Elizabeth Burgener

All Publications

• Bacteriophage and Bacterial Susceptibility, Resistance, and Tolerance to Antibiotics. Pharmaceutics Chen, Q., Dharmaraj, T., Cai, P. C., Burgener, E. B., Haddock, N. L., Spakowitz, A. J., Bollyky, P. L. 2022; 14 (7)

  Abstract

  Bacteriophages, viruses that infect and replicate within bacteria, impact bacterial responses to antibiotics in complex ways. Recent studies using lytic bacteriophages to treat bacterial infections (phage therapy) demonstrate that phages can promote susceptibility to chemical antibiotics and that phage/antibiotic synergy is possible. However, both lytic and lysogenic bacteriophages can contribute to antimicrobial resistance. In particular, some phages mediate the horizontal transfer of antibiotic resistance genes between bacteria via transduction and other mechanisms. In addition, chronic infection filamentous phages can promote antimicrobial tolerance, the ability of bacteria to persist in the face of antibiotics. In particular, filamentous phages serve as structural elements in bacterial biofilms and prevent the penetration of antibiotics. Over time, these contributions to antibiotic tolerance favor the selection of resistance clones. Here, we review recent insights into bacteriophage contributions to antibiotic susceptibility, resistance, and tolerance. We discuss the mechanisms involved in these effects and address their impact on bacterial fitness.

  View details for DOI 10.3390/pharmaceutics14071425

  View details for PubMedID 35890320

• Biochemical, biophysical, and immunological characterization of respiratory secretions in severe SARS-CoV-2 infections. JCI insight Kratochvil, M. J., Kaber, G., Demirdjian, S., Cai, P. C., Burgener, E. B., Nagy, N., Barlow, G. L., Popescu, M., Nicolls, M. R., Ozawa, M. G., Regula, D. P., Pacheco-Navarro, A. E., Yang, S., de Jesus Perez, V. A., Karmouty-Quintana, H., Peters, A. M., Zhao, B., Buja, M. L., Johnson, P. Y., Vernon, R. B., Wight, T. N., Stanford COVID-19 Biobank Study Group, Milla, C. E., Rogers, A. J., Spakowitz, A. J., Heilshorn, S. C., Bollyky, P. L. 2022; 7 (12)

  Abstract

  Thick, viscous respiratory secretions are a major pathogenic feature of COVID-19, but the composition and physical properties of these secretions are poorly understood. We characterized the composition and rheological properties (i.e., resistance to flow) of respiratory secretions collected from intubated COVID-19 patients. We found the percentages of solids and protein content were greatly elevated in COVID-19 compared with heathy control samples and closely resembled levels seen in cystic fibrosis, a genetic disease known for thick, tenacious respiratory secretions. DNA and hyaluronan (HA) were major components of respiratory secretions in COVID-19 and were likewise abundant in cadaveric lung tissues from these patients. COVID-19 secretions exhibited heterogeneous rheological behaviors, with thicker samples showing increased sensitivity to DNase and hyaluronidase treatment. In histologic sections from these same patients, we observed increased accumulation of HA and the hyaladherin versican but reduced tumor necrosis factor-stimulated gene-6 staining, consistent with the inflammatory nature of these secretions. Finally, we observed diminished type I interferon and enhanced inflammatory cytokines in these secretions. Overall, our studies indicated that increases in HA and DNA in COVID-19 respiratory secretion samples correlated with enhanced inflammatory burden and suggested that DNA and HA may be viable therapeutic targets in COVID-19 infection.

  View details for DOI 10.1172/jci.insight.152629

  View details for PubMedID 35730564

• Filamentous bacteriophage delays healing of Pseudomonas-infected wounds. Cell reports. Medicine Bach, M. S., de Vries, C. R., Khosravi, A., Sweere, J. M., Popescu, M. C., Chen, Q., Demirdjian, S., Hargil, A., Van Belleghem, J. D., Kaber, G., Hajfathalian, M., Burgener, E. B., Liu, D., Tran, Q., Dharmaraj, T., Birukova, M., Sunkari, V., Balaji, S., Ghosh, N., Mathew-Steiner, S. S., El Masry, M. S., Keswani, S. G., Banaei, N., Nedelec, L., Sen, C. K., Chandra, V., Secor, P. R., Suh, G. A., Bollyky, P. L. 2022; 3 (6): 100656

  Abstract

  Chronic wounds infected by Pseudomonas aeruginosa (Pa) are characterized by disease progression and increased mortality. We reveal Pf, a bacteriophage produced by Pa that delays healing of chronically infected wounds in human subjects and animal models of disease. Interestingly, impairment of wound closure by Pf is independent of its effects on Pa pathogenesis. Rather, Pf impedes keratinocyte migration, which is essential for wound healing, through direct inhibition of CXCL1 signaling. In support of these findings, a prospective cohort study of 36 human patients with chronic Pa wound infections reveals that wounds infected with Pf-positive strains of Pa are more likely to progress in size compared with wounds infected with Pf-negative strains. Together, these data implicate Pf phage in the delayed wound healing associated with Pa infection through direct manipulation of mammalian cells. These findings suggest Pf may have potential as a biomarker and therapeutic target in chronic wounds.

  View details for DOI 10.1016/j.xcrm.2022.100656

  View details for PubMedID 35732145

• Oral hymecromone decreases hyaluronan in human study participants. The Journal of clinical investigation Rosser, J. I., Nagy, N., Goel, R., Kaber, G., Demirdjian, S., Saxena, J., Bollyky, J. B., Frymoyer, A. R., Pacheco-Navarro, A. E., Burgener, E. B., Rajadas, J., Wang, Z., Arbach, O., Dunn, C. E., Kalinowski, A., Milla, C. E., Bollyky, P. L. 2022; 132 (9)

  Abstract

  BACKGROUNDHyaluronan (HA), an extracellular matrix glycosaminoglycan, has been implicated in the pathophysiology of COVID-19 infection, pulmonary hypertension, pulmonary fibrosis, and other diseases, but is not targeted by any approved drugs. We asked whether hymecromone (4-methylumbelliferone [4-MU]), an oral drug approved in Europe for biliary spasm treatment that also inhibits HA in vitro and in animal models, could be repurposed as an inhibitor of HA synthesis in humans.METHODSWe conducted an open-label, single-center, dose-response study of hymecromone in healthy adults. Subjects received hymecromone at 1200 (n = 8), 2400 (n = 9), or 3600 (n = 9) mg/d divided into 3 doses daily, administered orally for 4 days. We assessed safety and tolerability of hymecromone and analyzed HA, 4-MU, and 4-methylumbelliferyl glucuronide (4-MUG; the main metabolite of 4-MU) concentrations in sputum and serum.RESULTSHymecromone was well tolerated up to doses of 3600 mg/d. Both sputum and serum drug concentrations increased in a dose-dependent manner, indicating that higher doses lead to greater exposures. Across all dose arms combined, we observed a significant decrease in sputum HA from baseline after 4 days of treatment. We also observed a decrease in serum HA. Additionally, higher baseline sputum HA levels were associated with a greater decrease in sputum HA.CONCLUSIONAfter 4 days of exposure to oral hymecromone, healthy human subjects experienced a significant reduction in sputum HA levels, indicating this oral therapy may have potential in pulmonary diseases where HA is implicated in pathogenesis.TRIAL REGISTRATIONClinicalTrials.gov NCT02780752.FUNDINGStanford Medicine Catalyst, Stanford SPARK, Stanford Innovative Medicines Accelerator program, NIH training grants 5T32AI052073-14 and T32HL129970.

  View details for DOI 10.1172/JCI157983

  View details for PubMedID 35499083

• The filamentous Pseudomonas phage Pf disrupts airway basal cell proliferation Burgener, E., Hernandez, L., Bollyky, P., Milla, C. EUROPEAN RESPIRATORY SOC JOURNALS LTD. 2021

  View details for DOI 10.1183/13993003.congress-2021.PA3616

  View details for Web of Science ID 000747452104439

• Dynamic light scattering microrheology for soft and living materials. Soft matter Cai, P. C., Krajina, B. A., Kratochvil, M. J., Zou, L., Zhu, A., Burgener, E. B., Bollyky, P. L., Milla, C. E., Webber, M. J., Spakowitz, A. J., Heilshorn, S. C. 2021

  Abstract

  We present a method for using dynamic light scattering in the single-scattering limit to measure the viscoelastic moduli of soft materials. This microrheology technique only requires a small sample volume of 12 muL to measure up to six decades in time of rheological behavior. We demonstrate the use of dynamic light scattering microrheology (DLSmuR) on a variety of soft materials, including dilute polymer solutions, covalently-crosslinked polymer gels, and active, biological fluids. In this work, we detail the procedure for applying the technique to new materials and discuss the critical considerations for implementing the technique, including a custom analysis script for analyzing data output. We focus on the advantages of applying DLSmuR to biologically relevant materials: breast cancer cells encapsulated in a collagen gel and cystic fibrosis sputum. DLSmuR is an easy, efficient, and economical rheological technique that can guide the design of new polymeric materials and facilitate the understanding of the underlying physics governing behavior of naturally derived materials.

  View details for DOI 10.1039/d0sm01597k

  View details for PubMedID 33427280

• The Safety and Toxicity of Phage Therapy: A Review of Animal and Clinical Studies. Viruses Liu, D., Van Belleghem, J. D., de Vries, C. R., Burgener, E., Chen, Q., Manasherob, R., Aronson, J. R., Amanatullah, D. F., Tamma, P. D., Suh, G. A. 2021; 13 (7)

  Abstract

  Increasing rates of infection by antibiotic resistant bacteria have led to a resurgence of interest in bacteriophage (phage) therapy. Several phage therapy studies in animals and humans have been completed over the last two decades. We conducted a systematic review of safety and toxicity data associated with phage therapy in both animals and humans reported in English language publications from 2008-2021. Overall, 69 publications met our eligibility criteria including 20 animal studies, 35 clinical case reports or case series, and 14 clinical trials. After summarizing safety and toxicity data from these publications, we discuss potential approaches to optimize safety and toxicity monitoring with the therapeutic use of phage moving forward. In our systematic review of the literature, we found some adverse events associated with phage therapy, but serious events were extremely rare. Comprehensive and standardized reporting of potential toxicities associated with phage therapy has generally been lacking in the published literature. Structured safety and tolerability endpoints are necessary when phages are administered as anti-infective therapeutics.

  View details for DOI 10.3390/v13071268

  View details for PubMedID 34209836

• Filamentous Bacteriophages and the Competitive Interaction between Pseudomonas aeruginosa Strains under Antibiotic Treatment: a Modeling Study. mSystems Pourtois, J. D., Kratochvil, M. J., Chen, Q., Haddock, N. L., Burgener, E. B., De Leo, G. A., Bollyky, P. L. 2021: e0019321

  Abstract

  Pseudomonas aeruginosa (Pa) is a major bacterial pathogen responsible for chronic lung infections in cystic fibrosis patients. Recent work has implicated Pf bacteriophages, nonlytic filamentous viruses produced by Pa, in the chronicity and severity of Pa infections. Pf phages act as structural elements in Pa biofilms and sequester aerosolized antibiotics, thereby contributing to antibiotic tolerance. Consistent with a selective advantage in this setting, the prevalence of Pf-positive (Pf+) bacteria increases over time in these patients. However, the production of Pf phages comes at a metabolic cost to bacteria, such that Pf+ strains grow more slowly than Pf-negative (Pf-) strains in vitro. Here, we use a mathematical model to investigate how these competing pressures might influence the relative abundance of Pf+ versus Pf- strains in different settings. Our model suggests that Pf+ strains of Pa cannot outcompete Pf- strains if the benefits of phage production falls onto both Pf+ and Pf- strains for a majority of parameter combinations. Further, phage production leads to a net positive gain in fitness only at antibiotic concentrations slightly above the MIC (i.e., concentrations for which the benefits of antibiotic sequestration outweigh the metabolic cost of phage production) but which are not lethal for Pf+ strains. As a result, our model suggests that frequent administration of intermediate doses of antibiotics with low decay rates and high killing rates favors Pf+ over Pf- strains. These models inform our understanding of the ecology of Pf phages and suggest potential treatment strategies for Pf+ Pa infections. IMPORTANCE Filamentous phages are a frontier in bacterial pathogenesis, but the impact of these phages on bacterial fitness is unclear. In particular, Pf phages produced by Pa promote antibiotic tolerance but are metabolically expensive to produce, suggesting that competing pressures may influence the prevalence of Pf+ versus Pf- strains of Pa in different settings. Our results identify conditions likely to favor Pf+ strains and thus antibiotic tolerance. This study contributes to a better understanding of the unique ecology of filamentous phages in both environmental and clinical settings and may facilitate improved treatment strategies for combating antibiotic tolerance.

  View details for DOI 10.1128/mSystems.00193-21

  View details for PubMedID 34156288

• Hyaluronan is abundant in COVID-19 respiratory secretions. medRxiv : the preprint server for health sciences Kaber, G., Kratochvil, M. J., Burgener, E. B., Peltan, E. L., Barlow, G., Yang, S., Nicolls, M. R., de Jesus Perez, V., Rosser, J. I., Wardle, A. J., Kalinowski, A., Ozawa, M. G., Regula, D. P., Nagy, N., Heilshorn, S. C., Milla, C. E., Rogers, A. J., Bollyky, P. L. 2020

  Abstract

  COVID-19 respiratory infections are associated with copious, adherent respiratory secretions that prolong chronic ventilation and contribute to the morbidity and mortality caused by the disease. We hypothesized that hyaluronan, an extracellular matrix glycosaminoglycan produced at sites of active inflammation that promotes edema in other settings, might be a component of these secretions. To interrogate this, we examined the respiratory secretions collected from eight intubated patients with COVID-19, six control patients with cystic fibrosis (CF), a different respiratory disease also associated with thick adherent secretions, and eight healthy controls. In this sample set we found that hyaluronan content is increased approximately 20-fold in both CF and COVID-19 patients compared to healthy controls. The hyaluronan in COVID-19 samples was comprised of low-molecular weight fragments, the hyaluronan form most strongly linked with pro-inflammatory functions. Hyaluronan is similarly abundant in histologic sections from cadaveric lung tissue from COVID-19 patients. These findings implicate hyaluronan in the thick respiratory secretions characteristic of COVID-19 infection. Therapeutic strategies targeting hyaluronan should be investigated further for potential use in patients with COVID-19.

  View details for DOI 10.1101/2020.09.11.20191692

  View details for PubMedID 32935110

  View details for PubMedCentralID PMC7491514

• Area Under the Curve Achievement of Once Daily Tobramycin in Children with Cystic Fibrosis during Clinical Care. Pediatric pulmonology Brockmeyer, J. M., Wise, R. T., Burgener, E. B., Milla, C., Frymoyer, A. 2020

  Abstract

  BACKGROUND: The area under the concentration-time curve over 24 hours (AUC24 ) is frequently utilized to monitor tobramycin exposure in children with cystic fibrosis (CF). An understanding of exposure target achievement during clinical implementation of an AUC24 based approach in children is limited.METHODS: A retrospective chart review was performed in children with CF treated with once daily tobramycin and drug concentration monitoring at a pediatric CF center. During clinical care AUC24 was estimated using a traditional log-linear regression approach (LLR). AUC24 was also estimated retrospectively using a pharmacokinetic model-based Bayesian forecasting approach (BF). AUC24 achievement after both approaches were compared.RESULTS: In 77 treatment courses (mean age 12.7 ± 5.0 years), a target AUC24 100-125 mg*h/L was achieved after starting dose in 21 (27%) and after initial dose adjustment in 35 (45%). In the first 7 days of treatment, 24 (32%) required ≥3 dose adjustments, and the mean number of drug concentrations measured was 7.1 ± 3.2. Examination of a BF approach demonstrated adequate prediction of measured tobramycin concentrations (median bias -2.1% [95% CI -3.1 to -1.4]; median precision 7.6% [95% CI 7.1 to 8.2%]). AUC24 estimates utilizing the BF approach were higher than the LLR approach with a mean difference of 6.4 mg*h/L (95% CI 4.8 to 8.0 mg*h/L).CONCLUSIONS: Achievement of a narrow AUC24 target is challenging during clinical care, and dose individualization is needed in most children with CF. Implementing a BF approach for estimating AUC24 in children with CF is supported. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/ppul.25037

  View details for PubMedID 32827334

• Methods for Extraction and Detection of Pf Bacteriophage DNA from the Sputum of Patients with Cystic Fibrosis. PHAGE (New Rochelle, N.Y.) Burgener, E. B., Secor, P. R., Tracy, M. C., Sweere, J. M., Bik, E. M., Milla, C. E., Bollyky, P. L. 2020; 1 (2): 100–108

  Abstract

  Background: There is increasing interest in the pulmonary microbiome's bacterial and viral communities, particularly in the context of chronic airway infections in cystic fibrosis (CF). However, the isolation of microbial DNA from the sputum from patients with CF is technically challenging and the optimal protocols for the analysis of viral species, including bacteriophage, from clinical samples remains difficult. Materials and Methods: In this study, we evaluate a set of methods developed for processing and analyzing sputum from patients with CF with the goal of detecting Pf bacteriophage virion-derived nucleic acid. We evaluate the impact of bead beating, deoxyribonuclease digestion, and heating steps in these protocols focusing on the quantitative assessment of Pseudomonas aeruginosa and Pf bacteriophage in sputum. Results: Based on these comparative data, we describe an optimized protocol for processing sputum from patients with CF and isolating DNA for polymerase chain reaction or sequencing-based studies. Conclusion: These studies demonstrate the assessment of a specific bacteriophage and bacteria in sputum from patients with CF.

  View details for DOI 10.1089/phage.2020.0003

  View details for PubMedID 32626852

  View details for PubMedCentralID PMC7327540

• Pf Bacteriophage and Their Impact on Pseudomonas Virulence, Mammalian Immunity, and Chronic Infections. Frontiers in immunology Secor, P. R., Burgener, E. B., Kinnersley, M. n., Jennings, L. K., Roman-Cruz, V. n., Popescu, M. n., Van Belleghem, J. D., Haddock, N. n., Copeland, C. n., Michaels, L. A., de Vries, C. R., Chen, Q. n., Pourtois, J. n., Wheeler, T. J., Milla, C. E., Bollyky, P. L. 2020; 11: 244

  Abstract

  Pf bacteriophage are temperate phages that infect the bacterium Pseudomonas aeruginosa, a major cause of chronic lung infections in cystic fibrosis (CF) and other settings. Pf and other temperate phages have evolved complex, mutualistic relationships with their bacterial hosts that impact both bacterial phenotypes and chronic infection. We and others have reported that Pf phages are a virulence factor that promote the pathogenesis of P. aeruginosa infections in animal models and are associated with worse skin and lung infections in humans. Here we review the biology of Pf phage and what is known about its contributions to pathogenesis and clinical disease. First, we review the structure, genetics, and epidemiology of Pf phage. Next, we address the diverse and surprising ways that Pf phages contribute to P. aeruginosa phenotypes including effects on biofilm formation, antibiotic resistance, and motility. Then, we cover data indicating that Pf phages suppress mammalian immunity at sites of bacterial infection. Finally, we discuss recent literature implicating Pf in chronic P. aeruginosa infections in CF and other settings. Together, these reports suggest that Pf bacteriophage have direct effects on P. aeruginosa infections and that temperate phages are an exciting frontier in microbiology, immunology, and human health.

  View details for DOI 10.3389/fimmu.2020.00244

  View details for PubMedID 32153575

  View details for PubMedCentralID PMC7047154

• Filamentous bacteriophages are associated with chronic Pseudomonas lung infections and antibiotic resistance in cystic fibrosis SCIENCE TRANSLATIONAL MEDICINE Burgener, E. B., Sweere, J. M., Bach, M. S., Secor, P. R., Haddock, N., Jennings, L. K., Marvig, R. L., Johansen, H., Rossi, E., Cao, X., Tian, L., Nedelec, L., Molin, S., Bollyky, P. L., Milla, C. E. 2019; 11 (488)

  View details for DOI 10.1126/scitranslmed.aau9748

  View details for Web of Science ID 000465116400003

• Cystic fibrosis transmembrane conductance regulator modulators: precision medicine in cystic fibrosis CURRENT OPINION IN PEDIATRICS Burgener, E. B., Moss, R. B. 2018; 30 (3): 372–77

  View details for DOI 10.1097/MOP.0000000000000627

  View details for Web of Science ID 000434302200010

• Diffuse Large Pulmonary Nodules in a Young Child: Is It Always Metastatic? Burgener, E. B., Milla, C. E. AMER THORACIC SOC. 2018

  View details for Web of Science ID 000449980302091

• Teaching High-Value Care in Pediatrics: A National Survey of Current Practices and Guide for Future Curriculum Development. Journal of graduate medical education Tchou, M. J., Walz, A., Burgener, E., Schroeder, A., Blankenburg, R. 2017; 9 (6): 741-747

  Abstract

  Health care expenditures in the United States are increasing at an unsustainable pace. There have been calls to incorporate education on resource stewardship into medical training, yet the perceived need for and current use of high-value care (HVC) curricula in pediatrics residency programs is unknown.We described the current national landscape of HVC curricula in pediatrics residencies, including characterization of current programs, barriers to the practice of HVC, and clarification of preferred curricula types.Using a cross-sectional study design, we conducted a national, anonymous, web-based survey of pediatrics residency program directors and pediatrics chief residents in fall 2014.We received responses from 85 of 199 (43%) pediatrics program directors and 74 of 199 (37%) pediatrics chief residents. Only 10% (8 of 80) of program directors and 12% (8 of 65) of chief residents reported having a formal curriculum on HVC. Respondents identified the largest barriers to HVC as a lack of cost transparency (program directors) and attending physicians having the final say in treatment decisions (chief residents). The majority of respondents (83%, 121 of 146) agreed their program needs a HVC curriculum, and 90% (131 of 145) reported they would use a curriculum if it was available. Respondents significantly preferred a case-based conference discussion format over other approaches.Most pediatrics residency programs responding to a survey lacked formal HVC curricula. There is a desire nationally for HVC education in pediatrics, particularly in a case-based discussion format.

  View details for DOI 10.4300/JGME-D-17-00139.1

  View details for PubMedID 29270265

  View details for PubMedCentralID PMC5734330

• 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

• Eosinophilic Pneumonitis As Initial Presentation Of Acute Lymphoblastic Leukemia Burgener, E. B., Milla, C. E. AMER THORACIC SOC. 2016

  View details for Web of Science ID 000390749607630

• Case 3 Lactic Acidosis and Cardiovascular Collapse in a Teen With Ulcerative Colitis PEDIATRICS IN REVIEW Wallenstein, M. B., Burgener, E. B., Klotz, J., Kerner, J. A. 2014; 35 (10): 444–46

  View details for Web of Science ID 000421128400006

• 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