Research & Scholarship

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  • Pf Phage in Chronic Pseudomonas aeruginosa Wound Infections Bach, M. S., Sweere, J., Burgener, E. B., Bollyky, P. L., Suh, G. A. WILEY. 2018: A5
  • Cystic fibrosis transmembrane conductance regulator modulators: precision medicine in cystic fibrosis. Current opinion in pediatrics Burgener, E. B., Moss, R. B. 2018

    Abstract

    The aim of this study was to describe the newest development in cystic fibrosis (CF) care, CF transmembrane conductance regulator (CFTR) modulator therapies.Phase II results showing CFTR modulator triple therapies are more effective than current CFTR modulators.CFTR modulator therapy targets the protein defective in CF and boosts its function, but the drug must match mutation pathobiology. Ivacaftor, a CFTR potentiator, was the first modulator approved in 2012, with impressive improvement in lung function and other measures of disease in patients with gating and other residual function mutations (∼10% of CF patients). In 2015, the combination of lumacaftor, a CFTR corrector, and ivacaftor was approved for patients homozygous for the F508del mutation (∼40-50% of the CF population) with positive but less impressive clinical response and 10-20% incidence of intolerance. A next-generation CFTR corrector, tezacaftor, with ivacaftor equally effective and better tolerated than lumacaftor, has also received US Food and Drug Administration approval. Novel CFTR correctors, entering Phase 3 trials in triple modulator combination with tezacaftor-ivacaftor, appear substantially more effective for patients who are homozygous for the F508del mutation and can provide benefit for patients with a single F508del mutation. This offers promise of effective CFTR modulator therapy for nearly 90% of CF patients.

    View details for DOI 10.1097/MOP.0000000000000627

    View details for PubMedID 29538046

  • PF BACTERIOPHAGE IN PATIENTS WITH CYSTIC FIBROSIS (CF) IS ASSOCIATED WITH INCREASED SPUTUM ELASTASE AND PSEUDOMONAS AERUGINOSA LOAD Burgener, E. B., Sweere, J. M., Bollyky, P. L., Milla, C. WILEY. 2017: S350
  • Clinical characteristics and outcomes of pediatric patients with CMV DNA detection in bronchoalveolar lavage fluid. Pediatric pulmonology Burgener, E. B., Waggoner, J., Pinsky, B. A., Chen, S. F. 2017; 52 (1): 112-118

    Abstract

    Cytomegalovirus (CMV) infection can cause severe pulmonary disease in immunocompromised patients. There are no standard diagnostic criteria for CMV pulmonary disease beyond histopathology findings on lung tissue, which is challenging to obtain in pediatric patients. Bronchoalveolar lavage (BAL) fluid is easier to obtain. Since CMV remains latent after primary infection and can potentially reactivate due to any inflammatory response, CMV detection in BAL specimen may not indicate acute CMV pulmonary disease. Thus, we describe the clinical manifestations and outcomes of pediatric patients with CMV detection in BAL fluid.We reviewed the clinical, radiologic, and laboratory data of patients <19 years old with a BAL specimen positive for CMV during a 5-year period.Thirty-four encounters in 29 patients were found with CMV detected in their BAL specimen. Half (17/34) of the encounters were in immunocompromised patients. CMV, polymerase chain reaction (PCR) was the most common positive test. Forty-seven percent of the patients had other infections detected in BAL specimens. The majority of patients were never treated for CMV and resolved their acute respiratory illness. Only one patient had probable CMV pulmonary disease.CMV is frequently recovered from BAL specimens but does not usually indicate acute CMV pulmonary disease. We would suggest that other diagnoses be considered first, even if CMV is recovered. Pediatr Pulmonol. 2016; 9999:XX-XX. © 2016 Wiley Periodicals, Inc.

    View details for DOI 10.1002/ppul.23494

    View details for PubMedID 27280337

  • Molecular and Culture-Based Bronchoalveolar Lavage Fluid Testing for the Diagnosis of Cytomegalovirus Pneumonitis. Open forum infectious diseases Tan, S. K., Burgener, E. B., Waggoner, J. J., Gajurel, K., Gonzalez, S., Chen, S. F., Pinsky, B. A. 2016; 3 (1): ofv212-?

    Abstract

    Background.  Cytomegalovirus (CMV) is a major cause of morbidity and mortality in immunocompromised patients, with CMV pneumonitis among the most severe manifestations of infection. Although bronchoalveolar lavage (BAL) samples are frequently tested for CMV, the clinical utility of such testing remains uncertain. Methods.  Retrospective analysis of adult patients undergoing BAL testing via CMV polymerase chain reaction (PCR), shell vial culture, and conventional viral culture between August 2008 and May 2011 was performed. Cytomegalovirus diagnostic methods were compared with a comprehensive definition of CMV pneumonitis that takes into account signs and symptoms, underlying host immunodeficiency, radiographic findings, and laboratory results. Results.  Seven hundred five patients underwent 1077 bronchoscopy episodes with 1090 BAL specimens sent for CMV testing. Cytomegalovirus-positive patients were more likely to be hematopoietic cell transplant recipients (26% vs 8%, P < .0001) and less likely to have an underlying condition not typically associated with lung disease (3% vs 20%, P < .0001). Histopathology was performed in only 17.3% of CMV-positive bronchoscopy episodes. When CMV diagnostic methods were evaluated against the comprehensive definition, the sensitivity and specificity of PCR, shell vial culture, and conventional culture were 91.3% and 94.6%, 54.4% and 97.4%, and 28.3% and 96.5%, respectively. Compared with culture, PCR provided significantly higher sensitivity and negative predictive value (P ≤ .001), without significantly lower positive predictive value. Cytomegalovirus quantitation did not improve test performance, resulting in a receiver operating characteristic curve with an area under the curve of 0.53. Conclusions.  Cytomegalovirus PCR combined with a comprehensive clinical definition provides a pragmatic approach for the diagnosis of CMV pneumonitis.

    View details for DOI 10.1093/ofid/ofv212

    View details for PubMedID 26885542

    View details for PubMedCentralID PMC4752011

  • Eosinophilic Pneumonitis As Initial Presentation Of Acute Lymphoblastic Leukemia Burgener, E. B., Milla, C. E. AMER THORACIC SOC. 2016
  • Index of suspicion. Pediatrics in review Todd, S., Arora, R., Kannikeswaran, N., Allarakhia, I., Sivaswamy, L., Wallenstein, M. B., Burgener, E. B., Klotz, J., Kerner, J. A. 2014; 35 (10): 439-446

    View details for DOI 10.1542/pir.35-10-439

    View details for PubMedID 25274971

  • The impact of the central venous catheter on the diagnosis of infectious endocarditis using Duke criteria in children with Staphylococcus aureus bacteremia PEDIATRIC INFECTIOUS DISEASE JOURNAL Bendig, E. A., Singh, J., Butler, T. J., Arrieta, A. C. 2008; 27 (7): 636-639

    Abstract

    Infective endocarditis (IE) is a known complication of Staphylococcus aureus bacteremia in pediatric patients. We sought to evaluate the impact of prolonged bacteremia associated with a retained central venous catheter (CVC) in the diagnosis of IE using Duke criteria.We conducted a 13-year retrospective review of hospitalized patients with blood cultures positive for S. aureus from 1993 to 2005. Subjects were identified from the microbiology database and medical records. To identify patients with IE we retrospectively applied the Duke criteria by recording the number of positive blood cultures, time to sterilization, presence of congenital heart disease, fever >38.5 degrees C, and echocardiographic findings.During the study period, 344 events of S. aureus bacteremia were identified in 316 pediatric patients. S. aureus bacteremia attributable mortality was 1.7% (n = 6), all among patients with comorbid conditions. By applying the Duke criteria to the 206 (60%) patients who received echocardiographic evaluation, 78 (37.9%) patients were given a diagnosis of IE (7 definite; 71 possible). The incidence of definite IE in patients with CVC is 3.4% and the incidence in patients without CVC is 3.4% (P = 0.6305). The incidence of possible IE in patients with CVC is 42.9%, whereas the incidence in patients without CVC is 23% (P = 0.002).Evaluation for IE is inconsistently done. The presence of a CVC may skew the diagnosis of IE by prolonging the bacteremic state. We believe that a major microbiologic criteria should not be assumed unless cultures remain positive after removal of CVC.

    View details for DOI 10.1097/INF.0b013e31816b78c8

    View details for Web of Science ID 000257176600010

    View details for PubMedID 18520969