(Speaker Term: 7/1/13 - 6/30/15)
Chief of Microbiology Service
Department of Laboratory Medicine
National Institutes of Health
Building 10, Room 2C-385
10 Center Drive MSC 1508
Bethesda, MD 20892-1508
LECTURE TOPICS AND DESCRIPTIONS
MALDI-TOF Mass Spectrometry for Microbial Identification, Including Mold Database Validation at NIH Followed by Incorporation into Routine Clinical Workflow
Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) is a powerful tool for the rapid and highly accurate identification of clinical pathogens. Bacterial and yeast identification, as well as rapid identification directly from blood cultures, are now part of routine practice in some clinical laboratories. At NIH, a simple, fast mold extraction procedure was developed and a highly stringent, comprehensive mold database developed. Investigations are underway to expand the use of MALDI-TOF into new areas such as resistance testing, typing, and improved identification from direct specimens.
Investigations of Two Unexpected Fatal Infections: Disseminated Histoplasmosis in a Gene Therapy Trial and Yersinia pestis Septicemia in a Researcher
During what started as routine work-up, the clinical microbiology laboratory received specimens from two very unusual cases. The first investigation was of a case of disseminated histoplasmosis, complicated by retroperitoneal bleeding in a patient who was receiving systemic immunosuppressive therapy for rheumatoid arthritis and who was enrolled in a gene-therapy trial of a tumor necrosis factor α antagonist through an adeno-associated virus delivery system. The second investigation involved a case of lethal septicemic plague caused by an attenuated Yersinia pestis isolate in a researcher with previously undiagnosed hereditary hemochromatosis. The cases highlight multiple issues for current research studies and clinical trials, including safety, analysis of uncommon organisms, processes for the management of complications during clinical trials, and the balance of patient privacy with media involvement in such cases.
Quantitative Detection and Monitoring of Viremia in Transplant Patients
Viral infections are a significant cause of morbidity and mortality in patients who are immunocompromised due to solid-organ and bone marrow transplantation. Detection and monitoring of the viral load of cytomegalovirus, Epstein-Barr virus, BK virus, and adenovirus are increasingly used to guide patient management. The transplant population is growing, as is the need for more laboratories to offer this testing. While quantitative real-time PCR is a rapid and sensitive technique, validation of these assays is challenging; there is significant interlaboratory variability and a need for standardization and proficiency testing.
Molecular Testing for Respiratory Viruses: Integration into Clinical Practice
Molecular methods for rapid diagnosis of respiratory infections have superior sensitivity and specificity compared to more conventional methods, with more rapid turn-around-time than the slower culture methods. Efficiency and cost are important variables to consider as these molecular assays are implemented because the reagents can be quite expensive and the assays can be very labor intensive and may require a higher level of technical skill. Important issues to address include the ability to detect newly identified and newly emerging respiratory viruses, understanding the clinical significance of such viruses, and understanding the clinical significance of detecting multiple pathogens in a patient.
The Pathogenesis of Staphylococcal Pneumonia
Pneumonia due to Staphylococcus aureus causes significant morbidity and mortality in both children and adults. The alpha-hemolysin of S. aureus has been identified through animal models of pneumonia as one of the critical virulence factors for lung injury. Recent identification of ADAM10 as the host receptor for the bacterial toxin and studies demonstrating the role of Th17 cells in response to the toxin have further defined mechanism of action of this virulence factor and provided potential new therapeutic options in the form of vaccine candidates and small molecular inhibitors of Staphylococcal toxins.
BIOGRAPHICAL SKETCH – Karen M. Frank, M.D., Ph.D., D(ABMM)
Dr. Karen Frank is the Chief of the Microbiology Service of the Department of Laboratory Medicine at the NIH Clinical Center. She joined the NIH after serving as the Director of Microbiology and Immunology Laboratories at the University of Chicago. She received her M.D., Ph.D. from the University of Pennsylvania, performed her residency in Clinical Pathology at the Brigham & Women’s Hospital, and completed her postdoctoral training in a Howard Hughes Medical Institute Laboratory at the Boston Children’s Hospital. Dr. Frank is a board-certified Clinical Pathologist and a Diplomate of the American Board of Medical Microbiology. She is the incoming Chair of the Resident In-Service Exam Committee of the American Society of Clinical Pathology, has served on the executive council of the Academy of Clinical Laboratory Physicians and Scientists, and has been the Director of an ACGME-accredited Clinical Microbiology Fellowship. She has served as a consultant for medical student education in China as part of the Wuhan Medical Education Reform Project. Her research projects include an evaluation of MALDI-TOF identification of microorganisms, investigation of carbapenemase resistance in Gram-negative Enterobacteriaceae, and investigation of the mechanism of lung injury due to Staphylococcus aureus alpha-hemolysin using a murine model of pneumonia.
CV is available by request from firstname.lastname@example.org at ASM Headquarters
ASM MEMBERSHIP AFFILIATION – Karen M. Frank, M.D., Ph.D., D(ABMM)
Primary Division: C (Clinical Microbiology)
Secondary Division: E (Immunology)
LECTURER’S PERSONAL STATEMENT – Karen M. Frank, M.D., Ph.D., D(ABMM)
As a clinical microbiology lab director and a basic scientist, I see how the clinical work directs the questions for research, and how the approach to basic science improves quality and troubleshooting in the clinical lab. Having taught medical students, graduate students, residents, and fellows for 14 years, I have adapted my style of teaching to engage the trainee, and questions from students definitely increase my own learning. One of the most enjoyable aspects of my job is working with trainees to explore career options and choose a path about which they are most passionate. The field of microbiology is moving rapidly, and staying on top of the changes in diagnostics is challenging, but exciting. The ASM Distinguished Lecture Series is a way for ASM to bring the advances to the regional (Branch) meetings, sharing lectures with more laboratorians and keeping more microbiologists informed.