PCR For Respiratory Viruses Research Articles

Differences in antibiotic and antiviral use in people with confirmed influenza: a retrospective comparison of rapid influenza PCR and multiplex respiratory virus PCR tests

BackgroundInfluenza is a highly contagious respiratory virus with clinical impacts on patient morbidity, mortality and hospital bed management. The effect of rapid nucleic acid testing (RPCR) in comparison to standard multiplex PCR (MPCR) diagnosis in treatment decisions is unclear. This study aimed to determine whether RPCR influenza testing in comparison to standard MPCR testing was associated with differences in antibiotic and antiviral (oseltamivir) utilisation and hospital length of stay in emergency department and inpatient hospital settings.MethodsA retrospective cohort study of positive influenza RPCR and MPCR patients was performed utilising data from the 2017 influenza season. Medical records of correlating patient presentations were reviewed for data collection. An analysis of RPCR versus MPCR patient outcomes was performed examining test turnaround time, antibiotic initiation, oseltamivir initiation and hospital length of stay for both emergency department and inpatient hospital stay. Subgroup analysis was performed to assess oseltamivir use in high risk populations for influenza complications. Statistical significance was assessed using Mann-Whitney test for numerical data and Chi-squared test for categorical data. Odds ratio with 95% confidence intervals were calculated where appropriate.ResultsOverall, 122 RPCR and 362 MPCR positive influenza patients were included in this study. Commencement of antibiotics was less frequent in the RPCR than MPCR cohorts (51% vs 67%; p < 0.01, OR 0.52; 95% CI 0.34–0.79). People at high risk of complications from influenza who were tested with the RPCR were more likely to be treated with oseltamivir compared to those tested with the MPCR (76% vs 63%; p = 0.03, OR 1.81; 95% CI 1.07–3.08). Hospital length of stay was not impacted when either test was used in the emergency department and inpatient settings.ConclusionsThese findings suggest utilisation of RPCR testing in influenza management can improve antibiotic stewardship through reduction in antibiotic use and improvement in oseltamivir initiation in those at higher risk of complications. Further research is required to determine other factors that may have influenced hospital length of stay and a cost-benefit analysis should be undertaken to determine the financial impact of the RPCR test.

Epidemiology and clinical features of common community human coronavirus disease.

BackgroundWe would evaluate the epidemiology, clinical aspects, and prognostic factors of patients of all ages admitted with human corona virus (HCoV).MethodsThis study was retrospectively performed at five university teaching hospitals between 1st January 2018 and 31th March 2020. Routine molecular testing using for multiplex real-time reverse transcription-polymerase chain reaction (RT-PCR) methods was conducted on the respiratory viruses. We assessed the demographics, laboratory findings, and treatment of patients infected with coronavirus.ResultsThere were 807 coronavirus-infected patients from 24,311 patients with respiratory virus PCR test admitted to five hospitals over 27 months. All-cause mortality rates of patients admitted for seasonal HCoV disease were 3.1% in all patients and 10.8% in patients aged ≥18 years. The Cox proportional hazard regression analysis was performed in patients aged ≥18 years. After adjusting for other clinical variables, general weakness symptoms [hazard ratio (HR), 2.651; 95% confidence interval (CI), 1.147–6.125, P=0.023], National Early Warning Score (NEWS) ≥2 (HR, 5.485; 95% CI, 1.261–23.858, P=0.023), and coronavirus subtype OC43 (HR, 2.500; 95% CI, 1.060–5.897, P=0.036) were significantly associated with death from coronavirus.ConclusionsCoronavirus infection can reveal a higher mortality rate in patients of ≥18 than those of <18 years, thus, adult patients require more careful treatment. Furthermore, in adult patients, the factors associated with death from coronavirus include general weakness symptoms, NEWS higher than 2, and OC43 subtype.

Treating Pediatric Myocarditis with High Dose Steroids and Immunoglobulin

Purpose Though many pediatric centers use immunotherapy including immunoglobulin (IVIG) and corticosteroids to treat patients with acute myocarditis, given a lack of evidence supporting its efficacy there is considerable variability in practice. We report our approach using high dose steroids with IVIG to treat acute myocarditis. Methods This is a single center retrospective observational study of children diagnosed with myocarditis treated with high dose steroids and IVIG from January 2004-April 2020. Diagnostic criteria for myocarditis included positive endomyocardial biopsy, MRI meeting Lake Louise criteria, or clinical diagnosis including an elevated troponin, LVEDD Z score Results ty one patients met inclusion criteria. Median age at diagnosis was 10.7 years (1 wk-20 yrs). The majority were male (65%). Diagnosis was made clinically in 68% of cases (N=21), MRI in 16% (N=5) and biopsy in 16% (N=5). Ten patients had positive respiratory viral PCR, 6 had positive plasma viral PCR and 0 had positive biopsy viral PCR. Median EF at diagnosis was 41% (IQR 10-65). Mean duration of steroids received was 74 days (SD 13) with IV steroids for 7 days (IQR 3-13) prior to transition to an enteral regimen. The mean cumulative dose of steroids for first 7 days was 38 mg/kg. All patients received IVIG; median cumulative dose was 2 g/kg. Seven patients (23%) required mechanical circulatory support (5 ECMO, 1 Centrimag LVAD and 1 Centrimag BiVAD). There were no serious secondary bacterial. In-hospital mortality was 0%. Mean follow up was 2 years (SD=2yr); 1 patient died 2 years after discharge; 1 patient underwent transplant during initial hospitalization; no others were listed. Five required re-admission for cardiovascular reasons. Six patients (19%) had steroid course altered due to suspected side effects such as weight gain or hypertension which resolved at follow up. By 3 months from diagnosis, 84% (N=26) of patients regained normal LV function. Conclusion Our study demonstrates that use of high dose steroids with IVIG to treat myocarditis can be safe without significant infections or side effects. Our cohort had excellent recovery of ventricular function and survival without transplant (94%). Prospective comparison of a combination of high dose steroids with IVIG versus either therapy alone is needed.

Observational study of adult respiratory infections in primary care clinics in Myanmar: understanding the burden of melioidosis, tuberculosis and other infections not covered by empirical treatment regimes

BackgroundLower respiratory infections constitute a major disease burden worldwide. Treatment is usually empiric and targeted towards typical bacterial pathogens. Understanding the prevalence of pathogens not covered by empirical treatment is important to improve diagnostic and treatment algorithms.MethodsA prospective observational study in peri-urban communities of Yangon, Myanmar was conducted between July 2018 and April 2019. Sputum specimens of 299 adults presenting with fever and productive cough were tested for Mycobacterium tuberculosis (microscopy and GeneXpert MTB/RIF [Mycobacterium tuberculosis/resistance to rifampicin]) and Burkholderia pseudomallei (Active Melioidosis Detect Lateral Flow Assay and culture). Nasopharyngeal swabs underwent respiratory virus (influenza A, B, respiratory syncytial virus) polymerase chain reaction testing.ResultsAmong 299 patients, 32% (95% confidence interval [CI] 26 to 37) were diagnosed with tuberculosis (TB), including 9 rifampicin-resistant cases. TB patients presented with a longer duration of fever (median 14 d) and productive cough (median 30 d) than non-TB patients (median fever duration 6 d, cough 7 d). One case of melioidosis pneumonia was detected by rapid test and confirmed by culture. Respiratory viruses were detected in 16% (95% CI 12 to 21) of patients.ConclusionsTB was very common in this population, suggesting that microscopy and GeneXpert MTB/RIF on all sputum samples should be routinely included in diagnostic algorithms for fever and cough. Melioidosis was uncommon in this population.

Impacto del uso de PCR múltiple en diagnóstico etiológico y tratamiento de infecciones respiratorias agudas en un hospital privado del norte del país

Background and objective: Respiratory system diseases represent one of the leading cause of prescription of antibiotics. At present, new technologies for the diagnosis are being used, including the FilmArray Respiratory Panel. The objective was to identify the correlation between the diagnosis and treatment of respiratory tract infections with the result of PCR for respiratory viruses. Material and methods: Descriptive, cross-sectional, restrospective study. 134 patients were included treated at the Christus Muguerza Hospital in Saltillo, Coahuila. For all cases, the positive results of this test and the treatment patients received were analyzed. Results: 58 % received antibiotic treatment at admission, 13 % received combined treatment (antibiotic + antiviral), 27 % received symptomatic treatment since their admission and 2 % whit antiviral. After receiving a positive result for respiratory viruses, 38 % continued with antibiotics, 30 % with antibiotics and antivirals, 13.8 % only managed with antivirals and 18.2% with symptomatic treatment. Conclusion: Although we are currently on global alert for resistance to antibiotics, there is a lack of awareness about the prescription of antibiotics, due to a situation which is believed to be influenced by several factors.

Do I Need Proof of the Culprit? Decreasing Respiratory Viral Testing in Critically Ill Patients.

A 2-year-old, previously healthy boy with an upper respiratory infection presents to the emergency department with acute-onset stridor and respiratory distress. He quickly improves with intramuscular dexamethasone and initiation of heliox via high-flow nasal cannula. He is admitted to the PICU for respiratory insufficiency, requiring heliox, and high risk of respiratory failure. Before calling the PICU team for admission, the emergency department resident sends a respiratory viral polymerase chain reaction (PCR) panel. When her attending questions its necessity, she answers, “They [PICU admitting team] will ask for it. They always want to know which bug it is.” Historically, at our institution, respiratory viral PCR panels were commonly ordered for patients with more severe disease requiring PICU admission to find the culprit virus. Local practice had evolved to sending respiratory viral PCR tests for the majority of PICU patients with respiratory complaints, even before admission. Since its introduction, respiratory viral PCR panel–testing proponents have advocated its use to reduce unnecessary health care resource use.1–3 However, studies in which authors evaluate the clinical impact of respiratory viral PCR panel testing have varied in their results and lacked consistent evidence to support changes in management or outcomes, including antibiotic administration, chest radiographic imaging, hospital admission, and hospital length of stay.3–7 In addition, commonly held beliefs include the need to test for isolation and cohort practices or to identify treatable viruses. The Choosing Wisely guidelines of the American Society for Clinical Pathology recommend against routine, broad respiratory viral …

Clinical efficacy of respiratory virus detection by using the FilmArray method in children admitted with respiratory infection

Purpose: Respiratory virus infection is a common cause of hospitalization in children. Rapid testing for respiratory viruses, such as the FilmArray method, can be clinically useful. However, insufficient evidence exists to support its use in standard clinical care. Methods: We retrospectively analyzed data from children under 18 years old who received the multiplex real-time polymerase chain reaction array (multiplex RT-PCR) method in 2017 and by FilmArray respiratory panel (FilmArray RP) in 2018. Results: Between January, 2017 and December, 2018, we reviewed data from 1,480 hospitalized children. The number of children with virus detection in respiratory viral PCR was 523 in the multiplex RT-PCR method and 419 in the FilmArray method. Seasonal vi rus outbreak patterns were similar to those of Korea Centers for Disease Control and Prevention in both groups. There was no differ ence between the 2 groups in the mean length of hospital stay. The time from admission to isolation by influenza infection was sig nificantly shorter in the FilmArray group than in the multiplex RT-PCR group among patients who were not diagnosed with influ enza infection by rapid antigen test at the time of admission. Conclusion: The use of FilmArray method for respiratory viruses did not diminish length of hospital stay. However, the FilmArray method may quickly detect the prevalence of respiratory infection and aid in clinical treatment. In addition, it was related with a re duced time from admission to isolation by influenza infection in hospitalized children who were not identified with influenza infec tion by rapid antigen test at the time of admission. (Allergy Asthma Respir Dis 2021;9:12-20)

95. Assess reasons for continuing antibiotics in persons with positive respiratory viruses PCR in the emergency room

BackgroundRespiratory tract infections remain one of the major reasons for inappropriate antibiotic usage. The multiplex PCR respiratory viral panel improves the diagnostic ability of viral causes of RTI and have been advocated as a useful stewardship tool. We sought to evaluate factors leading to continued antibiotic following a positive respiratory viral PCR and to evaluate the impact of a targeted antimicrobial stewardship intervention on antibiotic use.MethodsIn this Quasi experimental study, adult patients presenting to RVH ER with positive respiratory PCR from January 13 2020 to February 27 2020 were reviewed. Patient demographics, clinical, comorbidities, laboratory and radiology reports, antibiotic and antiviral usage before and after test were recorded. For patients without microbiological or radiological evidence of bacterial infection, a standard questionnaire was administered to treating physician. Antibiotic prescribing rate before and following a positive PCR and antibiotic discontinuation following ASP questionnaire was tracked.ResultsDuring the study period, 147 adult patients presented to the ER with positive respiratory PCR were. Among the study population, antibiotic prescription rate was 49% prior to test result. Influenza was the most common respiratory virus isolated(89/147). Following the respiratory viral PCR, antibiotics were stopped 39% and continued in 51 % by the treating physician. Main reasons for antibiotic continuation included concurrent bacterial infection16/30 (pneumonia 9/30), COPD exacerbation 5/30, febrile neutropenia (5/30) and hemodynamic instability(4/30). Antibiotics were continued without obvious indications in 15 patients and were targeted for intervention. Overall 66% (10/15) of ASP interventions were accepted and antibiotics discontinued. Overall antibiotics were discontinued in 53 % of patients in whom they were initiated pretest result.ConclusionThis study shows that positive respiratory virus PCR is very useful as it led to discontinuation of antibiotics by treating physician in 40 % and further 13% by an antibiotic stewardship intervention. Adding a stewardship intervention after test result further adds reduction to antibiotic usage.Disclosures All Authors: No reported disclosures

112. Impact of Respiratory Viral PCR Panels (RVP) and Serum Procalcitonin (PCT) on Antibiotic Days of Therapy (DOT) in Patients Admitted with Lower Respiratory Tract Infections (LRTI)

BackgroundIDSA advocates for the use of RVP and PCT to reduce inappropriate antibiotic use. These assays were implemented in our health system without formal antimicrobial stewardship intervention. Herein, we evaluated assay utilization and impact on antibiotic DOT in patients admitted with LRTI.MethodsRecords of patients admitted to our health system in January 2019 with a diagnosis of LRTI (ICD 10 codes: J13-22, J44, or J85) were reviewed. Patients < 18 years old, receiving active treatment at time of admission for a concurrent infection, or had a RVP or initial PCT ordered > 48 hours from admission were excluded. Patients were cohorted based on at least one test ordered (VPPC) vs neither (CTRL). The primary endpoint was total antibiotic DOT, including inpatient and outpatient. Secondary endpoints were hospital length of stay (LOS), 30 day readmission (30DR), and all cause mortality (ACM). Multivariate linear regression was used to determine variables associated with DOT.ResultsOf 294 patients included, 15 (5.1%), 84 (28.6%), and 43 (14.6%) had RVP alone, PCT alone, or both ordered, respectively, resulting in 142 (48.3%) patients in the VPPC group. Providers modified therapy based on PCT and RVP results in 39.4% (50/127) and 33.3% (7/21) of patients, respectively. Median (IQR) DOT was similar between VPPC and CTRL groups (7 [5–9] vs 7 [3–8] days; p=0.159), respectively. Inpatient DOT (4 [2–5] vs 3 [2–4] days; p=0.001) and LOS (99.5 vs 81.7 hours; p=0.001) were longer in the VPPC group. VPPC patients were more likely to receive anti-pseudomonal B-lactams (anti-PSA) (26.8 vs 16.4%; p=0.044) and anti-MRSA antibiotics (45.1 vs 34.9%; p=0.096). No difference in 30DR (13.4 vs 15.1%; p=0.793) or ACM (2.1 vs 3.3%; p=0.794) was observed. Variables significantly associated with increased DOT were non-ICU admission, positive chest X-ray, LOS, younger age, and receipt of anti-MRSA or anti-PSA antibiotics.ConclusionOver one month, RVP or PCT was ordered in nearly half of admitted LRTI patients in our health system, but modification of therapy based on results was infrequent. The unrestricted use of these tests without stewardship intervention did not impact overall antibiotic DOT, LOS, 30DR, or ACM. These data emphasize the need for additional intervention to enhance the clinical utility of these tests.Disclosures Joseph L. Kuti, PharmD, Allergan (Speaker’s Bureau)bioMérieux (Research Grant or Support, Other Financial or Material Support, Speaker Honorarium)Melinta (Research Grant or Support)Merck & Co., Inc. (Research Grant or Support)Paratek (Speaker’s Bureau)Summit (Other Financial or Material Support, Research funding (clinical trials))

1412. The utility of respiratory viral panel testing for nosocomial fever in the neonatal intensive care unit

BackgroundPatients in the neonatal intensive care unit (NICU) often develop fevers during their inpatient stay. Many neonates are empirically started on antibiotics due to their fragile clinical status. We sought to evaluate whether the respiratory viral panel (RVP) PCR test is associated with use of antibiotics in patients who develop a fever in the NICU.MethodsWe conducted a retrospective chart review on patients admitted to the Level 4 NICU of the University of Maryland Medical Center from November 2015 to June 2018. We included all neonates who developed a fever 48 hours into their admission. We collected demographic information and data on length of stay, fever work-up and diagnostics (including labs, cultures, RVP), and antibiotic use. Descriptive statistics, Fisher exact test, linear regression, and Welch’s ANOVA were performed.ResultsAmong 347 fever episodes, the mean age of neonates was 72.8 ± 21.6 days, and 45.2% were female. Out of 30 total RVP samples analyzed, 2 were positive (6.7%). The most common causes of fever were post-procedural (5.7%), pneumonia (4.8%), urinary tract infection (3.5%), meningitis (2.6%), bacteremia (2.3%), or due to a viral infection (2.0%). Antibiotics were started in 208 patients (60%), while 61 neonates (17.6%) were already on antibiotics. The mean length of antibiotics was 7.5 ± 0.5 days. Neonates were more likely to get started on antibiotics if they had a negative RVP compared to those without a negative RVP (89% vs. 11%, p-value < 0.0001). Patients with a positive RVP had a decreased length of stay compared to those without a positive RVP (30.3 ± 8.7 vs. 96.8 ± 71.3, p-value 0.01). On multivariate linear regression, a positive RVP was not associated with length of stay.ConclusionNeonates with a negative respiratory viral PCR test were more likely to be started on antibiotics for fevers. Respiratory viral PCR testing can be used as a tool to promote antibiotic stewardship in the NICU.Disclosures All Authors: No reported disclosures

SARS-CoV-2 has displaced other seasonal respiratory viruses: Results from a prospective cohort study

ObjectivesThe effect of SARS-CoV-2 on existing respiratory viruses in circulation and the overall burden of viral respiratory disease remains uncertain. Traditionally, severe viral respiratory disease disproportionally affects those with underlying chronic lung diseases. This study aimed to assess the impact of SARS-CoV-2 on the prevalence and clinical characteristics of respiratory virus disease in hospitalised adults. MethodsData for this cohort study were from hospitalised adults who had multiplex PCR testing for respiratory viruses over several seasons in Hampshire, UK. Respiratory virus detection during the first epidemic peak of SARS-CoV-2 was compared to detection during the same time period across previous years. Results856 patients had multiplex PCR for respiratory viruses between March and May over 5 years. Before 2020, a non-SARS-CoV-2 virus was detected in 54% patients (202/371) compared to 4.1% (20/485) in 2020 (p < 0.0001). SARS-CoV-2 was associated with asthma or COPD exacerbations in a smaller proportion of infected patients compared to other viruses (1.0% vs 37%, p < 0.0001). ConclusionsThe emergence of SARS-CoV-2 was associated with substantial reductions in the circulation of seasonal respiratory viruses and large differences in the characteristics of viral-associated disease, including illness in a greater proportion of patients without underlying lung disease.

EVEROLIMUS-INDUCED PULMONARY ALVEOLAR PROTEINOSIS

SESSION TITLE: Medical Student/Resident Diffuse Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Pulmonary alveolar proteinosis (PAP) is a rare respiratory disease characterized by an excessive accumulation of lipoproteinaceous surfactant material in the distal air spaces. This is mostly the result of inadequate clearance of surfactant by alveolar macrophages. Autoimmune etiologies make up ∼90% of adult cases, however there are congenital and secondary etiologies as well (1). We present a unique case of drug induced PAP caused by everolimus use. CASE PRESENTATION: A 44 year old female, history of renal cell carcinoma (RCC) with lung metastasis, presents with 1 week of worsening shortness of breath following a round of chemotherapy and immunotherapy (nivolumab, ipilimumab, everolimus). Associated fever, vomiting and productive cough were also reported. On the scene, EMS reported an oxygen saturation of 81% on room air. In the ED, the patient was placed on BiPAP and started on scheduled breathing treatments, IV fluids and broad spectrum antibiotics. Chest exam revealed diffuse rales. Initial labs showed lactic acidosis without an elevated WBC. ABG showed PaO2 of 103 mmHg on 60% BiPAP. CT chest showed new onset loculated right-sided pleural effusion and extensive left-sided ground glassing, concerning for a crazy pavement appearance. Right-sided thoracentesis was attempted and failed as the fluid could not be aspirated. On Day 2, she was intubated due to worsening respiratory status. Bronchoalveolar lavage (BAL) sample was obtained. BAL cytology was negative for malignant cells or active inflammation, but showed an abundance of amorphous, eosinophilic, periodic acid-Schiff (PAS)-positive material. Bacterial, fungal and viral cultures and respiratory viral PCR were negative. She continued to decline and on day 8, in light of her terminal illness, her family decided to transition to hospice care. Compassionate extubation was done on day 9 and the patient expired shortly after. DISCUSSION: Everolimus is a mammalian target of rapamycin (mTOR) inhibitor, often used in breast, pancreatic and renal carcinoma. Though there have been reports of PAP complicating sirolimus use, no such reports exist for everolimus (2). PAS stains of BAL or lung biopsy samples confirm the diagnosis of PAP. But without a sample, high index of clinical suspicion is needed to differentiate PAP from other pulmonary processes and intervene early. If diagnosed early, stopping the offending agent may be all that is needed. In those with moderate to severe symptoms, whole lung lavage (WLL) is the most accepted intervention. 30-50% of cases only require one lavage, others will require repeat at 6-12-month intervals. Cases refractory to WLL may require trials of GM-CSF inhaled therapy and rituximab but their efficacy has only been shown in autoimmune PAP (3). CONCLUSIONS: We present a case of everolimus induced pulmonary alveolar proteinosis in a patient with metastatic RCC. Diagnosis was confirmed with a PAS-positive BAL sample. Reference #1: Trapnell BC, Whitsett JA, Nakata K. Pulmonary alveolar proteinosis. N Engl J Med 2003; 349:2527. Reference #2: Kadikoy H, Paolini M, Achkar K, et al. Pulmonary alveolar proteinosis in a kidney transplant: a rare complication of sirolimus. Nephrol Dial Transplant 2010; 25: 2795–2798 Reference #3: Kumar A, Abdelmalak B, Inoue Y, Culver DA. Pulmonary alveolar proteinosis in adults: pathophysiology and clinical approach. Lancet Respir Med 2018; 6:554. DISCLOSURES: No relevant relationships by Gnananandh Jayaraman, source=Web Response No relevant relationships by Ramesh Babu Kesavan, source=Web Response No relevant relationships by Robert Liu, source=Web Response No relevant relationships by Sivatej Sarva, source=Web Response

PULMONARY ALVEOLAR PROTEINOSIS IN MYELODYSPLASTIC SYNDROME SECONDARY TO GATA-2 MUTATION (MONOMAC SYNDROME)

SESSION TITLE: Medical Student/Resident Chest Infections Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: The majority of the cases of pulmonary alveolar proteinosis (PAP) occur in patients due to autoimmunity with the GM-CSF antibody. We present here a case of a 29-year-old female with GATA-2 mutation (monoMAC) syndrome who presented with dyspnea and was diagnosed with secondary PAP due to myelodysplastic syndrome. CASE PRESENTATION: A 29-year-old female presented to the hospital with the chief complaint of a nonproductive cough for 2 weeks associated with difficulty in breathing with exertion and intermittent fever. She had a history of heterozygous mutation for GATA-2 and was under treatment at a tertiary care center for early Myelodysplastic syndrome secondary to 9q34 deletion. Her medical history was extensive including Mycobacterium avium intracellulare (MAC) Pneumonia and bacteremia diagnosed 8 months before the presentation and was on azithromycin, ethambutol, and rifabutin for it to complete a total of 12 months of treatment. On presentation, she was febrile at 103 degrees Fahrenheit, tachycardiac at 135 beats per minute and saturating 88% on room air. She was placed on 4 L of oxygen by nasal cannula. Labs showed a WBC count of 8.4 10*3/uL (normal 4.0 - 12.0 10*3/uL) with differential showing a low monocyte count at <1 % (normal 2-8 %). Computed Tomography angiogram was obtained which ruled out a pulmonary embolism but showed diffuse and bilateral alveolar and interstitial pulmonary opacification. She had an extensive infectious, autoimmune, metabolic and cardiovascular workup which was all negative. So, bronchoscopy with bronchoalveolar lavage was obtained which showed an exudative effusion with 84 Polymorphonuclear cells, 2 Lymphocytes, 8 Histiocytes, 6 Eosinophils. BAL fluid was negative for respiratory viral PCR, AFB, fungal culture and bacterial culture, galactomannan and Pneumocystis culture. Cytology was also negative for pathogens or malignant cells. Post-Bronchoscopy the patient’s respiratory status improved, and she was weaned off of the oxygen. Pulmonary function tests (PFT) were also obtained there which revealed a non-specific ventilatory defect with decreased Diffusion lung capacity for Carbon monoxide (DLCO). A lung biopsy was obtained there confirming the diagnosis of pulmonary alveolar proteinosis (PAP). The patient had negative anti-GM-CSF antibodies indicating GATA-2 deficiency as the cause of PAP. The patient is scheduled to get a repeat full lung bronchoalveolar lavage and is currently being evaluated for a lung transplant. DISCUSSION: GATA-2 mutation is identified in cases of PAP secondary to hematological malignancies. Whole lung lavage is the standard of care. Treatment of the hematological malignancy may treat the PAP. There is no evidence of corticosteroids in the treatment of secondary PAP. CONCLUSIONS: Clinicians should be mindful of PAP in treating patients with hematological malignancies with respiratory distress. Reference #1: Ishii H, Seymour JF, Tazawa R, Inoue Y, Uchida N, Nishida A, et al. Secondary pulmonary alveolar proteinosis complicating myelodysplastic syndrome results in worsening of prognosis: a retrospective cohort study in Japan. BMC Pulm Med. 2014;14:37. Reference #2: Seymour JF, Presneill JJ. Pulmonary alveolar proteinosis: progress in the first 44 years. Am J Respir Crit Care Med 2002; 166: 215–235. Reference #3: Milleron BJ, Costabel U, Teschler H, et al. Bronchoalveolar lavage cell data in alveolar proteinosis. Am Rev Respir Dis 1991; 144: 1330–1332. DISCLOSURES: No relevant relationships by Fazal Raziq, source=Web Response No relevant relationships by Muhammad Usama, source=Web Response

Bacterial and fungal coinfection among hospitalized patients with COVID-19: a retrospective cohort study in a UK secondary-care setting

ObjectivesTo investigate the incidence of bacterial and fungal coinfection of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in this retrospective observational study across two London hospitals during the first UK wave of coronavirus disease 2019 (COVID-19). MethodsA retrospective case series of hospitalized patients with confirmed SARS-CoV-2 by PCR was analysed across two acute NHS hospitals (20 February–20 April 2020; each isolate reviewed independently in parallel). This was contrasted to a control group of influenza-positive patients admitted during the 2019–2020 flu season. Patient demographics, microbiology and clinical outcomes were analysed. ResultsA total of 836 patients with confirmed SARS-CoV-2 were included; 27 (3.2%) of 836 had early confirmed bacterial isolates identified (0–5 days after admission), rising to 51 (6.1%) of 836 throughout admission. Blood cultures, respiratory samples, pneumococcal or Legionella urinary antigens and respiratory viral PCR panels were obtained from 643 (77%), 110 (13%), 249 (30%), 246 (29%) and 250 (30%) COVID-19 patients, respectively. A positive blood culture was identified in 60 patients (7.1%), of which 39 were classified as contaminants. Bacteraemia resulting from respiratory infection was confirmed in two cases (one each community-acquired Klebsiella pneumoniae and ventilator-associated Enterobacter cloacae). Line-related bacteraemia was identified in six patients (three Candida, two Enterococcus spp. and one Pseudomonas aeruginosa). All other community-acquired bacteraemias (n = 16) were attributed to nonrespiratory infection. Zero concomitant pneumococcal, Legionella or influenza infection was detected. A low yield of positive respiratory cultures was identified; Staphylococcus aureus was the most common respiratory pathogen isolated in community-acquired coinfection (4/24; 16.7%), with pseudomonas and yeast identified in late-onset infection. Invasive fungal infections (n = 3) were attributed to line-related infections. Comparable rates of positive coinfection were identified in the control group of confirmed influenza infection; clinically relevant bacteraemias (2/141; 1.4%), respiratory cultures (10/38; 26.3%) and pneumococcal-positive antigens (1/19; 5.3%) were low. ConclusionsWe found a low frequency of bacterial coinfection in early COVID-19 hospital presentation, and no evidence of concomitant fungal infection, at least in the early phase of COVID-19.

Influenza B outbreak at an adult cystic fibrosis centre - Clinical impact and factors influencing spread

IntroductionAn outbreak of Influenza B occurred at a large United Kingdom (UK) regional adult cystic fibrosis (CF) centre in May 2016. This was late in the UK 2015–2016 influenza season and occurred on a specialist ward with strict infection control procedures. This study investigates the spread of influenza, clinical consequences and potential contributing factors. MethodsPatient records, clinical status and pulmonary function data were reviewed for all inpatients during this period. Respiratory viral PCR results, influenza vaccination status of patients and staff, and environmental factors were also recorded. Affected patients were prospectively monitored for the following three months. Results10 of 21 inpatients developed influenza B between 5th and 12th May 2016, an attack rate of 48%. All those characterised were confirmed as the same strain of influenza B/Victoria-lineage. Influenza infection resulted in a mean FEV1 reduction of 10.5% (SD 11.3, p = 0.012), which persisted at 3 months post infection (p = 0.003). Nine of the affected cases rooms were in close proximity on the ward while patients in the two isolation rooms with enhanced ventilation did not become infected. Ventilation measurements in affected rooms ranged from 1.75 to 2.10 air changes/hour, below national recommendations. Seventy percent of affected inpatients had received the 2015/16 trivalent seasonal influenza vaccine, which did not contain a B/Victoria-lineage influenza B virus. ConclusionThis influenza B outbreak in CF adults had a high attack rate and a significant clinical impact. Room ventilation and a limited protection from the seasonal influenza vaccine were possible contributory factors.

Impact of respiratory viral polymerase chain reaction testing on de-escalation of antibiotic therapy in children who require chronic positive pressure ventilation.

Children who require chronic positive pressure ventilation (CPPV) are frequently hospitalized with acute respiratory infections. Although respiratory viral testing is often performed, it is unclear how positive results impact antibiotic use. We sought to assess the impact of respiratory viral testing on antibiotic use in hospitalized children on CPPV. This retrospective cohort study included hospitalized children on CPPV who had respiratory viral polymerase chain reaction (RVP) testing on admission. Primary exposure was a positive RVP result; primary outcome was antibiotic de-escalation, defined as discontinuation of antibiotics or narrowing of antimicrobial spectra. To determine the independent association of positive RVP and antibiotic de-escalation, a generalized linear mixed effect model was used to account for within patient clustering and confounders defined a priori (blood and respiratory cultures, leukocytosis, bandemia, chest radiograph findings, aspiration risk, and recent admission). A total of 200 admissions representing 118 patients were included. A viral pathogen was identified in 46.5% (93/200) of admissions; rhinovirus was most frequently identified (61.5% of positive RVPs). Antibiotic de-escalation occurred in 33% of admissions (35.5% of RVP-positive admissions vs 30.8% of RVP-negative admissions; P = .49). In adjusted analysis, there was no association between positive RVP and antibiotics de-escalation (adjusted OR: 0.86; 95% confidence interval: 0.32-2.26). This single center cohort study suggests that respiratory viral testing may not impact antibiotic prescribing for hospitalized children on CPPV. There is need for improved stewardship of both diagnostic testing and antimicrobial use in this population.

COVID-19 &amp; Multiple Myeloma

COVID-19 &amp; Multiple Myeloma

COVID-19 and Renin Angiotensin Blockers: Current Evidence and Recommendations.

COVID-19 and Renin Angiotensin Blockers: Current Evidence and Recommendations.

Human Metapneumovirus Infections in Lung Transplant Recipients: The Effects on Lung Allograft and Clinical Outcomes

Human metapneumovirus infection (HMPVi) is a common community acquired infection in lung transplant recipients (LTRs), but data is very limited. This retrospective study of HMPVi in LTRs at the Johns Hopkins Hospital from Jan 2010 - April 2019 examined mortality, acute cellular rejection (ACR), donor specific antibody (DSA), chronic allograft dysfunction (CLAD) progression at 1 year after HMPVi as well as readmission, secondary bacterial/fungal infection at 90 days after HMPVi. The center's viral treatment practice included education for prompt diagnosis and consideration of ribavirin (RBV) usually with intravenous immunoglobulin (IVIG) for HMPVi. Of 31 HMPV infected LTRs, 22 received RBV (13 oral and 9 inhaled ribavirin) and 9 received supportive care only (SC). Baseline characteristics and infection parameters were similar among the 2 groups except concomitant respiratory bacterial pathogens at diagnosis, use of IVIG, and persistent HMPV shedding. In patients, whose respiratory viral PCR was repeated during day7-day30 post HMPVi, the SC group had significantly higher persistent viral shedding (66.7% vs 9.1% (RBV), p=0.03). There were no significant differences in readmission, death, CLAD progression, and DSA development among the 2 groups. The SC group had higher ACR rate (25% vs 0% (RBV), p = 0.03). Of 27 patients with complete pulmonary function tests, 11 (40.7%) developed CLAD progression within 1 year [50% (SC) vs 36.9% (RBV), p=0.53]. The SC group tended to have more fungal pathogen in respiratory samples (44.4% vs 13.6% (RBV), p= 0.06), but there were no significant differences in invasive fungal or bacterial infection at 90 days post HMPVs. Three patients reported side effects from RBV (nausea, diarrhea, and headache); none prematurely stopped RBV. RBV and IVIG may reduce risk of ACR and may help clear viral shedding. CLAD progression post HMPVi was 40% in this cohort and CLAD progression rates were not different among the 2 groups.

Viral Respiratory Infection, a Risk in Pediatric Cardiac Surgery: A Propensity-Matched Analysis.

1) To describe the postoperative course and outcomes of cardiac surgery in children with perioperative viral respiratory infection, 2) to evaluate optimal surgical timing for preoperative viral respiratory infection patients, and 3) to define risk stratification. Retrospective study of children undergoing cardiac surgery. Children were tested using a multiplex polymerase chain reaction (respiratory virus polymerase chain reaction) panel capturing seven respiratory viruses. Respiratory virus polymerase chain reaction testing was routinely performed in patients under 2 years old. Those with negative results yet highly suspected of viral respiratory infection after surgeries would be tested again. A pediatric cardiac surgical ICU of pediatric cardiac surgery department at Fuwai Hospital. Children admitted between January 1, 2014, and December 31, 2016, to perform respiratory virus polymerase chain reaction testing and cardiac surgery were included. None. A total of 2,831 patients had respiratory virus polymerase chain reaction testing, and viruses were detected in 91 patients (3.2%), including 35 preoperative and 56 postoperative. Of the 35 preoperative viral respiratory infection patients, there were 29 viral respiratory infection-resolved (patients for whom surgery was postponed until resolution of viral respiratory infection symptoms and negative respiratory virus polymerase chain reaction) and six viral respiratory infection-unresolved (who underwent cardiac surgery before resolution of symptoms and clearance of carriage) patients. Furthermore, there were seven deaths, including one in the preoperative viral respiratory infection-unresolved group and six in the postoperative viral respiratory infection group. A propensity score matching was performed to correct the selection bias and identify the comparable patient groups. Compared to their matched nonviral respiratory infection patients, viral respiratory infection-resolved patients had similar duration of mechanical ventilation and length of stay, while viral respiratory infection-unresolved patients had longer durations of postoperative mechanical ventilation (p = 0.033), PICU (p = 0.028) and hospital length of stay (p = 0.010), and postoperative viral respiratory infection patients had significantly greater duration of postoperative recovery (p < 0.001) and higher mortality (p < 0.001). Earlier diagnosis of postoperative viral respiratory infection was associated with longer mechanical ventilation duration (r = 0.422; p < 0.001). Palliative cardiac surgery was the only variable significantly associated with mortality in multivariate analysis (odds ratio, 12.0; 95% CI, 1.6-87.5; p = 0.014). The preoperative-unresolved and postoperative viral respiratory infection were associated with prolonged postoperative recovery, increased severity, and mortality in children with cardiac surgeries. Our results suggested the optimal surgical timing may be after the resolution of viral respiratory infection symptoms and carriage unless the perceived benefits of early surgery outweigh the risk of death, prolonged ventilation, and PICU length of stay. Palliative surgeries were associated with increasing mortality.