodes (19/77). CONCLUSIONS: RSV infection continues to be common among LT recipients and patients with established CLAD may be at an increased risk of developing this infection. While RSV was associated with significant all cause mortality at one year, mortality attributable to progressive CLAD was seen among <10% of the patients. Furthermore, RSV did not alter the average rate of lung function decline for the group. CLINICAL IMPLICATIONS: Modern management protocols using multimodality pharmacotherapeutic approaches may attenuate the potential adverse effects of RSV infections among LT patients. DISCLOSURES: My spouse/partner as a Employee relationship with St Jude’s Medical Please note: $20001 - $100000 Added 03/15/2019 by Amit Banga, source=Web Response, value=Salary Investigator relationship with Mallinckrodt pharmaceutical Please note: >$100000 Added 03/15/2019 by Amit Banga, source=Web Response, value=Grant/Research Support No relevant relationships by Srinivas Bollineni, source=Web Response No relevant relationships by John Joerns, source=Web Response No relevant relationships by Vaidehi Kaza, source=Web Response No relevant relationships by Ricardo La Hoz, source=Web Response No relevant relationships by Isaac Lill, source=Web Response No relevant relationships by Luke Mahan, source=Web Response No relevant relationships by Manish Mohanka, source=Web Response No relevant relationships by Fernando Torres, source=Web Response No relevant relationships by April Wiggins, source=Web Response

2359 Acute Liver Failure in the Setting of HSV-Induced Hemophagocytic Lymphohistiocytosis

INTRODUCTION: Acute liver failure (ALF) is characterized by acute (&lt; 26 weeks) liver injury, encephalopathy, and impaired synthetic function (INR ≥ 1.5) in a patient without a preexisting liver disease carries a poor prognosis1. Common etiologies of ALF include acetaminophen toxicity, sepsis, and toxin exposure2. Here, we present a rare case of ALF secondary to HSV-induced Hemophagocytic lymphohistiocytosis (HLH). CASE DESCRIPTION/METHODS: A 57-year old male with a history of hypertension presented with a week history of cough and fever. Review of systems also included fatigue, decreased appetite, and decreased interactiveness. Labs were remarkable for anemia, thrombocytopenia (plt 15,000), tranaminitis (AST/ALT 6943/1551), ferritinemia (&gt;105,000 ng/mL) and hypofibrinogenemia (134 mg/dL). Workup for causes of ALF was unrevealing, including acetaminophen, viral hepatitis, Wilson Disease, and autoimmune hepatitis. Blood and urine cultures, respiratory viral PCR, Adenovirus PCR, HIV Ab/Ag, Lyme IgM/IgG, ANA and RF were negative. HSV and EBV antibodies were collected early in admission. A CT Chest was unremarkable and a CT abdomen showed diffuse hepatic hypo-attenuation. His course was complicated by hypothermia, hypotension, and unresponsiveness prompting intubation and admission into the ICU. He was started on broad spectrum antibiotics as well as high dose steroids. His clinical status continued to deteriorate after-which his family requested comfort care measures. Postmortem autopsy demonstrated hepatomegaly with HSV hemorrhagic and necrotic hepatitis resulting in confluent non-zonal hepatic necrosis, as well as splenomegaly. Postmortem his HSV IgM (type 1 and 2) was not detected. His serum EBV IgM and IgG elevated with PCR showing 2246 copies/mL. DISCUSSION: This was a case of ALF due to suspected HSV-induced HLH. In review of the literature, only one other case study has reported ALF in the setting of HSV-induced HLH3. The diagnosis of HLH clinically requires 5/8 criteria [Table 1]4. Our patient met five of eight criteria for HLH. Notably, both EBV and HSV have been strongly implicated as potential triggers for HLH5. Although primary liver disease and HLH can present in a similar fashion, HLH tends to incorporate more extensive organ involvement, cytopenias, extremely high ferritin, and neurologic findings. Our case a rare precipitating cause of ALF, highlighting the importance of considering HSV-induced HLH early in the course of newly diagnosed ALF given their rapid deterioration.

CHARACTERISTICS AND OUTCOMES AFTER RESPIRATORY SYNCYTIAL VIRUS INFECTION AMONG PATIENTS WITH LUNG TRANSPLANTATION

SESSION TITLE: Outcomes of Respiratory Infections in the Immunocompromised Host SESSION TYPE: Original Investigations PRESENTED ON: 10/20/2019 2:15 PM - 3:15 PM PURPOSE: To describe the characteristics and outcomes in a large cohort of LT patients with respiratory syncytial virus (RSV) infection and elucidate the predictors of one-year survival. METHODS: This was a retrospective chart review study of LT patients with RSV infection between 2013 & 2017 (90 episodes among 87 patients; mean age 56.3±13.1 yrs, M:F 52: 35). Positive respiratory viral multiplex PCR assay confirmed the diagnosis of RSV. Baseline characteristics, presenting features, lung functions pre- and post-RSV episode, management strategies, and one-year survival were reviewed. Variables were compared among patients who survived to one year after RSV versus those who did not. RESULTS: The average time from LT to RSV infection was 34 months. Chronic lung allograft dysfunction (CLAD) was established at the time of RSV among 28 patients. More than three-fourth of the episodes were associated with lower respiratory tract (LRT) symptoms, while a third had radiological or CT changes at presentation. Hospital management (97.8%) was ubiquitous with 31.1% requiring ICU admission. Treatment included inhaled ribavirin (95.6%), palivizumab (95.6%) and pulse steroids (85.6%). The mean length of hospital stay was 8.4±4.7 days and two patients did not survive to discharge. At one year follow up 12 patients had died, with 7 deaths related to progressive CLAD (five of the seven had established CLAD before RSV). The incidence of new diagnosis of CLAD during the year after RSV was 13.8%. On univariate analysis, one year survivors had higher median FVC (2.8vs 1.96L; p=0.006) and FEV1 (2.15 vs 1.44 L; p=0.002) during the 3 months preceding the RSV episode. Established CLAD before the infection (30.4% vs 8.9%, p=0.01), presence of CT changes 44.4% vs 11.1%, p=0.007), and ventilator support (42.9% vs 12%, p=0.026) were associated with increased risk of one-year mortality. After adjusting for age and type of transplant, history of CLAD (adjusted OR: 5.7, 1.42-22.7; p=0.014) and presence of CT infiltrates (11.1, 1.85-67; p=0.009) were associated with one year mortality. CONCLUSIONS: RSV infection occurs frequently after LT. A significant proportion of patients develop parenchymal infiltrates and get acutely ill needing ICU admission. The overall hospital mortality, one year mortality, and the risk of new CLAD after an RSV infection in the current cohort is lower than previously reported. Previous diagnosis of CLAD and presence of CT infiltrates is associated with one-year mortality after RSV infection. CLINICAL IMPLICATIONS: In the largest series to date of RSV infections in a contemporary cohort of LT patients, the early and late outcomes after RSV infection appear to be improving. Aggressive management protocols based upon the early institution of multimodality pharmacotherapy may be associated with favorable outcomes. DISCLOSURES: My spouse/partner as a Employee relationship with St Jude’s Medical Please note: $20001 - $100000 Added 03/15/2019 by Amit Banga, source=Web Response, value=Salary Investigator relationship with Mallinckrodt pharmaceutical Please note: >$100000 Added 03/15/2019 by Amit Banga, source=Web Response, value=Grant/Research Support No relevant relationships by Srinivas Bollineni, source=Web Response No relevant relationships by John Joerns, source=Web Response No relevant relationships by Vaidehi Kaza, source=Web Response No relevant relationships by Ricardo La Hoz, source=Web Response No relevant relationships by Isaac Lill, source=Web Response No relevant relationships by Luke Mahan, source=Web Response No relevant relationships by Manish Mohanka, source=Web Response No relevant relationships by Fernando Torres, source=Web Response No relevant relationships by April Wiggins, source=Web Response

CONGENITAL BRONCHIAL ATRESIA: A RARE ENTITY

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: Congenital Bronchial Atresia (CBA) is a rare developmental anomaly, results from focal interruption of bronchus along with the formation of mucocele (mucus filled bronchus). It often presents in adulthood, as an incidental finding on radiography or recurrent pneumonia. Computed tomography (CT) angiogram of the chest remains the investigation of choice in the diagnosis of CBA while bronchoscopy should be done to rule out other etiologies of hyperinflation. Management of CBA is conservative for asymptomatic individuals while surgery is reserved for individuals who have the recurrent infection and severe symptoms. CASE PRESENTATION: 19-year-old male with no known past medical history presented to the ED for evaluation of dry cough and subjective fever for 5 days. Patient denied any shortness of breath, hemoptysis, chest pain, night sweats, weight loss or change in appetite. Patient was not taking any medication at home. Past surgical and family history was not significant. Patient denied smoking, alcohol use and any illicit drug abuse. On admission, he was afebrile, hemodynamically stable and saturating 99% on room air. In terms of labs, white cell count was elevated initially and then trended down; rest of the labs including molecular flu, pro-calcitonin, legionella antigen, mycoplasma antigen, respiratory syncytial virus PCR and blood culture were negative. Chest x-ray showed hyperlucency and decreased vascularity in the left upper lung zone along with consolidation in the left lower lobe. Patient was started on antibiotics and treated for community-acquired pneumonia. CT angiogram of the chest (1) showed round soft tissue density suggestive of mucoid impaction of the left bronchus likely mucocele along with hyperlucent left upper lobe and hypoplastic vasculature consistent with bronchial atresia (Figure 1 and 2). Bronchoscopy was normal which was done to rule out other etiologies like foreign body, bronchial adenoma, and lung cancer. V/Q scan showed no ventilation and perfusion to the majority of left upper lobe (figure 3). Patient showed signs of clinical improvement and discharged on oral antibiotics with outpatient follow up. DISCUSSION: CBA is a benign and rare entity with characteristic imaging finding resembling other serious underlying disease. Management can range from conservative measure to the surgery of an involved segment of the lung. Therefore, it is imperative to understand the nature of the disease and counsel the patient accordingly. CONCLUSIONS: Although benign entity, CBA should be kept in the differential especially in young patients who present with hyperinflation of one or more segment of lung which might cause compression atelectasis and/or pneumonia of the other adjacent segments as it presented in our case. CTA of the chest is usually the modality to diagnose with bronchoscopy and V/Q scan to guide further management. Reference #1: Psathakis K, Eleftheriou D, Boulas P, Mermigkis C, Tsintiris K. Congenital bronchial atresia presenting as a cavitary lesion on chest radiography: a case report. Cases J. 2009;2(1):17. Published 2009 Jan 7. https://doi.org/10.1186/1757-1626-2-17 Reference #2: Mahajan AK, Rahimi R, Vanderlaan P, Folch E, Gangadharan S, et al. (2017) Unique Approach to Diagnosing and Treating Congenital Bronchial Atresia (CBA): A Case Series. J Pulm Respir Med 7:402. https://doi.org/10.4172/2161-105X.1000402 DISCLOSURES: No relevant relationships by Anas Al-khateeb, source=Web Response No relevant relationships by mohammed halabiya, source=Web Response No relevant relationships by Muhammad Hussain, source=Web Response No relevant relationships by Muqueet Kadri, source=Web Response No relevant relationships by Richard Miller, source=Web Response No relevant relationships by Hari Sharma, source=Web Response

Ongoing outbreak of human adenovirus-associated acute respiratory illness in the Republic of Korea military, 2013 to 2018.

Background/AimsHuman adenovirus type 55 (HAdV-55), an emerging epidemic strain, has caused several large outbreaks in the Korean military since 2014, and HAdV-associated acute respiratory illness (HAdV-ARI) has been continuously reported thereafter.MethodsTo evaluate the epidemiologic characteristics of HAdV-ARI in the Korean military, we analyzed respiratory virus polymerase chain reaction (RV-PCR) results, pneumonia surveillance results, and severe HAdV cases from all 14 Korean military hospitals from January 2013 to May 2018 and compared these data with nationwide RV surveillance data for the civilian population.ResultsA total of 14,630 RV-PCRs was performed at military hospitals. HAdV (45.4%) was the most frequently detected RV, followed by human rhinovirus (12.3%) and influenza virus (6.3%). The percentage of the military positive for HAdV was significantly greater than the percentage of civilians positive for HAdV throughout the study period, with a large outbreak occurring during the winter to spring of 2014 to 2015. The outbreak continued until the end of the study, and non-seasonal detections increased over time. The reported number of pneumonia patients also increased during the outbreak. Case fatality rate was 0.075% overall but 15.6% in patients with respiratory failure. The proportion of severe patients did not change significantly during the study period.ConclusionsA large HAdV outbreak is currently ongoing in the Korean military, with a trend away from seasonality, and HAdV-55 is likely the predominant strain. Persistent efforts to control the outbreak, HAdV type-specific surveillance, and vaccine development are required.

15. Eosinophilic pneumonitis secondary to baricitinib

IntroductionWe present a case of drug-induced pneumonitis in a patient taking baricitinib.Case descriptionA 63-year-old patient with longstanding sero-positive erosive RA (anti-CCP >340) on long term methotrexate started taking baricitinib for his poorly-controlled arthritis 5 weeks prior to the hospital admission with two-week history of increasingly short of breath, productive cough with yellow sputum and right sided pleuritic chest pain.On examination, he was febrile with temperature 38.2, tachypnoeic, respiratory rate 22/min and O2 saturation 92% on room air, with stable blood pressure 130/75 and normal sinus rhythm. He had some crepitations and reduced air entry in both lung bases on auscultation. He had no rash. CRP was > 190, total white cell 4.5, neutrophils 2.9, and eosinophils 0.56 (0.02-0.5). He had a transient rise in liver enzyme ALT (52) and bilirubin (22), both normalised on discharge. Kidney functions remained normal.Influenza A, B and respiratory virus PCR, urinary legionella and pneumococcal antigen, blood, urine and sputum cultures were negative.CXR showed no obvious consolidations or acute changes. CT angiogram to exclude pulmonary embolism showed scattered ground glass opacification throughout both lungs affecting multiple zones with no architectural distortion and no confluent consolidation.Despite treatment with IV antibiotics for suspected community acquired pneumonia, he continued to spike temperatures and was dependent on oxygen. When we reviewed him, our impression was that his symptoms, clinical findings and CT changes were consistent with drug-induced pneumonitis, most likely due to baricitinib.Methotrexate and baricitinib were suspended. He responded well to 40 mg of prednisolone; his fever subsided and he became less dyspnoeic and CRP and eosinophil counts improved. He went home after 7 days of admission. A repeat CT chest 8 weeks later showed a complete resolution of the pneumonitis. He was still on a low but reducing dose of prednisolone and methotrexate was restarted and tolerated well.DiscussionWe believe this is one of the first few reported cases of drug-induced pneumonitis to baricitinib. The patient had been treated in the community with antibiotics for 2 weeks as well as during admission with very poor response.Baricitinib was the only new medication he took 4-5 weeks before the symptoms developed. Previously, he had been stable on his usual medications including methotrexate for over 10 years.The temporal relationship between the start of the new medication and the onset of the symptoms, clinical and laboratory findings and radiological changes suggested that this was baricitinib-induced pneumonitis.Key learning pointsIt is important to have a high index of suspicion for hypersensitivity pneumonitis in patients presenting with acute lung injury shortly after starting a new treatment as early diagnosis and treatment can lead to the complete resolution of the condition.Conflict of interestThe authors declare no conflicts of interest.

Enterovirus D68 respiratory infection in a children's hospital in Japan in 2015.

BackgroundOutbreaks of enterovirus D68 (EV‐D68) respiratory infections in children were reported globally in 2014. In Japan, there was an EV‐D68 outbreak in the autumn of 2015 (September–October). The aim of this study was to compare EV‐D68‐specific polymerase chain reaction (PCR)‐positive and EV‐D68‐specific PCR‐negative patients.MethodsPediatric patients admitted for any respiratory symptoms between September and October 2015 were enrolled. Nasopharyngeal swabs were tested for multiplex respiratory virus PCR and EV‐D68‐specific reverse transcription‐PCR. EV‐D68‐specific PCR‐positive and ‐negative patients were compared regarding demographic data and clinical information.ResultsA nasopharyngeal swab was obtained from 76 of 165 patients admitted with respiratory symptoms during the study period. EV‐D68 was detected in 40 samples (52.6%). Median age in the EV‐D68‐specific PCR‐positive and ‐negative groups was 3.0 years (IQR, 5.5 years) and 3.0 years (IQR, 4.0 years), respectively. The rates of coinfection in the two groups were 32.5% and 47.2%, respectively. There was no significant difference in the history of asthma or recurrent wheezing, length of hospitalization, or pediatric intensive care unit admission rate between the groups. The median days between symptom onset and admission was significantly lower for the EV‐D68‐positive group (3.0 days vs 5.0 days, P = 0.001). EV‐D68 was identified as clade B on phylogenetic analysis. No cases of acute flaccid myelitis were encountered.ConclusionsMore than half of the samples from the children admitted with respiratory symptoms were positive for EV‐D68‐specific PCR during the outbreak. Asthma history was not associated with the risk of developing severe respiratory infection.

Improvement in turnaround time for rapid respiratory virus testing using Xpert® Flu/RSV: a retrospective cohort study during a high incidence influenza season

Seasonal influenza like illness results in increased hospital presentations and unnecessary antibiotic use. Recent availability of rapid respiratory virus PCR testing allows rapid, accurate influenza diagnosis. A retrospective audit of turnaround time from sample collection to result availability after introduction of Xpert® Flu/RSV in a tertiary healthcare institution during a high incidence influenza season is described.

Episodic viral wheeze and multiple-trigger wheeze in preschool children are neither distinct nor constant patterns. A prospective multicenter cohort study in secondary care.

To evaluate whether episodic viral wheeze (EVW) and multiple-trigger wheeze (MTW) are clinically distinguishable and stable preschool wheezing phenotypes. Children of age 1 to 4 year with recurrent, pediatrician-confirmed wheeze were recruited from secondary care; 189 were included. Respiratory and viral upper respiratory tract infection (URTI) symptoms were recorded weekly by parents in an electronic diary during 12 months. Every 3 months, diary-based symptoms were classified as EVW or MTW and compared to phenotypes assigned by pediatricians based on clinical history. We collected nasal samples for respiratory virus PCR during URTI, respiratory symptoms and in absence of symptoms. Of 660 3-month periods, the diary-based phenotype was EVW in 11%, MTW in 54% and 35% were free from respiratory episodes. Pediatrician-based classification showed 59% EVW and 26% MTW. The Kappa measure of agreement between diary-based and pediatrician-assigned phenotypes was very low (0.12, 95%CI, 0.07-0.17). Phenotypic instability was observed in 32% of cases. PCR was positive in 71% during URTI symptoms, 66% during respiratory symptoms and 38% in the absence of symptoms. This study shows that EVW and MTW are variable over time within patients. Pediatrician classification of these phenotypes based on clinical history does not correspond to prospectively recorded symptom patterns. The applicability of these phenotypes as a basis for therapeutic decisions and prognosis should be questioned.

Parainfluenza III Outbreak in a Veterans’ Affairs affiliated Nursing Home

BACKGROUND Parainfluenza III is one of the four serotypes of the parainfluenza virus (PIV) that causes upper respiratory tract infections (URI) in adults. Clinical presentation can range from mild URI to pneumonia, to death. We report a cluster of respiratory illness due to PIV III in a Community Living Center, (CLC) Nursing Unit. METHODS An outbreak of PIV III URI occurred at a VAMC CLC - 30 bed unit in June 2018. Cases were confirmed via nasopharyngeal respiratory viral real-time PCR panel. Case definition included a resident with new onset respiratory complaints and positive PCR test. Clinical presentation, laboratory data and outcome were reviewed in each case. RESULTS Ten residents tested positive for PIV III from 6/2 to 6/26, 2018. All residents were men with ages ranging from 59 to 84?years. The index case occurred on 6/2 with temperature of 102.30F. Thereafter, a health care provider presented with symptoms of URI but continued to work. The Infection control team was notified on five cases detected on 6/12; 4 cases were detected 6/18 to 6/26. One patient required hospitalization due to post-viral bacterial pneumonia. No deaths occurred. Five healthcare providers presented with symptoms of URI during this outbreak. Aggressive infection control measures were implemented: temporally halting admissions; high index of suspicion for symptomatic patients with obtaining viral panel; encouraging them to remain in their room; and teaching respiratory etiquette; enforcing hand hygiene and symptomatic patients leaving the nursing unit had to wear a mask; terminal cleaning of virus-contaminated surfaces/objects; discouraging floating of staff, directing ill employees to stay home. CONCLUSIONS PIV III can cause a serious outbreak in nursing homes. Therefore, Infection Control Preventionists can have an instrumental role in rapid recognition of an outbreak and strategically implementing targeted measures to halt the outbreak.

Implementation of a Stewardship Initiative on Respiratory Viral PCR-based Antibiotic Deescalation.

Respiratory viral polymerase chain reaction (RV PCR) tests assist in rapidly identifying viral pathogens and differentiating viral versus bacterial causes of pneumonia. Studies evaluating the use of RV PCR tests on antibiotic use in adults have demonstrated mixed results. We implemented an antimicrobial stewardship (ASP) intervention for patients with a positive RV PCR test result who were receiving broad-spectrum antibiotics and aimed to assess the impact on antibiotic usage. Retrospective quasi-experimental study of adult hospitalized patients comparing time to antibiotic deescalation, duration of antibiotic therapy, and antiviral use preintervention (January-March 2016) and postintervention (January-March 2017). Of 172 ASP alerts reviewed, 55 (32%) were considered actionable. Of these, 47% of interventions were accepted. No significant difference was observed in median time to antibiotic deescalation (pre: 2.7days vs post: 2.3days, p=0.88). Time to discontinuation of antimicrobial therapy pre- and postintervention was reduced from 4 to 1.9days (p=0.057) for piperacillin-tazobactam, from 2.7 to 1.8days (p=0.75) for ceftriaxone, and from 3.6 to 2days (p=0.4) for levofloxacin, respectively. Time to initiation of oseltamivir for influenza was significantly shorter in the postintervention group (pre: 11.3hrs vs post: 3.6hrs, p=0.02). A third of patients receiving broad-spectrum antibiotics with a positive RV PCR had an opportunity for antimicrobial optimization, although this did not translate into a significant impact on the time to antibiotic deescalation or overall antibiotic use. Combination of RV PCR results with biomarkers to rule out bacterial coinfections and chest radiographic findings may help enhance the likelihood of accepted antibiotic deescalation recommendations and represents an area of future research.

Contribution of the FilmArray Respiratory Panel in the management of adult and pediatric patients attending the emergency room during 2015–2016 influenza epidemics: An interventional study

AimTo evaluate the contribution of a multiplex PCR for respiratory viruses on antibiotic and antiviral prescription, ancillary test prescription, admission and length of stay of patients. MethodsTwo hundred ninety-one adult and pediatric patients visiting the emergency department during the 2015–2016 influenza epidemic were prospectively included and immediately tested 24/7 using the FilmArray Respiratory Panel. The results were communicated to the practitioner in charge as soon as they became available. Clinical and biological data were gathered and analyzed. FindingsResults from the FilmArray Respiratory Panel do not appear to impact admission or antibiotic prescription, with the exception of a lower admission rate for children who tested positive for influenza B. Parameters that account for the clinical decisions evaluated are CRP level, white blood cell count, suspected or proven bacterial infection and, for adult patients only, signs of respiratory distress. Length of stay is also not significantly different between patients with a positive and a negative result. A rapid influenza test result permits a more appropriate prescription of oseltamivir.

Human Metapneumovirus or Influenza A Upper Respiratory Tract Infection Associated with Increased Risk of Bacterial Superinfection in Allogeneic Hematopoietic Cell Transplant Recipients

Introduction Bacterial superinfection following moderate to severe respiratory viral infections (RVIs), especially influenza (Flu), is well described in immunocompetent hosts. The clinical impact of preceding RVIs on the development of bacterial superinfection in hematopoietic cell transplant (HCT) recipients may be significant although data are limited. Furthermore, the impact of upper respiratory tract infection (URTI) on this outcome has not been systematically evaluated. Objectives To investigate whether URTI due to specific respiratory viruses was associated with increased risk of developing bacteremia or bacterial pneumonia post-HCT. Methods In a longitudinal surveillance study of RVIs among allogeneic HCT recipients conducted from 2005-10, weekly post-HCT nasal washes were collected through day 100. Nasal and bronchoalveolar lavage samples were tested by multiplex PCR for respiratory syncytial virus, parainfluenza viruses (PIV)1–4, Flu A/B, human metapneumovirus (HMPV), adenovirus, rhinoviruses and coronaviruses. URTI was defined as having respiratory virus detected from nasal samples with respiratory symptoms. Bacteremia and bacterial pneumonia were defined as growth of significant bacteria (e.g., Coagulase-negative staphylococci was defined as insignificant bacteria) from blood and lower respiratory tract samples including bronchoalveolar lavage, respectively. Separate Cox proportional hazards models were used to examine associations between first URTI for individual viruses and the subsequent development of first bacteremia and/or bacterial pneumonia by 100 days post-HCT. Results We identified 471 HCT recipients (median age: 51 years, range 8 months-75 years). Number of patients for each first outcome event by 100 days post-HCT included the following: Gram-positive bacteremia (n=64), Gram-negative bacteremia (n=53), Gram-positive pneumonia (n=46), Gram-negative pneumonia (n=8), and either bacteremia or pneumonia (n=152). After adjusting for pre-transplant factors only and pre- and post-transplant factors, significant URTI variables for outcomes in both models were (1) Flu A for gram-positive bacteremia, (2) HMPV for gram-positive pneumonia, and (3) HMPV for bacteremia or bacterial pneumonia (Figure). The association between PIV URTI and development of bacteremia or pneumonia approached statistical significance. Conclusion In HCT recipients, URTIs due to Flu A and HMPV are significant risk factors for the development of gram-positive bacteremia and pneumonia, respectively. Further studies are needed to assess whether prevention or early diagnostic and treatment strategies for RVIs can reduce the risk of bacterial infection.

Successful Treatment of Toxoplasma Induced Hemophagocytic Lymphohistiocytosis (HLH) after Undergoing Allogenic Stem Cell Transplantation (HSCT)

Introduction Toxoplasmosis is a well-known intracellular protozoan parasite with seroprevalence varying geographically. Relatively asymptomatic in healthy individuals, it's reactivation can be a devastating opportunistic infection in HSCT patients with rare documentation of associated HLH. Case A 25-year-old woman with Hodgkin lymphoma, refractory to multiple chemotherapies, autologous transplant and Nivolumab, who underwent haploidentical HSCT, was admitted on day +33 with persistent high-grade fevers. Blood counts were unremarkable, except for eosinophilia. She received broad spectrum antibiotics. PET/CT on day +36 demonstrated resolution of metabolic activity in multiple lymph nodes, but revealed ‘revved-up' bone marrow(Image 1). CT-chest (day +41) demonstrated widespread centrilobular nodules. Blood, urine, enteric cultures, HIV, Histoplasma studies, and respiratory viral panel PCR were negative. Pre-transplant serologies noted a positive toxoplasma IgG. Toxoplasma DNA was detected in blood on day +41; she received clindamycin, pyrimethamine, and atovaquone due to sulfa allergy but successfully underwent rapid sulfa desensitization. She developed progressive pancytopenia and hypoxemia (day +43) requiring intubation in the ICU. Ferritin was >50,000 ng/mL, and triglycerides 931 mg/dL. Bone marrow biopsy showed activated macrophages and hemophagocytosis (Image 2). She met 6/8 criteria described in HLH-2004 trial. She received dexamethasone and tocilizumab for HLH, leading to prompt reversal of HLH physiology within 72 hours of HLH-directed therapy initiation. She was extubated on day +48. She was discharged on sulfadiazine and pyrimethamine (day +60) with almost normal ferritin levels and transfusion-independency. Discussion HLH is characterized by cytopenias, extreme systemic inflammatory response, and high mortality. HLH can be triggered by infections, such as toxoplasmosis. Disseminated toxoplasmosis has a high mortality itself (>60 % treated, and 99% untreated), and HSCT recipients appear to have the highest risk. Early detection and treatment of the underlying infection is essential. Novel drugs, such as Tocilizumab, should be prospectively studied in HLH. In conclusion, HLH after HSCT should be suspected in cases of unexplained inflammatory response and cytopenias after successful engraftment; secondary causes must be explored and promptly treated.

An Outbreak of Human Parainfluenza Virus 3 (Phylogenetic Subcluster C5) Infection among Adults at a Residential Care Facility for the Disabled in Croatia, 2018

Introduction: Although highly pertinent for children, outbreaks of human parainfluenza virus (HPIV) may cause up to 15% of all respiratory illnesses in adults and predispose them to serious adverse outcomes, with HPIV serotype 3 (HPIV3) being the most common. This study represents the first report of an HPIV3 outbreak among adults at a long-term health-care facility in Croatia. Methods: A retrospective study was conducted to investigate an outbreak of acute respiratory infection (ARI) at a single residential care facility for the disabled in Croatia. Demographic, epidemiological, and clinical data were collected for all residents, while hospitalized patients were appraised in detail by laboratory/radiological methods. Multiplex PCR for respiratory viruses and sequencing was performed. Partial HPIV3 HN 581 nt sequences were aligned with HPIV3 sequences from the GenBank database to conduct a phylogenetic analysis, where different bioinformatic approaches were employed. Results: In late June 2018, 5 of the 10 units at the facility were affected by the outbreak. Among the 106 residents, 23 (21.7%) developed ARI, and 6 (26.1%) of them were hospitalized. HPIV3 was identified in 18 (73%) of the residents and 5 (83%) of the hospitalized individuals. Isolated HPIV3 strains were classified within the phylogenetic subcluster C5 but grouped on 2 separate branches of the phylogenetic tree. During the entire outbreak period, none of the institution’s employees reported symptoms of ARI. Conclusions: Our study has shown that this health care-associated outbreak of HPIV3 infection could have been linked to multiple importation events. Preventive measures in curbing such incidents should be enforced vigorously.

Causative Organisms and Resistance Patterns of Infection in Patients with Myelodysplastic Syndrome (MDS): A 20 Year Retrospective Analysis

Introduction: Although infections are a leading cause of morbidity and mortality in MDS patients, there is limited evidence on causative organisms and resistance patterns in this patient population. This study, the largest series of infection in MDS patients, seeks to comprehensively analyse infection in this cohort.Method: CT scan, microbiology results and hospital admission ICD codes from January 1999 to April 2017 were analysed for 657 MDS patients enrolled in the South Australian MDS (SA-MDS) registry. Cox regression analysis was performed to ascertain risk factors for developing infection.Results: There were 531 primary and 126 therapy-related myeloid neoplasm (t-MN) patients with median age of 69.2 (18-97) years. According to Revised International Prognostic Scoring System (IPSS-R), 44.7% of patients were classified as Intermediate, High and Very High risk. The majority of the cohort (377/657; 57.3%) received best supportive care and 265 had disease modifying therapy including azacitidine (n=142), chemotherapy (n=74) and stem cell transplantation (SCT) (n=25).There were 2450 hospital admissions and 1312(53.5%) were infection-related, in 464/657 patients. The most common sites of infection were lower respiratory tract infections (LRTI) n=449(33.2%), fever with no known source n=356(26.3%) and skin and soft tissue (SSTI; 235, 17.3%).During the study period, 1613/16176 (10%) of microbiology tests were positive. The most common positive tests were blood cultures (494, 30.6%), respiratory viral PCR (227, 14.0%) and bacteriology (other sites; 216, 13.4%).The most common isolates were bacteria (67.3%) followed by viruses (28.1%) and fungi (4.6%). The most common bacteria were gram negative bacilli (GNB); E. coli n=81(12%), Pseudomonas spp. n=64(9%) and Klebsiella spp. n=56(8%), and the most common gram-positive isolates were Staphylococcus aureus n=114(20%) and Enterococcus spp. (37, 7%).There were 192 episodes of bacteraemia in 179 patients. The most common causative organisms were E. coli n=32(16.7%), Klebsiella spp. n=18(9.4%) Pseudomonas spp. n=25(13%), coagulase negative staphylococci n=26(14%), Streptococcus spp. n=22(11%) and Enterococcus spp. n=14(11%). The proportion of GNB bacteremias significantly increased over time (45.8% 1999-2005; 40.0% 2006-2011 and 59.4% 2012-2017 [p=.004]) without increased resistance to commonly used antibiotics. There were 21 enterococcal bacteremias with significant increase in proportion of vancomycin resistant Enterococcus (VRE) after 2011 (p<0.001).The most commonly isolated respiratory viruses were rhinovirus (98, 43.2%), influenza (34, 15%) and parainfluenza (34, 15%), Cytomegalovirus was identified in 154 specimens from 31 patients, all following SCT.70 patients had probable or confirmed fungal infection, with 52 (74.3%) patients having positive fungal cultures or CT findings. The most common sites of fungal infection were chest n=21(76.9%), followed by skin n=5(9.6%), urine n=4(7.7%) and blood n=3(5.8%). Aspergillus n=17(44.7%) was most commonly isolated, followed by Candida spp. n=15(39.5%) and Rhizopus n=3(7.9%).We performed a Cox regression analysis of the risk factors for development of infection requiring hospitalisation, specifically with LRTI, fungal infection and bacteraemia (Table I). Significant predictors were increased age, t-MN, higher IPSS-R score and being transfusion dependent at diagnosis. Receiving disease modifying therapy was a significant risk factor for hospitalisation with fungal infection (p=0.022).Additionally, patients who had hospitalisations for infections had poorer overall survival compared to hospitalised patients without infection (p=0.002, Figure 1).Conclusions: Greater than 50% of hospital admissions in MDS patients were complicated by infection and this was associated with a significant reduction in survival. The most common sites were LRTI, followed by bacteraemia and SSTI.Bacteraemia from GNBs increased over the study period without significant change in resistance patterns, while prevalence of VRE increased since 2011. Respiratory viruses, including influenza, caused significant morbidity, suggesting a role for routine vaccination.RBC transfusion dependency, t-MN and disease modifying therapy are independent risk factors for fungal disease. This highlights a cohort of patients that would benefit from anti-fungal prophylaxis. [Display omitted] DisclosuresHiwase:Celgene: Research Funding; Novartis: Research Funding.